This study investigates the comparative performance of autoencoders and traditional machine learning (ML) algorithms in predicting tumor dynamics following Gamma Knife radiosurgery (GKRS) for brain metastases (BMs). The research retrospectively analyzed clinical data from 77 patients (median age: 64 years; 45 males, 32 females) treated at the “Prof. Dr. NicolaeOblu” Emergency Clinic Hospital-Iasi. The dataset comprised 12 variables, including socio-demographic, clinical, treatment, and radiosurgery-related factors. The primary outcome was tumor progression or regression within three months post-GKRS, with 71 cases of regression and 6 cases of progression observed. Traditional ML models—Logistic Regression, Support Vector Machine (SVM), K-Nearest Neighbors (KNN), Extra Trees, Random Forest, and XGBoost—were evaluated, achieving accuracy rates ranging from 0.91 (KNN) to 1.00 (Extra Trees). When incorporating features extracted by autoencoders, the performance of these models generally improved, especially with compression in the bottleneck layer. For instance, Logistic Regression's accuracy increased from 0.91 to 0.94, while SVM's accuracy improved significantly from 0.85 to 0.96. XGBoost consistently performed well across both traditional and hybrid setups, maintaining an accuracy of 0.94 with an AUC of 0.98. The findings suggest that hybrid approaches combining deep learning with traditional ML techniques can significantly enhance predictive accuracy and robustness, particularly in the context of GKRS for BMs. This improved performance has potential implications for more informed clinical decision-making in personalized medicine.

Background: Various vitamins and minerals have been implicated in the aetiology of depression. Objective: To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomization (MR). Methods: We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566), and rMDD (cases=17,451; controls=62,482). Results: None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g. cIVW), highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (OR_cIVW 0.90 per SD increase; 95% CI 0.85- 0.95; p=0.0003); erythrocyte copper (OR_cIVW 0.97; 95% CI 0.95- 0.99; p=0.0004); and 25(OH) vitamin D (OR_cIVW 0.81; 0.66- 0.99; p=0.04). Apparent adverse effects of increased selenium on the risk of MDD (OR_cIVW 1.03; 95% CI 1.02-1.05; p=0.0003) and rMDD (OR_cIVW 1.08; 95% CI 1.00-1.08; p=0.06), and serum magnesium on rMDD (OR_cIVW 1.21; 1.01- 1.44; p=0.04); were less consistent between methods and may be driven by pleiotropy. Conclusions: Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates, and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess.

Chronic noncommunicable diseases (NCDs) are responsible for approximately 74% of deaths globally. Medicinal plants have traditionally been used to treat NCDs, including diabetes, cancer, and rheumatic diseases, and are a source of anti-inflammatory compounds. This study aimed to evaluate the anti-inflammatory effects of Rhus trilobata (Rt) extracts and fractions in lipopolysaccharide (LPS)-induced inflammation models in vitro and in vivo. The aqueous extract (RtAE) and five fractions (F2 to F6) were obtained via C18 solid-phase separation and tested in murine LPS-induced J774.1 macrophages. Key inflammatory markers such as IL-1β, IL-6, TNF-α, and COX-2 gene expression were measured using RT-qPCR, and PGE2 production was assessed via HPLC-DAD. The in vivo effects were tested in an LPS-induced paw edema model in Wistar rats. Results showed that RtAE at 15 μg/mL significantly decreased IL-1β and IL-6 gene expression in vitro. Fraction F6 further reduced IL-1β, TNF-α, and IL-6 gene expression, COX-2 expression, and PGE2 production. In vivo, F6 significantly reduced LPS-induced paw edema, inflammatory infiltration, and IL-1β and COX-2 protein expression. These findings support the anti-inflammatory potential of RtAE and F6, reinforcing the medicinal use of Rt.

Background: Dietary fiber is a key component of a health-promoting diet, and it is acknowledged as a short-fall nutrient in most Western diets. Some sources of dietary fiber, such as hemp hull fiber, also include inherent small molecule bioactives that further promote health and well-being. While dietary fiber is a key component that supports digestive health, it also can cause digestive discomfort. Digestive symptoms such as gas, bloating, belly pain, and the resulting decrease in digestive quality of life are common among adults. The aim of this study was to evaluate changes in digestive comfort, in individuals who currently experience digestive discomfort, after consuming either a proprietary dietary fiber supplement from hemp hull, a dietary fiber supplement made from inulin, or a digestible control (maltodextrin). Methods: This study was a completely virtual, double-blind, placebo-controlled, randomized clinical trial of healthy adults. The parallel arm study tested two fiber supplements at a practical dose yielding a “Good Source of Fiber” based on United States Dietary Reference Intakes (2.8 grams of fiber per day) for six weeks. Results Five hundred seventy nine randomized participants provided follow-up outcomes data. Digestion-associated quality of life questionnaire, belly pain, and gas and bloating scores were assessed and found to be superior after hemp hull fiber intake compared to inulin intake at multiple time points in a post-hoc analysis (p<0.05). Conclusion This study demonstrated that a practical dose of bioactive-rich fiber from hemp hull is well-tolerated, provides superior digestive comfort relative to both placebo and inulin fiber, and can aid in reaching total fiber intake goals.

Accurate assessment of bone age (BA) is crucial for pediatric clinical practice. This study validated the Radiological Reference Atlas for Bone Age in the Canary Islands Population with a total of 203 anteroposterior left hand and wrist radiographs from healthy children (91 females, 112 males) across preschool, school-age, and adolescent stages. Intra-observer agreement, assessed by intraclass correlation coefficients (BAA1: ICC = 1.000, BAA2: ICC = 0.995, BAA3: ICC = 0.943), showed differing levels of precision among assessors. Inter-observer agreement was high (Pearson’s r = 0.905 - 0.951), suggesting consistent evaluations across different expertise levels. Accuracy analysis revealed significant BA underestimation compared to chronological age (CA) in preschool (MD = -17.036 months, p < 0.001) and school-age (MD = -8.165 months, p < 0.001) groups, but closer agreement in teenagers (MD = -0.33 months, p = 0.550). Furthermore, a relevant underestimation in the teenage stage for girls compared to boys was also noted. These findings underscore the atlas's precision; however, its accuracy for BA assessment in younger children and adolescent girls needs to be approached with caution.

Coronaviruses (CoVs) have recently emerged as significant causes of respiratory disease outbreaks. The novel coronavirus pneumonia of 2019, known as COVID-19, are highly infectious and triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding virus-host interactions and molecular targets in host cell death signalling is crucial for treatment development. Small natural compounds like celastrol and curcumin, acting as proteasome inhibitors, can potentially modify NF-κB signalling for treating SARS-CoV-2 infections. Various natural constituents, including alkaloids, flavonoids, terpenoids, diarylheptanoids, and anthraquinones, inhibit viral infection, progression, and amplification of coronaviruses. Derived from medicinal herbs, these compounds possess anti-inflammatory and antiviral properties, impacting the viral life cycle, including entry, replication, assembly, and release of COVID-19 virions. This review focuses on the development of small molecules of non-covalent inhibitors targeting the Main Protease (Mpro, also called 3CLpro) enzyme of SARS-CoV-2. It highlights the design using molecular dynamics (MD) studies and computational methods for further improvements in Mpro inhibitor design. The in-silico approach, which is pivotal in this process, provides an accelerated virtual avenue for exploring and developing potential inhibitors, representing the latest advancements in drug design.

Background: The lateral antebrachial cutaneous nerve (LACN) is the terminal sensory branch of musculocutaneous nerve and is rarely entrapped or injured. This study describes the electrodiagnostic (EDX) findings and etiologies of LACN neuropathy. Methods: This is a review of 49 patients with pain and/or paresthesia of the forearm who underwent EDX studies. The diagnosis of LACN neuropathy was based on clinical and sensory conduction abnormalities. Results: The most common etiology of LACN neuropathy was iatrogenic injury in 30 (61.2%) patients, primarily due to biceps tendon repair at the elbow (11 [36.7%]) and phlebotomy (5 [16.7%]. Fifteen (30.6%) patients sustained a non-iatrogenic injury at the proximal forearm/elbow, consisting of 6 (60%) laceration injuries and 5 (33.3%) stretch injuries. Four (8.2%) patients comprised the “other” etiology category, including 2 mass lesions causing LACN compression. Pain, paresthesia, and/or numbness in the LACN distribution were reported in 33 (67.3%), 27 (55.1%), and 23 (46.9%) patients, respectively. Hypoesthesia was detected in 45 (91.8%) patients, and dysesthesia in 7 (14.3%). The sensory nerve action potentials (SNAPs) of the LACN on the symptomatic side were absent in 44 (89.8%) patients. Of the 5 patients whose SNAPs of the LACN were detected, all had a decreased amplitude and 2 had increased sensory latency. Conclusion: The most common etiology for LACN neuropathy in this series was iatrogenic injury; repair of biceps tendon at the elbow was the most frequent provoking cause. Protection of the LACN during surgical procedures at the elbow and forearm is vital to prevent iatrogenic injury.

Objective Hypertension is one of the most common chronic diseases, affecting more than 20 % of the population. The side effects experienced due to antihypertensive medications such as tired-ness, muscle pain, and insomnia are often a significant predictor of poor adherence to therapy. The goal of the current study is to present the frequency, type, seriousness, and severity of adverse drug reactions reported to the BDA via Individual Case Safety Reports (ICSR) and following differentiation of messages found in more than one patient. Methods We conducted a retrospective analysis of the reported adverse drug reactions (ADR) reported in the Bulgarian Drug Agency database after treatment with antihyperlipidemic medicines, angiotensin-converting enzyme (ACE) - inhibitors, and sartans for the period 2017-2021. Each ICSR form was observed and data for suspected medicine and type of adverse reaction was analyzed. Results The total number of processed notifications for adverse drug reactions (ADR) included in the database is 142. The highest number of ADRs was reported for ARB (58), followed by antihyperlipidemic medicines (55) and ACE inhibitors (29.) Most of the assessed adverse events experienced by more than one patient fall into the probable and related categories based on Global Introspection method classification. Therefore, they have been investigated and are consistent with exposure in the population. Conclusion Cardiovascular medicines from the groups of ACE inhibitors, sartans and statins are with high share of reported ADRs in the BDA system. Some of them are severe and need further investigation.

Breast cancer in patients with prior breast augmentation poses unique challenges for detection, diagnosis, and management. Mastectomy rates are increasing, and patients with prior augmen-tation often have a lower body mass index, making autologous techniques unsuitable. This study aims to assess the best reconstructive option in patients with a history of subglandular or dual plane breast augmentation. Materials and methods: a prospective analysis was conducted on pa-tients who underwent breast reconstruction after mastectomy. Patients with subglandular or dual plane breast augmentation were included. Patients were divided into submuscular breast recon-struction (group 2) or prepectoral breast reconstruction (group 1) groups. Demographic and sur-gical data were collected. Results: A total of 47 patients were included, with 23 in Group 1 and 24 in the Group 2. Complications occurred in 11 patients (23.4%), with significant differences be-tween groups. The most common complication was seroma formation. Implant loss occurred in 4.3% of cases in the Group 1, while no implant loss was observed in the Group 2. Patient-reported satisfaction scores were similar between groups at 12 months postoperatively. Conclusions: sub-pectoral breast reconstruction with a tissue expander seems a safer and effective technique for pa-tients with prior breast augmentation. It resulted in fewer complications. This approach should be considered as an option for breast reconstruction after mastectomy in this cohort of patients.

Obesity is one of the most prevalent and damaging metabolic conditions and is a risk factor for the development of other disorders that define the metabolic syndrome. Recent studies have identified a significant role of AGE accumulation and RAGE signaling pathways in the underlying mechanisms that cause the chronic inflammatory response present in obesity which, ultimately, leads to adipose tissue dysfunction. Given the current interest and increasing evidence on possible therapeutic opportunities in the AGE-RAGE axis, the purpose of this work is to review the key findings on new small molecules and bioactive compounds that act as AGE or RAGE inhibitors and their effects on metabolic parameters of people with obesity. The search queries were defined according to the following PICO question: “What are the effects of AGE-RAGE antagonism on adipose tissue metabolism and other metabolic parameters of people with obesity? “. Article search was performed in three online databases: PubMed, Scopus, and Web of Science. In the end, 20 studies were selected for this review. Overall, the reviewed molecules showed beneficial effects on body weight, glucose tolerance, insulin resistance, inflammatory profile, and adipose tissue metabolism in mice models with obesity. There are still very few studies on human application of these molecules, but the ones that were reviewed revealed controversial data when compared to animal studies. Therefore, further human clinical trials should be performed to retrieve more conclusive data.

Synopsis Corneal epithelial wavefront error and epithelial thickness variance qualify as highly sensitive and specific biomarkers for epithelial basement membrane dystrophy (EBMD). The biomarkers show a normalization after treatment of EBMD with phototherapeutic keratectomy. Purpose: To gauge the diagnostic value of a novel spectral-domain optical coherence tomography (SD-OCT) based imaging modality for simultaneous morphological (thickness profile) and refractive (optical wavefront) assessment of the corneal epithelial layer in one of the most common but often underdiagnosed corneal dystrophies: epithelial basement membrane dystrophy (EBMD). Methods: In this prospective observational study, a total of 32 eyes of 32 patients diagnosed with EBMD and 32 eyes of 32 healthy control subjects were examined with high-resolution anterior segment SD-OCT (MS-39; CSO, Florence, Italy). Various epithelial thickness and epithelial wavefront derived terms were compared between groups and receiver operating characteristic (ROC) curves were computed to analyze the diagnostic capacity of the respective parameters. A total of 17 of 32 EBMD patients underwent treatment with phototherapeutic keratectomy (PTK) and were followed up for 3 months. Results: Epithelial thickness variance (60.4 ± 56.7 µm versus 7.6 ± 6.1 µm) and interquartile range (11.0±6.9 versus 3.3±1.9 µm) were markedly elevated in EBMD patients as compared with healthy controls (both with p < 0.001). Epithelial wavefront analysis showed a highly statistically significant excess in all examined aberration terms in EBMD patients (all with p < 0.001). Significantly greater areas under the curve (AUC) were yielded by the epithelial wavefront derived parameters (e.g. total epithelial wavefront error: AUC = 0.966; 95% confidence interval (CI) 0.932 – 1) than by the epithelial thickness-derived parameters (e.g., variance: AUC = 0.919; 95% CI 0.848 – 0.990). Conclusion: Corneal epithelial wavefront aberrometry proved valuable as an objective biomarker for EBMD with high sensitivity and specificity. PTK resulted in a reduction of morphological and refractive epithelial irregularities in EBMD.

In this study, we aimed to investigate the differences in tissue surface adaptation and the variations in distances between reference points on the polished surfaces of 3D-printed denture bases with different build angles. The build angles were 0°, 30°, 60°, and 90°, with 15 denture bases printed for each angle. Using the Geomagic Control® software, a 3D best-fit alignment was conducted between the denture base tissue surface and the reference shape of the edentulous maxilla model to calculate the root mean square error. The distances between reference points on the polished surface were measured using digital calipers. One-way analysis of variance was conducted for statistical analysis. The adaptation, as measured by the root mean square error, varied significantly among denture bases with different build angles. The distances between the anterior and posterior reference points of the polished surface were also significantly different. However, within the limitations of this study, the variations in adaptations and dimensional accuracy across different build angles were within clinically acceptable ranges. In clinical practice, the print angle can be adjusted based on factors, such as printing time, resin consumption, and the number of denture bases being printed simultaneously.

Introduction: Multiple sclerosis (MS) is a long-term inflammatory disease that affects the central nervous system due to an abnormal immune response. Hormonal and enzyme changes in these patients can influence the progression and prognosis of the disease. In this research, the levels of cortisol, adrenocorticotropic hormone (ACTH), melatonin, and lactate dehydrogenase (LDH) in the blood of MS patients were studied.Methods: This study involved 50 MS patients and 50 healthy individuals. The levels of ACTH, melatonin, and cortisol in the blood were measured using specific ELISA kits. The data obtained were then analyzed statistically using SPSS software.Results: The findings revealed a significant increase in the levels of cortisol and LDH in MS patients (P<0.05), while the levels of melatonin and ACTH showed a significant decrease (P<0.05). The elevated cortisol levels may be attributed to chronic stress and inflammation associated with MS. An increase in LDH levels can indicate tissue damage caused by myelin destruction. On the other hand, decreased melatonin levels may lead to sleep disturbances and increased stress in these patients, while decreased ACTH levels may be linked to disruptions in the hypothalamic-pituitary-adrenal (HPA) axis. Conclusion: The hormonal and enzyme changes observed in MS patients illustrate the wide-ranging impact of the disease on various body systems. The increase in cortisol and LDH as well as the decrease in melatonin and ACTH could serve as useful biomarkers for predicting disease progression and managing the condition. These findings align with previous studies and contribute to a deeper understanding of the pathological mechanisms of MS.

Background/Objectives: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular disease (CVD). Carotid intima-media thickness (C-IMT) is a non-invasive marker of atherosclerosis. Low omega-3 polyunsaturated fatty acids (PUFA) intake and vitamin D deficiency are potential cardiometabolic risk factors in patients with CKD. The aim of this study was to evaluate dietary intake and status of omega-3 PUFA and vitamin D in pre-dialysis and hemodialysis patients and to examine the link of dietary α-linolenic acid (ALA) and fish consumption with blood pressure and C-IMT in CKD patients. Methods: All 77 selected patients (36 pre-dialysis, 41 on hemodialysis) underwent standardized clinical, nutritional, and laboratory assessments. Repeated 24-hour recalls were performed to assess dietary intake. The fatty acid profile was determined by gas-liquid chromatography. Results: Inadequate vitamin D intake and vitamin D status were found in 95% of patients. PUFAs profiles did not differ between hemodialysis and pre-dialysis participants. Dietary intake of ALA was negatively correlated with systolic blood pressure (SBP) (p=0.007), C-IMT (p=0.002), serum CRP (p=0.044), iPTH (p=0.01) and 25(OH)D3 (p=0.006). ALA intake of more than 0.23 g/daily was associated with lower SBP (p=0.001), serum 25(OH)D3 (p=0.004), and C-IMT (p=0.002). Conclusions: This study contributes to a better understanding of the relationship between dietary ALA intake and C-IMT in CKD. The results of this study could emphasize the significant role of the high prevalence of vitamin D deficiency and inadequate omega-3 PUFA intake and status considering CVD health in CKD patients.

This thesis presents a comprehensive review of cancer, with a particular focus on its physical and biochemical basis. Cancer, a leading cause of mortality worldwide, is characterized by the uncontrolled growth and spread of abnormal cells. Understanding the fundamental differences between cancerous and normal cells is essential for developing effective diagnostic tools and therapeutic strategies. The review begins by exploring the physical anomalies of cancer cells, including their irregular shape, size, and structural organization. These cells often exhibit altered cell membranes, disrupted cytoskeletal architecture, and irregularities in cell adhesion and communication, which contribute to their invasive and metastatic potential. The biochemical basis of cancer is examined in detail, with an emphasis on the dysregulation of key metabolic pathways. Cancer cells undergo profound metabolic reprogramming, often referred to as the Warburg effect, where they preferentially utilize glycolysis over oxidative phosphorylation, even in the presence of oxygen. This metabolic shift supports the rapid proliferation of cancer cells and their survival in hypoxic conditions. Additionally, cancer cells produce abnormal proteins that contribute to tumor progression, such as mutant p53, and fail to produce critical tumor suppressor proteins like RB1, leading to unchecked cell division and evasion of apoptosis. Furthermore, the thesis reviews the role of oncogenes and tumor suppressor genes in cancer development, highlighting how mutations and epigenetic alterations drive the transformation of normal cells into malignant ones. The complex interplay between these genetic changes and the tumor microenvironment is also discussed, emphasizing the importance of signaling pathways, immune evasion, and angiogenesis in cancer progression. This detailed review synthesizes current research and insights from authoritative sources, including peer-reviewed journals and foundational medical texts, to provide a thorough understanding of the physical and biochemical underpinnings of cancer. The findings underscore the importance of continued research in these areas to advance the diagnosis, treatment, and prevention of cancer.

Introduction: People with severe and persistent mental illness (SPMI) present unique challenges in mental healthcare due to the enduring nature and complexity of their conditions. This study evaluated the clinical effectiveness and potential cost benefits of a multidisciplinary community psychosocial rehabilitation team catering to individuals with SPMI in Nova Scotia, Canada. Method: The Canadian billing system of Medical Service Insurance (MSI) was used to compare inpatient service use and emergency department visits during the year before and the year after receipt of one year of community rehabilitation for patients referred to the team from September 2016 to September 2017. Result: Results demonstrated a statistically significant reduction in mean admission rates and length of inpatient admissions in the year following rehabilitation compared to the pre-rehabilitation year. A substantial percentage of patients experienced no inpatient admissions (88% v. 60%) or ED visits (82% v. 67%) in the post-rehabilitation year compared to the pre-rehabilitation year. There was a significant reduction in inpatient days by 90%, translating into substantial cost savings. The findings highlight the potential economic benefits of community rehabilitation for people with SPMI. Conclusion: This uncontrolled study suggests that community rehabilitation is associated with favourable clinical outcomes for individuals with SPMI in terms of reduced inpatient service use and related costs. Further research into community psychosocial rehabilitation services in the Canadian setting is needed, including controlled and cost-effectiveness studies.

Background/Objectives: Multisystem Inflammatory Syndrome in children (MIS-C) is a rare but severe post-infectious complication of COVID-19, that often requires admission to the Pediatric Intensive Care Unit (PICU). The present study aimed to compare the demographic, clinical and laboratory characteristics between children diagnosed with MIS-C who were admitted to the PICU or did not require PICU admission. Methods: Children diagnosed with MIS-C from September 2020 to April 2023 were included in this case-control study. Patient’s demographic, clinical and laboratory data, were collected from medical records. Results: Fifty children with MIS-C were included in the study [median (IQR) age: 7.5 (4.3, 11.4) years, 28/50 (56%) males]. Twenty-two (22/50, 44%) children required admission to the PICU. In the multivariate regression analysis, hepatic (OR:12.89, 95%CI: 1.35-123.41, p-value=0.03) and cardiological involvement (OR:34.55, 95%CI: 2.2-541.91, p-value=0.01) were significantly associated with hospitalization at the PICU. Regarding the laboratory and imaging parameters during the first 48 hours from admission, D-dimer levels higher than 4μg/mL and decreased Left Ventricular Ejection Fraction were associated with an increased risk of PICU admission (OR:7.95, 95%CI:1.48-42.78, p-value=0.02 and OR=1.28, 95%CI:1.07-1.53, p-value=0.01). Children who were admitted to the PICU were more likely to develop complications during their hospitalization (10/22, 45.5% vs. 3/28, 10.7%, p-value=0.005) and were hospitalized for more days, than children in the pediatric wards (median length of stay (IQR): 20 (15,28) days vs. 8.5 (6, 14) days, p-value&lt;0.001). Conclusions: In the present study, cardiovascular, hepatic involvement and increased D-dimer levels in children with MIS-C were associated with admission to the PICU.

Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with efficacy against some NNRTI resistant mutants. Although DOR resistance mutations are established for HIV-1 subtype B, it is less clear for non-B subtypes. This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others didn’t significantly impact DOR susceptibility. We observed agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y188L caused high-level resistance, in agreement with the predictions. These mutations are frequently observed in patients failing efavirenz or nevirapine-based first-line regimens. However, they are also observed in those failing a protease inhibitor-based second-line regimen, as we have observed in our database. Genotypic drug resistance testing is therefore vital prior to initiation on DOR-based treatment for those previously exposed to efavirenz or nevirapine.

Currently, there are several drugs used for the treatment of type 2 diabetes (T2D), however, all of them have adverse effects. Benzothiazoles have a broad spectrum of biological activities such as antidiabetic. This study aimed to evaluate in silico and in vivo two series of 2-aminobenzothiazole derivatives linked to isothioureas (3a-w) or guanidines (4a-z) for the treatment of T2D. The ADMET properties were determined in silico from which it was possible to select compounds 3a, 3b, 4a, 4b, 4c, 4r, 4s, 4x, and 4y and, with molecular docking, it was shown that 3b and 4y showed high affinity for PPAR gamma (ΔG = -7.8 and -8.4 kcal/mol, respectively). In vivo, the LD50 value was estimated in rat based on OECD Guideline 425, being > 1750 mg/kg for both compounds. The pharmaco-logical effect of 3b and 4y was evaluated in the T2D rat model, showing that after oral admin-istration in equimolar ratio to pioglitazone (15 mg/kg) for 4 weeks, both compounds were able to reduce blood glucose levels (< 200 mg/dL) and improve the lipid profile. Therefore, 3b and 4y could be used in the future as antidiabetic agents.

Lichenochemical composition and antimicrobial, antibiofilm and antioxidant effects of a newly described arctic lichen Placidium doesaiense growing in Pakistan were investigated. HPLC–DAD methods were used for identification of secondary metabolites in acetone and methanol extracts. The total polyphenol and the total flavonoid content was determined spectrophotometrically. The study examined the antioxidant (DPPH scavenging activity and reducing power), antibacterial (minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)) and antibiofilm (inhibition of biofilm formation and reduction of mature biofilm) activities of extracts of the lichen P. doesaiense and isolated parietin. The chemical constituents olivetol, olivetolic acid, haematommic acid, fallacinol and parietin, were identified as major compounds in the tested extracts of the lichen. Parietin was isolated from the acetone extract on a separation column. The methanol extract had higher values of TPC (21.67 mg GA/g) and TFC (377.40 mg RE/g) than the acetone extract. Although the extracts showed the best antibacterial activity (especially against Proteus mirabilis ATCC 12453), parietin demonstrated superior antibiofilm activity (especially against Staphylococcus aureus ATCC 25923). Isolated parietin showed the best antioxidant activity measures according to DPPH scavenging activity (IC50= 51.616 μg/mL) and reducing power. This is the first report on the phytochemical composition of the lichen Placidium doesaiense and the first description of the chemical composition of some of the 28 species of the genus Placidia. This research will pave the way for further exploration of new activities of this lichen and its metabolites, which are important for medicine and pharmacy.

Background: Oxidative stress has emerged as a key contributor to numerous NCDs (Non Communicable Diseases), including cardiovascular diseases, cancer, and diabetes. This study aims to explore the potential of targeted interventions to mitigate oxidative stress as part of a primary prevention strategy. Methods: The study included 32 healthy participants (11 men, 21 women) aged 45-65 who completed both the initial and follow-up assessments of the Healthy Days Initiative, a community-based wellness program organized by the non-profit Associazione O.R.A. ETS. Through blood analysis, vital sign assessment, lifestyle questionnaires, and individualized recommendations, participants received guidance on improving their health and reducing disease risk. The initiative also offered the opportunity for participants to consume a flavonoid supplement containing quercitrin, rutin and hesperidin, with the goal of reducing oxidative stress. Participants who opted for supplementation were instructed to take 1-2 tablets daily for two weeks. Data collected included demographic information, anthropometric measurements, vital signs, dietary and lifestyle habits, medical history, WHO-5 Well-Being Index scores, and blood parameters. Results: Significant reductions were observed in glucose levels (from 82 to 74.5 mg/dL), reactive oxygen metabolites (d-ROMs) (from 394.5 to 365.5 U.CARR), and systolic blood pressure (from 133 to 122 mmHg) after the two-week flavonoid intervention. Most participants (26/31) reported no side effects, and the majority (30/31) expressed a willingness to continue using a product combination of quercitrin, rutin and hesperidin or a similar product long-term. Conclusions: While limited in scope and duration, the PREVES-FLAVON study contributes valuable insights to the growing body of evidence suggesting that flavonoid supplementation may play a significant role in reducing risk factors associated with NCDs in primary prevention settings. By targeting novel risk factors such as oxidative stress, this intervention holds promise for mitigating the global burden of NCDs and promoting healthy aging.

Background: The high global prevalence of prediabetes requires its early identification. Amino acids have emerged as potential predictors of prediabetes. This study aims to investigate the association between BCAAs and prediabetes in the Kazakh population. Materials and Methods: In this case-control study, plasma BCAAs levels were measured using the Trace GC 1310 gas chromatography system coupled with the TSQ 8000 triple quadrupole mass spectrometer (Thermo Scientific, Austin, TX, USA) followed by silylation with the BSTFA + 1% TMCS derivatization method. Biochemical parameters, including total cholesterol, HDL-C, LDL-C, triglycerides, fasting glucose, HbA1c, and creatinine, were assessed for each participant. Anthropometric and physical examinations, including blood pressure, heart rate measurements, and family history collection, were conducted by trained professionals. Results: The final analysis included data from 112 Kazakhs with prediabetes and 55 without prediabetes, aged 36-65 years. Of the thirteen AAs analyzed, only alanine showed a significant association with prediabetes risk. Our findings revealed an inverse relationship between alanine and aspartic acid levels, and direct association of lysine and prediabetes in Kazakh ethnicity. Conclusion: Lower plasma level of alanine and aspartic acid, and higher level of lysine may serve as predictive biomarkers for prediabetes in the Kazakh population. This research is funded by the Science Committee of the Ministry of Education and Science of the Republic of Kazakhstan (grant AP14871855).

Clopidogrel; a prescription drug to reduce ischemic events in cardiovascular patients; has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases; divided into poor and normal responders) were enrolled along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet function (PRU); PON1 abundance by western blotting and PON1 activity by enzymatic assays were measured. PON1 genotyping and computational haplotype phasing were performed on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (p> 0.05). However; a significantly lower enzymatic activity was found in poor responders (10.57 ± 6.79 µU/mL) when compared to controls (22.66 ± 8.30 µU/mL and 22.21 ± 9.66 µU/mL; p= 0.004). PON1 activity among carriers of the most prevalent PON1 haplotype (AA|AA) was significantly lower than in wild-types (7.90 µU/mL vs 22.03 µU/mL; p= 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.

Maternal obesity has been found to be impaired oxidative status in placenta and newborn which can lead to adverse pregnancy outcomes and long-term adverse influence on metabolic programming in the offspring. This study aimed to investigate the role of maternal obesity on maternal and umbilical cord plasma oxidative status and placental oxidative adaptation. Maternal obesity (n=20) defined as pre-pregnancy BMI ≥ 25 kg/m² and maternal lean (n=20) defined as pre-pregnancy BMI < 25 kg/m² were recruited into this study. Both groups were matched by gestational age at delivery. Maternal blood, umbilical cord blood and placental tissue were collected to assess nutritional content (cholesterol, triglyceride, and protein), oxidative stress marker (MDA and protein carbonyl) and antioxidant activity (SOD and catalase). Placenta protein expression (SOD2, catalase, UCP2 and Nrf2) was evaluated by western blot analysis. Catalase activity in maternal plasma significantly increased in maternal obesity group (p = 0.0200) with an increased trend in MDA and protein carbonyl levels. Umbilical cord plasma triglyceride, protein carbonyl and catalase activity significantly increased in maternal obesity compared with that in maternal lean (p = 0.0462, 0.0485, and 0.0348, respectively). Although placenta protein expression analysis exhibited significant decreased SOD2 (p = 0.0169) and catalase (p = 0.0067), accompanied by Nrf2 downregulation (p = 0.0453). An increased mitochondrial antioxidant UCP2 expressions was observed (p = 0.0143). Hence, our study provided evidence that maternal obesity is associated with placental and fetal oxidative stress with the parallel increased placental antioxidant UCP2 expression.

Applying cold to a bone injury can aid healing, though its mechanisms are complex. This study investigates how cold therapy impacts bone repair to optimize healing. Cold was applied to a rodent bone model, with physiological responses analyzed. Vasoconstriction was mediated by an increase in TRP channels, TRPA1 (p=0.012) and TRPM8 (p&lt;0.001), within cortical defects enhancing sensory response and blood flow regulation. Cold exposure also elevated hypoxia (p &lt; 0.01) and VEGF expression (p &lt; 0.001), promoting angiogenesis vital for bone regeneration. Increased expression of osteogenic proteins PGC-1α (p = 0.039) and RBM3 (p&lt;0.008) suggests stimulated reparative processes. Enhanced osteoblast differentiation and ALP presence at days 5 (three-fold, p=0.014) and 10 (two-fold, p=0.010) were observed, along with increased osteocalcin (OCN) at day 10 (two-fold, p = 0.010) indicating presence of mature osteoblasts capable of mineralization. These findings highlight cold therapy's multifaceted effects on bone repair, offering insights for therapeutic strategies.

Aim: To elucidate the international network structures and evolution of collaborations in capsule endoscopy research from 2000 to 2023 by analyzing co-authorship networks. Method: This study analyzed co-authorship patterns in capsule endoscopy research articles published from 2000 to 2023 using data from the Web of Science (WoS). I employed Python (version 3.10.5) in the PyCharm development environment (version 2022.1.3) to conduct a network analysis using social network analysis principles. The analysis included macro-level metrics (network density, clustering coefficient, components, and average path length) and micro-level metrics (degree centrality, closeness centrality, and betweenness centrality) to assess collaboration intensity, key contributors, and network cohesion. Result: The co-authorship network analysis revealed evolving collaboration patterns over three distinct periods (2000-2009, 2010-2019, and 2020-2023). Initially, the network exhibited low density and high fragmentation, with key contributors such as Guido Costamagna and Jonathan A. Leighton prominently positioned. Over time, the network expanded with increased density and clustering, though it remained fragmented. In recent years, the network showed increased cohesion with reduced components and notable contributors like Anastasios Koulaouzidis and Xavier Dray, reflecting the growing importance of international collaborations, particularly involving researchers from Japan, Italy, and Israel. Conclusion: The study highlights the dynamic nature of international collaborations in capsule endoscopy research, with increasing connectivity and influential contributors playing pivotal roles in advancing the field. These findings underscore the value of international cooperation in enhancing diagnostic and therapeutic approaches in capsule endoscopy, pointing to future opportunities for deeper collaboration and integration.

Sinonasal carcinomas are aggressive neoplasms that present a high morbidity and mortality rate with unfavorable prognosis. This group of tumors exhibits morphological and genetic diversity. Genetic and epigenetic alterations in these neoplasms are currently targets for diagnosis and treatment. The most common type of cancer originated in the sinonasal tract are sinonasal squa-mous cell carcinomas (SNSCC), which presents different histological patterns and variable his-tological aggressiveness. A significant number of alterations have been reported in sinonasal tu-mors, including deficiencies in the SwItch/Sucrose non-fermentable (SWI/SNF) chromatin remod-eling complex. In the sinonasal tract, deficiencies of the subunits SMARCB1/INI1, SMAR-CA4/BRG1 and SMARCA2 have been noted in carcinomas, adenocarcinomas, and soft tissue tu-mors with distinctive high-grade morphology and fatal prognosis. Objective: To identify the status of the SWI/SNF complex using immunohistochemistry in sinonasal squamous cell carci-nomas and its association with morphology and survival. Methods: A total of 1582 SNSCC cases were analyzed, selecting those with high-grade malignancy morphology, which were then evalu-ated immunohistochemically for SMARCB1 and SMARCA4 proteins. Their expression was compared with the biological behavior and survival of the patients. Results: Among the SNSCC, 47% corresponded to the non-keratinizing squamous cell carcinoma (NKSCC) type with high-grade characteristics, 40% were keratinizing squamous cell carcinomas (KSCC), 9% were SMARCB1-deficient carcinomas, and 4% were SMARCA4-deficient carcinomas. Mosaic expres-sion for SMARCB1 (NKSCC 33%, KSCC 21.9%) and SMARCA4 (NKSCC 14.6%, KSCC 12.2%) was identified, showing an impact on tumor size and progression. Conclusions: We identified that the mosaic expression of INI1 in NKSCC exhibited a worse prognosis compared to intact carcinomas and was similar to SMARCB1-deficent carcinoma.

Background/Objectives: The aim of this study is the operationalization of the International Classification of Functioning, Disability and Health in the rehabilitation care performed at the Institute of Cancer of the State of São Paulo through structuring a goal-oriented tool with relevant categories of evaluation and follow-up for cancer outpatients to be applied by physiatrists, physiotherapists, physical educators, occupational therapists, and psychologists. Methods: A qualitative study based on a literature review and a modified Delphi exercise, Estimate-Talk-Estimate (ETE) technique, was performed with the service’s rehabilitation experts. Consensus was obtained after four rounds under the 80% agreement threshold. Results: Forty categories were identified for neuropsychological evaluation and thirty-three for psychoaffective support, with 12 goals. Thirty-five categories with 13 goals were accounted for physiotherapy. Physical educators identified 18 categories, with 7 goals. Occupational therapists selected 54 categories, with 10 goals. A referral for personal factors was established. Functional Assessment of Cancer Therapy-General (FACT-G) was the quality of life tool chosen to be applied. Conclusions: A set of relevant ICF categories was structured, tailored by a clinically meaningful routine of assessment and follow-up of cancer outpatients based on specialists’ clinical practice and scientific literature. It will contribute for analyzable and more specific and quantifiable institutional health data. Its implementation and future discussion may promote the instrument’s refinement for its use in this population.

Over 2.2 billion people across the globe face significant barriers to accessing essential ophthalmic care, with elderly, rural, and refugee populations being disproportionately affected. These obsta-cles deepen existing disparities in eye care. 3D printing is a novel technology that has the potential to transform the field and improve access through alleviating many patient-specific barriers. This article delves into the evolution of 3D printing within ophthalmology, highlighting its current ap-plications and future potential. It explores various 3D printing techniques and biomaterials, dis-cussing their effectiveness in creating advanced solutions such as bioengineered corneas, ocular prosthetics, and innovative treatments for dry eye syndrome. Additionally, 3D printing has rev-olutionized drug delivery systems for conditions like glaucoma, retinal diseases, and for ocular brachytherapy. Despite its promise, the integration of 3D printing into clinical practice presents challenges, which the article addresses alongside strategies for overcoming them. By mapping out the technological advancements and challenges, this review offers a roadmap for enhancing global eye care accessibility and improving patient outcomes on a global scale.

Purpose: Testicular cancer (TC) is a rare cancer but due to early age at diagnosis and excellent cure rates, there is a big cohort of survivors. Recent studies have highlighted the late side effects of treatments of TC especially cisplatin based chemotherapy. These complications make the survivorship care challenging with detrimental effects on health and prognosis of TC survivors. In this study we provide a snapshot of common late side effects in TCS and a possible care pathway with nurse-led specialised clinic. Methods: We invited TCS in one of the cancer centre in Ireland for a comprehensive screening using questionnaires, examination and blood tests. Further investigations were performed as indicated. Mortality was assessed through retrospective chart reviews. Results: We recruited 78 TCS to participate in study. 3 patients who had died in survivorship phase were assessed through retrospective chart review. Second malignant neoplasms accounted for all three mortalities. Most common conditions in TCS after 5 years of diagnosis were hypertension (40%), dyslipidaemia (55.6%), hypogonadism (~45%) and high body mass index (52%). Majority of underlying conditions were diagnosed during screening in our clinic including two cases of coronary artery disease and one case of transient ischaemic attacks. Chemotherapy and age more than 30 years at the time of TC diagnosis were associated with a higher incidence of the late side effects. Conclusions: TC is a highly curable cancer but survivorship phase is marred by a range of late side effects. As we lack clear guidelines and care pathways for survivorship, this remains a challenge for patients and healthcare workers. A nurse-led, specialised, screening clinic can improve the care and prognosis of TC survivors.

Pancreatic cancer presents formidable challenges due to rapid progression and resistance to conventional treatments. Oncolytic viruses (OVs) selectively infect cancer cells and cause cancer cells to lyse, releasing molecules that can be identified by the host’s immune system. Moreover, OV can carry immune-stimulatory payloads such as interleukin-12 which when delivered locally can enhance immune system-mediated tumor killing. OV’s are very well tolerated by cancer patients due to their ability to selectively target tumors without affecting surrounding normal tissues. OV’s have recently been combined with other therapies including chemotherapy and immunotherapy to improve clinical outcomes. Several OVs including adenovirus, herpes simplex viruses (HSV), vaccinia virus, parvovirus, reovirus, and measles virus have been evaluated in preclinical and clinical settings for the treatment of pancreatic cancer. We evaluated the safety and tolerability of a replication-competent oncolytic adenoviral vector carrying two suicide genes (thymidine kinase, TK; and cytosine deaminase, CD) and human interleukin-12 (hIL12) in metastatic pancreatic cancer patients in a phase 1 trial. This vector was found to be safe and well-tolerated at the highest doses tested without causing any significant adverse events (SAE). Moreover, long-term follow-up studies indicated an increase in the overall survival (OS) in subjects receiving the highest dose of the OV. Our encouraging long-term survival data provide hope for patients with advanced pancreatic cancers, a disease that has not seen a meaningful increase in OS in the last five decades. In this review article, we highlight several preclinical and clinical studies and discuss future directions for optimizing OV therapy in pancreatic cancer. We envision OV-based gene therapy to be a game changer in the near future with the advent of newer generation OVs that have higher specificity and selectivity combined with personalized treatment plans developed under AI guidance.

Background/Objectives: Airway management techniques, including mask ventilation and tracheal intubation, are vital across medical settings. However, these procedures can be challenging, especially when environmental conditions are less than ideal. This study explores how the height of the operating table affects the difficulty of surgical procedures involving mask ventilation and tracheal intubation. Methods: Twenty anesthesiologists participated in this study. We assessed the difficulty of procedures- such as mask ventilation, Macintosh laryngoscopy, and video laryngoscopy with McGRATH and AWS- on a four-level scale. The operating table’s height was adjusted at four points: operator's umbilicus, inferior margin of the 12th rib, xiphoid process, and nipple. Results: Mask ventilation was easiest at the operating table’s height aligned with the inferior margin of the 12th rib. Conversely, direct laryngoscopic exposure was perceived easier at higher table heights, with nipple height being optimal. McGRATH laryngoscopy showed consistent difficulty across table height, whereas AWS tended to be somewhat more difficult at greater heights. Conclusions: The optimal bed height for video laryngoscopy coincided with that for mask ventilation. Video laryngoscopy offers enhanced flexibility in optimal patient positioning compared to Macintosh laryngoscopy, contributing to its advantages in tracheal intubation procedures.

A series of conditions can mimic musculoskeletal infections on imaging, complicating their diagnosis and affecting the treatment. Depending on the anatomical location, different conditions can manifest with clinical and imaging findings that mimic infections. Herein we present a wide spectrum of the musculoskeletal disorders of the axial skeleton, long bones, peripheral joints and soft-tissue which may manifest as an infectious process, besides focusing on the potential mimics of osteomyelitis, septic arthritis and infectious spondylodiscitis that are common in clinical practice. We present the typical imaging characteristics of each musculoskeletal infection, followed by mimicking conditions.

Whereas there is an increasing number of scientific publications investigating the optimal anti-biotic treatment for diabetic foot infections, we are lacking corresponding data in the adult non-diabetic (postsurgical) foot infection population. We therefore established one of the largest single-center databases on this topic and retrospectively investigate failures of a combined sur-gical and antibiotic therapy for surgical site foot infections. Overall, 17.4% of the episodes expe-rienced any therapeutic failures; especially among the infected ankle prostheses. In contrast, neither the age, the biological sex, pathogens, the duration of post-debridement antibiotic treatment, the number of surgical debridement, or the use of negative-pressure wound care could alter the failure risk. In multivariate logistic regression analyses, the duration of postsur-gical antibiotic use was completely indifferent (as a continuous variable with odds ratio 1.0, 95% confidence interval 0.96-1.03), or when stratified into inter-tertiary groups. Our results poten-tially enable shorter applications of systemic antibiotics in favor of a better stewardship in the non-diabetic adult population. Consecutive prospective-randomized trials are under way to identify eligible patient populations for a potentially shorter durations in surgical site infections after elective foot and ankle surgery.

Patients with heart failure (HF) with improved LVEF (HFimpEF) demonstrate better clinical outcomes when compared with individuals without restoration of cardiac function. Identification of predictors for HFimpEF may play a crucial role in individual management of HF with reduced EF (HFrEF). Cell-free nuclear (cf-nDNA) DNA are released from damaged cells and contribute to adverse cardiac remodeling, cardiac dysfunction and inflammation. The purpose of the study was to elucidate whether cf-nDNAs are associated with HFimpEF. It has been prescreened 1416 patients with HF using local database. Between October 2021 and August 2022 we included 452 patients chronic HFrEF after prescription of optimal guideline-based therapy and identified HFimpEF in 177 individuals from them according to the criteria of European Society of Cardiology. Measurements of circulating biomarkers were performed at baseline and in 6 months. Detection of cf-nDNA was executed with real time quantitative PCR (qPCR) using NADH dehydrogenase, ND2 and beta-2-microglobulin. We found that HFimpEF was associated with a significant decrease in the levels of cf-nDNA when compared with the patients from persistent HFrEF cohort. Presence of ischemia-induced cardiomyopathy (odds ration [OR] = 0.75; confidence interval [CI] = 0.62 – 0.88; p = 0.044), type 2 diabetes mellitus (OR = 0.77; CI = 0.71 – 0.82; p = 0.042) and digoxin administration (OR = 0.85; CI = 0.72-0.97; p = 0.042) were negative factors for HFimpEF, whereas NT-proBNP ≤1940 pmol/mL (OR = 1.42; 95% CI = 1.19-1.98, p = 0.001), relative decrease in NT-proBNP levels (&gt;35% vs. ≤35%) from baseline (OR = 1.52; 95% CI = 1.38-0.69, p = 0.001) and cf-nDNA ≤7.5 μmol/L (OR = 1.56; 95% CI = 1.07-2.94, p = 0.001) were positive predictors for HFimpEF. Multivariate logistic regression adjusted to ischemia-induced cardiomyopathy, IV HF NYHA class, and digoxin use yielded that NT-proBNP ≤1940 pmol/mL (OR = 1.43; 95% CI = 1.21-1.88, p = 0.001) and cf-nDNA ≤7.5 μmol/L (OR = 1.64; 95% CI = 1.19-2.15, p = 0.001) independently predicted HFimpEF. In conclusions: we established that the levels of cf-nDNA≤7.5 μmol/L independently predicted HFimpEF and improved discriminative ability of as single measured NT-proBNP as well as relative decrease in NT-proBNP levels ≤35% from baseline.

Purpose: The aim of this study was to compare the topical anesthetic effect of a 10% atomized lidocaine spray and an EMLA cream at different time intervals using parameters of visual analogue scale (VAS) score and heart rate (HR). Methods: The randomized split-month study included 30 patients (17 boys, 13 girls) aged 8.22 ± 1.8 years. Application of atomized lidocaine spray or cream was randomly used in the upper second premolar region. The parameters was measured before and at each needle insertion after 10,30,60 and 120 sec. Paired t -test and independent t-test were used for statistic analyses. Results: Compared to the first applications (10 sec), atomized lidocaine and EMLA cream applications significantly decreased scores of VAS at the applications at 30 and 120 seconds, respectively. Despite atomized lidocaine showed early effect compared to EMLA, there were no significant differences in VAS scores between the atomized lidocaine and EMLA cream at the 60 and 120 seconds measurements. Although HR significantly increased at first anesthetic administration with the atomized lidocaine spray, HR significantly decreased at 30 and 120 seconds administrations. Conclusion: Atomized 10% lidocaine-based topical anesthetics significantly reduced pain more rapidly and better than EMLA from needle pricks in the buccal mucosa. Therefore, atomized lidocaine topical anesthesia could be used as a substitute for EMLA cream before buccal anesthetic administration. On the other hand, further comprehensive studies are required to explore the effects of several doses of atomized lidocaine in various areas of the oral cavity.

Background: Despite tremendous advances in medicine, infective endocarditis (IE) continues to be a challenge for physicians due to increasing morbidity and unchanged high mortality. Objectives: Our aim was to evaluate clinical outcomes in patients with IE and to identify predictors of in-hospital mortality. Material and methods: The study was retrospective, single-centered, and included 270 patients diagnosed with IE, for the period 2005-2021 (median age 65 (51–74), man 177 (65.6%). Results: Native IE (NVIE) was found in 180 (66.7%), prosthetic IE (PVIE) in 88 (33.6%) and cardiac device-related IE (CDRIE) in 2 (0.7%), significantly more in the non-survivors group. Healthcare associated IE (HAIE) was 72 (26.7%), the most common pathogen were Staphylococci and the proportion of Gram-negative bacteria (GNB) non-HACEK were significantly higher in non-survivor’s vs survivors (11 (15%) vs 9 (4.5%), p=0.004). Overall, early surgery was performed in 54 (20%) patients, with a significant difference between deceased/alive (3 (4.5%) vs 51 (25.1%, p=0.000). The all-cause in-hospital mortality rate was 24.8% (67). The risk factors identified that increased the risk of death were septic shock (OR – 83 1; 95% CI (17.0-405.2), p=0.000) and acute heart failure (OR –24.6; 95% CI (9.2-65.0), p=0.000). Early surgery (OR – 0.03, 95% CI (0.01-0.16), p=0.000) and low Charlson comorbidity index (OR – 0.85, 95% CI (0.74-0.98, p=0.026) in turn reduce this risk. Conclusion: We found that acute heart failure and septic shock are independent predictors of in-hospital mortality. Low Charlson comorbidity index and early surgery increased survival. Knowing the predictors of death would change the therapeutic approach to a more aggressive one and improve the near and long-term prognosis of patients with IE.

Significant advancements have been made in controlled drug delivery systems in recent years, especially for oral administration. Conventional methods, although groundbreaking, encounter significant constraints when handling drugs with weak acidity or alkalinity because of their solubility being influenced by pH. The release rates of these ionizable drugs are subject to variability, which is influenced by factors such as the pH of the gastrointestinal tract (GIT), patient-specific conditions, and whether the patient is in a fed or fasted state. As a result, there is often a lack of correlation between in vitro and in vivo data. Therefore, it is imperative to develop drug delivery systems that are not affected by changes in pH in order to address these limitations. This review delves into different strategies that have been developed to achieve drug release that is not affected by changes in pH. These strategies include the utilisation of Diffucaps technology, the incorporation of pH modifiers and surfactants, the combination of non-ionic and ionic polymers, the implementation of supersaturating techniques with nucleation inhibitors, and the utilisation of osmotic drug delivery systems. We assess the efficacy of these methods in reducing the influence of pH fluctuations on the solubility and release rates of drugs. In addition, we explore the potential of these innovative techniques to enhance the reliability and predictability of drug delivery, ultimately leading to better therapeutic results. This review provides an in-depth information of various pH independent controlled drug delivery based formulation and By summarizing the existing technologies and looking into the future, the importance of innovation in pH independent delivery systems is emphasised, laying a good foundation for the future design of simple drug delivery systems, which will be conducive to achieving a wider range of applications in oral drug delivery system.

Background The increasing number of elderly individuals in South Korea, now entering a super-aging era, underscores the growing importance of understanding their specific oral health needs. This study investigated changes in oral health conditions, salivary parameters, halitosis, systemic diseases, and medication usage with aging. Methods This study was retrospectively conducted using the medical records of patients who presented with complaints of xerostomia or halitosis between August 2020 and May 2023. A total of 274 patients (66 males, 208 females, mean age 59.39 ± 16.10 years) were included in this study. Results Aging was found to be significantly associated with the presence of sticky saliva, poor oral hygiene, tongue coating, and halitosis (all p < 0.05). Correlation analyses further revealed significant associations between aging and several conditions, including hypertension (r = 0.495, p < 0.001), diabetes mellitus (r = 0.255, p < 0.001), amlodipine usage (r = 0.249, p = 0.001), osteoporosis (r = 0.195, p = 0.001), cardiovascular disease (r = 0.150, p = 0.013), and the presence of tongue coating (r = 0.205, p = 0.001). Conversely, none of the salivary parameters demonstrated a significant relationship with aging. Furthermore, halitosis did not exhibit significant differences across age groups (all p > 0.05), with the exception of methyl mercaptan levels, which were notably higher among patients in their 20s (p = 0.049). Conclusions The findings of this study can help clinicians develop targeted strategies to address specific oral health challenges associated with aging in elderly patients.

Introduction: Pulmonary hypertension (PH) in systemic sclerosis (SSc) can be caused by different pathophysiological mechanisms, including precapillary PH (pulmonary arterial hypertension), post-capillary PH (secondary to left heart diastolic dysfunction), or combined pre- and post-capillary PH. To unmask occult post-capillary PH, fluid loading with saline during right heart catheterization (RHC) is recommended. In the present study, we investigated the response to fluid challenge test (FCT) in patients with SSc who were referred for RHC due to their high likelihood of PH on screening echocardiography. Methods: Demographic data, clinical characteristics, echocardiographic and RHC data, and cardiac magnetic resonance imaging (CMR) results were obtained from the patients' hospital records or by contacting their rheumatologist. A positive FCT was defined as an increase in pulmonary capillary wedge pressure (PCWP) to more than18 mmHg with rapid saline infusion. Patients were followed for a median (IQR) of 15 (7-20) months. Results: Of the total 98 scleroderma patients 34 patients (29 female) were included. The mean age (SD) was 50.6(8.2) years. Baseline RHC data showed that 20 patients had no PH and 14 patients had mild precapillary PH (mPAH). Ten patients (50%) of the patients with no PH and 10 patients (71.4%) with mPAH had a significant increase in PCWP after a fluid loading. There was no statistically significant difference between the patients with positive and negative FCT in terms of the presence of LGE/inflammation on CMR examination. During follow-up, 3 patients died. Mortality was due to SSc-related complications in two patients. Conclusion: This study provides preliminary evidence that FCT may be a useful adjunct to baseline RHC testing to identify SSc patients with latent postcapillary PH. Further studies are needed to confirm these results and determine the optimal role of the fluid challenge test in the clinical management of SSc patients with suspected PH.

This work aims to assess the impact of the COVID-19 pandemic on mortality and incidence of complications in patients with bacteremia due to Staphylococcus aureus (BSA). All episodes of BSA at the Costa del Sol University Hospital (Marbella, Spain) were recorded during the acute phase of the COVID-19 pandemic (March 2020 - March 2022), compared with a previous period (February 2018 - February 2020). Demographic, clinical and prognostic variables were recorded. The outcome was measured as 14 and 30-day mortality and the incidence of complications-death. Mortality during the pandemic was 28.7% at 14 days and 35% at 30 days, while in the pre-pandemic group it was 18.9% and 23.3%, respectively. In overall complication-death, the incidence rate is higher in the pandemic group with 42.7%. No significant differences were obtained between groups. 17 patients with COVID-19 were identified, with a mortality rate of 64.7% and 70.6% at 14 and 30 days. Multivariate analysis established the presence of sepsis at diagnosis as a predictor of mortality, but not BSA during the pandemic phase. In conclusion, BSA is a disease with high mortality, slightly higher during the pandemic phase. No differences were found in adherence to the bundle in our centre.

Background: Diagnostic accuracy of Parkinson’s disease (PD), a synucleinopathy, based on diagnostic criteria is suboptimal. A biomarker for synucleinopathies is pivotal both from a clinical and from a research aspect. CSF a-synuclein has been extensively studied over the past two decades as a candidate biomarker of synucleinopathies. Herein we present data on studies focusing on total, phosphorylated and oligomeric CSF a-synuclein in PD. Methods: Pubmed, Scopus and Web of Science were searched for studies with &gt;10 PD patients and control subjects, with data (mean, SD) on total, phosphorylated or oligomeric a-synuclein. Cohen’s d, as a measure of effect size, was calculated for all a-synuclein forms. Subgroup analysis and meta-regression were performed in an effort to explain between-study heterogeneity. Results: Thirty studies on total, six studies on oligomeric and one study on phosphorylated a-synuclein were included. Total a-synuclein was decreased and oligomeric a-synuclein increased in PD patients vs. controls. Effect size was medium for total and high for oligomeric a-synuclein. A-syn forms provided suboptimal combined sensitivity/specificity for the differentiation of PD from controls. There was significant between-study heterogeneity. PD cohort characteristics (sex, age, disease duration, UPDRS, H&amp;Y) and study characteristics (study design, healthy vs. neurological controls, control for CSF blood contamination, method of a-syn measurement) could not account for between-study heterogeneity. Publication bias was limited. Conclusions: CSF a-synuclein levels lack sufficient accuracy to be used as biomarkers for PD. Standardization of (pre)analytical variables may improve the discriminatory power of a-synuclein forms in the future.

Fractional flow reserve (FFR) is regarded as the gold standard for assessing the functional significance of coronary artery lesions, yet it remains underutilized in clinical practice. Our objective was to investigate whether FFR results have the potential to alter treatment decisions for coronary lesions compared to visual assessments of angiographic images made by three operators at a high-volume interventional center. In this retrospective study, we aimed to reassess the angiographic images of 63 patients presenting with chronic coronary syndrome (n=39, 61.9%) and acute coronary syndrome (n=24, 38.1%) who underwent FFR. Three experienced interventional cardiologists (with >300 PCI procedures per year) reevaluated, blinded to FFR results, 105 ambiguous lesions in 63 patients to determine angiographic significance and treatment strategy. The observers reached a concordant agreement (≥2 operators made the same decision) to perform PCI in 60 (57.1%) of the lesions based on angiographic evaluation. Interestingly, 9 (15%) of these lesions were functionally non-significant (FFR &gt;0.80). The observers agreed to defer PCI in 45 (42.9%) of the lesions; however, 4 (8.9%) of these were functionally significant (FFR ≤0.80) and required PCI. Thus, inter-observer concordance in visual-guided therapeutic decision-making is variable and not always confirmed by the functional significance of coronary lesions.

Objective: To investigate the causal relationships between intestinal microbiome biomarkers and colorectal cancer (CRC) and its subtypes. Method: The meta-analysis method was used to integrate the largest genome-wide association study data from the MiBioGen consortium (n=18,340). Single nucleotide polymorphisms (SNPs) significantly associated with intestinal microbial relative abundance were extracted as instrumental variables (IVs). Based on the Finnish database (R9 version) with 326,322 participants, the two-sample Mendelian randomization (MR) analysis was adopted to explore the causal relationships between intestinal microbes and CRC and its specific subtypes, such as colon cancer and rectal cancer. Result: A total of 3,310 SNPs were screened as IVs. The MR analysis revealed significant associations between various microbial traits and CRC, including its subtypes. Specific microbes, such as Erysipelotrichaceae, exhibited protective effects, while others, like Orato, were demonstrated as risk factors. Notably, specific biomarkers (e.g., Streptococcus thermophilus) for CRC were determined. This study provides new insights and potential targets for the pathogenesis, diagnosis, and treatment of CRC. Conclusion: Significant causal relationships exist between intestinal microbes and CRC and its pathological types. Specific microbes, such as Erysipelotrichaceae, play a protective role, whereas others, like Orato, serve as risk factors. These findings offer new insights into the pathogenesis of CRC and provide a foundation for future prevention and treatment strategies.

Background: Ventilatory strategies in acute respiratory distress syndrome patients aim to mitigate the risk of acute lung injury (ALI). However, prolonged utilization of these strategies may precipitate alveolar carbon dioxide elevation and pH reduction. This scoping review endeavors to present extant knowledge concerning hypercapnia effects in experimental models, with or without ALI, specifically focusing on delineating the immunologically mediated pulmonary tissue damage; Methods: A systematic exploration encompassing PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and Scielo databases was undertaken. Articles published between January 1, 2008, and December 31, 2022, were screened for their elucidation of hypercapnia's immunological impact on lung tissue, utilizing experimental or biological models, irrespective of ALI presence; Results: Following duplicate removal and predefined criteria filtering, 30 pertinent articles scrutinizing hypercapnia's influence on pulmonary epithelium were identified. It was observed that hypercapnia induces perturbations in innate immune response gene transcription, mediated via Nuclear Factor-kappa B attenuation. Furthermore, a compromised innate immune response against injurious agents was noted. Concurrently, disruption and subsequent resealing of alveolar epithelial cells were evidenced, primarily through Na/K-ATPase endocytosis, impeding fluid reabsorption at the alveolar epithelium level; Conclusions: In experimental settings, with or without ALI, hypercapnia's immunomediated mechanisms exacerbate innate immune system impairment and disrupt the respiratory epithelium's repair and healing processes.

Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by local and systemic inflammation independently of the risk factor; during the exacerbations, such inflammation is accentuated and amplified. A practical inflammatory marker and one with an applicable predictive value in the follow-up has been sought. FeNO has shown an excellent performance in that respect within the context of asthma and has also been studied in tobacco-smoke COPD (COPD-TS). In Biomass-smoke COPD (COPD-BS), this, to our knowledge, has not been evaluated. Objective: To measure FeNO levels in patients with COPD-BS and to compare these with those of patients with stable COPD-TS and in healthy controls. Methods: Transversal, observational, descriptive, comparative, and analytical study. A total of 57 patients, including 23 with COPD-BS, 17 with COPD-TS, and 17 healthy control subjects. The measurement of FeNO was carried out on all of these by means of the on-line chemiluminescence technique; the values were expressed in parts per billion (ppb) for their analysis. Results: It was observed that the FeNO values were similar between COPD-BS and COPD-TS and were significantly different between the healthy and stable COPD (both groups). No correlation was found between pulmonary function and symptoms with FeNO in any of the groups. Conclusions: The level of FeNO in stable COPD is found to be increased in a similar manner in COPD-BS and COPD-TS, with a significant difference on comparing it with that of the healthy subjects.

Canada is known to have a complex pathway for new drug approval and reimbursement resulting in delayed access to patients with serious and life-threatening diseases such as cancer. Several recent publications from key stakeholders including patients, physicians and policymakers highlight patient helplessness, physician frustrations and policymakers entangled in a massive network of bureaucracy unable to make headway. Several quantitative assessments using time from regulatory approvals to successful reimbursements confirm long review times and high rejection rates for oncology drugs especially those receiving conditional approvals. A consensus forum of 18 Canadian oncology clinicians recently voiced frustration with the process and inability to deliver guideline-supported efficacious therapies to their patients. This manuscript compares data extracted from publicly available data sources from 2019 to June 2024 to previous publications. Methods: Public databases from Health Canada, the Canadian Agency for Drugs and Technologies in Health (CADTH), which is in the process of changing to Canada’s Drug Agency, and the pan-Canadian Pharmaceutical Alliance (pCPA) were reviewed and data collected were analyzed with descriptive statistics. Results: From the data, three trends emerge, i) an increasing number of oncology drugs are receiving conditional approvals from Health Canada, ii) the percentage of conditionally approved oncology drugs receiving positive reimbursement recommendations from CADTH is still low but appears to be improving, but delays in access are now contingent upon pCPA deciding whether to negotiate price and then the duration of any negotiation, and iii) real-world evidence is no longer part of decision-making for conditional approvals. A slight increase in positive endorsement of RWE used to support CADTH recommendations was observed. Conclusion: Lack of timely access to oncology drugs hurts Canadian patients. While a small trend of improvement appears to be emerging, longer-term data collection is required to ensure sustained patient benefits.

Introduction: The balance of bioelements is crucial as it ensures the organism's homeostasis and proper execution of reactions within the body, nerve conductivity, and correct polarity of cell membranes, but it is also very important for fertility. It is known that disturbances in the balance of bioelements lead to reproductive dysfunction. In women, changes in the composition of follicular fluid can occur, which can lead to limited follicular growth and lack of oocyte activation. Objective: The main objective was to examine whether the concentration of bioelements Na, K, Ca, Mg, and Fe in follicular fluid influences the outcome of the in vitro fertilization process. Methods: The study involved 120 female patients undergoing in vitro fertilization. Follicular fluid obtained after follicle aspiration in the ovaries was used as biological material for analysis. The values of Na (selective electrode method), K (selective electrode method), Ca (arenajo method), Mg (spectrophotometric method), and Fe (colorimetric method) in follicular fluid were determined using the AU 680 apparatus, Beckman Coulter. Istanbul Consensus criteria for clinical embryologists were used to assess embryo quality. Statistical analysis was performed using the SPSS 20 software package. Results: Analysis of follicular fluid samples showed no correlation between the concentration of bioelements in follicular fluid and the quality of oocytes or the outcome of in vitro fertilization. Conclusion: Based on our results, it can be concluded that the concentration of bioelements in follicular fluid does not affect the outcome of in vitro fertilization.

The contemporary treatment for metastatic castration-sensitive prostate cancer (mCSPC) has evolved significantly, building on successes in managing metastatic castration-resistant prostate cancer (mCRPC). Although androgen deprivation therapy (ADT) alone has long been the cornerstone of mCSPC treatment, combination therapies have emerged as the new standard of care based on recent advances, offering improved survival outcomes. Landmark phase 3 trials demonstrated that adding chemotherapy (docetaxel) and androgen receptor pathway inhibitors to ADT significantly enhances overall survival, particularly for patients with high-volume, high-risk, or de novo metastatic disease. Despite these advancements, a concerning gap between evidence-based guidelines and real-world practice remains, with many patients not receiving recommended combination therapies. The challenge in optimizing therapy sequences, considering both disease control and treatment burdens, and identifying clinical and biological subgroups that could benefit from personalized treatment strategies remains. The advent of triplet therapy has shown promise in extending survival, but the uro-oncology community must narrow the gap between evidence and practice to deliver the most effective care. Current research is focused on refining treatment approaches and utilizing biomarkers to guide therapy selection, aiming to offer more personalized and adaptive strategies for mCSPC management. Thus, aligning clinical practices with the evolving evidence is urgently needed to improve outcomes for patients facing this incurable disease.

Liver injury caused by various factors significantly impacts human health. Stem cell transplantation has potential for enhancing liver functionality, but safety concerns such as immune rejection, tumorigenesis, and the formation of emboli in the lungs remain. Recent studies have shown that stem cells primarily exert their effects through the secretion of extracellular vesicles (EVs). EVs have been shown to play crucial roles in reducing inflammation, preventing cell death, and promoting liver cell proliferation. Additionally, they can function as carriers to deliver targeted drugs to the liver, thereby exerting specific physiological effects. EVs possess several advantages, including structural stability, low immunogenicity, minimal tumorigenicity targeting capabilities, and convenient collection,. Consequently, these factors have garnered significant attention from researchers and are expected to become alternative therapeutic agents to stem cell therapy. This article provides a comprehensive review of the current research progress on the use of stem cell-derived EVs in the treatment of liver injury.

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality globally, posing significant challenges to public health. The rapid development of artificial intelligence, particularly Large Language Models like ChatGPT, has revolutionized various fields, including cardiovascular medicine. ChatGPT, recognized for its broad applicability, efficiency, and public acceptance, has been integrated into multiple facets of CVD management. This comprehensive review examines the current applications of ChatGPT in cardiovascular medicine, emphasizing its innovative and significant role in enhancing diagnosis and clinical decision-making, improving medical education, and facilitating research and academic communication. Furthermore, the review article addresses the significant challenges associated with ChatGPT and proposes directions for future development to overcome these obstacles and boost its effectiveness. By exploring the vast potential of ChatGPT to meet the needs of the large CVD patient population and the extensive community of cardiovascular professionals, this review aims to provide valuable insights for optimizing its use in cardiovascular medicine, ultimately improving patient outcomes and advancing the field.

Background/Objectives: Transforaminal endoscopic lumbar discectomy (TELD) under local anesthesia is a promising minimally invasive surgical option for intractable lumbar disc herniation (LDH). However, our understanding of access pain prediction during foraminal pathological procedures is limited. To our knowledge, no predictive rules for access pain during TELD have been established for foraminal or extraforaminal LDH. This study, with its potential to predict access pain during TELD and to discuss strategies for pain prevention and management, could significantly impact the field of endoscopic spine surgery. Methods: This observational study included 73 consecutive patients who underwent TELD for foraminal or extraforaminal LDH between January 2017 and December 2022. Preoperative clinical and radiographic factors affecting significant access pain and the impact of access pain on clinical outcomes were evaluated. Results: The rate of significant access pain was 13.70% (10 of 73 patients). Extraforaminal LDH tended to cause more severe pain than foraminal LDH during TELD under local anesthesia (p &lt; 0.05). Although the degree of access pain was not related to global outcomes, increased pain was strongly associated with a prolonged operative time and length of hospital stay (p &lt; 0.05). Conclusions: TELD can be an effective surgical option for foraminal or extraforaminal LDH under local anesthesia. More access pain may develop during TELD for extraforaminal LDH. The extraforaminal component of LDH can narrow the safety working zone. Significant access pain may prolong the duration of surgery and hospitalization. Thus, a specialized technique is required for the clinical success of TELD.

Purpose: This study was designed to investigate the ability of telemonitoring involving a secure elec-tronic database called “Alsayed System for Applied Medical-Care Improvement” (ASAMI) to detect at least 95% of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Methods: This prospective observational study, which took place over 16 months in 2022-2023, was based at a medi-cal center in Jordan. The study group participants were patients with COPD (from seven countries) with mixed levels of airflow limitation severity, and every participant was followed for six months. A customized, password-protected version of ASAMI was used to collect data during the study. The implemented diary included questions on daily symptoms such as cough, dyspnea, sputum, and daily physical activities. The detection of AECOPD events was initially based on daily questionnaires com-pleted by patients, followed by the assessment of a healthcare practitioner. Results: 87 participants were monitored for AECOPD. During the study, 78/87 (89.7%) patients presented with one or more exacerbation episodes. The mean (range) age was 59.7 (45-81) years, predominantly male (66%), with moderate airflow limitation (n=42, 48%). Compliance with the provision of daily symptom data was very high, 98% over the entire study period. A total of 189 confirmed AECOPD episodes were reported. Almost all patients and practitioners showed favorable satisfaction with the role of the ASAMI-related service (96% reported a score of 10 satisfaction). The telemonitoring tool was able to detect 99% of AECOPD episodes. Conclusion: The novel ASAMI software was effective as a telemonitoring tool to detect the episodes of AECOPD. The tool was suggested for daily, continuous reporting of respiratory symptoms, with the key benefits being ease of use, patient acceptance, and collation of supplementary data when exacerbations occur. The effects of its widespread use on decision-making can be clarified by evaluating its impact on routine clinical decision-making.

Purpose: This pilot ex-vivo study and first clinical experience in Italy evaluate the impact of using pre-implantation crosslinking on all-femtosecond laser-cut corneal allogenic intracorneal ring segments (AFXL CAIRS). Methods: Six human donor eye-bank corneas were used for the preclinical ex-vivo human study. Three corneas were used for AFXL CAIRS. First, they were prepared (D) with the IntraLase™ femtosecond laser (Johnson & Johnson, USA). The allogenic tissue rings were crosslinked before implantation with Riboflavin -UV-A accelerated crosslinking protocol (ACXL) with a 0.1% HPMC Riboflavin isotonic solution (Vibex Rapid, Glaukos-Avedro, USA) and the new KXL UV-A emitter (Glaukos-Avedro, USA). Three corneas were used as recipients (R) of the AFXL CAIRS. After completing the ex-vivo phase, the first two Italian patients were treated. A single ACXL CAIRS was implanted in a 51-year-old male with 53.53 D K steep, 363 m minimum corneal thickness (MCT) and a double ACXL CAIRS was implanted in a 46-year-old male patient with 58.30 D K steep and 443 m MCT. The follow-up was at three months. Results: Crosslinking of the segments enhanced tissue strength and grip, facilitating manipulation and CAIRS insertion into the recipient tunnels and the yellowish color of the crosslinked segments improved visibility. The segment’s thickness and volume remained unaltered during the follow-up. Both patients improved UDVA and BSCVA. K steep and HOAs were reduced and MCT increased. Conclusions Pre-implantation ACXL facilitated CAIRS insertion by increasing the viscoelastic consistency without altering physical characteristics and volume during the follow-up, rendering this important step a promising candidate in method standardization. Functional data and MCT improved significantly without adverse events.

Periprosthetic joint infection (PJI) is one of the major complications resulting from the implantation of a joint prosthesis. Staphylococci are responsible for more than 50% of prosthetic infections, about 20% can be polymicrobial, 15% are gram-negative and about 10% of cultures are negative. The complete eradication of the infection is extremely difficult. For a correct treatment is first of all useful to perform a clinical staging based on the anatomical location of the infection and on the immune characteristics of the host. However, regardless the area of infection, the role of the surgeon is crucial, firstly in terms of timing and secondly in assessing the degree of invasiveness of the infected and necrotic tissues required. The goal of the treatment must be to eradicate the infection ensuring the maximum functional result.

Aortic transection, a near-complete tear through the layers of the aorta, is a critical condition often resulting from trauma such as motor vehicle collisions. The urgency of managing aortic transection underscores the critical need for effective interventions. We report the case of a male in his early 50’s with no significant medical history who presented to the emergency department following a motor vehicle collision, sustaining multiple injuries including a descending thoracic aortic transection. Rapid diagnostic assessment confirmed the severity of the injury, necessitating immediate intervention. Endovascular aortic repair (EVAR) was successfully employed, highlighting its efficacy in managing acute aortic injuries. The patient responded well to treatment, underscoring the importance of timely intervention in improving patient outcomes. This case emphasizes the critical role of rapid diagnostic assessment and endovascular intervention in managing life-threatening thoracic aortic injuries, particularly in the acute setting.

The COVID-19 pandemic has led to the widespread use of face masks to reduce disease transmission, but one unintended consequence is that this may negatively impact sleep and arousal by altering the expression of yawning. Yawns are defined by an involuntary and powerful gaping of the jaw with inspiration, and the typical design of face masks may restrict and/or disrupt the mandibular jaw movement and counter-current heat exchange during this behavior. Face masks additionally impair the contagious nature of yawning by disrupting the recognition of yawning in others within social/community settings. Given that the neurophysiological consequences of yawning function in facilitating changes in state and arousal, and most notably transitions in waking and sleeping via thermoregulation, face mask usage could be an important variable to consider within sleep studies. We briefly outline these connections, highlight some important factors to consider, and discuss the implications for both prior and current research on sleep.

Polycystic Ovarian Syndrome (PCOS) is a common endocrine condition that affects 8–13% of women of reproductive age and is one of the leading causes of anovulation and infertility. In Kazakhstan, the prevalence of this syndrome is particularly high compared to other countries and the global average. Currently, the diagnosis of polycystic ovarian syndrome is based on internationally established Rotterdam criteria, using hyperandrogenism, i.e. high testosterone levels, as a key parameter. These criteria are applied to diagnose PCOS in all female patients, although obese patients may have excess testosterone produced by adipose tissue. To avoid possible false PCOS diagnoses, an additional criterion could be considered to diagnose PCOS among obese women. Anti-Müllerian hormone (AMH) is promising as a more effective diagnostic criterion, since its level represents the state of the ovarian reserve and adipose tissue does not produce AMH. Therefore, the use of AMH instead of hyperandrogenism as a diagnostic criterion for PCOS among obese women might improve diagnostic precision and patient treatment. In this study, data on the levels of various hormonal indicators such as estrogen, progesterone, and others were analyzed for a large cohort of female patients with and without PCOS to explore possible correlations between these indicators, AMH, and testosterone. The findings suggest that the absence of a negative correlation between AMH and follicle-stimulating hormone (FSH), and a positive correlation of AMH with testosterone could support the use of AMH as a reliable additional criterion for PCOS diagnosis among obese women.

PARP inhibitors are used in tumor therapy exploiting their inhibitory role in DNA repair. Radiation therapy leads to DNA damage in the affected region comprising both tumor tissue and adjacent normal tissue. In addition, radiotherapy has long-standing effects on DNA integrity. The mechanisms for this are not well understood. We studied normal tissue damage of the lung after application of ionizing radiation (IR) in two well established rat models comprising both external (eIR) and internal (iIR) ionizing radiation. We found a nearly complete (~350-fold) loss of PARP-1 in the irradiated tissue in both models but no change in PARylated protein. This may be explained by the strong decrease in both ARH3 and PARG, both deparylating enzymes. We demonstrate, that of all these proteins are expressed in type II pneumocytes, but also in type I pneumocytes and the bronchiolar epithelium. The data suggest a severe disturbance of PARylation in these cells which may affect their major functions such as maintenance of the integrity of the alveolar wall. It is likely that the application of PARP inhibitors could have cumulative effects in radiation-damaged normal tissue.

Aim. The aim of this study is to compare data from two cohorts separated by a 17-year interval. We assessed the prevalence and severity of symptoms with the “dialysis symptom index” in these two groups recruited in 2007 and 2024 to determine how advancements in dialysis therapy have influenced symptom burden’s prevalence and severityMethods. We conducted a cross-sectional study of patients receiving thrice weekly, in-center hemodialysis. The population, recruited between February and March 2007, was comprised of patients receiving maintenance hemodialysis at the outpatient dialysis unit of our hospital. This dialysis facility is staffed by academic nephrologists. In May 2024, in the same unit, another population sample was recruited and studied as in 2007. Study coordinators administered the Dialysis Symptom Index (DSI) during the dialysis treatment. The DSI is made up of 30 questions, each of which addresses a specific physical or emotional symptom. Patients were asked to report symptoms that had been present at any time during the previous week by responding “yes” or “no”. For symptoms that were present, the patient was then asked to describe the symptom severity on a five-point Likert scale (1= not bothersome to 5=bothers very much). We generated a total symptom burden score that represents the total number of symptoms reported as being present, as well as a total symptom severity score that represents the sum of individual severity scores assigning a severity score of zero for symptoms that were not present. Results. We studied 71 patients in 2007 and 61 patients in 2024. The demographic, clinical and laboratory characteristics of the two study populations did not differ significantly. The total symptom burden score did not differ significantly between 2007 and 2024. The prevalence of most symptoms was similar in the two groups. The prevalence of constipation, decreased interest in sex and difficulty becoming sex aroused was higher in 2024 than in 2007. The total symptom severity was similar in the two periods. The severity of most symptoms was similar in the two groups. The severity of decreased interest in sex and difficulty becoming sex aroused was higher in 2024 than in 2007. Conclusion. The present study shows that, 17 years apart, the prevalence and severity of the symptom burden in patients on maintenance hemodialysis has not changed significantly. These results suggest that effort should be made to design adequate studies on the causes and pathogenesis of physical and emotional symptoms of patients on chronic hemodialysis and, once the underlying mechanisms are identified, it is amenable that high-quality studies on possible therapeutic pharmacological and non-pharmacological interventions will be performed.

Rotator cuff (RC) repair leads to less than optimal results when dealing with massive lesions, so the use of scaffolds as biological support has been proposed to improve RC repair site biology. The present study aims to evaluate the clinical and radiographical outcomes in a series of patients suffering from massive or irreparable RC tears treated with patch (porcine or human scaffolds) repair (augmentation or bridging). Twenty-three patients with a minimum follow up of 24 months were subjectively with 3 patient-related outcome measurements (PROMs) (American Shoulder and Elbow Surgeons score, Constant score, visual analog scale), clinically and radiographically assessed before and after surgery. Regardless the technique (augmentation or bridging) or type of scaffold (porcine or human) employed, at follow up all patients experienced a statistically signif-icant improvement in all PROMs, and clinically. Patch repair represents a valid salvage procedure in massive or irreparable RC tears improving the quality of life and eventually delaying the need for prosthetic replacement.

Silver nanoparticles (AgNPs) have arisen as promising specialists in malignant growth treatment, especially in further developing radiotherapy results. In vitro examinations feature AgNPs' capacity to increment radiosensitivity in disease cell lines, prompting uplifted cell demise and decreased clonogenic endurance. Outstandingly, AgNPs display insignificant poisonousness to ordinary cells, recommending potential for specific focusing of disease cells during radiotherapy. The blend of AgNPs with cisplatin shows huge cytotoxicity and oxidative pressure, particularly in tumoral cells, underscoring the requirement for additional investigation of this therapeutic methodology. AgNPs likewise show guarantee in prompting oxidative pressure in pancreatic disease cells, recommending an expected application in pancreatic malignant growth treatment. In co-openness situations, AgNPs, when joined with cadmium, prompt metabolic variation, showing compromised cell safeguard systems. Moreover, AgNPs display potential in tweaking ABC carrier action, offering a procedure to defeat multidrug obstruction in disease cells. While featuring the significant capability of AgNPs in disease treatment, the rundown highlights the need for continuous exploration to clarify their components, well-being profiles, and clinical applications. Combining AgNPs with radiotherapy presents a promising road, tending to limits in ordinary disease therapies and underlining their multifunctionality in forming the eventual fate of malignant growth therapeutics.

Bioimpedance analysis (BIA) is a validated non-invasive technique already proven to be useful for the diagnosis, prognosis, and management of body fluids in subjects with heart failure (HF) and chronic kidney disease (CKD). Although BIA has been widely employed for research purposes, its clinical application is still not fully widespread. The aim of this review is to provide a comprehensive overview of the state of art of BIA utilization by analysing the clinical benefits, limitations, and the potential future developments in this clinically unexplored field.

Background: Inflammatory Bowel disease (IBD) is one of the worldwide health issues with increasing incidence. Recent data point out that those patients can have a defective immune system, rendering response to vaccinations suboptimal. Since 1990, Hepatitis B Virus (HBV) vaccination has been introduced among the compulsory childhood vaccinations in Oman. Given the questionable immunogenicity of vaccinations in IBD patients, we designed this study to quantify the immune response to scheduled HBV vaccine in IBD patients and compare it with that in a matching control cohort of healthy blood donors at Sultan Qaboos University Hospital (SQUH). Methods: This is a retrospective case-control study that was conducted between the 1st of July 2023 and the 31st of May 2024 at SQUH. Using the hospital information System (HIS), a total of 252 participants were enrolled in our study and divided into two groups. Group (1) included 126 IBD patients and group (2) included 126 healthy controls. Baseline demographics, medical comorbidities and viral serologies before and after vaccination were collected. The primary outcome of the study was to compare the long term immune response to HBV vaccine between the two groups. The secondary outcomes included identifying possible risk factors for suboptimal vaccine response. Results: One hundred and twenty-six participants were included in each group. Durable protective immune response to HBV vaccine was attained in 29 patients (23%) of the IBD group compared to 109 participants (86.5%) of the control group. There was a statistically significant association (p = 0.0156) between prednisolone treatment and low immune response to HBV vaccine. Moreover, esomeprazole usage exhibited a statistically significant association (p < 0.0001) with suboptimal response to HBV vaccine. Meanwhile, there was no statistically significant correlation between low immunogenicity to HBV vaccine and age, sex, type of IBD, comorbidities, and BMI. Conclusions: IBD patients are less immunogenic to HBV vaccination compared to healthy controls. Factors like esomeprazole and/or corticosteroid therapy might be associated with poor immune response. These findings highlight the importance of reassessing the immunogenicity of HBV vaccination and probably other protective vaccinations in all IBD patients as part of their standard of care.

It is known that Radon gas within the air could reach lung cells and cause cancer. We suggest a technique to absorb alpha particles radiated by Radon decay near DNAs within human cells. In this technique, we create some non-paired negative electrons on graphene sheets and build some negative graphene tubes. Alpha particles are attracted and negative beta particles are repelled by the graphene tubes.

To verify the efficacy of placental extracts (Pla-Ext) and human mesenchymal stem-cell-derived exosomes (hMSC-Exo) against human skin aging, we investigated the human dermal fibroblast (HDF) response following hMSC-Exo and Pla-Ext treatment and whether they elicited resistance to damage when HDFs were subjected to several types of aging stresses. The effect of hMSC-Exo alone, the combined effect of Pla-Ext and hMSC-Exo, and the effect of hMSC-Exo (Pla/MSC-Exo) recovered from cultures with Pla-Ext added to hMSC were verified using collagen, elastin, and hyaluronic acid synthase mRNA levels for each effect. Cells were subjected to photoaging (UV radiation), glycation (glycation end product stimulation), and oxidation (H2O2 stimulation) as HDF stressors. Pla-Ext did not significantly affect normal skin fibroblasts considering intracellular parameters; however, a pro-proliferative effect was observed. Pla-Ext induced resistance to several stresses in skin fibroblasts (UV irradiation, glycation stimulation, H2O2 stimulation) and inhibited reactive oxygen species accumulation following H2O2 stimulation. Although the combined efficacy of hMSC-Exo and Pla-Ext was unclear, some changes resulted in senescence stress resistance due to preconditioned hMSC-Exo stimulated by Pla-Ext. This suggests that Pla-Ext supplementation may cause some changes in the surface molecules or hMSC-Exo content (e.g., microRNA).

Background: Contrast-induced acute kidney injury (CIAKI) is a common complication in hospital-acquired renal conditions, yet its pathogenesis remains unclear and effective treatments are limited. Intermedin (IMD), a peptide related to the calcitonin gene, exhibits vasodilatory and endothelial barrier-stabilizing effects via the calcitonin receptor-like receptor (CLR). However, the potential of IMD in mitigating CIAKI has not been thoroughly investigated. Aims: This study aimed to delineate the protective role of IMD in CIAKI through both in vitro and in vivo models, with a particular focus on elucidating the underlying mechanisms, specifically the cAMP/Rac1 signaling pathway. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with iohexol to simulate kidney injury in vitro. The protective effects of IMD were evaluated using the CCK8 assay, flow cytometry, ELISA, and western blotting. A CIAKI rat model was developed to assess renal peritubular capillary endothelial cell injury and renal function using a range of techniques, including histopathology, immunohistochemistry, immunofluorescence, western blotting, and transmission electron microscopy. Results: In vitro, IMD significantly enhanced HUVEC viability and mitigated iohexol-induced toxicity by preserving intercellular adhesion junctions and activating the cAMP/Rac1 pathway. The protective effects of IMD were attenuated by Rac1 inhibition. In vivo, CIAKI caused considerable damage to peritubular capillary endothelial cell junctions, leading to impaired renal function. IMD treatment markedly improved renal function, an effect that was abolished by Rac1 inhibition. Conclusion: IMD protects against renal injury in CIAKI by activating the cAMP/Rac1 pathway, thereby preserving the integrity of peritubular capillary endothelial cells and mitigating acute renal injury induced by contrast media. These findings underscore the therapeutic potential of IMD in CIAKI and emphasize the critical role of the cAMP/Rac1 pathway in renal protection.

Background: The skin prick test (SPT) is used to diagnose sensitization to antigens. This study proposes a deep learning approach to infer wheal dimensions, aiming to reduce dependence on human interpretation. Methods: A dataset of SPT images (n=5844) was used to infer a convolutional neural network for wheal segmentation (ML model). Three methods for inferring wheal dimensions were evaluated: the ML model; the standard protocol (MA1); and approximation of the area as an ellipse using diameters measured by an allergist (MA2). The results were compared with assisted image segmentation (AIS), the most accurate method. Bland-Altman, distribution analyses, and correlation tests were applied to compare the methods. The study also compared the percentage deviation among these methods in determining the area of wheals with regular geometric shapes (n = 150) and with irregular shapes (n=150). Results: The Bland-Altman analysis showed that the difference between methods was not correlated with the absolute area. The ML model achieved a segmentation accuracy of 85.88% and a strong correlation with the AIS method (ρ=0.88), outperforming all other methods. Additionally, MA1 showed significant error (13.44±13.95%) for pseudopods. Conclusions: The ML protocol can potentially automate the reading of SPT, offering greater accuracy than the standard protocol.

(1) Background: Allergic reactions and angioedema are important immunologic conditions in acute care settings. Prior data indicate an association between the severity of symptoms and maximum lysis (ML) in thromboelastography. We aimed to evaluate the dynamics of ML after two hours of observation after admission to the emergency department. (2) Methods: We deter-mined ML with thromboelastography using extrinsic testing (EXTEM, ROTEM®, Werfen GmbH, Munich, Germany) at the presentation of patients with immunologic reactions and approximately two hours thereafter. The median test was used to compare the extent of ML between individuals who were still symptomatic at follow-up and those who were asymptomatic. (3) Results: We pro-spectively enrolled 16 individuals (10 (63%) female, mean age 50±14 years). Of these, 6 (38%) were still symptomatic at follow-up. Patients who had persistent symptoms had significantly higher ML than those who were asymptomatic (14% (IQR 12-17) vs. 8% (IQR 4-10), p=0.002). (4) Conclusions: ML is elevated in patients who are still symptomatic two hours after presenting to the emergency department due to an immunologic reaction.

Objectives. To compare the audiological benefits of a non-implantable wearing option of a bone conduction (BC) implant mounted on an arch (SoundArc) to traditional BC hearing aids (HA) mounted on eyeglasses (BCHA) in patients with moderate to severe conductive or mixed hearing loss. Methods: A preliminary cross-sectional observational prospective cohort study was conducted at a Tertiary Audiological Department, University Hospital. Fourteen adults with conductive or mixed hearing loss (PTA at 0.5-1-2-4 KHz = 67 ± 15 dB HL) had been wearing conventional BCHA on eyeglasses for at least 3 years, and refused the surgical implantation of a BC hearing implant (BCHI). Unaided and aided pure-tone AC and BC thresholds and speech test in quiet and in noise were recorded at baseline and in two different settings: with a BCHI mounted on SoundArc®, and with their own BCHA with two couplers, mounted on eyeglasses. International Inventory for Hearing Aids [IOI – HA], the Hearing Handicap Inventory [HHIA/E], Speech, Spatial, Qualities of Hearing Scale [SSQ], a 10-scores visuo-analogic scale [VAS], and Fatigue impact scale [FIS] score were asked in both conditions. Results: a statistical significative functional gain was observed for both settings. (p=.0001) Better speech perception performances in quiet and in noise were observed with SoundArc compared to their conventional BCHA on eyeglasses (word repetition score in noise improvement of +19.3 at SNR +10 dB, p=.002; + 12.1 at SNR 0 dB, p=.006; and +11.4 at SNR -10 dB, p=.002) No significant differences were found in IOI–HA, FIS, and HHIA/E scores, while significative better SSQ scores in all domains were reported for SoundArc. (p=.0038) Conclusions: Although patients were accustomed to their BCHA on eyeglasses, the non-implanted wearable option of the BCHI proved to be a viable alternative in adult patients with conductive or mixed hearing loss unable to receive or refusing BCHI surgery.

Advances in molecular biology, polymerase chain reaction (PCR), and next-generation sequencing (NGS) have transformed the concept of minimal residual disease (MRD) from a philosophical idea into a measurable reality. Acute promyelocytic leukemia (APL) led the way in this transformation, initially using PCR to detect MRD in patients in remission, and more recently, aiming to eliminate it entirely with modern treatment strategies. Along the way, we have gained valuable insights that, when applied to other forms of acute leukemia, hold the potential to significantly improve outcomes in these challenging diseases. In this review, we explore the current use of MRD in the management of acute leukemia and delve into the biological processes that contribute to MRD persistence, including its overlap with leukemia stem cells and the role of the bone marrow microenvironment.

The aim of this study was to detect seasonal and species differences in serum 25-hydroxy vitamin D (25(OH)D) concentrations during summer and winter months in Asian (Elephas maximus) and African elephants (Loxodonta africana), black (Diceros bicornis) and Indian rhinoceroses (Rhinoceros unicornis) and Malayan tapirs (Tapirus indicus) - when kept in captivity in (Western) Europe. Both elephant species had a low circulating level of serum 25(OH)D while African elephants (median 33.2 nmol/l – range: 21.2-58.8 nmol/l,) did not show a seasonal variation. Asian elephants had significant higher circulating levels of serum 25(OH)D compared to their African counterparts, but also did not show a seasonal difference (median 68.7, – range 55.5-110.6 nmol/l). Both rhinoceros species investigated had higher serum 25(OH)D levels compared to both elephant species; the Indian rhinoceros had high circulating levels year around (median 107.9 – range: 106.3-132.8 nmol/l), while the black rhinoceroses showed significant lower 25(OH)D levels in winter (summer median 109.0– range 51.5-251.0 nmol/l; winter median 58.3 nmol/l - range 23.5-226.0 nmol). Malayan tapirs have very low levels of serum 25(OH)D (median &lt; 20.3 – range &lt; 20.3-33.5 nmol/l), which is comparable to horses. Higher levels of circulating 25(OH)D of elephants and rhinoceroses compared to horses, could indicate that elephants and rhinoceroses are capable of producing vitamin D. However, this requires further testing. If this is indeed the case, this might indicate that the Indian rhinoceros are capable of producing enough endogenous vitamin D year around at latitudes around 52°N, while both elephant species and the black rhinoceros are not. To the author’s knowledge, this is the first report of vitamin D levels in tapirs.

Background: Despite procedural advancements in the management of univentricular heart patients palliated with a Fontan-type circulation, their exercise capacity and quality of life remain limited. Postoperative exercise training programs offer potential benefits, yet practical implementation and adherence to guidelines are often inadequate. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Method: A systematic search was conducted on August 24, 2023, using PubMed, Scopus, Web of Science, and Cochrane Library. Studies were screened via Rayyan QCRI based on pre-set exclusion criteria, and their quality was assessed using the Cochrane RoB Tool 2 and the STROBE checklist. A meta-analysis employed a continuous random-effects model to assess the efficacy of cardiac rehabilitation interventions. Results: The study included twenty-six studies (7 RCTs, 19 cohorts) representing 22 individual cohorts. The key findings were that aerobic exercise, lower-extremity resistance training, and inspiratory muscle training significantly improved VO2, enhancing exercise capacity in Fontan patients. Conclusion: While the results are promising, it's crucial to remember that training programs varied widely. Exercise training shows promise for postoperative management, potentially improving exercise capacity, cardiac biomarkers, lung function, and lower limb strength. However, further research is not just a suggestion, but a necessity. It's necessary to refine protocols, assess long-term impacts, and investigate underlying mechanisms, especially for Fontan patients with severe clinical conditions. This emphasizes the importance and urgency of further research in this area.

Background: Staphylococcus aureus is a major contributor to biofilm-associated infections, which complicate the treatment of chronic conditions like osteomyelitis and prosthetic infections. Bio-films, characterized by bacterial communities encased in a protective matrix, hinder the effec-tiveness of antimicrobial agents and contribute to persistent infections. Objective: This study aimed to evaluate the activity of delafloxacin, a novel fluoroquinolone, against biofilm-forming S. aureus strains, including methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) isolates. Methods: Delafloxacin’s efficacy was compared with traditional antibiotics (vancomycin, line-zolid, doxycycline, sulfamethoxazole/trimethoprim, and rifampicin) using minimal inhibitory concentration (MIC) assays, including testing at different pH levels to simulate acidic biofilm conditions. Synergistic interactions between delafloxacin and other antimicrobials were assessed using the checkerboard method. Biofilm eradication was tested through minimal biofilm eradi-cation concentration (MBEC) assays, biomass quantification, and cell viability (MTT assay). Re-sults: The results showed that all isolates were susceptible to vancomycin and linezolid, with varying resistance to other antibiotics. Delafloxacin demonstrated potent activity, with MIC re-ductions observed in acidic conditions. Synergistic effects were minimal, with only a few isolates showing synergy with vancomycin and doxycycline. Biofilm eradication tests revealed limited success in eradicating biofilms at breakpoint concentrations. However, rifampicin in combination with delafloxacin significantly reduced biofilm biomass in some isolates. No significant changes in cell viability were noted across treatments. Conclusion: This study highlights delafloxacin's potential against biofilm-associated infections, particularly in acidic environments. Despite the challenges in biofilm eradication, delafloxacin combined with rifampicin shows promise for im-proved treatment strategies.

Objectives: This study aimed to compare the similarities and differences between the Kawasaki disease (KD) during the SARS-CoV-2 pandemic and multisystem inflammatory syndrome in children (MIS-C). Methods: The medical records of patients diagnosed with KD and MIS-C at a single center between July 2020 and November 2021 were retrospectively reviewed. Results: The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. Compared with the KD patients, MIS-C patients were older (p<0.001), had longer hospital stays (p=0.023), elevated neutrophil count (p<0.001), C-reactive protein (p<0.001), procalcitonin (p<0.001), interleukin-6 (p<0.014), ferritin (p<0.001), fibrinogen (p<0.001), troponin I (p=0.001), NT-proBNP (p<0.001), and, D-dimer levels (p<0.001). They had more hypotension (p=0.024), decreased left ventricular function (p=0.023), and a greater need for corticosteroids (p<0.001), enoxaparin (p=0.045), and therapeutic plasma exchange (p<0.001). Patients with KD displayed a higher frequency of rash (p<0.001), oral mucosal changes (p<0.001), conjunctival injection (p<0.001), extremity changes (p<0.001), and cervical lymphadenopathy (p<0.001). They had a longer duration of fever (p<0.001), elevated white blood cell count (p<0.001), platelet count (p<0.001), and alanine aminotransferase level (p<0.001). The two groups were similar in terms of hemoglobin levels, erythrocyte sedimentation rate, albumin levels, or the frequency of coronary dilation/aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Conclusions: Older patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas a longer duration of fever and classical clinical features of KD favor KD.

Urethral catheterization, a common procedure in canine patients, often compromises urinary tract defenses, leading to bacterial colonization and potential systemic infection. Despite posi-tive urine cultures, clinical signs of urinary tract infection (UTI) may be absent in catheterized dogs. This study evaluated the correlation between urinalysis results and catheter-associated UTIs in hospitalized dogs, considering prior antibiotic treatment and antibiotic resistance. Twen-ty-eight dogs at Kasetsart University Veterinary Teaching Hospital were included. Urine cul-tures and antibiotic sensitivity tests were performed on days 0, 3, and 7 and prior to catheter re-moval, with a positive urine culture defined at ≥104 CFU/mL. Instances of pyuria (>5 WBCs/HPF), hematuria (>5 RBCs/HPF), and bacteriuria were recorded. A statistical analysis showed no significant association between the urine culture results and urinalysis parameters, catheterization duration, breed, sex, neutering status, or age. Dogs with prior antibiotic treat-ments exhibited UTI-free periods after catheter placement that were longer than those previous-ly reported. A Kaplan–Meier analysis showed a probability of being UTI-free of 92.8% at 3 days, declining to 60.7% by 7 days and 53.6% by 10 days. Alarmingly, eighty percent of the isolates (12/15) were multidrug-resistant organisms (MDROs), resistant to ≥3 antimicrobials. Routine urinalysis cannot reliably predict catheter-associated UTI, and the high rate of MDROs under-scores the need for judicious antibiotic use and improved diagnostic tools.

Can the type of implant rehabilitation influence peri-implant bone loss in case of full-arch mandibular prosthesis? The purpose of the study was to assess, by orthopantomograms (OPG), bone loss around implants in different types of implant-supported prosthetic rehabilitations and evaluate potential risk factors associated with the number and location of implants that may have an association with bone defect. A radiographic study was conducted on 22317 OPGs in the time range from 2010 to 2024. All OPGs with implant-supported prosthetic mandibular rehabilitations were included in the study. A total of 155 OPGs were evaluated, with peri-implant bone loss identified in 64 (41.3%). Distal implants (furthest from the center) across various positioning patterns were most susceptible to bone loss, with positions 3.6 and 4.6 demonstrating the most frequent occurrences (25 and 26 cases, respectively). χ² test revealed significant associations between both implant positioning pattern (p &lt; 0.001) and number of implants (p &lt; 0.001) with peri-implant bone loss. Also by updating the sample of OPGs, increased susceptibility to bone resorption was found for implants placed distal to the mental foramen compared to mesial ones in full-arch implant-supported fixed prostheses. Prospective clinical studies will then be useful to investigate this finding further.

Current treatments for medial meniscus lesions in association with CCL ruptures [1–5] have shown disappointing long-term outcomes [6]. Meniscal suturing may improve the outcome, but their clinical application remains limited [7–9]. This study aims to assess the practicability of a minimally invasive DNT to facilitate meniscal suturing in dogs. Ten stifles of eight client-owned dogs with arthroscopically confirmed CCL disease and medial meniscal tears in the abaxial third of the meniscus were included. The described suture technique was applied under joint distraction using the Titan joint distractor.[8] Surgical stabilization of all stifles was then accomplished through a X-Porous TTA procedure [10]. The DNT allowed for the precise placement of meniscal sutures. Minor intraoperative complications included reduced arthroscopic visibility (n=2) and suture breakage during its passage through the meniscus (n=3). No complications related to the meniscal sutures were noted throughout the six-month follow-up. The described DNT proved to be a viable and effective method for suturing lesions of the caudal horn of the medial meniscus, provided there is adequate visualization during the procedure. Appropriate stifle stabilization postoperatively is mandatory for protecting the suture and avoiding concomitant meniscal lesions due to joint instability.

Dendritic cells (DCs) are known as major antigen-presenting cells, and lymph nodes (LNs) play an important role in the DC-mediated immune response. This study focused on infiltration of CD1a-positive DCs (CD1a-DCs) in regional LNs in 70 cases of gallbladder cancer (GBC). The results showed that LNs infiltration by CD1a-DCs was associated with unfavorable clinical outcomes in patients with GBC in univariate analyses, but all cases categorized as CD1a-DCs high group at regional LNs had nodal metastasis. Therefore, LNs infiltration by CD1a-DCs was not an independent prognostic factor identified by multivariate analyses. The subgroup analyses in cases with LN metastasis group (n = 32), significant impact of CD1a-DCs infiltration into metastatic LNs was not observed. In contrast, CD1a-DCs infiltration into primary tumor had a significant impact on surgical outcomes. As the results of previous reports that focused on CD1a-DCs infiltration in regional LNs of other organs were varied, the role and significance of CD1a-DCs infiltration in regional LNs may be different according to the tumor histology or primary site. Accumulation of further studies is needed to clarify the role and significance of CD1a-DCs infiltration into regional LNs of solid cancers.

Introduction: This review explores the literature and presents institutional cases of concurrent robotic multisite surgery—in particular, robot-assisted radical prostatectomy (RARP) and robot-assisted partial nephrectomy (RAPN) for synchronous prostate and kidney cancers. We highlight dual-console synchronous robotic procedures, emphasizing the unique docking tech-nique developed. Aim: The aims of the study were to evaluate the feasibility, safety, and clinical outcomes of concurrent RARP and RAPN for synchronous prostate cancer and small renal tumors, as well as other concurrent robotic multisite surgeries, and to compare institutional findings with the existing literature. Materials and Methods: We describe the unique docking technique used in our procedures, which facilitates atraumatic transitions between surgeries using the same port sites. Additionally, eligible studies on concurrent robotic multisite surgery that were published in English were retrieved from the MEDLINE, Embase, and Cochrane Library databases. Data on operative time, blood loss, complications, and postoperative outcomes were extracted. Results: Eight cases from our institution demonstrated the feasibility and safety of the proposed approach, which is consistent with previous reports. The unique docking technique and dual-console setup enhance surgical precision, offering significant benefits in patient outcomes. As part of the litera-ture review, nine retrospective studies involving 40 cases of concurrent RARP and RAPN were reviewed. Additionally, eleven retrospective studies involving 392 cases of concomitant RARP and robotic transabdominal preperitoneal inguinal hernia repair (RTAPPIHR) were analyzed. Conclusions: Concurrent RARP and RAPN for synchronous prostate and kidney tumors is a viable and effective approach. Our early experience suggests that this and other combined procedures can optimize patient care and reduce costs. Prospective trials are needed to validate these findings and further refine the techniques.

This study presents a detailed comparative analysis of Molecular Docking data, focusing on the binding interactions of conventional ligands and natural compounds, Apigenin and Luteolin, with TP-53, pRb, and APOBEC. Utilizing advanced bioinformatics techniques, coupled with Ar-tificial Intelligence software and High-Performance Computing (HPC), we measured and con-trasted the binding energies of these interactions. Additionally, we investigated protein-protein interactions between HPV-16 oncoprotein E6 and tumor suppressors TP-53 and pRb. Our findings demonstrate that the natural compounds Apigenin and Luteolin exhibit significantly higher binding affinities to TP-53, pRb, and APOBEC compared to conventional pharmacological ligands. The binding energies for Apigenin and Luteolin were approximately -6.9 kcal/mol and -6.6 kcal/mol, respectively, indicating their strong potential as therapeutic agents in inhibiting the oncogenic functions of HPV-16. In contrast, conventional ligands showed lower binding affinities, with energies around -4.5 to -5.5 kcal/mol. The study further revealed that the protein-protein interactions between E6 and TP-53, and E6 and pRb, exhibited considerably higher binding en-ergies, approximately -976.7 kcal/mol, due to the multiple interaction sites and the complex nature of protein interfaces. A conversion formula was developed to translate these high-energy inter-actions to a comparable scale for non-protein-protein interactions, highlighting the superior binding potential of natural compounds, which, through the same conversion formula, was shown to be higher than that of interaction between E6 with TP-53 and E6 with pRb. These results underscore the therapeutic promise of Apigenin and Luteolin in preventing HPV-16-related on-cogenesis. By demonstrating their higher binding affinities to crucial tumor suppressors, this study supports the development of natural compound-based therapies. The findings also em-phasize the necessity for further experimental validation to explore these compounds' efficacy in clinical settings. This comprehensive analysis provides a robust framework for understanding the comparative binding interactions and lays the groundwork for innovative therapeutic strategies against HPV-16.

Identification of the individuals having impaired kidney function is essential in preventing the complications of this disease. We measured 1 009 metabolites at the baseline study in 10 159 Finnish men of the METSIM cohort and associated the metabolites with estimated glomerular filtration rate (eGFR). A total of 7 090 men participated in the 12-year follow-up study. Non-targeted metabolomics profiling was performed at Metabolon, Inc. (Morrisville, NC, USA) on EDTA plasma samples obtained after overnight fasting. We applied Liquid chromatography-mass spectrometry (LC-MS/MS) to identify the metabolites (the Metabolon DiscoveryHD4 platform). We performed association analyses between the eGFR and metabolites using linear regression adjusted for confounding factors. We found 108 metabolites significantly associated with a decrease in eGFR, and 28 of them were novel including 12 amino acids, 8 xenobiotics, 5 lipids, 1 nucleotide, 1 peptide, and 1 partially characterized molecule. The most significant associations were with five amino acids, N-acetylmethionine, N-acetylvaline, gamma-carboxyglutamate, 3-methylglutaryl-carnitine, and pro-line. We identified 28 novel metabolites associated with decreased eGFR in the 12-year follow-up study of the METSIM cohort.

Background:In view of fact, the drawback of the armed conflict between Sudanese army and rapid support force was shocking, mass migration to neighboring countries, and many civilian were died, behind the war there were another factors for death, among these factors is brain tumors. The objectives of this study: To build up information and correlation between demographic data, brain tumors, surgery type and limitation of surgical resources, and to identify neurosurgical practice during armed conflict and how surgical resources can be utilized. Methods:This was a case report study, done at Almubarik hospital from April 2024 to July 2024.Ethical approval was taken from the National Center for Neurological Sciences.The operating room at Almubarik hospital includes X-ray viewing box, operating table, which is design for obstetrical and gynecology operation. very limited instruments for completing the surgery (forceps, straight dissector and scissors).Moreover, regarding anesthesia in this new situation there is no invasive BP, CVP, core temperature or even capnograph, all this made difficulties in monitoring the patient. In this conflict period, due to the lake of monitoring of the drugs and inappropriate storage, we used to give IV propofol , midasolam , morphine , lidocaine and nondepolrising muscle relaxant. ETT size 7 for all adult patients as it is the only big size available. Halothane MAC was used as volatile agent with propofol. pracetamol , magnisum sulphate ,are given as analgesia.Nevertheless,, for positing we manipulate our operating table by adding special head rest which was manually made from iron par and semi firm bellows are constructed on it tightly, so prone position was made. Conclusion: Despite of the infrastructural limitations, brain tumor surgery has special nature in the context of this conflict. Brain tumor surgery is challenges, and need not only skillful neurosurgeon but advance technology and well trained staff.

Dye-based angiography is the main imaging modality in evaluating the vasculature of the eye. Although most commonly used to assess retinal vasculature, it can also delineate normal and abnormal blood vessels in the anterior segment diseases – but is limited due to its invasive, time-consuming methods. Thus, anterior segment optical coherence tomography angiography (AS-OCTA) is a useful non-invasive modality capable of producing high-resolution images to evaluate the cornea and ocular surface vasculature. AS-OCTA has demonstrated the potential to detect and delineate blood vessels in the anterior segment with quality images comparable to dye-based angiography. AS-OCTA has a diverse range of applications for the cornea and ocular surface, such as objective assessment of corneal neovascularization and response to various treatments; diagnosis and evaluation of ocular surface squamous neoplasia; and evaluation of ocular surface disease including limbal stem cell deficiency and ischemia. Our review aims to summarize the new developments and clinical applications of AS-OCTA for the cornea and ocular surface.

Background/Objectives: The management of early breast cancer (BC) includes surgery, followed by adjuvant radiotherapy, chemotherapy, hormone therapy, or immunotherapy. However, the influence of these interventions in metabolic reprogramming remains unknown. This study explored alterations in the plasma metabolome of BC patients following distinct treatments to deepen our understanding of BC pathophysiology, outcomes, and the identification of potential biomarkers. Methods: We included 52 women diagnosed with BC and candidates for surgery as primary oncological treatment. Blood samples were collected at diagnosis, two weeks post-surgery, and one month post-radiotherapy. Plasma samples from 49 healthy women served as controls. Targeted metabolomics assessed 74 metabolites spanning carbohydrates, amino acids, lipids, nucleotide pathways, energy metabolism, and xenobiotic biodegradation. Results: Before treatment, BC patients exhibited notable changes in carbohydrate, nucleotide, lipid, and amino acid metabolism. We noticed a gradual restoration of specific metabolite levels (hypoxanthine, 3-phosphoglyceric acid, xylonic acid, and maltose) throughout different treatments, suggesting a normalization of nucleotide and carbohydrate metabolic pathways. Moreover, we observed increased dodecanoic acid concentrations, a metabolite associated with cancer protection. These variations distinguished patients from controls with high specificity and sensitivity. Conclusion: Oncological treatments modified the metabolism of patients towards a favorable profile with a decrease in the pathways that favor cell proliferation and an increase in the levels of anticancer molecules. These findings emphasize the pivotal role of metabolomics in recognizing the biological pathways influenced by each cancer treatment and the resulting metabolic consequences. Furthermore, it aids in identifying potential biomarkers for disease onset and progression.

Diabetes mellitus (DM) is currently regarded as a global public health crisis for which lifelong treatment with conventional drugs present limitations in terms of side effects, accessibility and cost. Type 2 diabetes (T2DM), usually associated with obesity, is characterized by elevated blood glucose levels, hyperlipidemia, chronic inflammation, impaired β-cell function and insulin resistance. If left untreated or when poorly controlled, DM increases the risk of vascular complications such as hypertension, nephropathy, neuropathy, retinopathy that can be severely debilitating or life-threatening. Plant-based foods represent a promising natural approach for the management of T2DM due to the vast array of phytochemicals they contain. Numerous epidemiological studies have highlighted the importance of a diet rich in plant-based foods (vegetables, fruits, spices, condiments) in the prevention and management of DM. Unlike conventional medications, such natural products are widely accessible, affordable, and generally free from adverse effects. Integrating plant-derived foods into the daily diet not only helps control the hyperglycemia observed in DM, but also supports weight management in obese individuals and has broad health benefits. In this review, we provide an overview of the pathogenesis and current therapeutic management of DM, with a particular focus on the promising potential of plant-based foods.

Reactive oxygen species (ROS) are intermediates in oxidation-reduction reactions with the capacity to modify biomolecules and temporarily or permanently alter cell behaviour through signalling pathways under physiological and pathophysiological conditions where there is an imbalance between oxidative factors and the antioxidant response of the organism, a phenomenon known as oxidative stress. Evidence suggests that differential modulation of ROS-mediated oxidative stress occurs in the pathogenesis and progression of melanoma, and that this imbalance in redox homeostasis appears to be functionally linked to microRNA-mediated non-mutational epigenetic reprogramming involving genes and transcription factors. The relationship between ROS-mediated stress control, tumour microenvironment and microRNAs expression in melanoma is not fully understood. The aim of this review is to analyze the involvement of miRNAs in the modulation of signalling pathways involved in ROS-mediated oxidative stress in melanoma. It is hoped that these considerations will contribute to the understanding of the mechanisms associated with a potential epigenetic network regulation, where the modulation of oxidative stress is consolidated as a common factor in melanoma and therefore a potential footprint poorly documented.

Introduction Cochlear implants are a modern approach for the treatment of multiple cases of profound sensorineural hearing loss. Factors such as the ethiology of hearing loss and the potential for achieving good postoperative outcomes are considered in cochlear implantation. Additionally, surgical strategies, protocols, the experience of the surgeon and audiologist, and the presence of postoperative issues and risks that may require revision surgery should also be taken into account. The surgeon specialized in cochlear implantation must inform the patient and his relatives not only about the surgical technique but also about possible complications. The literature shows different rates of complications evaluated both in adults and in children. An evaluation of adverse events in order to prevent complications can be made if the definition of medical complications and mistakes is strictly approached based on the CLAVIEN-DINDO classification system. The rate of complications can be compared with existing literature. Studies demonstrate the need for preoperative vaccination for pneumococcus, which can prevent complications, especially in patients with inner ear malformations who present an increased postoperative risk Relevant Sections This review is structured around the collection of specialized literature from PubMed, organized into subchapters related to intraoperative complications such as Gusher syndrome, foreign body reaction, endocochlear inflammation phenomena, issues related to electrode positioning and associated complications, vestibular phenomena related to cochlear implantation, as well as late complications related to the surgical wound and cochlear implant extrusion. The important sections in this review are: Inner Ear Malformations and Gusher Syndrome: Intraoperative Complication Risks, Electrode Insertion and Positioning Issues, Intracochlear Inflammation, Foreign Body Reaction, and Intracochlear Fibrosis: Phenomena That Can Occur with Cochlear Implantation, Vestibular Disorders, Tardive Postoperative Complications: Wound Injuries and Cochlear Implant Extrusion and Otitis Media and Cholesteatoma as Complications of Cochlear Implantation Conclusions: Postoperative complications, although considered quite rare. The surgical limits and long-term evolution of cochlear implants cannot be concretely established, despite the fact that this intervention is considered safe in the medium and long term. Future directions Given that cochlear implants represent the most modern surgical technique for auditory rehabilitation in adults and children, with massive implications for quality of life, there is a tendency to extend surgical indications in the future, and especially to inform doctors in related specialties about the benefits of this medical device. Surgeons must be knowledgeable about cochlear implantation methods, as well as the methods for managing complications that can arise immediately postoperatively, as well as in the medium and long term.

This study aimed to explore the intricate relationship between mitochondrial dysfunction, infections, and neuroinflammation, focusing specifically on the impact of pathogenic epitopes of Epstein-Barr Virus (EBV) nuclear antigen 1 (EBNA1) in a mouse model of mitochondrial dysfunctions. The investigation included female middle-aged PARK2^-/- and C57BL/6J wild-type mice immunized with EBNA1_386-405 or with active experimental autoimmune encephalomyelitis (EAE) induction by myelin oligodendrocyte glycoprotein (MOG)_35-55 peptide. PARK2^-/- mice developed more severe EAE than wild-type mice. Following immunization with EBNA1_386-405, only PARK2^-/- exhibited symptoms resembling EAE. During the acute phase, PARK2^-/- mice immunized with either MOG_35-55 or EBNA1_386-405 exhibited similar infiltration of T cells and macrophages in the spinal cord and decreased GFAP expression in the brain. However, EBNA1_386-405 -immunized PARK2^-/- mice showed significantly increased frequencies of CD8a+ T cells and CD11c+ B cells, and distinct cytokine profiles in the periphery compared to wild-type controls. These findings highlight the role of EBV in exacerbating inflammation, particularly in the context of mitochondrial deficiencies.

Both aging and chronic obstructive pulmonary disease (COPD) are strongly associated with changes in the metabolome; however, it is unknown whether there are common aging/COPD metabolomic signatures and if accelerated aging is associated with COPD. Plasma from 5,704 subjects from COPDGene and 2,449 subjects from SPIROMICS were profiled using the Metabolon global metabolomics platform (1,013 annotated metabolites). Post-bronchodilator spirometry measures of airflow obstruction (forced expiratory volume at one second (FEV₁)/forced vital capacity (FVC) < 0.7) were used to define COPD. Elastic net regression was trained on never and former smokers with normal spirometry and no emphysema to create a metabolomic age score which was validated in SPIROMICS subjects. Our metabolic age score was strongly associated with chronic age in the validation cohort (correlation coefficient 0.8). COPD subjects with accelerated aging (> 7 years difference between metabolic and actual age) had more severe disease compared with those who had decelerated aging (< -7 years difference between metabolic and actual age). COPD and aging metabolites were shared more than expected (P < 0.001) with overrepresented included amino acid and glutathione metabolism pathways. These findings suggesting a common mechanism between aging and COPD and that COPD is associated with accelerated metabolic aging.

Background/Objectives: Hematopoietic stem cell transplantation (HSCT) in pediatric and young adult (YA) patients can lead to endotheliopathy, such as thrombotic microangiopathy (TMA), sinusoidal obstruction syndrome (SOS), and diffuse alveolar hemorrhage (DAH). Natriuretic peptides have been studied as markers of endotheliopathy and critical illness. We hypothesized that elevation in NT-proBNP was associated with development of endotheliopathy (DAH, SOS, or TMA) in the first 100 days following HSCT in pediatric and YA patients. Methods: IRB exempt status was obtained. This retrospective case-control study reviewed HSCT at our institution from 2016-2020. Cases were selected based on an endotheliopathy diagnosis in the first 100 days after HSCT. Cases were matched with controls. Baseline and near-event NT-proBNP levels were compared between cases and matched controls. Effect of NT-proBNP levels on developing endotheliopathy was estimated using conditional logistic regression. Results: Sixty-two patients were included (31 cases, 31 controls). Near-event NT-proBNP was significantly higher in cases compared to controls (Median: 473 vs. 187 pg/mL, p = 0.03, Wilcoxon rank-sum test), in contrast to comparison in baseline NT-proBNP (Median: 86 vs. 86 pg/mL, p = 0.51). After adjusting for co-variates, association between near-event NT-proBNP and odds of developing endotheliopathy did not achieve statistical significance. However, trends from most common transplant indications suggested an association between elevated near-event NT-proBNP level and endotheliopathy, particularly in acute lymphoblastic leukemia (ALL) patients. Conclusions: NT-proBNP should be studied further as a biomarker for endotheliopathy in pediatric and YA patients undergoing HSCT. This may be particularly relevant for patients undergoing HSCT for ALL.

Objective: The diagnostic efficacy of the apparent diffusion coefficient (ADC) on diffusion-weighted magnetic resonance imaging for lymph node metastasis in biliary tract cancer was investigated in the present study. Methods: Surgically resected 112 lymph nodes from 35 biliary tract cancer (BTC) patients were examined in this study. Values of the ADC mean and minimum of lymph nodes, as well as short-axis and long-axis diameters of lymph nodes were assessed by computed tomography (CT). The relationship between these parameters and the presence of histological lymph node metastasis was evaluated. Results: Histological lymph node metastasis was detected in 31 (27.7%) out of 112 lymph nodes. The short-axis diameter in metastatic lymph nodes was significantly larger than that in non-metastatic lymph nodes (P = 0.002), but the long-axis diameter was not significantly different between metastatic and non-metastatic lymph nodes. Both ADC mean and minimum values in metastatic lymph nodes were significantly lower than those in non-metastatic lymph nodes (P < 0.001, respectively). However, the ADC minimum value showed the highest accuracy for the diagnosis of histological lymph node metastasis, with an area under the curve of 0.877, sensitivity of 87.1%, specificity of 82.7%, and accuracy of 83.9%. Conclusions: The ADC minimum value on diffusion-weighted magnetic resonance imaging was very useful for the diagnosis of lymph node metastasis in BTC.

Background/Objectives: Douglasectomy is defined as the removal of the pelvic peritoneum of the entire pouch of Douglas. In presumed FIGO Stage I ovarian cancer isolated microscopic cancer cells might disseminate from the ovaries to their neighboring pelvic peritoneum. However, simple hysterectomy with bilateral salpingo-oophorectomy and a staging procedure is the standard of care. This study aims to investigate the safety and feasibility of douglasectomy, compared to random pelvic biopsies, and its on the survival of patients with early ovarian cancer; Methods: We retrospectively analyzed the records of patients with presumed FIGO Stage I ovarian cancer that underwent surgery in the 1st Department of Obstetrics – Gynecology Clinic from 2012 – 2022. Patient characteristics, oncological and follow-up information were collected.; Results: 88 patients were categorized into two groups: Group A (27 patients) with douglasectomy and Group B (61 patients) with random biopsies. There was no statistically significant difference in age, BMI, comorbidities, intraoperative blood loss and ICU admittance between the two groups. On the other hand, patients with en-block hysterectomy-douglasectomy had a statistically significant higher pre-operative CA-125 values, surgery duration, rate of postoperative complications and hospital stay. Concerning survival rates, there was a statistically significant difference in dis-ease-free survival (p=0.033), but no difference was observed in overall survival (p=0.66); Conclu-sions: En-block removal of the pelvic peritoneum of the entire pouch of Douglas with the uterus is a safe and feasible technique during surgery for early ovarian cancer, which leads to improved disease-free survival and local control.

Porphyromonas gingivalis is the major pathogenic bacteria found in the subgingival plaque of patients with periodontitis, leading to neuroinflammation. The bacteria destroy periodontal tissue through its virulence factors which are retained in the bacteria’s outer membrane vesicles (OMV). The purpose of this study was to determine the real time effect of intraperitoneal in-jection of P. gingivalis OMV on the production and expression of inflammatory markers as well as histopathological changes in the central nervous system (CNS) of adult zebrafish. Fol-lowing the LD50 (21 µg of OMV), the zebrafish were injected intraperitoneally with 18 µg of OMV and control group with normal saline at 7 different time points. Brains of experimental zebrafish were dissected at desired time points for colorimetric assays, ELISA and histology. This study discovered that nitric oxide and PGE2 were significantly increased at 45 minutes while IL-1β and IL-6 were expressed at subsequent 12- and 24-hours. respectively. Histopatho-logical changes such as blood coagulation, astrocytosis, oedema, spongiosis, and necrosis were also observed between 6- and 24-hours. The two apoptotic enzymes, caspases 3 and 9 were not expressed at any time point. In summary, the OMV induced neuroinflammatory responses and histopathological changes in adult zebrafish were time point dependent

Objectives: In recent years, ear endoscopy has gradually become an important tool in ear surgery. This study further explored its application in ear surgery, to establish a surgical approach for semicircular canal obstruction (SOC) via the ear canal to control vertigo in Meniere's disease. Methods: With the approval of the ethics committee, recruitment started in June 2019. ​Four patients with Meniere's disease who had been treated conservatively for more than six months received SCO via an external ear canal approach under otoendoscopy and were followed for two years after surgery to assess the safety and efficacy of the procedure. Results The control of vertigo after the operation was satisfactory (100%), and the frequency and degree of vertigo were significantly improved. Tinnitus improved in 1 case (25%) and did not progress in the other 3 cases. Hearing loss did not progress in all patients. Postoperative walking instability occurred in 1 patient (25%), and there were no obvious complications. All patients reported significant improvements in their quality of life. Conclusions: SCO via the external auditory canal approach is safe, effective, easy to accept, and an alternative to conservative treatment of Meniere's disease with no actual hearing for more than 6 months.

This study checked whether vitamin D (Vit-D) supplementation improves the efficacy of resistance training (RT) in terms of increasing muscle strength and lean body mass (LBM) and influencing cardiorespiratory fitness (VO2max) in Vit-D insufficient middle-aged healthy men. Participants (n = 28) were quasi‐randomly assigned to one of the two groups, which, in a double‐blind manner, supplemented their diet daily with either Vit‐D (8000 IU; VD) or placebo (PLC) during participation in a 12‐week supervised RT program. During the intervention, serum Vit‐D concentrations increased 2.6‐fold (p < 0.001) in the VD group, while no changes occurred in the PLC group. Muscle strength gains (p < 0.001) as measured in seven exercises performed on RT equipment and increases (p < 0.001) in LBM were similar in the two groups. Total fat mass, percent total fat, and percent android fat decreased (p < 0.05) to a similar extent in both groups, but there was no change in VO2max in either group. In conclusion, in healthy Vit‐D insufficient middle-aged men engaged in resistance training, Vit‐D supplementation increases serum 25(OH)D levels but does not enhance gains in muscle strength and LBM or decreases in fat mass and fat percentage and does not affect cardiorespiratory fitness.

Forty percent of patients with acute coronary occlusion myocardial infarction (OMI) do not present with STEMI criteria, which delays their treatment and increases morbidity and mor-tality. The need to identify these patients promptly is crucial, and this sets the stage for the pro-posed reclassification. Many of these patients can be identified by other ECG and clinical fea-tures. Background/Objectives: We sought to evaluate STEMI/NSTEMI cases that result in OMI and the consequences of delayed revascularization immediately among NSTEMI patients who have ACO (NSTEMI-OMI). Methods: The study is a retrospective analysis conducted on 334 pa-tients who underwent coronary angiography for acute coronary syndrome at UHC ‘‘Mother Te-resa,’’ Tirana, Albania, during January-May 2023. OMI was defined as an acute culprit lesion with TIMI 0-2 flow, or TIMI 3 flow with highly elevated troponin (cTnI>10.0 ng/mL, hs-cTnI>5000 ng/L). Ejection fraction (EF), total ischemia time, hospital day stay and complications were com-pared between groups. Results: There were 334 patients included of whom NSTEMI-OMI were 98 patients (29.3%) of patients with ACS. 96 patients (40%) of OMI patients did not fulfill the STEMI criteria. Only 11 patients (11%) of STEMI(-)OMI had PCI performed within the first 12 hours vs 76 patients (77%) of STEMI(+)OMI, p<0.001. There was no difference in the percent of patients requiring PCI between the STEMI(+)OMI 98 patients (93%) and STEMI(-)OMI 87 patients (89%) (p<0.001). The overall in-hospital mortality was 19 patients (5.7 %), with subgroup mortality of 14 patients (4.2%) STEMI(+)OMI, two patients (0.6%) STEMI(+) NOMI, three patients (0.9%) STEMI(-)OMI, 0% STEMI(-)NOMI, (p=0.013). Patients with mechanical complications were: 67 patients (46.8%) STEMI(+)OMI and 45 patients (46.4%) STEMI(-)OMI. 26 patients (18.5%) STEMI(+)OMI and 13 patients (13.1%) STEMI(-)OMI developed electrical complications. Conclusions STEMI(-)OMI patients had significant delays in catheterization, yet had angiographic findings, rate of PCI, and complications similar to STEMI(+)OMI. These data add further support to refocusing the paradigm of acute MI to improve recognition and rapid reperfusion of all OMIs, rather than only those with STEMI criteria.

A degree in physiology in Nigeria offers a enormous opportunities that many undergraduates may be unaware of.This article explores different career paths available to physiology undergraduate and graduates in Nigeria. It outlines various fields within clinical and healthcare settings, research and academia, biotechnology and pharmaceuticals, and even alternative careers. It also details specific specializations within clinical physiology, including cardiovascular, respiratory, neurophysiology, sleep, gastrointestinal, and renal physiology.The article emphasizes the importance of gaining practical experience through internships, volunteer work, and networking to equip physiology them with essential skills for job market.

Background and Objectives: The new molecular classification of endometrial cancer continuously changes the management of the disease in every day clinical practice. Lately, FIGO released a new staging system for endometrial cancer, which incorporates molecular sub-stages and subdivides further early-stage disease. The aim of this study is to investigate the differences between the two FIGO staging systems and evaluate the prognostic precision of the new one. Materials and Methods: We retrospectively analyzed the records of patients with endometrial cancer that were fully treated in the 1st Department of Obstetrics-Gynecology, 2012-2023. Patient characteristics, oncological outcome and follow-up information were collected. The primary outcomes were the stage shifts and the survival data. Results: 67 (15.5%) patients had a stage shift and the majority of them concerned early-stage disease and specifically up-shift from 2009 stages IA and IB to 2023 stage IIC. Concerning, survival a better median and 5-year PFS was present in Stage II disease and when compering the prognostic precision of the two FIGO staging systems no significant difference was present. Conclusions: The new 2023 FIGO staging system better distinguishes early-stage endometrial cancer into its prognostic groups and seems to be as precise as the old 2009 FIGO staging system.

Introduction: Immune checkpoint inhibitors (ICI) are used to treat various malignancies. They block the inhibitory signals of tumor cells and enhance the inflammatory cascade which results in tumor killing. However, this can lead to unchecked inflammation throughout the body, leading to various adverse effects. A rare gastrointestinal adverse effect of ICI therapy is the development of immune-mediated celiac disease. This entity has a similar clinical presentation to the more common ICI-induced enterocolitis. Our study aims to determine the clinical characteristics and optimal treatment strategies for this rare ICI toxicity, and differentiate it from ICI-induced enterocolitis. Methods and Material: We conducted a retrospective analysis of eight cases of ICI-induced celiac disease and 24 cases of ICI-induced enterocolitis from the literature. Data on patient demographics, clinical history, therapeutic interventions and outcomes were collected. Comparative analysis was performed to identify the key differences between the two groups. Results: Patients with ICI-induced celiac disease were more likely to have a pre-existing autoimmune condition and HLA-DQ2 positivity. Significant differences in clinical manifestations, histological findings, and treatment outcomes were observed. Notably, weight loss, nutritional deficiencies and electrolyte abnormalities were more commonly associated with ICI-CD. On pathology, duodenal villous blunting was noted more commonly with ICI-induced celiac disease. Initiating a gluten-free diet led to rapid improvement in patients with ICI-induced celiac disease, while immunosuppressive therapy did not have an impact. Conclusion: ICI-induced celiac disease is a rare and underrecognized gastrointestinal adverse effect of ICI therapy, often misdiagnosed as ICI-induced enterocolitis. Early recognition and treatment with a gluten-free diet can lead to rapid symptom resolution, sparing patients from unnecessary systemic immunosuppression and discontinuation of antineoplastic immunotherapy.