The present clinical study was approved by the Review Board for Animals Care of the University of Parma prot N. 03/CESA /2023, which provided a consent to the clinical study: regulation (EU) no. 536/2014. (22A01712) (GU General Series n.65 of 18-03-2022); European Law (O.J. of E.C. L 358/1 12/18/1986), and USA Laws (Animal Welfare Assurance No A5594-01, Department of Health and Human Services, USA). The owners signed a voluntary informed consent form prior to the dogs’ enrollment in the study. Twenty female dogs, aged 1±1.5 months, and weighing 16± 0.5 kg were enrolled in the study. The inclusion criterion of the patients was to undergo ovariectomy surgery; dogs enrolled in this study had normal physiological, haematological and biochemical parameters.

Ingrown toenails are a commonly occurring foot complaint. The condition occurs when the nail plate pierces the sulcus, giving rise to pain, inflammation and infection. As the skin attempts to heal itself, hypergranulation tissue may form. This is a case report of phenolic nail surgery treatment for a bilateral presentation with sharp resection of hypergranulation tissue performed in only one (the lateral) of the two affected sulci. Sharp resection of the residual medial hypergranulation tissue was performed two months after the index procedure when this had not settled. The case highlights the potential role of sharp resection in the overall improvement of treatment outcomes.

Cryptococcosis is one of the most serious opportunistic diseases in patients living with HIV. For this reason, it is important to have early diagnosis and appropriate treatment. Objectives. The aim of the study was to know the evolution of patients diagnosed with cryptococcosis by detection of Cryptococcus antigen in serum by lateral flow (CrAg LFA) without nervous system involvement and with treatment in accordance with the results. Materials and Methods. A retrospective, longitudinal, analytical study was performed. Seventy patients with cryptococcosis initially diagnosed by serum CrAg LFA without meningeal involvement between January 2019 and April 2022 were analyzed for medical records. The treatment regimen was adapted to the results of blood culture, respiratory material or pulmonary tomography imaging. Results. Seventy patients were included, 13 had probable pulmonary cryptococcosis, 4 had proven pulmonary cryptococcosis, 3 had fungemia and 50 had pre-emptive therapy without microbiological or imaging findings compatible with cryptococcosis. Among the 50 patients with pre-emptive therapy, none had meningeal involvement or cryptococcosis recurrences to date. Conclusion. Pre-emptive therapy avoided progression to meningitis in patients with CrAg LFA-positive patients. Pre-emptive therapy with dose adjustment of fluconazole in patients with the mentioned characteristics was useful despite the use of lower doses than recommended.

Fibrosis is an important health problem and its pathogenetic activation is still largely unknown. It can develop either spontaneously or, more frequently, as a consequence of various underlying diseases, such as chronic inflammatory autoimmune diseases. Fibrotic tissue is always characterized by mononuclear immune cells infiltration. The cytokine profile of these cells shows clear proinflammatory and profibrotic characteristics. Furthermore, the production of inflammatory mediators by non-immune cells, in response to several stimuli, can be involved in the fibrotic process. It is now established that defects in the abilities of non-immune cells to mediate immune regulation may be involved in the pathogenicity of a series of inflammatory diseases. The convergence of several, not yet well identified, factors results in the aberrant activation of non-immune cells, such as epithelial cells, endothelial cells and fibroblasts, that producing pro-inflammatory molecules, exacerbate the inflammatory condition leading to the excessive and chaotic secretion of extracellular matrix proteins. However, the precise cellular mechanisms involved in this process have not yet been fully elucidated. In this review we explore the latest discoveries on the mechanisms that initiate and perpetuate the vicious circle of abnormal communications between immune and non-immune cells, responsible for fibrotic evolution of inflammatory autoimmune diseases.

Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria, whether IL-17A gene polymorphisms are involved in severe malaria susceptibility and the polymorphism’s influence on the IL-17A serum levels. 125 malaria patients and 48 free malaria controls were enrolled in this research. Malaria patients were classified into severe malaria (SM) and uncomplicated malaria (UM). IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum level and malaria outcome. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P<0.0001). Also, the IL-17A levels were lower in SM patients who were deceased than in those who survived. In addition, the minor allele frequencies (MAF) of two IL-17A polymorphisms (rs3819024 and rs3748067) were more prevalent in SM patients than UM patients indicating an essential role in SM. Interestingly, the heterozygous rs8193038 AG genotype was significantly associated with higher levels of IL-17A than the homozygous wild type (GG). According to our results, it can be concluded that IL-17A may play a role in protection against fatal malaria outcomes.

Cervical cancer is a significant global health concern, with human papillomavirus (HPV) infection being a crucial risk factor. Photodynamic therapy (PDT) is an attractive, minimally invasive treatment for HPV-related cervical lesions, which uses photosensitizers and light to selectively de-stroy abnormal cells. We aim to provide an overview of the various sorts of dyes that are utilized in PDT for decreasing the incidence and mortality of cervical cancer. Besides, the article discusses ongoing clinical trials for PDT in low-grade squamous intraepithelial neoplasia (LSIL) and high-grade squamous intraepithelial lesions (HSIL), as well as preclinical approaches for PDT in cervical cancer using various dyes. Moreover, it highlights potential dyes for PDT, examine them in in-silico condition, their pros and cons and also the solutions for enhancing their anticancer com-patibility. We also display that PDT is a promising therapeutic strategy for the diagnosis and treatment of HPV-associated cervical lesions. Moreover, it shows that using different classes of dyes improves the anticancer effects of PDT. Finally, among all dyes which are used in PDT, Fullerene demonstrated high tendency to over expressed receptors in cervical cancer cells and seems to be a proper candidate for be used in PDT more than before, but further research is necessary to assess its long-term efficacy and safety.

Peyronie's disease (PD) is a benign condition caused by plaque formation on the tunica albuginea of the penis. It is associated with penile pain, curvature, and shortening, and contributes to erectile dysfunction, which worsens patient quality of life. In recent years, understanding of the detailed mechanisms and risk factors involved in development of PD has been increasing. In this review, the pathological mechanisms and several closely related signaling pathways, including TGF-β, WNT/β-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT, are described. Findings regarding cross-talk among these pathways are then discussed to elucidate the complicated cascade behind tunica albuginea fibrosis. Finally, various risk factors including genetic involved in the development of PD are presented and their association with the disease summarized. The purpose of this review is to provide better understanding regarding involvement of risk factors in the molecular mechanisms associated with PD pathogenesis, as well as provide insight into disease prevention and novel therapeutic interventions.

The traditionally dismal outcome of acute myeloid leukemia (AML) patients carrying the FMS-related tyrosine kinase 3 (FLT3) mutations has been mitigated by the recent introduction into the clinics of tyrosine kinase inhibitors (TKI) such as midostaurin and gilteritinib. The present work summarizes the clinical data that led to the use of gilteritinib in clinical practice. Gilteritinib is a 2nd generation TKI with deeper single-agent activity than 1st generation drugs against both FLT3-ITD and TKD mutations, in human studies. Moreover, the phase I/II dose-escalation, dose-expansion Chrysalis trial showed an acceptable safety profile of gilteritinib (diarrhea, elevated aspartate aminotransferase, febrile neutropenia, anemia, thrombocytopenia, sepsis, and pneumonia) and a 49% overall response rate (ORR) in 191 FLT3-mutated relapsed/refractory (R/R) AML patients. In 2019, the pivotal ADMIRAL trial showed that the median overall survival was significantly longer in patients treated with gilteritinib than among those receiving chemotherapy (9.3 vs 5.6 months, respectively) and the ORR to gilteritinib was 67.6%, outperforming the 25.8% for chemotherapy arm and leading to the license for its clinical use by the US Food and Drug Administration. Since then, several real-world experiences confirmed the positive results in the R/R AML setting. Finally, gilterinib based combinations currently under investigation with several compounds (venetoclax, azacitidine, conventional chemotherapy, etc.) and some practical tips (maintenance after allogeneic transplantation, interaction with antifungal drugs, extramedullary disease, and onset of resistance) will be analyzed in detail in the review.

Background: this retrospective study aimed to analyze the results of the combination of the Haigis formula and Total Keratometry (TK) to calculate the IOL power in eyes with previous corneal refractive surgery. Methods: The TK value provided by the IOL Master 700 (Carl Zeiss Meditec) was introduced into the Haigis formula; the mean prediction error (PE), mean absolute error (MAE), median absolute error (MedAE) and percentage of eyes with a PE within ±0.25 D, ±0.5 D, ±0.75 D and ±1.00 D were calculated. Results: Ninety-three eyes of 93 patients with previous laser refractive surgery were evaluated. Two groups were defined: Group A included 51 previously myopic eyes, Group B included 42 previously hyperopic eyes. The mean PE in Group A was +0.09 ±0.44 D and 76.47% of eyes had a PE within ±0.50 D. In Group B the mean PE was -0.15 ±0.46 D and 66.67% of eyes had a PE within ±0.50 D. Discussion: The Haigis formula combined with TK is one of the most accurate available methods for IOL power calculation in eyes with prior myopic and hyperopic corneal refractive surgery. In such eyes the results are similar to or better than those reported in previous studies.

As the world's population ages and the resulting health problems become more serious, medical and health policies in developed countries are focused on how to prevent and treat the diseases of the aging population and how to maintain their quality of life. Typical age-related diseases include deafness, cataracts, osteoarthritis, chronic obstructive pulmonary disease, diabetes mellitus, and dementia. Although the mechanisms by which these diseases develop differ, they are all caused by the accumulation of molecular and cellular damage over time. In addition, age-related diseases can cause a decline in physical and mental functions and the ability to perform activities of daily living, as well as the loss of roles in society and a sense of fulfillment in life. Therefore, there is a need for treatment and measures to accurately grasp and maintain their quality of life.

Effective communication is key for healthcare providers to provide optimal care for patients. Pharmacists’ fluency in a patient’s native language is vital to communicate effectively. Additionally, language concordance improves patients’ trust and ensures health equity. In the United States (US), Hispanics are the largest minority group, but only 36% of the pharmacy schools in the US offer Spanish courses in their curriculum. Conversely, Middle Eastern countries have implemented English as the language of instruction in pharmacy schools, though the native language of the patient population is Arabic. The discrepancy between the language of education and the language used by patients might lead to communication problems, thus limiting a pharmacist’s role in practice. This review aims to describe the efforts of pharmacy schools both in the US and Middle Eastern countries to incorporate second language (Spanish and Arabic, respectively) in their curriculum. Spanish language content has scarcely been introduced into the pharmacy curriculum in the US either as didactic elements (elective courses, lab sessions, modules within a course, or co-curricular programs) or as language immersion experiences (rotations and internships nationally or abroad). In Arabic-speaking countries, an Arabic course was introduced to the pharmacy curriculum to enhance students’ communication skills. This review provides an overview of what has been done in various pharmacy programs to prepare students for adequate multilingual speaking. The findings reveal the need for additional strategies to assess the impact of language courses on student performance and patient experience, as well as language competence in pharmacists and pharmacy students.

Mechanical bowel obstruction is a common symptom for admission to emergency services, diagnosed annually in more than 300,000 patients in the States, from whom 51% will undergo emergency laparotomy. This condition is associated with serious morbidity and mortality, but it also causes a high financial burden due to long hospital stay. The EUPEMEN project aims to incorporate the expertise and clinical experience of national clinical specialists into development of perioperative rehabilitation protocols. Providing special recommendations for all aspects of patient perioperative care and the participation of diverse specialists, the EUPEMEN protocol for bowel obstruction, as presented in the current paper, aims to provide faster postoperative recovery and reduce length of hospital stay, postoperative morbidity and mortality rate.

An impaired healing response underlies diabetic foot wounds chronicity, frequently translating in amputation, disability, and early mortality. In addition, diabetics frequently suffer of the underappreciated episode of post-epithelization ulcer recurrence. Recurrence epidemiological data are alarmingly high; so that the ulcer is considered in “remission” and not healed for the time it remains epithelialized. Recurrence may result from the conspiracy of behavioral and biological factors. Although the damaging role of behavioral, clinical predisposing factors is undebatable, the role of endogenous biological signalers that prime the residual scar tissue to recurrence has remained elusive. We propose that ulcer recurrence is deeply impinged by chronic hyperglycemia and its downstream biological effectors, which originate epigenetic drivers that enforce abnormal pathologic phenotypes to dermal fibroblasts, and keratinocytes as memory cells. Hyperglycemia-derived cytotoxic reactants accumulate and modify dermal proteins, reduce scar tissue mechanical tolerance, and disrupt fibroblasts-secretory activity. Accordingly, the combination of epigenetic and local and systemic cytotoxic signalers, induce the onset of “at-risk phenotypes” as premature skin cells aging, dysmetabolism, inflammatory, pro-degradative, and oxidative programs that may ultimately converge to scar cells demise. Unfortunately, post epithelialization recurrence rates data are missing in clinical studies of accepted ulcer healing therapies during follow-up periods. Intra-ulcer infiltration of epidermal growth factor exhibits the most consistent remission data with the lowest recurrences during 12-month follow-up. Recurrence data should be regarded as a valuable clinical endpoint during the investigational period for each emergent healing candidate.

Introduction: The reduced implementation of surveillance programs and limited bedside infectious diseases consultations due to the pressure of COVID-19 pandemic in healthcare systems led to increased rates of irrational use of antimicrobials and incidence of infections by multidrug-resistant microorganisms. The aim of the present study is to evaluate the incidence of antimicrobial resistance and the management of bloodstream infections before and during COVID-19 pandemic at the University General Hospital of Alexandroupolis (Greece). Material-Methods: This is a retrospective study conducted from January 2018 to December 2022. Data were collected from the University Microbiology Laboratory per semester regarding the isolated strains of Gram positive and negative bacteria in blood cultures and respiratory samples in hospitalized patients in medical and surgical wards and in the Intensive Care Unit (ICU). Additionally, bloodstream infections with requested infectious diseases consultation were reported (n=400), determining whether these were carried out via telephone contact or at the patient's bedside. Demographic data, comorbidities, focus of infection, antimicrobial regimen, duration of treatment, length of hospitalization and clinical outcome were analysed. Results: A total of 4569 strains of Gram positive and negative bacteria were isolated. An increasing trend was reported compared to the pre-pandemic period in the incidence of resistant Gram-negative bacteria, particularly in ICUs. Prior antimicrobial use and the rate of hospital-acquired infections were increased significantly during the pandemic. In the pre-pandemic period 2018-2019, a total of 246 infectious diseases consultations were carried out, while during the period 2020-2022 154, with the percentage of telephone consultations 15% and 76% respectively. Detection of the source of infection and timely administration of appropriate antimicrobial agents were more frequently recorded before the pandemic and 28-day mortality was significantly reduced in cases with bedside consultations. Conclusion: Empowering of infectious diseases surveillance programs and committees, rational use of antimicrobials agents and bedside infectious diseases consultations are vital in order to reduce the impact of infections caused by multidrug-resistant strains.

(1) Birth asphyxia is the major cause for delivery room resuscitation. Subsequent organ failure and hypoxic-ischemic encephalopathy (HIE) account for 25% of all early postnatal deaths. The neonatal Sequential Organ Failure Assessment (nSOFA) considers platelet count, respiratory and cardiovascular dysfunction in neonates with sepsis. To evaluate whether nSOFA is also a useful predictor for in-hospital mortality in neonates (≥ 36+0 weeks of gestation (GA)) following asphyxia with HIE and therapeutic hypothermia (TH), (2) nSOFA was documented at ≤ 6 hours of life. (3) 65 infants fulfilled inclusion criteria for TH. All but one infant received cardiopulmonary resuscitation and/or respiratory support at birth. nSOFA was lower in survivors (median 0 [IQR 0-2]; n = 56, median GA 39+3, female n = 28 (50%)) than in non-survivors (median 10 [4-12], p < 0.001; n = 9, median GA 38+6, n = 4 (44.4%)). This was also observed for the respiratory (p < 0.001), cardiovascular (p < 0.001), and hematologic sub scores (p = 0.003). The odds ratio for mortality was 1.6 [95% CI = 1.2 – 2.1] per one-point increase in nSOFA. The optimal cut-off value of nSOFA to predict mortality was 3.5 (sensitivity 100.0%, specificity 83.9%). (4) Since early accurate prognosis following asphyxia with HIE and TH is essential to guide end-of-life decisions, nSOFA (≤ 6 hours of life) offers the potential to identify infants at risk of mortality.

Renal cell carcinoma (RCC) is the second most common cancer of the urinary system. The current therapeutic strategies are based on partial or total nephrectomy and/or targeted therapies based on immune checkpoint inhibitors to which patients are often refractory. Preventive and screening strategies are not existing and the few available biomarkers for RCC are characterized by the lack of sensitivity, outlining the need of novel noninvasive and sensitive biomarkers for an early diag-nosis and a better disease monitoring. Blood liquid biopsy (LB) is a non- or minimally invasive procedure for a more representative view of tumor heterogeneity than the tissue biopsy, poten-tially allowing real-time monitoring of cancer evolution. Growing interest is focused on the extra-cellular vesicles (EVs) secreted by either healthy or tumoral cells and recovered in a variety of bio-logical matrices, blood included. EVs are involved in cell-to-cell crosstalk transferring their mRNAs, miRNAs, and proteins content. In particular, transferred miRNAs may regulate the tu-morigenesis and proliferation also impacting on resistance to apoptosis, thus representing poten-tial useful biomarkers. Here we present the latest efforts in the identification of circulating miR-NAs in blood samples, focusing on the potential use of EV derived miRNAs as RCC diagnostic, prognostic markers.

Despite the recent approval of novel immunotherapies, as immunomodulatory drug, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable and the acquisition of triple-refractoriness leads to really dismal outcomes, in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody drug conjugates, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. Here, starting from Belantamab Mafodotin clinical trials also exploring combination studies and different schedules in order to improve its efficacy and toxicity, we focused on real life experiences all over the world, which have confirmed clinical trial data and encourage further Belantamab Mafodotin investigations

Rice bran arabinoxylan compound (RBAC) is a polysaccharide modified by Lentinus edodes mycelial enzyme widely used as a nutraceutical. To explore translational research on RBAC, a scoping review was conducted to synthesise research evidence from English, Japanese, Korean, and Chinese sources while combining bibliometrics and network analyses for data visualisation. Ninety-eight articles on RBAC and the biological activities related to human health or disease were included. Research progressed with linear growth (median=3/year) from 1998 to 2022, predominantly on Biobran MGN-3 (86.73%) and contributed by 289 authors from 100 institutions across 18 countries. Clinical studies constitute 61.1% of recent articles (2018 to 2022). A shifting focus from immuno-cellular activities to human translations over the years was shown via keyword visualisation. Beneficial effects of RBAC include immunomodulation, synergistic anticancer properties, hepatoprotection, antiinflammation, and antioxidation. Cancer patients reported reduced side effects from chemoradiotherapy and improved quality of life in human studies, indicating RBAC’s impact on the psycho-neuro-immune axis. RBAC has been studied in 17 conditions, including cancer, liver diseases, HIV, allergy, chronic fatigue, gastroenteritis, cold/flu, diabetes, and in healthy participants. Further translational research on the impact on patient and community health is required for the evidence-informed use of RBAC in health and disease.

Neuroinflammation is one disease hallmark on the road to neurodegeneration in primary tauopathies. Thus, immunomodulation might be a suitable treatment strategy to delay or even prevent the occurrence of symptoms and thus relieve the burden for patients and caregivers. In the last years, the peroxisome proliferator-activated receptor γ (PPARγ) received increasing attention as it is immediately involved in the regulation of the immune system and can be targeted by the anti-diabetic drug pioglitazone. Previous studies have shown significant immunomodulation in amyloid-β (Aβ) mouse models by pioglitazone. In this study, we performed long-term treatment over six months in P301S mice as a tauopathy model with either pioglitazone or placebo. We performed serial 18 kDa translocator protein positron-emission-tomography (TSPO-PET) imaging and terminal immunohistochemistry to assess microglial activation during treatment. Tau pathology was quantified via immunohistochemistry at the end of the study. Long-term pioglitazone treatment had no significant effect on TSPO-PET, immunohistochemistry read-outs of microglial activation, or tau pathology levels in P301S mice. Thus, we conclude that pioglitazone modifies the time course of Aβ-dependent microglial activation, but does not significantly modulate microglial activation in response to tau pathology.

It has been proposed that upregulation of the noradrenergic (NA) system through exposure to novelty might be one of the key components for building cognitive reserve and resilience to neurodegeneration. A personality trait that promotes greater interest in novel experiences is Openness to Experience (OE). Individuals who are high in OE exhibit strong curiosity towards novelty and are more likely to be exposed to novel stimuli throughout the lifespan.Performing voxel-based morphometry analyses, we examined whether OE in 135 healthy young adults was associated with Locus Coeruleus (LC) - the main core of the noradrenergic system. We also investigated whether LC mediates the relationship between OE and a key measure of reserve, I.Q. In comparison with other neuromodulators’ seeds (Dorsal and Median Raphe [DR-MR] -5-HT, Ventral Tegmental Area [VTA] -DA- and Nucleus Basalis of Meynert [NBM] -Ach-), results show that greater LC integrity was related to greater OE and IQ. Additionally, mediation analyses revealed that only LC mediated the relationship between OE and IQ. Furthermore, a Bayesian multiple regression was conducted to model the contribution of both isolated and combined neuromodulator seeds to OE trait express. This approach found that the LC + VTA could account for more variance in OE expression compared to the LC alone. Other weaker but significant associations were observed between DR and OE, between LC + NBM and Conscientiousness and between DR + NBM and Extraversion. These results are together suggestive that OE is primarily underpinned by monoaminergic functioning, and that the LC-NA system plays a central role mediating the interdependence between OE expression and cognition (IQ level). While offering further understanding of the neurobiology of human personality, these findings indicate a pivotal role of LC-NA system integrity in novelty seeking in daily life. This provides a psychobiological account for how OE expression may be beneficial for maintaining the noradrenergic system to facilitate cognitive reserve and resilience to neurodegenerative conditions.

The FDA has concluded that a biosimilar candidate capable of demonstrating pharmacodynamic biomarkers in a healthy subject need not be tested for clinical efficacy in patients, regardless of if the biomarker correlates with clinical response. Since monoclonal antibodies (mAbs) do not trig-ger pharmacodynamic response, they can be substituted with robust functional disqualifying them for this waiver that can be overcome by allowing comparison of functional properties that eventually result in clinical response. This suggestion is based on the FDA's preference for more sensitive testing methods. However, clinical efficacy testing in patients is the least sensitive method, as confirmed by statistical modeling, a fact that regulatory agencies need to admit. In this paper, I present a logical and rational argument to establish the biosimilarity of products that do not have pharmacodynamic biomarkers based on their orthogonally proven functional bio-similarity. This understanding will significantly lower the development cost of biosimilars, a goal that the FDA outlined in all its guidance. Keywords: biosimilarity 1; biosimilars 2; pharmacodynamic biomarkers 3; monoclonal antibodies 4; FDA 5; clinical efficacy testing in healthy subjects 6; clinical efficacy testing in patients 7; functional assays 8; receptor binding 9.

The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as Lung Cancer associated with Cystic Airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs biennial pace of LDCT, choice between opportunistic or population-based recruitment and between uni or multi-center screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention and prospective validation of the biomarkers.

The gut microbiota plays a crucial role in maintaining host health and has a significant impact on human health and disease. In this study, we investigated the alpha diversity of gut microbiota in COVID-19 patients and analyzed the impact of COVID-19 variants, antibiotic treatment, type 2 diabetes (T2D), and metformin therapy on gut microbiota composition and diversity. We used a culture-based method to analyze the gut microbiota and calculated alpha-diversity using the Shannon H' and Simpson 1/D indices. We collected clinical data, such as length of hospital stay (LoS), C-reactive protein (CRP) levels, and neutrophil-to-lymphocyte ratio (NLR). We found that patients with T2D had significantly lower alpha-diversity than those without T2D. Antibiotic use was associated with a reduction in alpha-diversity, while metformin therapy was associated with an increase. We did not find significant differences in alpha-diversity between the Delta and Omicron groups. Length of hospital stay, CRP levels, and NLR showed weak to moderate correlations with alpha diversity. Our findings suggest that maintaining a diverse gut microbiota may benefit COVID-19 patients with T2D. Interventions aimed at preserving or restoring gut microbiota diversity, such as avoiding unnecessary antibiotic use and promoting metformin therapy, may improve patient outcomes.

Surgical ciliated cysts occur primarily in the maxilla after radical maxillary sinus surgery. We report a first case of a surgical ciliated cyst that developed in the infratemporal fossa 25 years after the patient sustained severe facial trauma. The patient complained of mandibular pain and limited mouth opening. The patient’s condition was completely resolved 5 months after marsupialization via Le Fort I osteotomy. Surgical morbidities can be minimized by proper diagnosis and less invasive surgery.

Germanium is an essential microelement, and its deficiency can result in numerous diseases, particularly oncogenic conditions. Consequently, water-soluble germanium compounds, including inorganic and coordination compounds, have attracted significant attention due to their biological activity. The review analyzes the primary research from the last decade related to the anticancer activity of germanium compounds. Furthermore, the review clarifies their actual toxicity, identifies errors and misconceptions that have contributed to the discrediting of their biological activity, and suggests a putative mechanism of germanium-mediated protection from oxidative stress. Finally, the review provides clarifications on the discovery history of water-soluble organic germanium compounds, which was distorted and hushed up for a long time.

While investigating the outcomes of balloon dilatation procedures in patients with congenital obstructive lesions of the heart, several parallel observations have been made. The purpose of this review is to present these observations/phenomena/innovations related to balloon dilatation of pulmonary stenosis (PS), aortic stenosis (AS), and aortic coarctation (AC). In subjects who had balloon pulmonary valvuloplasty (BPV), development of infundibular obstruction, electrocardiographic (ECG) changes, changes in right ventricular filling, role of balloon/annulus ratios on the results of BPV, and double balloon vs. single balloon BPV will be reviewed. In patients who had balloon aortic valvuloplasty (BAV), causes of aortic insufficiency and trans-umbilical venous approach for BAV will be tackled. In children who had balloon angioplasty (BA) of AC, aortic remodeling and biophysical response after BA of AC will be discussed.

Due to their increased surface area, extent of swelling and active substance loading capacity and flexibility, nanogels made from natural and synthetic polymers have gained significant interest in the scientific and industrial areas. Especially, customized design and implementation of non-toxic, biocompatible, and biodegradable micro/nano carriers makes their usage very feasible for a range of biomedical applications, including drug delivery, tissue engineering, and bioimaging. The design and application methodologies of nanogels have been outlined in this review. Additionally, the most recent advancements in nanogel biomedical applications have been discussed, with a particular emphasis on applications for the delivery of drugs and biomolecules.

Introduction Currently, the increase in the percentage of obese people observed along with the development of civilization, reaching the level of a global pandemic, has forced the search for methods of effective and permanent obesity treatment. Obesity is a multifactorial disease, it coexists with many disease entities and requires multidisciplinary treatment. Obesity leads to metabolic changes in the form of metabolic syndrome, which includes, among others, atherogenic dyslipidemia. The proven relationship between dyslipidemia and cardiovascular risk enforces the need to effectively improve the lipid profile of obese patients. Laparoscopic sleeve gastrectomy is a method of surgical treatment of morbid obesity which improves bariatric and metabolic parameters. The aim of the study was to assess the effectiveness of laparoscopic sleeve gastrectomy (LSG) in improving lipid profile parameters in 1-year follow-up. Material and Methods Bariatric parameters of 196 patients who underwent laparoscopic sleeve gastrectomy as well as lipid profile of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-NDL, and triglycerides (TG) in 1-year observation were analyzed. Results Improvements in bariatric parameters were observed in patients after LSG. Total cholesterol, low-density lipoprotein (LDL), triglycerides and non-HDL levels decrease were observed along with the increase of high-density lipoprotein (HDL) cholesterol level. Conclusions Sleeve gastrectomy is an effective method of treating obesity and improving the lipid profile in obese patients.

Introduction: Austere environments include the wilderness and many lower-and-middle-income countries, many of these facing unrest and war. The access to advanced diagnostic equipment is often unaffordable even if available and is often liable to breakdown. This short review paper examines the options available to medical professionals to undertake clinical and point of care diagnostic testing in resource constrained environments and also illustrates the development of mobile advanced diagnostic equipment. The aim is to provide an overview of the spectrum and functionality of these devices beyond clinical acumen.

Background: This study investigated the biological effects on circulating monocytes after challenge with SARS-CoV-2 recombinant spike protein. Methods: Whole blood collected form seven ostensibly healthy healthcare workers was incubated for 15 min with 2 and 20 ng/mL recombinant spike protein of Ancestral, Alpha, Delta and Omicron variants. Samples were analyzed with Sysmex XN and DI-60 analyzers. Results: Cellular complexity (i.e., presence of granules, vacuoles and other cytoplasmic inclusions) increased in all samples challenged with the recombinant spike protein of Ancestral, Alpha and Delta variants, but not in those containing Omicron. The cellular content of nucleic acids was constantly decreased in most samples, achieving statistical significance in those containing 20 ng/mL of Alpha and Delta recombinant spike proteins. The heterogeneity of monocyte volumes significantly increased in all samples, achieving statistical significance in those containing 20 ng/mL of recombinant spike protein of Ancestral, Alpha and Delta variants. The monocyte morphological abnormalities after spike protein challenge included dysmorphia, granulation, intense vacuolization, platelet phagocytosis, development of aberrant nuclei and cytoplasmic extrusions. Conclusions: The SARS-CoV-2 spike protein triggers important monocyte morphological abnormalities, more evident in cells challenged with spike protein of the more clinically severe Alpha and Delta variants.

The kidney and the heart work together in balancing the body circulation and although their physiology is based on strict inter dependence, their performance fulfills different aims. While the heart can rapidly increase its own oxygen consumption to comply with the wide changes in metabolic demand linked to body function, the kidney physiology is primarily designed to maintain a stable metabolic rate and has limited capacity to cope with any steep increase in renal metabolism. In the kidneys the glomerular population filters a large amount of blood and the tubular system has been programmed to reabsorb 99% of filtrate by reabsorbing sodium together with other filtered substances including all glucose molecules. Glucose reabsorption involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane in the proximal tubular section; it also enhances bicarbonate formation so as to preserve the acid-base balance. The complex work of reabsorption in the kidney is the main factor in renal oxygen consumption; analysis of renal glucose transport in disease states is providing better understanding of the renal physiology changes that occur when clinical conditions alter the neurohormonal response leading to an increase in glomerular filtration pressure. In this circumstance glomerular hyperfiltration occurs, imposing a higher metabolic demand on kidney physiology and causing progressive renal impairment. Albumin urination is the warning signal of renal engagement over-exertion and most frequently heralds heart failure development, regardless of disease etiology. The review analyzes the mechanisms linked to renal oxygen consumption, focusing on sodium-glucose management.

The pathophysiology of bipolar disorder (BD) remains mostly unclear. Yet, a valid biomarker is necessary to improve early detection of this serious disorder. Patients with manifest BD display reduced volumes of the hippocampal subfields and amygdala nuclei. In this pre-registered analysis, we used structural MRI (N=271, 7 sites), to compare volumes of hippocampus, amygdala, and their subfields/nuclei between help-seeking subjects divided in risk groups for BD as estimated by BPSS-P, BARS and EPIbipolar. We performed between-group comparisons using linear mixed effects models for all three risk assessment tools. Additionally, we aimed to differentiate the risk groups using linear support vector machine. We found no significant volume differences between the risk groups for all limbic structures during the main analysis. However, the SVM could still classify subjects at risk according to BPSS-P criteria with a balanced accuracy of 66.90% (95% CI 59.2– 74.6) for 10-fold cross-validation and 61.9% (95% CI 52.0– 71.9) for leave-one-site-out. Structural altera-tions of hippocampus and amygdala may not be as pronounced in young people at risk, nonetheless, ma-chine learning can predict estimated risk for BD above chance. This suggests that neural changes may not merely be a consequence of BD and may have prognostic clinical value.

Background: Children suffering from COVID-19 constitute about 10% of the entire population infected with the virus. In most of them, we observe asymptomatic or mild course; however, about 1% of affected children require a stay in the pediatric intensive care unit (PICU) due to the severe life-threatening course. The risk of respiratory failure, as in adults, is associated with the coexistence of concomitant diseases. The aim of our study was to analyze patients admitted to PICUs due to severe course of SARS-CoV-19 infection. Methods: A retrospective multi-center study, the analysis covered all children with a confirmed diagnosis of SARS-CoV-2 virus infection, who were admitted to PICUs, in the period from November 2020 to August 2021. We studied epidemiological and laboratory parameters, and the endpoint – survival or death. Results: The study analyzed 45 patients (0.075% of all children hospitalized in Poland due to COVID-19 at that time). Mortality calculated in the entire study group was 40% (n=18). Statistically significant differences between the compared groups (survived and died) concerned the parameters of the respiratory system, Lung Injury Score and Pediatric Sequential Organ Failure Assessment . A significant correlation between disease severity and the patient's prognosis was shown by the liver function parameter AST (p=0.028). Analyzing patients requiring mechanical ventilation and assuming survival as the primary outcome, a significantly higher oxygen index on the first day of hospitalization, lower pSOFA scores and lower AST levels (p: 0.007; 0.043; 0.020; 0.005; 0.039, respectively) were found. Conclusions: As in adults, children with comorbidities are most frequently at risk of severe SARS-CoV-2 infection. Increasing symptoms of respiratory failure, the need for mechanical ventilation and persistently high values of aspartate aminotransferase are indicators of poor prognosis.

Understanding the subtle signs of carpal instability and other unique injury patterns in the wrist is a critical skill for radiologists. Proper patient management and outcomes are directly dependent on the accurate interpretation of wrist imaging studies. This review will provide a detailed overview of typical imaging features of carpal trauma and instability, management, and complications, using multimodality imaging and original medical illustrations. A detailed overview of the osseous, ligamentous, arterial anatomy of the wrist, arcs of Gilula, and zones of vulnerability will be provided. Carpal fractures, dislocations, special radiographic views, and imaging pearls will be discussed. Instability patterns and the myriad of associate abbreviations (CID, CIND, CIC, CIA, VISI, DISI, SLD, LTD, MCI, SLAC, SNAC) will be clarified. Expected outcomes, potential complications, and management will be reviewed.

Electrical impedance tomography (EIT) can monitor the real-time hemodynamic state of a conscious and spontaneously breathing patient noninvasively. However, cardiac volume signal (CVS) extracted from EIT images has a small amplitude and is sensitive to motion artifacts (MAs). This study aimed to develop a new algorithm to reduce MAs from the CVS for more accurate heart rate (HR) and cardiac output (CO) monitoring in patients undergoing hemodialysis based on the source consistency between the electrocardiogram (ECG) and the CVS of heartbeats. Two signals were measured at different locations on the body through independent instruments and electrodes, but the frequency and phase were matched when no MAs. As the number of motions per hour (MI) increased over 30, the proposed algorithm had a correlation of 0.83 and a precision of 1.65 beats per minute (BPM) compared to the conventional statical algorithm of a correlation of 0.56 and a precision of 4.04 BPM. For CO monitoring, the precision and upper limit of the mean ∆CO were 3.41 and 2.82 liters per minute (LPM), respectively, compared to 4.05 and 3.82 LPM of the statistical algorithm. The developed algorithm could reduce MAs and improve HR/CO monitoring accuracy and reliability, particularly in high-motion environments.

Asthma is a common chronic respiratory disease that affects millions of people worldwide, and its prevalence continues to increase. Vitamin D has been proposed as a potential environmental factor in asthma pathogenesis, due to its immunomodulatory effects. This systematic review aimed to evaluate the effect of vitamin D supplementation on airway remodeling in asthma. We conducted a comprehensive search of electronic databases and identified experimental studies and randomized controlled trials that investigated the impact of vitamin D supplementation on airway remodeling in asthma. The studies included in this review suggest that vitamin D inhibits airway smooth muscle cell contraction and remodeling, reduces inflammation, and regulates collagen synthesis in the airways, and modulates the action of bronchial fibroblasts. However, one study suggests that TGF-β1 can impair vitamin D-induced and constitutive airway epithelial host defense mechanisms. Overall, vitamin D appears to influence many of the pathways central to asthma progression, indicating a promising potential in asthma management and prevenation of asthma progression.

Background and Objectives: Peanut allergy is the most common single cause of anaphylaxis in children. The risk factors for anaphylaxis in children with peanut allergy are not well defined. Therefore, we aimed to identify epidemiological, clinical and laboratory characteristics of children with peanut allergy that may predict the severity of allergic reaction and anaphylaxis. Materials and Methods: We conducted a cross-sectional study and included 94 children with peanut allergy. Allergy testing was performed, including skin prick testing and determination of specific IgE levels to peanut and its Ara h2 component. In case of discordance between patient history and allergy testing, an oral food challenge with peanut was performed. Results: Anaphylaxis, moderate and mild reactions to peanuts occurred in 33 (35.1%), 30 (31.9%) and 31 (33.0%) patients, respectively. The severity of the allergic reaction only weakly correlated (p = 0.04) with the amount of peanuts consumed. The median number of allergic reactions to peanut was 2 in children with anaphylaxis compared with 1 in other patients (p = 0.04). The median level of specific IgE to Ara h2 was 5.3 IU/ml in children with anaphylaxis compared to 0.6 IU/ml and 10.3 IU/ml in children with mild and moderate peanut allergy (p = 0.06). The optimal cutoff for distinguishing between anaphylaxis and a less severe allergic reaction to peanut was a specific IgE Ara h2 level of 0.92 IU/ml with 90% sensitivity and 47.5% specificity for predicting anaphylaxis (p = 0.04). Conclusions: Epidemiological and clinical characteristics of the patient cannot predict the severity of allergic reaction to peanut in children. Even standard allergy testing, including component diagnostics, is a relatively poor predictor of the severity of allergic reaction to peanuts. Therefore, more accurate predictive models including new diagnostic tools are needed to reduce the need for oral food challenge in most patients.

Blood gas analysis is a diagnostic tool to evaluate the partial pressures of gas in blood and acid-base content. The use of blood gas analysis enables to clear understanding the respiratory, circulatory, and metabolic disorders. The arterial blood gas (ABG) explicitly analyzes blood taken from an artery, assessing the patient's partial pressure of oxygen (PaO2), carbon dioxide (PaCO2) pH (acid/base). PaO2 indicates the oxygenation status, and PaCO2 indicates the ventilation status (chronic or acute respiratory failure). PaCO2 is affected by hyperventilation characterized by rapid or deep breathing, and hypoventilation characterized by slow or shallow breathing. The acid-base balance tested by the ABG procedure measures the pH and PaCO2 directly while the use of the Hasselbach equation gives the serum bicarbonate (HCO3) and base deficit or excess. The measured HCO3is based on strong alkali that frees all CO2 in serum, including dissolved CO2, carbamino compounds, and carbonic acid the calculation uses a standard chemistry analysis giving the amount of "total CO2", the difference will amount to around 1.2 mmol/L. Though ABG is frequently ordered in emergency medicine contests for acute conditions it may also be needed in other clinical settings. The ABG analysis shows to be an exceptional diagnostic tool including the group of those diseases known as acid-base diseases (ABDs) which include a great variety of conditions as such severe sepsis, septic shock, hypovolemic shock, diabetic ketoacidosis, renal tubular acidosis, chronic respiratory failure, chronic heart failure, and diverse metabolic diseases.

Vascular calcification (VC) is associated with increased cardiovascular risks in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors, like empagliflozin, can improve cardiovascular and renal outcomes. We assessed the expression of Runt-related transcription factor 2 (Runx2), interleukin (IL)-1β, IL-6, AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase 1 (HO-1) in inorganic phosphate–induced VC in mouse VSMCs to investigate the mechanisms underlying empagliflozin’s therapeutic effects. We evaluated biochemical parameters, mean artery pressure (MAP), pulse wave velocity (PWV), transcutaneous glomerular filtration rate (GFR), and histology in an in vivo mouse model with VC induced by an oral high-phosphorus diet following a 5/6 nephrectomy in ApoE−/− mice. Compared to the control group, empagliflozin-treated mice showed significant reductions in blood glucose, MAP, PWV, and calcification, as well as increased calcium and GFR levels. Empagliflozin inhibited osteogenic trans-differentiation by decreasing inflammatory cytokine expression and increasing AMPK, Nrf2, and HO-1 levels. Empagliflozin mitigates high phosphate–induced calcification in mouse VSMCs through the Nrf2/HO-1 anti-inflammatory pathway by activating AMPK. Animal experiments suggested that empagliflozin reduces VC in CKD ApoE−/− mice on a high-phosphate diet.

Ischemia-reperfusion injury (IRI) is a complex pathophysiological process that can lead to severe and irreversible consequences, including the complete loss of renal function. While standardized strategies for preventing IRI during "back-table" and cold preservation are available, various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and reperfusion of the kidney. These methods include pharmacological agents, mechanical interventions, and surgical techniques such as renal capsulotomy, ischemic preconditioning, venous blood reperfusion, renal perfusion, and the use of tissue engineering techniques like mesenchymal stromal/stem cells and/or decellularization. In this comprehensive analysis, we provide a detailed overview of pharmacological agents and intraoperative methods and approaches for the prevention and treatment of renal IRI. We begin by discussing the mechanisms of IRI and the challenges of preventing it during surgery. Then using a bibliometric analysis and molecular docking of brand-new legends we showed eplerenone have the most binding affinity to Aldehyde dehydrogenase (AD), Estrogen receptor (ER), Klotho protein, Mineralocorticoid receptor (MR), and Toll-like receptor 4 (TLR4) for preventing IRI comparing with other available therapeutics, Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. Next, we provide a comprehensive analysis of the potential benefits and limitations of various prevention strategies, including an in-depth discussion of the mechanisms of action of pharmacological agents, mechanical interventions, and surgical techniques. Furthermore, we introduce a novel scoring system for the prevention methods of kidney IRI, which takes into account the effectiveness, feasibility, and safety of each method. We then analyze the current state of clinical research in this area and discuss the implications of these methods for future clinical practice. Overall, this article provides a valuable resource for clinicians and researchers seeking to prevent and treat renal IRI in surgical settings, and introduces a new scoring system that can be used to guide the selection of the most effective and safe prevention methods.

Based on the marine natural products piperafizine B, X334 and our previously reported compound 4m, fourteen novel 3,6-diunsaturated 2,5-diketopiperazine (2,5-DPK) derivatives (1-2, 4-6, 8-16), together with two known ones (3 and 7), were designed and synthesized as anticancer agents against cell lines A549 and Hela. The MTT assay results showed that the derivatives 6, 8-12 and 15 had moderate to good anticancer capacities with the IC50 values ranging from 0.7 to 8.9 μM. Among them, compound 11 with naphthalen-1-ylmethylene and 2-methoxybenzylidene functions at the 3- and 6-positions of 2,5-DPK ring, respectively, displayed good inhibitory activities to both cancer cells A549 (IC50 = 1.2 μM) and Hela (IC50 = 0.7 μM). It could also induce apoptosis and obviously block the cell cycle progression at G2/M phase in both cells at 1.0 μM. The electron withdrawing functions might not be favorable for the derivatives with high anticancer activities. Additionally, compared to piperafizine B and X334, these semi-N-alkylated derivatives have high liposolubilities (&gt; 1.0 mg•mL-1). Compound 11 can be further developed aiming to the discovery of novel anticancer candidate.

Abstract: Background: Trauma is the leading cause of morbidity and mortality in young patients, acute surgical conditions cause morbidity and mortality in patients of all ages. Computed tomography scan (CT) assist greatly in the investigation and management of these patients with blunt and penetrating trauma, facilitating early diagnosis and expedites early appropriate treatment of these patients. Acute non-traumatic surgical conditions also mimic non-surgical pathologies and differentiating the two is important because management is different and any delay in surgical intervention results in high morbidity and some may even result in mortality. Method: Literature review of the role of multidetector CT scan (MDCT) in managing acute surgical emergencies and trauma-diagnosis in the trauma patient and patients presenting with acute surgical emergencies. The focus is on the role of the MDCT in the management of these patients. Results highlight that the use of MDCT expedites management of these patients, allowing early surgical intervention and preventing unnecessary surgical interventions where the intervention is not indicated, based on the MDCT results. Conclusion: This paper emphasizes the important role that is played by the MDCT in the management of the above patients.

Since the first description of COVID-19 infection, among clinical manifestations of the disease including fever, dispnea, cough, fatigue, it was observed a high incidence of thromboembolic events potentially evolving towars ARDS and COVID-associated-coagulopathy (CAC).The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status in COVID-19 disease can be explained by the increase of coagulation levels of D-dimer, lymphocytes, fibrinogen, IL-6 and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.

The oral cavity is environment to a diverse range of organisms that make up an essential element of the human microbiota. There are 50-1000 kinds of microorganisms capable of colonizing the mouth. The entamoeba parasites have at minimum 7 species (E. histolytica, E. dispar, E. moshkovskii, E. coli, E. polecki E. hartmann, E. gingivalis). These parasites are parasitic single-celled organisms and Entamoeba gingivalis was the first amoeba to be described in 1849 that was capable of existing in humans. It was shown that only Entamoeba gingivalis is able to colonize the oral cavity. The aim of this study was to evaluate prevalence of E. Gingivalis in periodontal disease using two electronic database search engines. In order to have a broader view of the subject, a comprehensive manual search was conducted on these content aggregators and the initial search resulted in 277 articles using the keywords „Entamoeba gingivalis”, „periodontitis”, „E. gingivalis”, „periodontal disease”, „prevalence”, and „incidence”, in different combinations. The results showed that 755 cases were infected with Entamoeba gingivalis out of a total number of 1,729 patients diagnosed with periodontal disease indicating a global prevalence of 43%. When comparing different stages of periodontal diseases results revealed that the prevalence in patients with gingivitis was 58% while in periodontitis group the prevalence was 44%. Overall prevalence of Entamoeba Gingivalis based on gender was 43 % in female patients whilst in male patients was 47%. Based on the results it can be concluded that the higher incidence of Entamoeba Gingivalis in people with periodontal disease compared to healthy people is more than just a sign of the disease; it may also be linked to the severity of the condition and its propensity to progress.

Background and Objectives: The novel double-pigtail catheter (DPC) has an additional pigtail coiling at the mid-shaft with centripetal multiple side holes. The aim of the present study was to investigate the advantages and efficacy of DPC in overcoming the complications of conventional single-pigtail catheters (SPC) used to drain pleural effusion. Materials and Methods: Between July 2018 and December 2019, 382 pleural effusion drainage procedures were reviewed retrospectively (DPC, n = 156; SPC without multiple side holes, n = 110; SPC with multiple side holes [SPC+M], n = 116). All patients showed shifting pleural effusion in the decubitus view of chest radiography. All catheters were 10.2 Fr in diameter. One interventional radiologist performed all procedures and used the same anchoring technique. Complications (dysfunctional retraction, complete dislodgement, blockage, and atraumatic pneumothorax) were compared among the catheters using chi-square and Fisher’s exact tests. Clinical success was defined as improvement in pleural effusion within 3 days without additional procedures. A survival analysis was performed for calculating the indwelling time. Results: The dysfunctional retraction rate of DPC was significantly lower than that of the other catheters (p < .001). Complete dislodgement did not occur in any of the DPC cases. The clinical success rate of DPC (90.1%) was the highest. The estimated indwelling times were nine (95% confidence interval [CI]: 7.3–10.7), eight (95% CI: 6.6–9.4), and seven (95% CI: 6.3–7.7) days for SPC, SPC+M, and DPC, respectively, with DPC showing a significant difference (p < .05). Conclusions: DPC had a lower dysfunctional retraction rate compared to conventional drainage catheters. Furthermore, DPC were efficient for pleural effusion drainage with a shorter indwelling time.

Staphylococci sp. have become the primary pathogens implicated in infective endocarditis, especially within high-income nations. This along with the increasing burden of healthcare, aging populations and the protracted course the infections may take, contribute to a significant challenge for healthcare systems. A systematic review was conducted using relevant search criteria from PubMed, Ovid’s version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. 35 studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions was identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents was also explored giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. Ameliorating these molecular pathways may serve as a therapeutic avenue for the prevention and treatment of these infections in near future.

Even after debridement and chemical root canal preparation, multispecies bacterial biofilms can still be found in root canals and dentinal tubules. This demonstrates the necessity of using suitable antibacterial endodontic sealers. Due to their well-known biological qualities, calcium silicate based root canal sealers or “bioceramic’ sealers have recently been launched and can be successful in endodontic procedures. This study's objective was to compare the impact of CerasealR, Total Fill BC SealerR, Bio-C SealerR, AH Plus BioceramicR, K-biocerR and SealiteR on the elimination of a multispecies’ endodontic biofilm at 3, 7 and 14 days. Enterococcus faecalis, Pseudomonas Aeruginosa, Candida Albicans and Proteus Mirabilis were cultured on specific agars and later grown in Brain Heart Infusion broth on hydroxyapatite discs pretreated with collagen type 1 and incubated for 18 days. The resulting biofilm was then placed on a 10mm round shaped blotting paper set on a metallic net in a 6cm petri dish with an orthodontic bend filled with the calcium silicate based root canal sealer in direct contact with the biofilm. In all tested groups, the total bacterial count has significantly decreased between day 3 and day 14 (P<0.05) with no statistically significant differences among the different sealers’ groups at all time points. Sealite group was capable of decreasing the Candida Albicans count significantly between day 3 and day 14 (P<0.05) in comparison with the bioceramic groups. All sealers had antibacterial activity against the multispecies biofilm between day 3 and day 14.

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here we analysed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a posthoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, taper/stop) as the predictor. 282 patients were analysed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that functional decline after tapering or stopping DMARDs in RA patients with stable remission is small and related to relapses but to on overall functional decline.

Background: Histoplasmosis is a systemic mycosis, present globally. We aimed to describe cases of histoplasmosis (Hc) and to establish a risk profile associated to Hc in HIV-infected patients (HIV+). Methods: This was a retrospective study of patients with a clinical-. laboratorial diagnosis of Hc. Data was fed into REDCap and statistical analysis was done with R . Results: We included 99 records, 65 HIV+ and 34 HIV-. Average age was 39 years. Median time from onset to diagnosis was 8 weeks in HIV- and 22 weeks in HIV+. Disseminated histoplasmosis occurred in 79.4% HIV+, vs 36.4% HIV-. Median CD4 count was 70. Co-infection with tuberculosis was present in 20% of HIV+. Blood cultures were positive in 32.3% of HIV+ vs 11.8% of HIV- (p=0.025); bone marrow culture was positive in 36.9% vs 8.8%(p=0.003). Most HIV+ patients (71.4%) were hospitalized. On univariate analysis, anemia, leukopenia, intensive care, use of vasopressors and mechanical ventilation were associated with death in HIV+. Conclusions: Most of our patients with histoplasmosis were HIV+, presenting advanced AIDS. Diagnosis was late in HIV+ patients, and they frequently presented disseminated Hc, required hospitalization, and died. Early screening for Hc in HIV+ and drug induced immunosuppressed patients is crucial.

Growth-preserving instrumentation techniques are utilized in early-onset scoliosis (EOS) cases requiring surgical intervention. Shilla technique corrects the deformity and may reduce the need for surgical treatment with its growth-directing effect. As with other techniques, various prob-lems can be encountered following the administration of the Shilla technique. The aim of this study was to examine the effect of complications encountered with Shilla treatment on correction and growth. Sixteen patients with a follow-up period of at least 1 year who received Shilla growth guidance for EOS were included in the study. No complications occurred in 50% cases and no unplanned surgery was required. Of the remaining 8 patients with postoperative im-plant-related complications (50%), 6 (37.5%) required unplanned surgery; this consequently caused implant failure in the proximal region in 5 cases (31.25%) and deep tissue infection around the implant in 1 case (6.25%). Deformity correction, spine length, and quality-of-life scores significantly improved in EOS through Shilla growth guidance. Although implant-related com-plications were observed and related unplanned surgeries were required with Shilla growth guidance in our patients, these complications did not have a significant negative effect on correc-tion and spine growth.

Subarachnoid hemorrhage (SAH) is most commonly seen in patients over 55 years of age and often results in a loss of many productive years. SAH has a high mortality rate, and sur-vivors often suffer from early and secondary brain injuries. Understanding the pathophysiology of the SAH is crucial to identifying potential therapeutic agents. One promising target for diagno-sis and prognosis of SAH is circulating microRNAs, which regulate gene expression and are in-volved in various physiological and pathological processes. In this review, we discuss the poten-tial of microRNAs as a target for diagnosis, treatment, and prognosis in SAH.

We have established earlier a cell line from the human limbal area to study cell growth and response to the toxic effects of antibiotics used in ophthalmology. In the recent work, the effect of multi-walled carbon nanotubes (MWCNTs) in cornea damage was investigated in vitro and in vivo in mice. In the in vitro experiments, the physiological effects of multi-walled carbon nano-tube (MWCNT) bundles on corneal wound healing were mimicked in vitro by a reepithelization limbal stem cell model. Murine in vivo experiments were performed with intact, non-functionalized MWCNTs to confirm the validity of in vitro tests. The MWCNTs of 10 -30 nm outer diameter at low concentration (5 µg/ml) did not interfere with the wound healing of the damaged limbal cell monolayer. Higher than 50 µg/ml concentrations: a) generated MWCNT aggregates, b) restrained the movement and prolonged the time of wound healing, c) increased the amplitudes of the oscillations of the cells, and d) resulted in scar formation affecting both cor-neal function and refraction. Chromatin condensation, a sensitive test of the viability of cells, including limbal stem cells revealed that the presence of a low concentration of nanotubes (5 µg/ml), did not significantly affect the viability of limbal cells. Chromatin condensation was completed and metaphase chromosomes were seen at higher MWCNT concentration proving that their aggregates did not affect the viability of limbal cells. This concentration of MWCNTs (5 µg/ml) did impact neither the reepithelization in vitro nor in vivo in the scratched eyes of mice. Scar formation took place at higher than 50 µg/ml concentrations and the healing of the cornea was prevented by the lack of movement of increasingly larger macroaggregates. In vivo murine experiments vali-dated in vitro monolayer regrowth followed by time-lapse microscopy portraying realistically the reepithelization of the damaged cornea that process was gradually slowed down by macro aggregate formation and caused the scarring of the cornea.

Background. Chest CT is widely regarded as a dependable imaging technique for detecting pneumonia in COVID-19 patients, but there is growing interest in microwave radiometry (MWR) of the lungs as a possible substitute for diagnosing lung involvement. Aim. The aim of the study is to examine the utility of the MWR approach as a screening tool for diagnosing pneumonia with complications in patients with COVID-19. Methods. Our study involved two groups of participants. The control group consisted of 50 individuals (24 male and 26 female) between the ages of 20 to 70 years who underwent clinical evaluations and had no known medical conditions. The main group included 142 participants (67 men and 75 women) between the ages of 20 to 87 years who were diagnosed with COVID-19 complicated by pneumonia and were admitted to the emergency department between June 2020 to June 2021. Skin and lung temperatures were measured at 14 points, including 2 additional reference points, using a previously established method. Lung temperature data were obtained with the MWR2020 (RTM-01-RES) (MMWR LTD, Edinburgh, UK), a CE Class I device. All participants underwent clinical evaluations, laboratory tests, chest CT scans, MWR of the lungs, and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Results. The MWR exhibits a high predictive capacity as demonstrated by its sensitivity of 98.6% and specificity of 84.0%. Conclusions. MWR of the lungs can be a valuable substitute for chest CT in diagnosing pneumonia in patients with COVID-19, especially in situations where chest CT is unavailable or impractical.

Antibiotics have become a widely used drug classes worldwide. Its indiscriminate use in the clini-cal-hospital environment ended up causing antibiotic-resistance genes. Pharmaceutical technology is an essential ally for new formulation development in the antibacterial field. Cyclodextrins (CDs) are ap-proaches that can potentially improve the effectiveness of antibacterial drugs. Thus, this study aimed to review experimental models using CDs as inclusion complexes to improve antibacterial drugs’ physi-cochemical characteristics and biological activities. The review was carried out using the three online journals database PubMed, Scopus, and Embase, limited to Medical Subjects Headings Index. The search protocol was registered in the Open Science Framework database. The following terms and their com-binations were used: cyclodextrins and antibacterial agents in title or abstract, and a total of 1580 studies were identified in a period up to October 2022. Finally, 27 articles were selected for discussion in this review. The biological results reveal that the antibacterial effect of the compounds, complexed with CDs, was extensively improved when compared to the free drugs. CDs can improve the therapeutic effects of antibiotics, already existing on the market, natural products, and synthetic molecules. Therefore, these inclusion complexes using CDs increase the new pharmaceutical products development for clinical ap-plication.

Preliminary clinical data suggest pain reduction through fasting in different diagnoses. This uncontrolled observational clinical study examined the effects of prolonged modified fasting on pain and functional parameters in hip and knee osteoarthritis. Patients admitted to the inpatient department of Internal Medicine and Nature-based Therapies of the Immanuel Hospital Berlin between February 2018 and March 2020, answered questionnaires at the beginning and end of inpatient treatment, as well as 3, 6 and 12 months after discharge. Additionally, selected blood and anthropometric parameters were routinely assessed during the inpatient stay. Fasting was performed as part of a multimodal integrative treatment program, with daily caloric intake of <600 kcal for 7.7 ± 1.7 days. N=125 consecutive patients were included. Results revealed an amelioration of overall symptomatology (WOMAC Index score: -14.8±13.31; p<0.001; d=0.78), and pain alleviation (NRS Pain: -2.7±1.98, p<0.001, d=1.48). Pain medication was reduced, stopped, or replaced by herbal remedies in 36% of patients. Improvements were also observed in secondary outcome parameters, including increased quality of life (WHO-5: +4.5±4.94, p<0.001, d=0.94), reduced anxiety (HADS-A: -2.1±2.91, p<0001, d=0.55) and depression (HADS-D: -2.3±3.01, p<0.001, d=0.65), decreases in body weight (-3.6 kg ± 1.65, p< 0.001, d=0.21), and blood pressure (systolic: -6.2±15.93, p<0.001, d= 0.43; diastolic: -3.7±10.55, p<0.001, d=0.43). Results suggest that patients with osteoarthritis of the lower extremities may profit from a prolonged fast embedded in a multimodal integrative treatment regarding quality of life, pain, and disease-specific functional parameters. Confirmatory RCTs are warranted to further investigate these hypotheses.

Background: Primary infection has been questioned as the pathogenetic cause of acute appendicitis. We attempted to identify the bacteria involved, and to investigate if their species, types, or combinations affected the severity of acute appendicitis in children. Methods: Samples from both the appendiceal lumen and the peritoneal cavity of 72 children who underwent appendectomy were collected to perform bacterial culture analysis. The outcomes were studied to see if and how they were associated with the severity of the disease. Regression analysis was performed to identify any risk factors associated with complicated appendicitis. Results: Escherichia coli, Pseudomonas aeruginosa and Streptococcus species were the most common pathogens found in the study population. The same microorganisms, either combined or separate, were the most common in the appendiceal lumen and the peritoneal cavity of patients with complicated appendicitis. Gram-negative bacteria, polymicrobial cultures in the peritoneal fluid and in the appendiceal lumen, were associated with complicated appendicitis. Polymicrobial cultures in the peritoneal cavity presented four times higher risk of complicated appendicitis. Conclusion: Polymicrobial presentation and gram-negative bacteria are associated with complicated appendicitis. Antibiotic regimens should target the combinations of the most frequently identified pathogens, speculating the value of early antipseudomonal intervention.

Assessing corneal biomechanics in vivo has long been a challenge in the field of ophthalmology. Although recent wave-based optical coherence elastography (OCE) methods have shown promise in this area, the effect of intraocular pressure (IOP) on mechanical wave propagation in the cornea remains unclear. To address this, we constructed an artificial eye model and performed surface wave OCE measurements in the radial directions (54–324°) of the silicone cornea at varying IOP levels (10–40 mmHg). The results demonstrated increases in wave propagation speeds (mean ± STD) from 6.55 ± 0.09 m/s (10 mmHg) to 9.82 ± 0.19 m/s (40 mmHg), leading to an estimate of Young’s modulus, which increased exponentially from 145.23 ± 4.43 kPa to 326.44 ± 13.30 kPa. Our implementation of an artificial eye model highlighted that the impact of IOP on Young’s modulus (ΔE = 165.59 kPa, IOP: 10–40 mmHg) was more significant than the effect of stretching of the silicone cornea (ΔE = 15.79 kPa, relative elongation: 0.98%–6.49%). Our study sheds light on the potential of using an artificial eye model in OCE research for corneal biomechanics. Furthermore, it is critical to consider the impact of IOP on measurement results when utilizing wave-based OCE in clinical settings for enhanced assessment of corneal biomechanics.

Community-acquired pneumonia (CAP) is among the most common causes of death and one of the leading healthcare concerns worldwide. It can evolve into sepsis and septic shock, which have a high mortality rate, especially in critical patients and comorbidities. The definitions of sepsis were revised in the last decade as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. Procalcitonin (PCT), C-reactive protein (CRP), and complete blood count including white blood cells are among the most commonly analyzed sepsis-specific biomarkers also used in pneumonia in a broad range of studies. It appears to be a reliable diagnostic tool to expedite care of these patients with severe infections in the acute setting. PCT was found superior to most other acute phase reactants and indicators, including CRP as a predictor of pneumonia, bacteremia, sepsis and poor outcome. In addition, PCT use is beneficial to judge timing for cessation of antibiotic treatment in most severe infectious states. The clinicians should be aware of strengts and weaknesses of known and potential biomarkers in expedient recognition and management of severe infections. This manuscript is intended to present an overview of the definitions, complications and outcomes of CAP and sepsis, with special regard to PCT and other important markers.

The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. 2 years follow-up of the study population after initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF), and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was done. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the chest CT changes) – blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes and a number of lung nodules on chest CT at the time of the diagnosis. Cut-off values, sensitivity, specificity, and odds ratio for predictors of sarcoidosis progression were calculated. These markers may be reasonable predictors of sarcoidosis progression.

The oncologic disease is a big global health issue that causes thousands of deaths annually, and it has a significant impact in the life quality of patients. Prostate cancer (PCa) is the second most diagnosed cancer and the fourth leading cause of cancer-related death in men in the western world. Delineation of pathogenetic pathways and key driver molecular alterations involved in PCa development has provided a roadmap for the evaluation of biomarkers in predicting disease outcome and to identify potential therapeutic targets. Chemotherapeutic agents introduced from the 1990s include the taxanes (paclitaxel, docetaxel and cabazitaxel), which are the most anticancer drugs used for PCa treatment. This review presents the current knowledge about the onset and development of PCa, state-of-art on the use of taxane-based therapy, and their combination with targeting different transmembrane oncoproteins in PCa. The silencing of some transmembrane proteins can improve taxane sensitivity, and therefore, may be a mechanism to improve the ef-fectiveness of these drugs in PCa treatment. This combined therapy needs to be explored as po-tential therapeutic agent for reducing cell proliferation, migration, and invasiveness in PCa.

Background Systemic sclerosis (SSc) is a rare, multisystemic disorder of connective tissue, characterized by widespread inflammation, vascular abnormalities, and both skin and visceral organ fibrosis. Tissue fibrosis is the final phase of a complex biological process of immune activation and vascular damage. Objectives The aim of study was to assess hepatic fibrosis and steatosis in SSc patients by transient elastography (TE). Methods Fifty-nine SSc patients, satisfying the 2013 ACR/EULAR classification criteria, were recruited. Clinical and laboratory findings, modified Rodnan skin score (mRSS), ac-tivity index, video-capillaroscopy, echocardiography, and lung function data were ana-lyzed. Liver stiffness (LS) was measured by transient elastography (TE), with 7 kPa used as the cut-off value for significant liver fibrosis and steatosis. Specifically, values ≥ 238 CAP ≤ 259 dB/m were considered consistent with mild steatosis (S1), 260 ≥ CAP ≤ 290 dB/m with moderate steatosis (S2) and ≥291 dB/m with severe steatosis (S3) Results The median age of patients was 51 years, with a median disease duration of 6 years. Median LS was 4.5 (2.9–8.3) kPa; 41 patients (69.5%) had no evidence of fibrosis (F=0), 16 (27.1%) displayed LS values between 5.2 and 7 kPa; only 2 patients (3.4%) had LS values >7 kPa (F3). The median CAP value for liver steatosis was 223 dB/m (IQR: 164–343). Overall, 39 patients (66.1%) did not show evidence of steatosis (CAP values <238 dB/m); 9 patients (15.2%) showed values consistent with mild (S1) steatosis (CAP value ≥238 ≤259 dB/m); 8 patients (13.5%) had moderate (S2) steatosis (CAP value ≥260 ≤290 dB/m); 3 patients (5.1%) were deemed to have severe steatosis (S3) due to CAP values ≥291 dB/m. Conclusions Only 3.4% of our patient population showed evidence of marked liver fibrosis, which is the same prevalence as that expected in the general population. Likewise, the prevalence of significant steatosis was low (5.1%) and depending on the same variables associated with fatty liver in the general population. TE was shown to be an easy and valuable method for detection and screening of liver fibrosis in SSc patients with no additional risk factors for liver disease.

At present there is a huge demand for experimental periodontal models to expand the knowledge in periodontal health related to Microbiome Medicine. Thus far none of the periodontal pathogens or cocktail of pathogens reported as aetiological agents of infectious chronic periodontitis to link with oral squamous cell carcinoma as the way Helicobactor pyroli linked with gastric carcinoma and other related gastric malignancies. Nevertheless, invasive pathogenic mechanisms of virulent strains of Porphyromonas gingivalis and Fusobacterium nucleatum singly as well as a duo demonstrated the progression and devastation of oral, pancreatic, and colorectal cancers in different study populations. Periodontal disease may be an inevitable consequence or complication of oral cancer patients who comprise a section of digestive tract cancers, due to suboptimal or poor oral hygiene practices due to unbearable pain and other complications of stage four oral cancer. Periodontitis is a reversible oral condition when it is treated properly at the correct stage and good oral hygiene practices and treating chronic periodontitis showed successful interventions in the prognosis of oral cancer. In the light of these scientifically proven epidemiological, laboratory, and clinical evidence this communication highlights the implication of ATP scavenging behavior and upregulation of immune regulatory receptors by intracellular Porphyromonas gingivalis based on in-vitro models on the prognosis of digestive tract cancers regarding the oral cancer patients.

SARS-CoV-2 was detected in China in December 2019. Myocardial injury is a crucial presentation of COVID-19, based on the association of ACE-2 and SARS-CoV-2. Down-regulating ACE-2 decreases the cardioprotective effects of angiotensin, leading to a higher TNF-α activation. TNF-α causes the inflammatory response in the myocardial damage as an apoptotic inducer. Moreover, as an inducer of necroptosis, TNF-α binds to a part of TNF receptor 1, which involves receptor-interacting protein 1 (RIP1) and causes cell death through RIP1 inhibition and NF-κB stimulation, which are also done through Tpl-2. Calcineurin controls the Tpl-2-driven NFAT stimulation. Bcl-2 or Bcl-X_L entirely blocks these pathways. Bcl-2 overexpression reduces FasL expression with a mechanism based on Bcl-2 inhibiting the NFAT. Moreover, the Fas/FasL system activates apoptosis in various cells. Bcl-XL stimulates Fas-related cell death. Additionally, TNF-α, as a part of inflammatory cytokine storms, indirectly interacts with NFAT/Bcl-2 through Tpl-2/NF-κB. Diversely, TNF-α and IL-1ẞ, the basis of inflammatory cytokine storms in COVID-19, can stimulate generating NO. Also, IL-2 is highly up-regulated in COVID-19 patients and stimulates NO generation in patients. TNF-α can provoke the generation of superoxides in neutrophils. A well-determined mechanism is the intracellular production of NO via calcium-calmodulin-dependent NO synthase (NOS). NO enhances NFAT’s calcium-dependent activity. Also, Intra/extracellular calcium exchange activates calcineurin and its related molecule, NFAT. Nitration provokes RIP1 necroptosis cascade, with respiratory complex I. Nitrites converse protection against ischemia-reperfusion injuries in the myocardium. Regulating this intrinsic molecular pathway can prevent the necroptosis of cardiomyocytes.

The precise differentiation of renal cell tumours (RCTs) is sometimes hard to achieve using standard imaging and histopathological methods. This study investigated 43 cell renal cell car-cinomas (ccRCC), 15 papillary renal cell carcinomas (pRCC), 20 chromophobe renal cell carcino-mas (chRCC), and 18 renal oncocytomas (RO), stained with anti-mitochondria antibody (Thermo Scientific) by immunohistochemistry and immunofluorescence, and assessed by electron micros-copy, in order to define mitochondria distribution pattern (coarse scanty, moderate granular and diffuse granular). Thus, the majority of males had coarse granular staining in the tumours, while females were almost equally distributed among groups (p=0.005). An average patient age, tumour side and dimension, and tumour stage were similar in all staining pattern groups. However, pathohistological tumour types had significantly different expression patterns, with the lower amount of staining detected in majority of ccRCC, moderate expression in all chRCC, and diffuse expression in all RO, pRCC and two cases of ccRCC (p<0.001) presented with higher nuclear grade (p=0.005). Moreover, with increased distribution of mitochondria, the intensity of staining was higher (p<0.001). Here we present a strategy that utilizes mitochondria detection to differentiate RO from chRCC, as well as to distinguish other frequent RCTs, such as ccRCC and pRCC.

The ability to predict the likelihood of a live birth after single fresh embryo transfer is important for treatment planning and managing patient expectation, particularly in their first in vitro fertilization (IVF) cycle. Cryopreservation of supernumerary embryos is often regarded as an important prognostic variable and a surrogate marker of success for several reasons. While previous large studies have examined the association between the number of oocytes retrieved and cleavage-stage embryos available, and the odds of a live birth following a fresh embryo transfer, the relationship between the number of supernumerary blastocysts cryopreserved following a fresh embryo transfer has not been rigorously studied. We performed a retrospective analysis of data collected between 2006 and 2018 for all first time IVF patients with a fresh autologous day 5 single blastocyst transfer. The relationship between the likelihood of a live birth and number of supernumerary blastocysts cryopreserved was assessed according to patient age group. In patients aged <35 years and 35-39 years old, the likelihood of a live birth increased linearly from 0.33 (95%CI:0.31–0.34) to 0.80 (95%CI:0.74–0.86; P<.0001) and 0.30 (95%CI:0.28–0.32) to 0.82 (95%CI:0.73–0.91;P<.0001) between 1-6 blastocysts cryopreserved and then non-linearly to 0.95 (95% CI 0.92–0.97; P<.0001) and 0.96 (95%CI:0.93–0.99; P<.0001) if 10 or more blastocysts were cryopreserved, respectively. When aged 40 years and above, the likelihood of a live birth increased linearly from 0.26 (95%CI:0.19–0.32) to 0.83 (95%CI:0.68–0.97; P<.0001) between 1-4 blastocysts cryopreserved and then non-linearly to 0.99 (95%CI:0.98–0.99; P<.0001) if 10 or more blastocysts were cryopreserved. The present study demonstrated a non-linear relationship between the number of supernumerary blastocysts cryopreserved and the likelihood of a live birth after single blastocyst transfer in the first autologous fresh IVF/ICSI cycle across different age groups.

(1) Background: The prevalence of SARS-CoV-2 infection among healthcare workers (HCWs) in Poland is not exactly known. This study aims to present secondary epidemiological data identifying the scale of the spread of novel coronavirus infection in selected professional groups of HCWs in Poland. (2) Methods: The secondary epidemiological data included both the number of infections and the number and percentages of deaths in individual occupational groups, which occurred throughout the observation period, both in the country and in individual voivodeships. (3) Results: The prevalence of SARS-CoV-2 infections among HCWs was 16.48%. The highest percentage of infected concerned laboratory scientists (21.62%) and paramedics (18%). The highest frequency of infections among HCWs occurred in the province of Zachodnio-Pomorskie (18.9%). Due to COVID-19, 558 healthcare workers died during the analysed period, mostly nurses (n=236) and doctors (n=200). The results regarding the vaccination coverage of HCWs against COVID-19 indicate the highest percentage of vaccinated were among doctors (83.63%) and the smallest among physiotherapists (38.2%). (4) Conclusions: In general, the percentage of infections was high in Poland during the pandemic (16.48%). Significant territorial differences were observed in the frequency of infections, deaths, and percentage of vaccinated workers in individual voivodeships.

Dietary iron assimilation is critical for health and essential to prevent iron deficient states and related comorbidities, such as anemia. The bioavailability of iron is limited, while its absorption and metabolism are tightly controlled to keep body iron stores within a relatively narrow range. Genetic inactivation of the iron hormone hepcidin causes hereditary hemochromatosis, an endocrine disorder of iron overload characterized by chronic hyperabsorption of dietary iron, with deleterious clinical complications if untreated. The impact of high dietary iron intake and elevated body iron stores in the general population is not well understood. Herein, we summarize epidemiological data suggesting that high intake of heme iron, which is abundant in meat products, poses a risk factor for metabolic syndrome pathologies, cardiovascular diseases, and some cancers. We discuss clinical relevance and potential limitations of data from cohort studies, as well as the need to establish causality and elucidate molecular mechanisms.

Angiotensin II (Ang II) plays a role in several inflammatory diseases and is capable of inducing the release of inflammatory mediators in several cell types. The objective was to investigate the potential of Ang II to induce mRNA expression of inflammatory mediators by cultured primary human periodontal cells. A synergistic effect of a co-treatment with Ang II and IL1β on mRNA expression of inflammatory mediators was also explored. Primary cultures of human fibroblast-like cells isolated from gingival and periodontal ligament tissues from 3 subjects were established using explant techniques. Immunophenotyping of STRO-1, AT1 and AT2 receptors was performed by flow cytometry analysis. Cell cultures were challenged with Ang II (1M) for 3, 6 and 24h with or without a co-treatment with IL1β (0.1ng/mL) for 24h. mRNA expression of inflammatory mediators was performed by real time quantitative polymerase chain reaction (RT-qPCR). We present, for the first time, a precise quantification for AT1 and AT2 receptors on human gingival and periodontal fibroblast-like cell types; the percentage of positive immunostaining compared to the total population of cells varied from 3.35% through 5.29% for AT1 and 2.97% through 4.57% for AT2. Ang II slightly upregulated mRNA expression of IL6 and CCL2/MCP1 in gingival cells and IL8 and PTGS2/COX2 in periodontal ligament cells. IL1β induced upregulation of IL8, IL6 CCL2/MCP1, PTGS2/COX2 and IL1β mRNA in both cell types. Co-treatment with Ang II and IL1β did not show a synergistic effect under these experimental conditions. Ang II shows a low potential to induce mRNA upregulation of inflammatory mediators in cultured primary human gingival and periodontal ligament cells, most likely due to the low percentage of Ang II receptors in such cells, and no synergistic effect with the co-treatment with IL1β.

Schizophrenia patients with an earlier age of onset have been found to have more serious negative symptoms and cognitive deficits. Oxidative stress is thought to be implicated in cognitive impair-ment in schizophrenia. Total antioxidant capacity (TAOC) is an essential indicator of oxidative stress. However, the association between age of onset, TAOC, and cognitive performance in schizophrenia is still unexplored. In this study, 201 patients (age: 26.5±9.6 years, male: 53.2%) with drug naïve schizophrenia were recruited. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Cognitive functioning was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma TAOC levels were an-alyzed using established procedures. Results showed that early-onset (EO) patients had higher TAOC levels, more severe negative symptoms and performed worse on Visuospatial/Constructional, Language and RBANS total score compared with non-EO patients. After Bonferroni correction, only non-EO patients showed a significant inverse relationship between TAOC levels and RBANS language, attention, and total scores. Our findings suggest that early /late age of onset may be correlated with psychopathological symptoms, cognitive impairment and oxidative responses in schizophrenia. Furthermore, the age of onset may moderate the relationship between TAOC and cognitive function in patients with schizophrenia. These findings suggest that improving oxidative stress status in non-EO schizophrenia patients may enhance their cognitive function.

Objective. Whether a minimum quantity of saliva is needed to inhibit the caries process is unclear. Here, we evaluated the effect of saliva dilutions on an in vitro caries model with Streptococcus mutans (S. mutans) biofilms. Methods. S. mutans biofilms were grown on enamel and root dentin slabs, in culture media containing different proportions of saliva (v/v): 0%, 5%, 10%, 25%, 50%, 75% and 100% saliva, and exposed to a 10% sucrose solution (5 min, 3x/day), with appropriate controls. After 5 (enamel) and 4 (dentin) days, demineralization, biomass, viable bacteria and polysaccharide formation were analyzed. The acidogenicity of the spent media was monitored overtime. Assays were carried out in triplicate in 2 independent experiments (n=6). Results. An inverse relationship was observed between acidogenicity, demineralization, and saliva proportion, both in enamel and dentin. A marked reduction in enamel and dentin demineralization was observed when small amounts of saliva were incorporated in the medium. For both tissues, a significant reduction in biomass, viable S. mutans cells and polysaccharides were observed when saliva was present, in a concentration-dependent manner. Conclusions. High quantities of saliva can almost completely inhibit sucrose-induced cariogenicity, but small amounts can also exert a dose-dependent caries-protective effect.

Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades, to over 80% as per today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is the cardiotoxicity. The chemotherapeutic agents that have been implicated as a cause of cardiotoxicity, are mostly anthracyclines and mitoxantrone, alkylating agents, proteasome inhibitors and to a lesser extent anti-microtubule agents, cisplatin, monoclonal antibodies, small molecular tyrosine kinase inhibitors, and nucleotide synthesis inhibitors. Routine diagnosis and monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite refinements in diagnostics still severe limitations exist, due to the increase of the above-mentioned biomarkers, only after significant cardiac damage has occurred. Lately, research has been expanded by introducing new technologies and finding new markers by omics approach. These new markers could be used not only for early detection, but also for early prevention of cardiotoxicity. The omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide understanding of mechanisms of cardiotoxicity, beyond traditional technologies. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents mainly involved in cardiotoxicity and the methods of early and preventive diagnosis, using omics technology.

Background: This literature review investigates qualitative and quantitative uses of indocyanine green (ICG) in surgical treatment, as this novel technique has become increasingly popular in ORs (operating rooms) worldwide due to its many advantages. Method: An extensive literature review was performed by searching for relevant terms in 5 international databases (www.pubmed.gov, www.sciencedirect.com, www.scopus.com, www.Oxfordjournals.com, www.reaxys.com). The results of this search were summarized into the main advantages of employing ICG in colorectal surgery as follows: a) intraoperative fluorescence angiography capability; b) fluorescence-guided identification of lymph node involvement in colorectal cancer and the sentinel lymph node method; c) positive fluorescence flagging of a liver tumour as small as "only" 200 tumour cells; d) facilitation of fistula diagnosis; and e) tumour tattooing. Moreover, in addition to qualitative intraoperative ICG use, this technique can be combined with quantitative methods and parameters, such as maximum intensity, relative maximum intensity, and different inflow parameters (time-to-peak, slope, and t1/2max). The conclusion of this article is that fluorescence surgery with ICG aided by near-infrared (NIR) light is a relatively recent technology, an advantage of which is improving the specific anatomic and functional information provided, thus allowing more comprehensive and safer tumour removal as well as preservation of important structures.

Introduction- The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods- We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested by RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results- A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.

Measuring the non-pathogenic Torque Teno Virus (TTV) load allows assessing the net immunosuppressive state after kidney transplantation (KTx). Currently, it is not known how exposure to maintenance immunosuppression affects TTV load. We hypothesized that TTV load is associated with the exposure to mycophenolic acid (MPA) and tacrolimus. We performed a prospective study including 54 consecutive KTx. Blood TTV load was measured by an in-house PCR at months 1 and 3. Together with doses and trough blood levels of tacrolimus and MPA, we calculate the coefficient of variability (CV), time in therapeutic range (TTR) and concentration/dose ratio (C/D) of tacrolimus, and the MPA-area under the curve (AUC-MPA) at the third month. TTV load at the first and third month discriminated those patients at risk of developing opportunistic infections between months 1 and 3 (AUC-ROC 0.723, 95%CI 0.559-0.905, p = 0.023) and between months 3 to 6 (AUC-ROC 0.778, 95%CI 0.599-0.957, p = 0.028), respectively, but not those at risk of acute rejection. TTV load did not relate to mean tacrolimus blood level, CV, TTR, C/D and AUC-MPA. To conclude, although TTV is a useful marker of net immunosuppressive status after KTx, it is not related to exposure to maintenance immunosuppression.

Background: In this study, we aimed to evaluate the effect of s-FLT-1 and PlGF concentrations in women in the first trimester of pregnancy on the pulsatility index of the ductus venosus and the right and left uterine arteries. Methods: A total of 108 pregnant women in their first trimester were included in the study, with 87 assigned to the experimental group and 21 to the control group. Ultrasound examination were performed to measure the uterine artery pulsatility index, resistance index, ductus venosus pulsatility index, and blood sampling levels of biomarkers such as b-HCG; PAPP-A; s-FLT-1 and PlGF. Results: There was a significant negative relationship between PAPP-A concentration and the risk of fetal growth restriction, and a significant negative relationship between PlGF concentration and the risk of preeclampsia and fetal growth restriction in women in their first trimester of pregnancy. There was also a significant positive relationship between sFLT-1/PLGF ratio and the risk of developing preeclampsia. No significant relationships were found between the concentrations of biomarkers beta-HCG, PAPP-A, sFLT-1, PlGF, and any of the parameters PIUARt, PIUALt, Mean uterine arteries, and DVPI. Summary: In conclusion, this study did not find conclusive evidence to support the hypothesis that beta-HCG, PAPP-A, s-FLT-1, and PlGF concentrations in women in the first trimester of pregnancy have a significant effect on the Pulsatility Index of the ductus venosus and the Right and left Uterine Arteries. Further research is needed to investigate these potential associations.

Attempts to use computers to aid in the detection of breast malignancies date back more than 20 years. Despite significant interest and investment, this has historically led to minimal or no significant improvement in performance and outcomes with traditional computer aided detection. However, recent advances in artificial intelligence and machine learning are now starting to deliver on the promise of improved performance. There are at present more than 20 FDA approved AI applications for breast imaging, but adoption and utilization are widely variable and overall low. Breast imaging is unique and has aspects that create both opportunities and challenges for AI development and implementation. Breast cancer screening programs worldwide rely on screening mammography to reduce the morbidity and mortality of breast cancer and many of the most exciting research and available AI applications focus on cancer detection for mammography. There are however multiple additional potential applications for AI in breast imaging including decision support, risk assessment, breast density quantitation, workflow and triage, quality evaluation, response to neoadjuvant chemotherapy assessment, and image enhancement. In this review the current status, availability, and future directions of investigation of these applications are discussed, as well as the opportunities and barriers to more widespread utilization.

Sepsis is a major health problem and accounts for 20 per cent of deaths worldwide. It is the most expensive condition treated in United States hospitals at $27 billion per year or about $20,000 per patient. Treatment consisting largely of fluid resuscitation and antibiotics has only marginal impact. Mortality is about 27 per cent for hospitalized patients and about 42 per cent for patients in intensive care.There are two phases of sepsis – a hyper inflammatory phase and a subsequent hypo inflammatory phase.During the hyper inflammatory phase the metabolic rate increases associated with an increase in body temperature and a rapid escalation of immune system functioning including increased numbers of leucocytes and migration of those leucocytes to infected and damaged tissues and an increased supply and consumption of glucose to fuel this immune system.During the subsequent hypo inflammatory phase the metabolic rate declines and this is associated with a decrease in body temperature and a generalized decrease in the physiological activity of many organs including the immune system akin to hibernation. The activated immune system has priority for the available glucose over most other organs and physiological functions during such potentially life threatening circumstances. Thus adenosine triphosphate (ATP) production by mitochondria (the source of energy at the cellular level for the organism as a whole) also has a lower priority for the available glucose relative to the activated immune system. If glucose availability is threatened then mitochondrial production of ATP is partially or substantially suppressed in favor of glycolysis because glycolysis can rapidly produce large quantities of ATP that are necessary for immune cell function in infected, anaerobic, ischemic, or damaged tissues.However, glycolysis is only a temporary fix as it cannot produce the quantities of ATP necessary on an ongoing basis for the normal functioning of the healthy animal. Mitochondrial production of ATP must be recommenced for full recovery.It appears that the partial or substantial suppression of mitochondrial production of ATP by activation of the immune response becomes relatively fixated in some patients leading to a substantial ATP deficit. This is the fundamental issue of sepsis.This paper reviews the metabolism of glucose and insulin during sepsis and concludes that high dose insulin with mild hyper glycaemia in conjunction with the intravenous administration of thiamine, an inhibitor of the pyruvate dehydrogenase kinase enzymes, to re-establish physiological ATP production by mitochondria, administered early in the hypo metabolic (hypo inflammatory) phase of sepsis should significantly improve survival.

Objectives: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. Methods: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. Results: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogenously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HP and PPI-L were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). Conclusion: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.

Abstract: (1) Background: Minimally-invasive sacroiliac joint (SIJ) fusion is the preferred surgical intervention to treat chronically severe pain associated with SIJ degeneration and dysfunction. (2) Methods: This paper details the ten-step surgical procedure associated with the postero-inferior approach using the PsiF™DNA Sacroiliac Joint Fusion System. (3) Results: The posterior surgical approach with an inferior operative trajectory (postero-inferior) utilizes easily identifiable landmarks to provide the safest, most direct access to the articular joint space for transfixing device placement. Implanting the device through the subchondral bone, provides maximum fixation and stabilization of the joint by utilizing an optimal amount of cortical bone-implant interface. Approaching the joint from the inferior trajectory also places the implant perpendicular to the S1 endplate at a “pivot point” near the sacral axis of rotation, which addresses the most significant motion of the joint. (4) Conclusions: Further observational data from real-world clinical use are encouraged to further validate this procedure as the surgical preference for minimally-invasive SIJ fusion.

Background: The ageing process starts in the center of the face, in the periocular region and around the mouth, with a combination of volume loss and tissue descent, wrinkles deepen, and loss of skin structure and quality. Recently, several studies proved the efficacy of therapies based on the autologous adipose tissue grafting that leverages the properties of stromal vascular fraction (SVF) and adipose derived mesenchymal stem cells (ADSCs) to accelerate the regenerative processes of the skin. This study aimed to verify the ability of the guided Superficial Enhanced Fluid Fat Injection (SEFFI) in the facial area to correct volume loss and skin aging and proved the very low rate of complications of this standardized procedure . Methods: we retrospectively collected data from 2,365 procedures performed in Italian centers between 2019 and 2021. Guided SEFFI was performed alone or combined with cosmetic treatments, including the use of hyaluronic acid filler, suspension threads, synthetic calcium hydroxylapatite, botulin toxin, and microneedling. Results: SEFFI was used alone in more than 60% of the patients, and in all face areas. In about one tenth of patients SEFFI was combined with botulin toxin treatment or hyaluronic acid filling. Other procedures were used more rarely. Ecchymosis in the donor or injection sites was the most frequent event, and yet observed in only 14.2% and 38.6% of patients, respectively. Conclusions: The SEFFI technique is standardized and minimally invasive, leading to very few complications. It can be a promising antiaging medical treatment that combines effectiveness, safety, and simplicity.

Initially, renal resistive index (RRI) was investigated to improve diagnosis in kidney diseases, but failed to meet this goal. Recently many papers highlighted the prognostic significance of RRI in chronic kidney disease, in the estimation of revascularization success of renal artery stenoses or the evolution of the graft and recipients in renal transplantation. Moreover, RRI gained importance in prediction of acute kidney injury in critically ill patients. Along with RRI study in renal pathology have been revealed correlations of this index with parameters of systemic circulation. The theoretical and experimental premises of this connection were reconsidered, and studies for analyzing the link between RRI and arterial stiffness, central and peripheral pressure or left ventricular flow were conducted with this purpose. A high amount of data is currently indicating that RRI is influenced more by pulse pressure and vascular compliance than by renal vascular resistance – assuming that RRI reflects the complex interplay between systemic circulation and renal microcirculation and should be considered as a marker of systemic cardiovascular risk beyond its prognostic relevance for kidney disease. In this review we will go through clinical research that revealed the implications of RRI in renal and cardiovascular disease.

INTRODUCTION There have been several advances in the treatment of hepatitis C virus (HCV) infection which have resulted in major reductions in the morbidity and mortality from liver-associated disease. These are not widely available in the Caribbean, due in part, to lack of knowledge of the epidemiology of infections with HCV. As efforts are made to eliminate HCV from the region, these and other existing barriers such as lack of an established database on HCV must be addressed. This review seeks to identify gaps in the knowledge of HCV in the Caribbean with respect to seroprevalence, genotype distribution and general epidemiologic characteristics. MATERIALS AND METHODS The literature for the period January 1, 2005, to October 2022, was reviewed to gather country specific data on HCV across the Caribbean. References were identified through indexed journals accessed through established databases. The usage pattern of HCV drugs was determined from data obtained from Pharmacists and Infectious Diseases Specialists across the region. RESULTS The prevalence of HCV in the Caribbean was 1.5%; the region should therefore be considered an area of moderate prevalence. Notably, data from specific countries were limited. The prevalence of HCV among intravenous drug users (21.9-58.8%); persons living with HIV/AIDS (0.8 to 58.5%); prisoners (32.8-64%) and men who have sex with men (MSM) (0.8-6.9%) was generally higher than in the general population (0.8-2.3%). Genotype 1 (83% was most prevalent followed by genotypes 2 (7.2%) and 3(2.1%), respectively. Drugs currently being used for treatment of HCV infections across the Caribbean include Epclusa (Sofosbuvir/velpatasvir), and Harvoni (Ledipasvir/sofosbuvir). Some of these drugs, are only available in the private sector and are sourced externally whenever needed. CONCLUSION There is a paucity of current data on the seroprevalence of HCV in the Caribbean and well-designed prospective studies are indicated to drive the implementation of treatment and control programs for HCV in the region. Barriers which need to be first overcome include unavailability and high cost of drugs used to treat HCV infections, injecting drug use and limited access to medical care and laboratory testing.

Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analysed by flow cytometry, and IFNγ, IL-6 and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month and 18 years. The majority, 52.8%, had mild disease, and 30.6 % were diagnosed with MIS-C. The main symptoms reported were fever, cough and diarrhoea. A correlation was found between IL-10 and IL-6 concentrations and age group; lymphocyte subpopulations and nutritional status and steroid use; IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.

Background: Air-pouch balloon-assisted probes have proven to be both simple and reliable tools for intracranial pressure (ICP) monitoring. However, we experienced reproducible falsely high ICP measurement when the ICP probe was inserted in the intracerebral hematoma cavity. Thus, the aim of the experimental and translational study was to analyze the influence of ICP probe placement with regard to measured ICP values. Methods: Two Spiegelberg 3PN-sensors were simultaneously inserted into a closed drain system and were connected to two separate ICP monitors thereby allowing for simultaneous ICP measurements. This closed system was also engineered to allow for pressure to be gradually increased in a controlled fashion. Once the pressure was verified using two identical ICP probes, one of the probes was coated with blood in an effort to replicate placement within an intraparenchymal hematoma. Pressures recorded using the coated probe and control probe were then recorded and compared across a range of 0-60 mmHg. In an effort to further the translational relevance of our results two ICP probes were inserted in a patient that presented with a large basal ganglia hemorrhage that met criteria for ICP monitoring. One probe was inserted into the hematoma and the other into brain parenchyma; ICP values were recorded from both probes and the results compared. Results: The experimental set-up demonstrated a reliable correlation between both control ICP probes. Interestingly, the ICP probe covered with clot displayed a significantly higher average ICP value when compared to the control probe between 0mmHg and 50mmHg (p<0.001); at 60mmHg there was no significant difference noted. Critically, this trend in discordance was even more pronounced in the clinical setting with the ICP probe placed within the hematoma cavity having reported significantly higher ICP values as compared to the probe within brain parenchyma. Conclusion: Our experimental study and clinical pilot highlight a potential pitfall in ICP measurement that may result secondary to probe placement within hematoma. Such aberrant results may lead to inappropriate interventions in an effort to falsely addresses falsely elevated ICPs.

Background: This paper examined the gap between obesity and its diagnosis for cohorts of patients with overweight, obesity, and morbid obesity in the Veterans Administration (VA) population. Using the risk adjustment models, it also identified factors associated with the underdiagnosis of obesity. Methods: Analysis was performed on a VA data set. We identified diagnosed patients and undiag-nosed patients (identified through BMI but not diagnosed by ICD-10 codes). The groups’ de-mographics were compared using nonparametric chi-square tests. We used logistic regression analysis to predict the likelihood of the omission of diagnosis. Results: Of the 2,900,067 veterans with excess weight, 46% were overweight, 46% had obesity, and 8% of them had morbid obesity. The overweight patients were the most underdiagnosed (96%), followed by the obese (75%) and morbidly obese cohorts (69%). Older, male, and White patients were more likely to be undiagnosed as overweight and obese; younger males were more likely to be undiagnosed as morbidly obese. (p<.05) Comorbidities significantly contributed to diagnosis. Conclusion: Underdiagnosis of obesity continues to be a significant problem despite its prevalence. Diagnosing obesity accurately is necessary to provide effective management and treatment.

Quantification of bone loss for follow-up comparisons has not been routinely performed in patients with parietal thinning so far. This study compares different methodological approaches including both 2- and 3-dimensional methods in computerized tomographies of a single patient. The 2-dimensional method provides accurate measurements of bone thickness, while the 3-dimensional method allows for a more comprehensive view of the bone's structure, including parameters like shape, size, and thickness. The techniques provided valuable data for the treating physician and suggest a possible effect of corticosteroids in this individual patient. The study concludes that 3-dimensional reconstruction of computerized tomographies with subsequent 2-dimensional analyses appears justified for routine radiological practice to increase clinical awareness of the size of the parietal bone defects and allow for quantification of bone loss during long-term follow-ups. Further validation of the proposed analytical approaches is warranted in larger studies to investigate patterns of bone thinning across the skull and changes in bone volumes over time, with specialized software to be approved for such analyses.

Type A acute aortic dissection are associated with significant morbidity and mortality with prompt referral imaging and management to tertiary referral centres needed urgently. Surgery is usually needed emergently but the choice of surgery often varies depending on the patient and presentation. Staff and center expertise also play a major role in determining the surgical strategy employed The aim of this study is to compare early and medium term outcomes of patient across 3 European referral centers. We also identified risk factors for poorer outcomes irrespective of surgical strategy employed. A retrospective study was conducted across 3 sites between January 2008 and December 2021. 601 patients were included within the study of which 30% were female and the median age was 64.4 years. The most common operation was ascending aorta replacement (n= 246, 40.9%). The aortic repair was extended proximally (i.e., root n= 105; 17,5%) and distally (i.e., arch n = 250; 41,6%). A more extensive approach, extending from the root to the arch, was employed in 24 patients (4.0%). Operative mortality occurred in 146 patients (24.3%), and the most common morbidity was stroke (75, 12.6%). An increased length of ICU admission was noted in the extensive surgery group who were younger and more frequently male No significant differences were noted in surgical mortality from patients managed with extensive surgery vs those managed conservatively. However, age, arterial lactate levels, “intubated/sedated” status on arrival, and “emergency or salvage” status at presentation were independent predictors of mortality both within the index hospitalization and also during follow-up. Overall survival was similar between the groups.

There is great interest in thoracic kyphosis as it is thought to be a contributor to neck pain, neck disability, and sensorimotor control measures; though this has not been completely inves-tigated in treatment or case control studies. This case control design investigated participants with non-specific chronic neck pain. Eighty participants with a defined hyper-kyphosis (> 55°) were compared to 80 matched participants with normal thoracic kyphosis (< 55°). Participants were matched for age and neck pain duration. Hyper-kyphosis was further categorized into two distinct types: postural kyphosis (PK) and Scheuermann’s kyphosis (SK). Posture measures included formetric thoracic kyphosis and the craniovertebral angle (CVA) to assess forward head posture. Sensorimotor control was assessed by the following measures: smooth pursuit neck torsion test (SPNT), overall stability index (OSI) and left and right rotation repositioning accuracy. A measure of autonomic nervous system function included the amplitude and latency of skin sympathetic response (SSR). Differences in variable measures were examined using the Student’s t-test to compare the means of continuous variables between the two groups. Pearson correlation was used to evaluate the relationship between participant’s thoracic kyphosis magnitude (in each group separately and as an entire population) and their CVA, SPNT, OSI, head repositioning ac-curacy, and SSR latency and amplitude. Hyper-kyphosis participants had a significantly greater neck disability index compared to the normal kyphosis group (p < 0.001) with the SK group having greatest disability (p < 0.001). Statistically significant differences between the two kyphosis groups and the normal kyphosis group for all the sensorimotor measured variables were identified with the SK group having the most decreased efficiency of the measures in the hyper-kyphosis group, including: SPNT, OSI and left and right rotation repositioning accuracy. Also, there was a signif-icant difference in neurophysiological findings for SSR amplitude (entire sample of kyphosis vs. normal kyphosis, p < 0.001), but there was no significant difference for SSR latency (p = .07). The CVA was significantly greater in the hyper-kyphosis group (p < 0.001). The magnitude of the thoracic kyphosis correlated with worsening CVA (with the SK group having the smallest CVA; p < 0.001) and the magnitude of the decreased efficiency of the sensorimotor control measures and the amplitude and latency of the SSR. The PK group, overall, showed the greatest correlations between thoracic kyphosis and measured variables. Participants with hyper-thoracic kyphosis exhibited abnormal sensorimotor control and autonomic nervous system dysfunction compared to those with normal thoracic kyphosis.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally used for diabetes mellitus, are gaining more popularity for other indications owing to their positive cardiovascular and renal effects. Initially, SGLT2 inhibitors were shown to reduce heart failure (HF) hospitalization and improve cardiovascular outcomes in patients with type 2 diabetes. Later, SGLT2 inhibitors were evaluated in patients with HF with reduced ejection fraction (HFREF) and had beneficial effects independent of the presence of diabetes. Recently, reduction in cardiovascular outcomes were also observed in patients with HF with preserved ejection fraction (HFPEF). SGLT2 inhibitors also reduced renal outcomes in patients with chronic kidney disease. Overall, these drugs have an excellent safety profile with a negligible risk of genitourinary tract infections and ketoacidosis. In this review, we discuss the current data regarding SGLT2 inhibitors in special populations including acute myocardial infarction, acute HF, right ventricular (RV) failure, patients with left ventricular assist device (LVAD), and patients with type1 diabetes. We also discuss the potential mechanisms behind the cardiovascular benefits of these drugs.

We explored the outcomes of germline BRCA1/2 pathogenic/likely pathogenic variants (PVs/LPVs) in the endocrine-sensitive disease treated with first line standard of care cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Three studies retrospectively showed a reduction in overall survival (OS) and progression free survival (PFS) in gBRCA1/2m patients compared to both germinal BRCA1/2 wild type (gBRCA1/2wt) and to the untested population. Regarding the efficacy of PI3K inhibitors, there are no subgroup or biomarker analyses in which germinal BRCA status was explored. However, the biological interactions between the PIK3CA/AKT/mTOR pathway and BRCA1/2 at a molecular level could help us to understand the activity of these drugs when used to treat BC in BRCA1/2 PVs/LPVs carriers. The efficacy of trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC) targeting HER2 for HER2-low and HER2-positive (HER2+) BC, has been increasingly described. Unfortunately, data on T-DXd in HER2+ or HER2-low metastatic BC harboring germinal BRCA1/2 PVs/LPVs is lacking. Including germinal BRCA1/2 status in the subgroup analysis of the registration trials of this ADC would be of great interest, especially in the phase III trial DESTINY-breast04. This trial enrolled patients with HER2-negative (HER2-) and both HR+ and HR- metastatic disease, which can now be categorized as HER2-low. The HER2-low subgroup includes tumors that were previously classified as triple negative, so it is highly likely that some women were germline BRCA1/2 PVs/LPVs carriers and this data was not reported. Germline BRCA1/2 status will be available for a higher number of individuals with BC in the near future and data on the prognostic and predictive role of these PVs/LPVs is needed in order to choose the best treatment options.

Probabilistic and parsimony-based arguments regarding available genetics data are used to propose that Hardy and Higgin’s amyloid cascade hypothesis is valid but is commonly interpreted too narrowly to support, incorrectly, the primacy of the amyloid beta peptide (Aβ) in driving Alzheimer’s disease pathogenesis. Instead, increased activity of the βCTF (C99) fragment of APP is likely the critical pathogenic determinant altered by mutations in the APP gene. This model is consistent with the regulation of APP mRNA translation via its 5’ iron responsive element (IRE). Similar arguments support that the pathological effects of familial Alzheimer’s disease mutations in the genes PSEN1 and PSEN2 are not exerted directly via changes in APP cleavage to produce different ratios of Aβ length. Rather, these mutations likely affect the stability of presenilin holoprotein and/or γ-secretase multimers with consequences for γ-secretase activity and other important cellular functions. All fAD mutations in APP, PSEN1, and PSEN2 likely find unity of pathological mechanism in their actions on endolysosomal acidification and mitochondrial function, with detrimental effects on iron homeostasis and promotion of “pseudo-hypoxia” being of central importance. Aβ production is enhanced and distorted by oxidative stress and accumulates due to decreased lysosomal function. It may act as a disease-associated molecular pattern (DAMP) enhancing oxidative stress-driven neuroinflammation during the cognitive phase of the disease. We also discuss fascinating, but largely ignored, data on presenilin biology that may be important in understanding presenilins’ central role in familial Alzheimer’s disease.

The appropriate carbapenem use is a critical concern for patient safety, public health, and a national priority. We investigated the nationwide status of carbapenem prescription in patients within their last 14 days of life to guide judicious-use protocols from the previous study comprising of 1,350 decedents. Carbapenem use was universally restricted by computerised authorisation at all centres during the study period. Carbapenem prescribing patterns and their optimality were evaluated. A total of 1201 patients received antimicrobial agents within the last 2 weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was 7 days. Of the 533 patients receiving carbapenems, 510 (95.7%) patients had microbiological samples drawn and 196 (36.8%) yielded carbapenem-resistant pathogens. A total of 200 (37.5%) were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) without ID consults, 194 (58.2%) were assessed as “not optimal”: 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients within their last days of life, a majority of whom do not require it.

In recent years, the FDA has approved numerous antitumor drugs that are mutation-based for clinical use. These drugs have improved the precision of treatment and reduced adverse effects and side effects. Personalized therapy is a prominent and hot topic of current medicine and also represents the future direction of development. With the continuous advancements in gene sequencing and high-throughput screening, research and development strategies for personalized clinical drugs have developed rapidly. This review elaborated the recent personalized treatment strategies, which include artificial intelligence, multi-omics analysis, chemical proteomics, and computation aided drug design. These technologies rely on the molecular classification of diseases, the global signaling network within organisms, and new models for all targets, which significantly support the development of personalized medicine. Meanwhile, we summarized chemical drugs such as lorlatinib, osimertinib, and other natural products that deliver personalized therapeutic effects based on genetic mutations. This review also highlights potential challenges in interpreting genetic mutations and combining drugs, while providing new ideas for the development of personalized medicine and pharmacogenomics in cancer study.

In implantology, among the key choices, to obtain predictable results, it is essential to establish, on the basis of radiographic examinations, the bone site where to insert the implants; these selected locations must be identified first on the mucosa and then on the cortical bone. Surgical guides represent a valid aid especially in complex cases with more than 3 or 4 implants, whereas in single implant cases they are rarely used. This study evaluates the clinical precision with which the implant sites, on the patient's mucosa, are identified in surgical procedures planned without any templates. The verification of this precision is carried out through thermo-printed templates with radiopaque references which could however help the clinician to identify these sites in a simple, rapid and economical way.

Drug induced liver injury (DILI) is the most common cause of acute liver failure and 5-10% of patients hospitalized for jaundice are diagnosed with DILI. For a diagnosis of DILI to be made, there should be exclusion of other etiologies of liver injury and the use of a precipitator drug, latency of symptoms, and resolution of liver injury once the offending drug is identified and discontinued. In our case report, we present a patient with idiosyncratic hepatocellular pattern DILI after two doses of ocrelizumab for treatment of multiple sclerosis. Ocrelizumab was given 16 and 27 days prior to the onset of icterus, jaundice, and fatigue, in a patient without the evidence of prior exposure to hepatitis B virus. At presentation labs revealed severe acute hepatocellular liver injury with R factor of 30.42, marked hyperbilirubinemia, and transient hypoalbuminemia. No evidence of latent or active hepatitis B infection was detected. Drug dechallenge led to return of liver chemistries to near-normal levels 31 days after the onset of her symptoms. This case indicates DILI diagnosis associated with the use of ocrelizumab, and warrants careful monitoring of liver functions in patients even in the absence of hepatitis B.

Keywords: Hypertensive emergency; diagnosis; lactate dehydrogenase; high sensitivity cardiac troponin T; brain natriuretic peptide; area under the curve.

Antisense oligonucleotides (ASONs) have proven potential for the treatment of various diseases. However, their limited bioavailability restricts their clinical application. New structures with improved enzyme resistance stability and efficient drug delivery are needed. In this work, we propose a novel category of ASONs bearing anisamide conjugation at phosphorothioate sites for oncotherapy. ASONs can be conjugated with the ligand anisamide very efficiently and flexibly in solution. The conjugation sites and ligand amount both influence anti-enzymatic stability and cellular uptake, resulting in changes in antitumor activity that are detectable by cytotoxicity assay. T6 (with double end AA-conjugation) was identified as the optimal conjugate, and its antitumor activity and the underlying mechanism were examined further in vitro and in vivo. This paper presents a new strategy for the design of nucleic acid–based therapeutics with improved drug delivery and biophysical and biological efficacy.

Hashimoto’s thyroiditis (HT) is a gender autoimmune disease that is manifested by chronic inflammation of thyroid. Clinical trial studies (CTSs) use molecular biotechnologies (MB) to approach HT appearance. Aims of this study was to analyze the applications of MB in CTSs carried out in HT populations (HT-CTSs). Further, to evaluate the role of MB in the context of hygiene hypothesis (HH). From 75 HT-CTSs found at https://beta.clinicaltrials.gov/ web place, forty-five were considered for this investigation. Finally, six HT-CTSs were reported as molecular HT-CTSs (mHT-CTSs) because of these were planning to utilize MB. Two of mHT-CTSs were settled on French population to isolate DNA viral sequences. Blood, urine, and thyroid tissues biospecimens were analyzed to pick out parvo and polyoma viruses. Two mHT-CTSs carried out in China, were aimed to identify oral and fecal microbiotas by measuring PCR sequencing of 16S rRNA gene. Two mHT-CTSs were programmed in USA and Greece, respectively, for interception of DNA polymorphisms to associate with genetic susceptibility to HT. In conclusion, MB are mainly employed in HT-CTSs for infective pathogenesis and genetic fingerprinting of HT. Besides, MB don't prove the evidence of HH; however, they are useful for direct evidence of the presence of viruses.

The COVID-19 pandemic and associated lockdown measures have been associated with substantial disruptions to health care services, including screening for human immunodeficiency virus (HIV) and management of people living with HIV (PLWH). Methods: Data from 3265 patients were examined in a retrospective cohort study. We compared outpatient follow-up for PLWH, the number of new patients, treatment adherence, hospitalizations, and deaths during the “pandemic period” (March 2020 to February 2021) to the “pre-pandemic period” (the equivalent timeframe in 2019) and the “post-pandemic period” (March to September 2021). Results: During the pandemic period, the number of new patients seen at the HIV clinic (116), as well as the requested viral load tests (2414), decreased significantly compared to the pre-pandemic (204 and 2831, respectively) and post-pandemic periods (146 and 2640, respectively)(p<0.01 for all the comparisons). However, across the three study periods, the number of drug refills (1385, 1330, 1411, respectively), the number of patients with undetectable viral loads (85%, 90%, 93%, respectively), and the number of hospital admissions among PLWH remained constant. Conclusions: Despite the COVID-19 pandemic impact, our findings show stability in the retention of clinical care, adherence to treatment, and viral suppression of PLWH, with no significant impact on hospitalization rates and all-cause mortality.

Biomarkers have become an important tool in the diagnosis and management of cardio renal syndromes (CRS), a complex condition characterized by dysfunction in both the cardiovascular and renal systems. These biomarkers can help identify the presence and severity of CRS, predict its progression and outcomes, and facilitate personalized treatment options. Several biomarkers, including natriuretic peptides, troponins, and inflammatory markers, have been extensively studied in CRS and have shown promising results in improving diagnosis and prognosis. In addition, emerging biomarkers such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin offer potential for early detection and intervention of CRS. However, the use of biomarkers in CRS is still in its infancy, and further research is needed to establish their utility in routine clinical practice. This review highlights the role of biomarkers in the diagnosis, prognosis, and management of CRS and discusses their potential as valuable clinical tools for personalized medicine in the future.