The multifactorial nature of some diseases, and in particular neurodegenerative diseases such as Alzheimer’s disease, frequently requires the use of several drugs. These drug cocktails are not without drawbacks in terms of increased adverse effects, drug-drug interactions or adherence to treatment. The concept of pleiotropic drugs, which combine, within a single molecule, several activities directed against distinct therapeutic targets, makes it possible to overcome some of these problems. In addition, these pleiotropic drugs, generally, lead to the expression of a synergy of effects, sometimes greater than that observed with a combination of drugs. This article will review, through recent examples, the different kinds of pleiotropic drugs being studied or already present on the market of medicines.

Progressive loss of retinal ganglionic cells (RGC) causes blindness in glaucoma. Elevated intraocular pressure (IOP) is the most important, treatable risk factor. Currently, the management of glaucoma is centred at reducing the IOP, and drugs in the form of topical drops are the first line of management. Drugs reduce IOP either by suppressing aqueous humour secretion or improving the aqueous humour outflow. Newer drugs added during the past three decades to the armamentarium of glaucoma treatment have targeted the aqueous outflow. With an evolving understanding of the pathogenesis of glaucoma, the role of 24-hour IOP control and other IOP-independent risk factors affecting ocular blood flow and RGC toxicity is also recognised. The role of available drugs in controlling IOP over 24-hours is being evaluated. Improvement of ocular blood flow and neuroprotection are seen as potential drug targets in preventing the loss of RGC. In this article, we review the pharmacotherapy of glaucoma based on current therapeutic principles.

Endometrial cancer (EC) is the most frequent gynaecological malignancy. The ESGO/ESTRO/ESP 2020 guidelines identify prognostic groups based on morpho-molecular characteristics. This study aims to evaluate the clinical applicability of NGS analysis to define an appropriate risk class and application for a better diagnostic and prognostic stratification of ECs. Cases of serous carcinoma (OHEC), high (HGEC) and low (LGEC) grade endometrioid carcinoma diagnosed with the morphological and immunohistochemical (IHC) protocols were considered. After a standardized pre-analytical phase, the tumor DNA was semi-automatically extracted and analyzed by NGS with a panel of 14 genes. A total of 63 cases were considered. NGS analysis was successful in 60 cases; all of these were classified according to the new diagnostic algorithm. The molecular risk classification showed a good correlation with the morphological (k=0.8). The study showed that the protocols of the pre-analytical and analytical phases used are robust and can lead to molecular results that fall within the standards required for use in clinical practice for a more precise diagnostic-therapeutic management of patients. The implementation of the classification is particularly relevant for better prognostic stratification of HGECs. In addition, the identification of a suspicious VUS in POLE questions the classification of truncating variants.

Spinal cord injury is a traumatic injury that causes a catastrophic state in patients due to neuronal deficits, loss of motor and sensory function, and this is due to secondary deleterious events subsequent to mechanical damage that expands the death of neural cells beyond the initial trauma. One of the most important events is inflammation, which activates molecules like pro-inflammatory cytokines (IL-1beta, IFN-gamma, TNF-alpha) that provoke a toxic environment, inhibiting axonal growth and exacerbating CNS damage. As there is no effective treatment, one of the strategies developed is neuroprotection to preserve healthy neural tissue and reduce neuroinflammation. Some of the neuroprotective treatments that have been practiced are the use of cell therapy, the administration of peptides and molecules or supplements that have been shown to favor an anti-inflammatory environment, and help to preserve the cells and tissues surrounding the injured area, favoring axonal growth and improving locomotor function. In this review we will explain some of these strategies used in different animal models of spinal cord injury, their activity as modulators of the immune system and the benefits they have shown.

Hepatic macrophages act as the liver’s first line of defense against injury. Their differentiation into pro-inflammatory or anti-inflammatory subpopulations is a critical event that maintains a delicate balance between liver injury and repair. In our investigation, we explored the influence of the small heterodimer partner (SHP), a nuclear receptor primarily associated with metabolism, on macrophage differentiation during the innate immune response. During macrophage differentiation, we observed significant alterations in Shp mRNA expression. Deletion of SHP promoted M1 differentiation while interfering with M2 polarization. Conversely, overexpression of SHP resulted in increased expression of peroxisome proliferator activated receptor gamma (Pparg), a master regulator of anti-inflammatory macrophage differentiation, thereby inhibiting M1 differentiation. Upon lipopolysaccharide (LPS) injection, there was a notable increase in the pro-inflammatory M1-like macrophages, accompanied by exacerbated infiltration of monocyte-derived macrophages (MDMs) into the livers of Shp myeloid cell specific knockout (Shp-MKO). Concurrently, we observed significant induction of tumor necrosis factor alpha (Tnfa) and chemokine (C-C motif) ligand 2 (Ccl2) expression in LPS-treated Shp-MKO livers. Additionally, the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kB) pathways were activated in LPS-treated Shp-MKO livers. Consistently, both pathways were hindered in SHP overexpression macrophages. Finally, we demonstrated that SHP interacts with p65, thereby influencing macrophage immune repones. In summary, our study uncovered a previously unrecognized role of SHP in promoting anti-inflammatory macrophage differentiation during the innate immune response. This was achieved by SHP acting as a regulator for the Pparg, MAPK and NF-kB pathways.

Despite the efforts to deliver the best evidence-based care, in-hospital death is an inevitable event among some patients hospitalized in cardiology departments. We retrospectively evaluated mortality events from inpatient admissions to Cardiology Department between 2010-2019. Data were collected from morbidity & mortality meeting presentations which evaluated comorbidities, medical history, treatments, and causes of death for the overall cohort and according to age group and sex. There were 1,182 registered deaths. The most common causes of death among patients were acute myocardial infarction (AMI) (53.0%), heart failure (HF, 11.7%), cardiac arrest (CA, 6.6%), HF with complication/defined cardiomyopathy (6.3%) and sepsis (4.4%). We observed a decline in deaths from AMI from 61.9% in 2010 to 46.7% in 2019 while there was an apparent increase in deaths from HF (11.1% in 2010 to 25.9% in 2019). Compared to patients ≥65 years, younger patients were more likely to have died from CA (15.7% vs. 4.3%, p<0.001) and other cardiac reasons (3.0% vs. 0.4%, p<0.001). The majority of deaths were due to AMI, HF, and CA. We observed a significant decline in the proportion of deaths due to AMI in recent years with an increase in deaths due to HF.

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no GE product has been approved, as opposed to 22 GT products that cost up to millions of dollars per dose. The FDA has recently added a guideline specific to gene editing that should be understood to enable faster development of GE products; at the same time, the FDA also needs to bring more clarification and make several amendments to this guideline to make it more rational.

Abstract: Accurately predicting a fetus's gestational age (GA) is of utmost importance in prenatal care. This study aimed to develop an artificial intelligence (AI) model that can automatically predict GA using biometric measurements derived from fetal brain mag-netic resonance imaging (MRI). Additionally, we aimed to assess the significance of con-sidering different references when interpreting GA predictions. To achieve this, we obtained measurements such as Biparietal Diameter (BPD), Fron-to-occipital Diameter (FOD), and Head Circumference (HC) from a dataset comprising 52 normal fetal MRI cases with T2 Haste sequences from Rush University. Both manual and AI-based methods were utilized to acquire these measurements. We also employed three reference papers (Garel, Freq, and Bio) for comparison purposes. The results demonstrated a strong correlation between manual and AI measure-ments, indicating consistency between the two methods. The AI-based measurement of HC exhibited a higher correlation with actual values compared to BPD, FOD, and correct-ed BPD (BPDC). When comparing these measurements with GA in the Picture Archiving and Communication System (PACS), the differences varied depending on the reference used. Specifically, the differences ranged from 0.47 to 2.17 weeks for BPD, 0.46 to 2.26 weeks for FOD, and 0.75 to 1.74 weeks for HC. Furthermore, the Pearson correlation coeffi-cient analysis revealed that all correlation coefficients between PACS records and GA pre-dictions using different references were greater than 0.97. In conclusion, the AI model based on fetal brain MRI accurately predicts GA by uti-lizing BPD, FOD, and HC measurements. The AI approach, which involves combining line segments to calculate fetal head circumference, offers improved accuracy and con-venience compared to manual estimation. This study underscores the potential of AI models in accurately estimating gestational age and highlights their utility in prenatal care. By integrating AI as a valuable tool in prenatal care, we can enhance the accuracy, ef-ficiency, and decision-making involved in assessing fetal development and monitoring pregnancies using MRI measurements.

Small molecule kinase inhibitors (SMKIs) are one of the heightened concerns in the field of drug research and development. There are seventy-nine (up to July 2023) small molecule kinase inhibitors have been approved by FDA and hundreds kinase inhibitors candidates in clinical trials, which shed light on the treatment of some major diseases. As an important strategy of drug design, computer-aided drug design (CADD) plays an indispensable role in the discovery of SMKIs. CADD methods, such as docking, molecular dynamic, pharmacophore have been applied to the design and optimization of small molecule kinase inhibitors. In the review, we provide an overview of recent advances in CADD and SMKIs; and the application of CADD for discovery of SMKIs.

Objective: To explore the application effect of predictive psychological nursing in the nursing of outpatients with indwelling needle intravenous infusion .Methods: Select 80 patients who received intravenous indwelling needle infusion therapy in the outpatient department of our hospital from January 2022 to December 2022 as the research objects , and divided them into observation group and experimental group according to the different nursing plans received by the patients . 40 cases in each group. The observation group received routine nursing intervention, and the experimental group received predictive psychological nursing intervention. The puncture situation, psychological state level, self-care ability, adverse reactions and nursing satisfaction were compared between the two groups of patients .Results: The puncture success rate of the observation group was 72.5% (29/40), and that of the experimental group was 95.0% (38/40). The puncture success rate of the experimental group was significantly higher than that of the observation group (P<0.05) ; The SAS scores and SDS scores of the treatment group after nursing were significantly lower than those of the observation group (all, P<0.05) ; the self-care skills, self-concept, self-responsibility, health knowledge and ESCA total scores of the experimental group after nursing were significantly higher than those of the observation group. group (all, P<0.05); the incidence of adverse reactions in the observation group was 25.0% (10/40), the incidence of adverse reactions in the experimental group was 7.5% (3/40), and the incidence of adverse reactions in the experimental group was significantly lower than that in the observation group group (P<0.05); the nursing satisfaction of the observation group was 80.0% (32/40), and the nursing satisfaction of the experimental group was 100.0% (40/40), and the nursing satisfaction of the experimental group was significantly higher than that of the observation group (P<0.05 ).Conclusion: The application effect of the predictive psychological nursing intervention model in the outpatient department for intravenous indwelling needle infusion therapy is significant. The implementation of this model can effectively improve the success rate of puncture, improve the patient's psychological state, improve the self-care ability of patients, and reduce the adverse effects of patients. Risk of reaction, so as to further obtain the satisfaction and recognition of patients and their families.

Oxidative stress (OS) is reported in several chronic diseases. Extra-cellular superoxide dismutase (ec-SOD) catalyzes the dismutation of superoxide anion with a protective role on endothelial cells. In chronic kidney diseases (CKD), OS and thyroid dysfunction (low T3 syndrome) are fre-quently present, but their relationship has not been investigated. This cohort study evaluated ec-SOD activity in CKD patients during haemodialysis, divided into: “acute hemodialytic pa-tients” (AH, 1-3 months of treatment) and “chronic hemodialytic patients” (CH, treated for a longer period). We also evaluated plasmatic total antioxidant capacity (TAC) and the relation-ships with thyroid hormones. Two basal samples (“basal 1”, 3 days after the last dialysis and “basal 2”, 2 days after the last dialysis) were collected. On the same day of basal 2, a sample was collected 5 and 10 min after the standard heparin dose and at the end of the procedure. The ec-SOD values were significantly higher in CH vs AH in all determinations. Moreover, they pre-sented lower TAC values. Dividing CH patients into two subgroups according to fT3 levels (nor-mal or low) we found significantly lower ec-SOD values in the group with low fT3 at basal, 5 and 10 min samples. Finally, a significant correlation was observed between fT3 and ec-SOD in the basal 1 samples. These data, confirming OS and low T3 syndrome in CKD, suggest that low fT3 concentrations can influence ec-SOD activity and therefore contribute to possible endothelial oxi-dative damage in such a situation.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

University students, particularly those in the healthcare disciplines, constitute a category of particular interest in regard to COVID-19 vaccines and the attitudes to vaccination, as their future professional role will enable them to inform and educate citizens regarding vaccination. The objectives of the study were to investigate the vaccination coverage with a COVID-19 vaccine among students from different degree programs at the Medical universities in Bulgaria behaviors and attitudes toward vaccination with a COVID-19 vaccine. A prospective cross-sectional study in the period September 2021- March 2022 was conducted. Information on demographics, university program, year of study, general attitudes and behavior towards vaccines and attitudes and personal experience with COVID-19 and COVID-19 vaccines were collected. The chi-square test was used to test for associations and binominal logistic regression was used to identify possible predictors for vaccination. A total of 3050 students with a median age of 22 years, predominantly female took part in the study. Three-thirds of the students (73.5%) have been vaccinated against COVID-19. The main reasons for vaccine hesitancy in both group of students were the fear of side effects and the doubts about the safety of the vaccines although non-vaccinated students significantly more frequently express those fears. Respondents who considered to have: a) limited access to sufficient information to inform COVID-19 vaccine uptake; b) lack of public awareness and education campaigns about effectiveness and safety of COVID-19 vaccines; c) insufficient information about COVID-19 vaccines during the University education; and d) had a positive COVID-19 diagnosis were less likely to be vaccinated. Students who have not completed the mandatory immunization cycle according to country schedule were also less likely to have completed COVID-19 vaccination. The students showed an overall positive attitude towards the COVID-19 vaccines. Promoting informational campaigns that emphasize the vaccine's safety will be more effective to further increase the vaccination coverage with COVID-19 vaccines.

Various vestibuloplasty techniques have been reported to increase the attached mucosa (AM) and vestibular depth around dental implants. However, these surgical methods have disadvantages, such as limitations in manipulation, necessity of suturing, postoperative discomfort, swelling, and pain. This study aimed to evaluate the efficacy of laser-assisted periosteal fenestration (LA-PF) in treating a patient with a shallow vestibule and insufficient AM around dental implants. The LA-PF technique was performed using an Er:YAG laser. First, a partial-thickness apically positioned flap (APF) was performed. Horizontal periosteal fenestration was performed using an Er:YAG laser to expose the bones. Periosteal suturing was not required. After 12 months, sufficient AM and deepened vestibule were obtained and maintained. Thus, the LA-PF technique may be a simple and predictable treatment modality for vestibuloplasty around dental implants.

The prediction of corticosteroid responses in coronavirus disease 2019 (COVID-19) patients is crucial in clinical practice, and exploring the role of artificial intelligence (AI)-assisted analysis of chest radiographs (CXR) is warranted. This retrospective case-control study involving hospitalized COVID-19 patients treated with corticosteroids was conducted from September 4th, 2021, to August 30th, 2022. The primary endpoint of the study was corticosteroid responsiveness, defined as the advancement of two or more of the eight-categories-ordinal scale. Serial abnormality scores for consolidation and pleural effusion on CXR were obtained using a commercial AI-based software based on days from onset of symptoms. Amongst the 258 participants included in the analysis, 147 (57%) were male. Multivariable logistic regression analysis revealed that high pleural effusion score at 6–9 days from onset of symptoms (adjusted odds ratio of [aOR]: 1.022, 95% confidence interval [CI]: 1.003-1.042, p=0.020) and consolidation scores up to 9 days from onset of symptoms (0-2 days: aOR: 1.025, 95% CI: 1.006-1.045, p=0.010; 3-5 days: aOR: 1.03 95% CI: 1.011-1.051, p=0.002; 6-9 days: aOR; 1.052, 95% CI: 1.015-1.089, p=0.005) were associated with an unfavorable corticosteroid response. AI-generated scores could help intervene in the use of corticosteroids in COVID-19 patients who would not benefit from them

Background Enfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who previously received platinum-based chemotherapy and immune checkpoint inhibitors. The EV-301 phase III trial demonstrated a significantly improved overall survival and response rates compared with standard chemotherapy. However, more data, especially from larger real-world studies, are needed to assess its effectiveness in Japanese patients. Methods A total of 6,007 urothelial cancer patients treated with pembrolizumab as second-line treatment were analyzed. Among them, 619 patients received enfortumab vedotin after pembrolizumab, while 394 received docetaxel or paclitaxel after pembrolizumab. Results The enfortumab vedotin group showed a longer overall survival than the paclitaxel/docetaxel group (p=0.013, hazard ratio: 0.71). In the multivariate analysis, enfortumab vedotin induction was an independent risk factor for the overall survival (p=0.013, hazard ratio: 0.70). There were no significant differences in the cancer-specific survival. Conclusions Enfortumab vedotin prolonged the overall survival in Japanese patients with advanced or metastatic urothelial carcinoma compared with paclitaxel or docetaxel after pembrolizumab treatment.

Background: Ceramides are a new kind of lipid biomarkers and have already been demonstrated to be valuable risk predictors in coronary patients. Patients with peripheral artery disease (PAD) are a population with worse prognosis and higher mortality risk compared to coronary artery disease (CAD) patients. However, the value of ceramides for risk prediction in PAD patients is still vague and has been addressed in the present study. Methods: This observational study included 379 PAD patients. The primary endpoint was all-cause mortality at 10 years of follow-up. A set of ceramides was measured by LC-MS/MS and combined according to the coronary event risk test (CERT) score which categorizes patients into one of four risk groups (low risk, moderate risk, high risk, very high risk). Results: Kaplan Meier survival curves revealed that the overall survival of patients has decreased with the increasing risk predicted by the four CERT categories, advancing from low risk to very high risk. Cox regression analysis demonstrated that every 1-step increase in category resulted in a 35% rise in overall mortality risk (HR=1.35 [1.16-1.58]). Multivariable adjustment, including amongst others age, T2DM, and statin treatment before baseline, did not abrogate this significant association (HR=1.22 [1.04-1.43]). Moreover, we found that the beneficial effect of statin is significantly stronger in patients with a higher risk according to CERT. Conclusion: We conclude that the ceramide-based risk score CERT is a strong predictor of the 10-year mortality risk in patients with PAD.

The osteoarthritis (OA), the main cause of disability, is a chronic condition that most frequently affects older adults. As the population ages, the cost of treatment is placing pressure on the healthcare budget. As a result, it is imperative to evaluate the medicines' cost-effectiveness and the influence they have on health resource allocation. Hence, our study aims to summarize the cost and outcome of utilizing glucosamine in OA treatment. Authentic databases like Medline, Cochrane, and Scopus were adopted for the identification process up until July 2023. Our primary inclusion criteria centered on the economic evaluation of Glucosamine in OA treatments with provided the incremental cost-effectiveness ratio (ICER) at least. The Quality of Health Economic Studies (QHES) instrument was applied to grade the quality of the studies. A total of 7 qualified studies were selected and discussed the cost-effectiveness of glucosamine with or without other formulations. All of them demonstrated that glucosamine was cost-effective. There was an in-creasement of QALY when incorporating Glucosamine into conventional care. Moreover, Crystalline Glucosamine Sulfate (pCGS) was more cost-effective than the Other Formulations of Glucosamine (OFG). In overall, utilizing pCGS was more beneficial than OFG in terms both of cost and quality of life.

This study aimed to compare the efficacies and safety of enhanced and standard monofocal intraocular lenses (IOLs) in eyes with early glaucoma. Patients with concurrent cataracts and open-angle glaucoma (OAG) were enrolled. They underwent cataract surgery with IOL implantation. Manifest refraction; monocular uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), and uncorrected near visual acuity (UNVA); visual field (VF); contrast sensitivity (CS); defocus curves and questionnaires were assessed three months postoperatively. Thirty-four and 38 patients had enhanced and standard monofocal IOLs, respectively. The enhanced monofocal IOL provided better UIVA than the standard monofocal IOL (p = 0.003) but similar UDVA, CDVA and UNVA. The enhanced monofocal IOL had more consistent defocus curves than the standard monofocal IOL, especially at -1 (p = 0.042) and -1.5 (p = 0.026) diopters. The enhanced monofocal IOL provided better satisfaction (p = 0.019) and lower spectacle dependence (p = 0.004) than the standard monofocal IOL for intermediate vision, with similar VF and CS. In conclusion, the enhanced monofocal IOL is recommended for patients with OAG because they provide better intermediate vision, higher satisfaction, and lower dependence on spectacles than standard monofocal IOL, without worsening other visual outcomes.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumor microenvironment. To extend their efficacy to patients who fail to respond or achieve durable responses, it is now becoming evident that complex combinations of immunomodulatory agents may be required to extend efficacy to patients with immunologically “cold” tumours. Oncolytic viruses (OVs) have the capacity to selectively replicate within and kill tumour cells resulting in the induction of immunogenic cell death and the augmentation of anti-tumour immunity and have emerged as a promising modality for combination therapy to overcome the limitations seen with ICIs. Pre-clinical and clinical data has demonstrated that OVs can increase immune cell infiltration into the tumour and induce anti-tumour immunity, thus changing a “cold” tumour microenvironment that is commonly associated with poor response to ICIs, to a “hot” microenvironment which can render patients more susceptible to ICIs. Here, we review the major viral vector platforms used in OV clinical trials, their success when used as a monotherapy and when combined with adjuvant ICIs, as well as pre-clinical studies looking at the effectiveness of encoding OVs to deliver ICIs locally to the tumour microenvironment through transgene expression.

Background: Deficiency of alpha-1 antitrypsin (AAT1) is a rare disorder that represents a significant health threat and early diagnostic a priority issue. We investigate the usefulness of the serum protein electrophoresis (SPE) as an opportunistic screening tool for AAT1 deficiency. Methods: For 6 months, all SPE carried out for any reasons were evaluated in our center. In those with less than 3% of Alpha-1 globulins, AAT1 concentrations were studied. The SERPINA1 gene was subsequently sequenced in those subjects displaying concentrations below 100 mg/dL. Results: Out of the total, 14 patients (0.3%) were identified with low AAT1 concentrations, 11 of them agreeing to enter the study. Of those, mutations in the SERPINA1 gene were discovered in 10 subjects (91%). Heterozygous mutations were detected in 7 patients; 3 had the c.1096G>A mutation (p.Glu366Lys; Pi*Z), 2 the c.863A>T mutation (p.Glu288Val; Pi*S), one the c.221_223delTCT mutation (p.Phe76del; Pi*Malton) having the last one the c.1066G>A (p.Ala356Thr) mutation not previously described. Finally one patient had the c.863A>T mutation in homozygosis whereas two double heterozygous patients c.863A> T/ c.1096G>A were detected. Conclusions: an altered result in the concentration of AAT1 anticipates a mutation in the SERPINA1 gene in a manner close to 91%. The relationship between a decrease in the Alpha-1 globulin band of the SPE and an alteration in the AAT1 concentration is direct in basal states of health. The SPE is presented as a highly sensitive test for opportunistic screening of AAT1 deficiency.

Treatment with the anti-CGRP antibody fremanezumab is successful in the prevention of chronic migraine. In preclinical rat experiments, fremanezumab has been shown to reduce calcitonin gene-related peptide (CGRP) release from trigeminal tissues and the aversive behaviour to noxious facial stimuli, which are characteristic pathophysiological changes accompanying severe primary headaches. To further decipher the effects of fremanezumab underlying these antinociceptive effects in rats, immunohistochemistry and ELISA techniques were used to analyse the content and concentration of CGRP in the trigeminal ganglion as well as the ratio of trigeminal ganglion neurons immunoreactive to CGRP and CGRP receptor components 1-10 days after subcutaneous injection of fremanezumab (30 mg/kg) compared to an isotype control antibody. After fremanezumab treatment, the fraction of trigeminal ganglion neurons immunoreactive to CGRP and the CGRP receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) was significantly lowered compared to the control. The content and concentration of CGRP in trigeminal ganglia were not significantly changed. A long-lasting reduction of CGRP receptors expressed in trigeminal afferents may contribute to the attenuation of CGRP signalling and antinociceptive effects of monoclonal anti-CGRP antibodies in rats.

Background: Cancer-related cognitive impairment (CRCI) is one of the most serious side effects of cancer that negatively impact the quality of life of cancer patients and survivors. There is evidence of CRCI in Hodgkin lymphoma patients (HL); however, there is a lack of studies examining the presence of cognitive deficits before starting any treatment in HL patients. Methods: Forty patients (N=40) newly diagnosed with HL (with no previous cancer diagnoses) and 40 healthy controls (N=40) matched for age, sex, education, and premorbid intellect completed the neuropsychological battery and subjective and objective measures of affective distress and quality of life. Results: The results showed impairment in three out of six cognitive domains: verbal memory and learning, speed of processing/ psychomotor speed, and abstraction/executive functions in the HL patients before the initiation of any treatment. Speed of processing/psychomotor speed domain negatively correlated with depression. Conclusion: Impairment in verbal memory and learning and abstraction/executive functions domains in HL patients seems to occur before the initiation of treatment independently of anxiety, depression, or physical symptoms. This suggests that HL itself may cause cognitive deficits in these cognitive domains. However, the underlying causes of CRCI still remain unclear.

The aim of this review was to summarize the available literature regarding resident and medical student education utilizing the spaced repetition program Anki. This review enables current residents and medical students to recognize and utilize evidence-proven study techniques to increase learning efficacy. A systemic review of papers across all medical journals available on Pubmed was conducted to identify studies published without time constraints. The search was for (Anki) and (spaced repetition residency). Available outcome data was collected and discussed independently for students and residents. Many studies showed a statistically significant increase in exam performance associated with Anki use and high levels of satisfaction among residents and medical students. Further research is warranted to provide high-quality evidence of Anki’s applications and there is a need for exploration in additional residency specialties. Anki use has steadily increased with both medical students and residents. The application demonstrated consistent improvement on exam-based performance and was regarded highly by users. As burnout and time constrictions threaten educational workflow, Anki may serve as a powerful tool to improve the quality of learning. Further data needs to be collected and analyzed in specialties where Anki use may already exist.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and biologically heterogeneous disease. Approximately 40% of patients with DLBCL will experience disease relapse or will be refractory to first line chemoimmunotherapy. In recent years there have been several new therapeutic agents approved for the treatment of relapsed/refractory (R/R) DLBCL. These agents include anti-CD19 chimeric antigen receptor T-cell therapies (CAR T-cells) and monoclonal antibodies as polatuzumab and tafasitamab. Nevertheless, despite the high efficacy of all these new therapies, there are still patients who do not respond or relapse, representing an unmet clinical need. This review describes new promising therapies that are under investigation to treat R/R DLBCL.

Background: This study assessed the nephrotoxicity of oral BRAF inhibitors (BRAFi), regorafenib (REG) and encorafenib (ENC), in metastatic colorectal cancer (mCRC), through an analysis of re-ports from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) da-tabase. Methods: A descriptive and disproportional analyses were performed for all reports with ENC and REG as the primary suspect. Results: A total of 379 reports had at least one renal ADR, mainly related to REG (93.1%). Potential safety signals for REG particularly included chromaturia (n = 44; ROR = 12.00, CI 95% = 8.92-16.16; IC = 2.36, IC025-IC075 = 2.06-2.66), hydronephrosis (10; 8.70, 4.67-16.19; 1.85, 1.23-2.47), nephrotic syn-drome (7; 5.73, 2.73-12.03; 1.47, 0.73-2.21), renal impairment (53; 4.16, 3.17-5.45; 1.39, 1.12-1.66), dys-uria (19; 3.06, 1.95-4.81; 1.06, 0.61-1.52), renal failure (38; 1.66, 1.20-2.28; 0.49, 0.17-0.81), and acute kidney injury (AKI) (43; 1.46, 1.08-1.97; 0.37, 0.07-0.67). For ENC, consistent disproportionalities were observed for AKI (n = 11; ROR = 3.79, CI 95% = 2.09-6.90; IC = 1.32, IC025-IC075 = 0.72-1.91) and dysuria (4; 6.50, 2.43-17.39; 1.86, 0.88-2.85). Conclusions: These findings highlighted some not extensively reported renal ADRs that required further investigations to better characterize the safety profile of BRAFi in patients with mCRC.

Long Covid is a term used for patients who have recovered from COVID-19 but exhibit persistent cognitive dysfunction, including mental confusion, difficulties in attention, impairment in executive functions and slow movements, among other common symptoms. A study was conducted with 65 patients who had a positive RT-PCR diagnosis and reported symptoms of cognitive impairment, such as memory loss and attention difficulties after recovery. The patients underwent neuropsychological evaluation and completed questionnaires on cognition, mood, and quality of life. During the cognitive screening, 71% of the patients showed alterations, with deficits in visual memory (69%), language (54%), visuospatial construction (49%), verbal episodic memory (37%), executive functions (36%), attentional abilities (34%), and premorbid intelligence (12%). It is important to highlight the need for treatments and further studies to understand the long-term side effects of this disease.

Background: Recently the role of nutraceutical compounds in the prevention of human diseases is rapidly increasing. Here, we aim to evaluate the beneficial effect of dietary supplementation with seven active principles, lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan, green tea catechins, on human health. Methods: An extensive search of PubMed and Medline database was performed with the following keywords: “silymarin”, “sulforaphane”, “lycopene”, “green tea catechins”, “tryptophan”, “glutathione” and “escin” accompanied by the keywords “supplement”, “supplementation”, “nutraceutics”. All pre-clinical and clinical trials have been considered for this review. Results: One-hundred and eighteen full-text articles were eligible for inclusion in this review. The papers examined presented considerable variability due to the wide heterogeneity of dosages administered, population involved and outcomes pursued. Conclusion: Nutritional supplementation with lycopene, sulphoraphane, silymarin, glutathione, escin, tryptophan and green tea catechins appears to exert a wide range of benefits on human health, ranging from mood and cognition to cardiovascular health, fertility, metabolism, antioxidant and anti-inflammatory capabilities, potential anti-cancer effects. Further studies are required to better define the potential synergic effect, optimal dosage, mechanism of action and tolerability profile of these substances.

Background: It is assumed that the prevalence of hepatitis D in HBsAg-positive individuals reaches 4.5-13% in the world, and on average about 3% in Europe. Data from several European countries, including Slovakia, are missing or are from an older period. Methods: We analyzed all available data on hepatitis D from Slovakia, including reports from the Slovak Public Health Authority and the results of one prospective study, and three smaller surveys. The determination of anti-HDV IgG and IgM antibodies and/or HDV RNA was used to detect hepatitis D. Results: In the years 2005-2022, no confirmed case of acute or chronic HDV infection was reported in Slovakia. The presented survey includes a total of 343 patients, of which 126 were asymptomatic HBsAg carriers, 33 acute hepatitis B, and 184 chronic hepatitis B cases. In a recent prospective study of 206 HBsAg-positive patients who were completely serologically and virologically examined for hepatitis B and D, only 1 anti-HDV IgG positive and no anti-HDV IgM or HDV RNA positive cases were detected. In other smaller surveys, 2 anti-HDV IgG positive patients were found without the possibility of HDV RNA confirmation. In total, only 3 of 329 HBsAg-positive patients (0.91%) tested positive for anti-HDV IgG antibodies and none of 220 tested positive for HDV RNA. Conclusion: The available data show that Slovakia is one of the countries with a very low prevalence of HDV infection reaching less than 1% in HBsAg-positive patients. Routine testing for hepatitis D is lacking in Slovakia, and therefore it is necessary to implement testing of all HBsAg-positive individuals according to international recommendations.

A considerable number of infective endocarditis (IE) patients require cardiac surgery with an increased risk for postoperative sepsis. Intraoperative hemoadsorption may diminish the risk of postoperative hyperinflammation with potential economic implications for intensive care unit (ICU) occupation. The present study aimed to theoretically investigate the budget impact of a reduced length of ICU stay in IE patients treated with intraoperative hemoadsorption in the German healthcare system. Data on ICU occupation were extrapolated from a retrospective study on IE patients treated with hemoadsorption. An Excel-based budget impact model was developed to simulate the patient course over the ICU-stay. A base-case scenario without therapy reimbursement and a scenario with full therapy reimbursement were explored. The annual eligible German IE patient population was derived from official German Diagnostic Related Group (DRG) volume data. One-way deterministic sensitivity analysis and bootstrap analysis were performed to evaluate the uncertainty over the model results. Use of intraoperative hemoadsorption resulted in 2,298€ saved per patient in the base-case scenario without therapy reimbursement. Savings increased to 3,804€ per patient in case of full device-specific reimbursement. Deterministic and probabilistic sensitivity analyses confirmed the robustness of savings, with a probability of savings of 99% and 100% in the base-case and full reimbursement scenario, respectively. Intraoperative hemoadsorption in IE patients might have relevant economic benefits related to reduced ICU stay, resulting in improved resource use. Further evaluations in larger prospective cohorts are warranted.

This study reports on allelic and genotypic frequencies of OCT1, OCT2, OCT3 polymorphisms among metformin-treated DMT2 patients. It also reports the association with HbA1c control on 59 DMT2 patients. They were genotyped through real-time PCR (TaqMan assays). Metformin plasmatic levels were determined through mass spectrometry. Neither the analysis of HbA1c control by SNPs in SLC22A1, SLC22A2, and SLC22A3, nor the dominant genotypic model analysis yielded statistical significance across genotypes in polymorphisms rs72552763 (p=0.4678), rs622342 (p= 0.2215), rs316019 (p=0.2209), and rs2076828 (p=0.215). HbA1c levels were different in rs72552763 (p= 0.0220) and rs622342 (p=0.0093) genotypes. The dominant genotypic model found the lowest HbA1c levels by GAT/GAT (p= 0.0058) and A/A (p=0.0108), in rs72552763 and rs622342 respectively. We may conclude that rs72552763 and rs622342 polymorphisms in SLC22A1, exercise a relevant effect in metformin response determined by HbA1c levels among Mexican-Mestizo DMT2 patients.

Atherosclerosis (AS) is an age-related disease. Mitochondria and telomere links have been considered to play important roles in AS. PinX1 is a potent and highly conserved endogenous telomerase inhibitor. However, the role of pinX1 in AS and its role in oxidative stress have not been reported. In order to investigate the role of pinX1 in AS, we established a classical AS mice model in the present work and increased pinX1 protein expression using pinX1 overexpression adeno-virus by tail vein injection. Then, red-oil O and HE staining were employed to evaluate the severity of AS. Serum lipid profile and oxidative stress were also detected by using its specific chemical testing kit. The results indicated that high-fat diet (HFD) markedly decreased pinX1 and increased p66shc protein expression, whereas overexpression of pinX1 protein expression in mice produced the opposite results. In addition, pinX1 significantly minimized plaque area and alleviated the abnormal serum lipid profile. By using Western blot and Biochemical assay kits, overexpression of pinX1 decreased p66shc and MMP-9 protein expression and reduced oxidative stress. This study showed pinX1 can inhibit p66shc, MMP-9, and related oxidative stress, pinX1 may be considered as a new candidate target for the treatment of AS.

Introduction: The aim of the present systematic review was to evaluate the clinical and radiographic success of partial pulpotomies in deep caries processes or post-eruptive defects in young, vital permanent teeth. Methods: Electronic databases, PubMed, Scopus, and Embase, were searched, followed by a manual search. Randomized controlled trials evaluating partial pulpo-tomy with a follow-up period of ≥12 months were included. Meta-analyses using a random effect model were performed. Results: A total of 3.127 articles were retrieved, and after duplicate re-moval, 2.642 were screened by title and abstract; 1 additional article was found during the manual search in the reference lists, and 79 were identified. Finally, 6 papers were included in the review. Regardless of the partial pulpotomy modalities or material used, there were no signifi-cant differences between clinical and radiographic success rates (cumulative success rate 91,8%-92,3%, respectively). Five studies were included in the meta-analysis that did not indicate any statistically significant differences in success rates when Mineral Trioxide Aggregate was compared to other materials (95% CI 0,239 to 1,016 p=0.055). Conclusion: This research system-atically evaluates the evidence and summarises the available data on partial pulpotomy in young permanent teeth. Given its high clinical and radiographic success rate, partial pulpotomy should be considered when vital pulpal therapy needs to be performed in highly damaged young per-manent teeth, as this procedure provides a biological benefit and allows more invasive endodon-tic treatments to be postponed.

Background: COVID-19 pneumonia caused by SARS-Cov-2 virus induces alveolar collapse and hypoxia that may become severe. The aim of the study is to analyze the effects of chest physiotherapy using a threshold valve in patients with acute respiratory failure due to COVID-19 pneumonia. Methods; Retrospective observational study, in hospitalized patients from March to May 2020. Breathing exercises were performed with a threshold valve of 10 cmH2O. Fraction of inspired oxygen, oxygen saturation, heart rate, respiratory rate and dyspnea were collected before and after the first session and at the end of the 5th day of chest physiotherapy treatment. Results: The final sample included 125 patients. Significant differences (p&lt;0.01) were found in the pre-post intervention SpO2/FiO2 ratio (250±88.4 vs 275.6±97.5, p&lt;0.001), reaching 354.4±110.2 after 5 days of therapy (p&lt;0.001 with respect to baseline). Mean baseline respiratory, heart rate and level of dyspnea measure by the Borg scale did not change during the technique performance. In patient maneuvers with FiO2&gt;0.4, the SaO2/FiO2 ratio increase was higher than in patients with milder severity (46.85 ± 77.69, p&lt;0.01). Conclusions: Chest physiotherapy with a 10 cmH2O threshold valve is a safe and tolerated intervention with short-term improvement in oxygenation in patients with COVID-19 pneumonia.

Industrial hemp (Cannabis sativa L.), due to its bioactive compounds (terpenes and cannabinoids), has gained an increasing interest in different fields, including medical purposes. The evaluation of the safety profile of hemp essential oil (EO) and its encapsulated form (nanoemulsion, NE) is a relevant aspect for potential therapeutic applications. This study aimed to evaluate the toxicolog-ical effect of hemp EOs and NEs from cultivars Carmagnola CS and Uso 31, on three cell lines se-lected as models for topical and inhalant administration, by evaluating the cytotoxicity and the cytokine expression profiles. Results show that EOs and their NEs have comparable cytotoxicity, if considering the quantity of EO present in the NE. Moreover, cells treated with EOs and NEs showed, in most of the cases, lower levels of pro-inflammatory cytokines compared to Etoposide used as positive control, and the basal level of inflammatory cytokines was not altered, suggest-ing a safety profile of hemp EOs and their NEs to support their use for medical applications.

This study compared condylar volume, length, and articular eminence (AE) characteristics in normal individuals and those with unilateral and bilateral juvenile idiopathic osteoarthritis (JOA). The 116 patients were divided into four groups: control (n=16), affected condyle of unilateral JOA (Aff-Uni) (n=36), non-affected condyle of JOA (NonAff-uni) (n=36), and bilateral JOA (Bi-JOA) (n=28). Volume and length differences in the condyle and AE were analyzed using ANOVA and Bonferroni post hoc tests. The results showed that Bi-JOA had significantly different condylar volume, especially in the condylar head (p&lt;0.01), specifically the middle, anterior, and medial parts (p&lt;0.05). Condylar length also differed among the groups, with differences observed between the control group and the other three groups, as well as between the bilateral group and the other three groups (p&lt;0.01). AE total volume differed between the control group and Aff-Uni. In the detailed comparison, Aff-Uni and NonAff-Uni were smaller than the control group in the posterior, lateral, and medial sections (p&lt;0.05). In conclusion, depending on the involvement of unilateral or bilateral JOA, there were differences in condylar volume and AE compared to the normal control group. Therefore, prognosis should be evaluated by distinguishing between patients with unilateral and bilateral JOA.

Non-alcoholic fatty liver disease (NAFLD) has gained attention in the last few years due to its increasing prevalence worldwide becoming a global epidemic. This review aims to discuss the latest recommendations regarding diagnosis and treatment of NAFLD-associated HCC and the remaining challenges. Thus, there is a high amount of data derived from basic and clinical studies that revealed the molecular pathways which drive NAFLD-associated hepatocellular carcinoma (HCC). Based on these findings, new prevention, surveillance and treatment strategies are emerging. However, current data on treatment modalities in NAFLD-associated HCC are still scarce, but based on subgroup analysis results from non-NAFLD HCC studies are promising and could provide a basis for future research agenda to address NAFLD/NASH patients. Conclusion: Due to the pandemic proportions that NAFLD gained in the last few years, there is a high amount of data derived from basic and clinical studies that revealed the molecular path-ways which drive NAFLD-associated HCC. Based on these findings, new prevention, surveillance and treatment strategies could be developed at an individual level.

Machine learning (ML) offers potential opportunities to enhance the learning, teaching and assessments within veterinary medical education including but not limited to assisting with admissions processes as well as student progress evaluations. The purpose of this primer is to assist veterinary educators in appraising and potentially adopting these rapid upcoming advances in data science and technology. In the first section, we introduce ML concepts and highlight similarities/differences between ML and classical statistics. In the second section, we provide a step-by-step worked example using simulated veterinary student data to answer a hypothesis driven question. Python syntax with explanations is provided within the text to create a random forest ML prediction model and within each step, specific considerations such as how to manage incomplete student records are highlighted when applying ML algorithms within the veterinary education field. The results from the simulated data demonstrate how decisions by the veterinary educator during ML model creation may impact the most important features contributing to the model. These results highlight the need for the veterinary educator to be fully transparent during the creation of ML models and future research is needed to establish guidelines for handling data not missing at random in medical education, and preferred methods for model evaluation.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex genetic architecture, showing monogenic, oligogenic, and polygenic inheritance. In this study, we describe the case of a 71 years-old man diagnosed with ALS with an atypical phenotype, due to the presence of a progressive ocular ptosis. Genetic analyses revealed two variants in SOD1 and TBK1 genes respectively and the LHON-associated m.14484T>C variant in the mitochondrial DNA (mtDNA). We discuss how all these variants may synergically impinge on mitochondrial function, contributing to the pathogenic mechanisms which might ultimately lead to the neurodegenerative process, possibly influencing the clinical ALS phenotype.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These pa-tients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmaco-logic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infec-tious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and modalities of vaccination in SOT adult candidates and recipients.

Type 1 diabetes imposes a complex and challenging routine on patients and caregivers. Therefore, considering individual experiences and personal facilitators to promote assertive interventions is crucial. However, no studies have addressed these perspectives in the Brazilian adult population. We aimed to identify psycho-behavioral characteristics perceived as facilitators for coping with the condition. We used a biographical method to conduct semi-structured, face-to-face, in-depth interviews for each participant. Transcripts were analyzed using inductive thematic analysis. Participants (n = 22) were aged 18–57 years (mean: 30.2, standard deviation (SD): 8.7), and the duration since diagnosis was approximately 20.6 years (SD: 4.6). Twelve (54.4%) were women, 13 (59.1%) used insulin pumps, 14 (63.6%) had at least a college degree, and 13 (59.1%) had HbA1C (glycated hemoglobin) levels above 58 mmol/mol (7.5%). Five major themes emerged: 1) peer learning, 2) ownership, 3) welcoming experiences, 4) equity, and 5) reframe the path (P.O.W.E.R.). All themes appeared in the lived experiences shared by participants with HbA1C levels below 58 mmol/mol (7.5%). Improved glycemic control can be achieved, and the challenges encountered in diabetes care within similar socioeconomic contexts can be addressed, by an interdisciplinary care team that takes P.O.W.E.R into consideration when providing person-centered care strategies.

Objective: The main purpose of the study is to investigate the combined effects of polydeoxyribonucleotide (PDRN) and extracorporeal shock wave therapy (ESWT) sequences on the regenerative processes in atrophied animal muscles. Methods: Thirty male New Zealand rabbits, aged 12 weeks, were divided into five groups: normal saline, PDRN, ESWT, PDRN injection before ESWT, and PDRN injection after ESWT. Following 2 weeks of cast immobilization, the respective treatments were administered to the atrophied calf muscles. Radial ESWT was performed twice weekly. The evaluation included measurements of calf circumference, tibial nerve compound muscle action potential (CMAP), and gastrocnemius (GCM) muscle thickness after 2 weeks of treatment. Histological and immunohistochemical staining, as well as Western blot analysis, were conducted 2 weeks post-treatment. Staining intensity and extent were assessed using semi-quantitative scores. Results: Groups 4 and 5 demonstrated significantly greater calf muscle circumference, GCM muscle thickness, tibial nerve CMAP, and GCM muscle fiber cross-sectional area (types I, II, and total) than in the remaining three groups (p < 0.05), while they did not did not differ significantly in these parameters. Groups 2 and 3 showed the higher values for all the observations compared to group 1 (p < 0.05). Group 4 had the greatest ratio of vascular endothelial growth factor (VEGF) to platelet endothelial cell adhesion molecule-1 (PECAM-1) in the gastrocnemius muscle fibers than in the other four groups (p < 0.05). Western blot analysis revealed significantly higher expression of angiogenesis cytokines in groups 4 and 5 than in the remaining (p < 0.05). Conclusion: The combination of ESWT and PDRN injection demonstrated superior regenerative efficacy for atrophied calf muscle tissue in rabbit models than these techniques alone or saline. Particularly, administering ESWT after PDRN injection yielded the most favorable outcomes in specific parameters.

Background: Neurosarcoidosis is a great mimic, and its distinction from multiple sclerosis and other disorders can be particularly troublesome. We investigated whether cerebrospinal fluid (CSF) examination could help distinguish these two conditions and propose new diagnostic criteria. Methods: Stringent hierarchical diagnostic criteria were formulated. These were then applied prospectively to 531 neurological patients in whom neurosarcoidosis entered the differential diagnosis. The CSF total protein (TP), white cell count (WCC) and angiotensin-converting enzyme (ACE) levels were measured. The CSF and serum IgG patterns after isoelectric focusing were compared. Not all CSF parameters were measured in every patient. Results: 85/531 (16%) cases examined were diagnosed with neurosarcoidosis. Only 22 of these 85 (26%) met stringent diagnostic criteria. Intrathecal synthesis of oligoclonal IgG was evident in only 1/19 (5%) who fulfilled these criteria compared to 19/59 (32%) cases who did not (p = 0.03). CSF TP levels > 1g/L were more common in patients meeting the stringent criteria compared to the remainder of the patients, i.e. 11/22 (50%) vs 14/58 (24%) (p<0.05). Eleven out of 20 cases (55%) fulfilling stringent criteria had elevated CSF WCCs, and 6/12 cases (50%) had raised CSF ACE, neither significantly different from the remaining cases. Mean CSF TP, WCC, and ACE levels did not differ significantly between any groups of patients. Interpretation: Large elevations in CSF total protein, white cell count, and ACE occur in neurosarcoidosis but are rare in multiple sclerosis. However, the diagnostic use of these tests is limited since minimal changes may occur in both conditions. In contrast, intrathecal synthesis of oligoclonal IgG is a powerful discriminator because it is very uncommon in neurosarcoidosis whilst occurring in 95-98% of cases of multiple sclerosis. This observation implies that the immunopathogenesis of the two disorders is quite different. We suggest caution in diagnosing neurosarcoidosis when intrathecal oligoclonal IgG synthesis is detected. We propose new diagnostic criteria for neurosarcoidosis for future research.

Heartland virus (HRTV) is an emerging tick-borne bandavirus that is capable of causing severe disease characterized by acute thrombocytopenia and lymphopenia. The virus is endemic to the eastern United States, and is carried by the Lone Star tick (Amblyomma americanum). Since its discovery in 2009, at least 60 human infections have been recorded across this area, with an overall 5-10\% estimated mortality rate. All infections reported thus far have occurred following a known tick bite or exposure to tick-infested areas, but the possibility of nosocomial transmission has not been ruled out. Despite relatively high rates of seroprevalence among certain wildlife species such as white-tailed deer, the reservoir species for HRTV remains unknown, as the virus has never been isolated from any mammalian wildlife species. Furthermore, how the virus is transmitted to its vector species in nature remains unknown, though laboratory studies have confirmed both horizontal and vertical transmission of HRTV in A. americanum. In addition, the recent 2017 introduction of the Asian longhorned tick (Haemaphysalis longicornis) to the US has raised concerns about possible spillover of HRTV into a new tick species that has been confirmed to be a competent vector for HRTV in the laboratory. Thus, an increased awareness of its clinical presentation is needed, and further research is urgently required to establish the natural transmission cycle and develop new countermeasures for this novel zoonotic pathogen

Study Objectives: To (1) investigate the prevalence of sleep disorder symptoms in caregivers of children with autism spectrum disorder (ASD) and (2) the relationships between caregiver sleep problems and their health-related quality of life and family quality of life. Methods: Descriptive cross-sectional study of caregivers (N=62) of children ages 6 to 11 years old diagnosed with ASD receiving care at a regional autism research and resource center. Measurements and Results: Participants completed the Sleep Habits Questionnaire (SHQ), the Medical Outcomes Study (MOS) SF-12, and the Beach Center Family Quality of Life Scale (FQOL). Caregivers with longer sleep duration reported better mental health and better family quality of life. Caregivers who reported insomnia symptoms, non-restorative sleep, and insufficient sleep were more likely to report poorer mental health than caregivers who did not report these sleep disorder symptoms. Caregivers with obstructive sleep apnea and restless legs syndrome experienced worse physical quality of life. Conclusions: The physical and mental health of the primary caregiver is essential to the support of the child with ASD and to the functioning of the family. The study findings point to the importance of future research and interventions to enhance sleep health in order to improve quality of life for caregivers of children with ASD.

Bromodomain-containing protein 4 (BRD4) is an intracellular protein that regulates expression of various cellular functions. This study investigated whether BRD4 inhibition can alter the immunomodulatory and antitumor effects of radiation therapy (RT). A murine breast cancer cell line was implanted into BALB/c mice. The dual-tumor model was used to evaluate the abscopal effects of RT. A total of 24 Gy was delivered and BRD4 inhibitor was injected intravenously. Tumor size was measured and in vivo imaging was performed to evaluate tumor growth. Flow cytometry and immunohistochemistry were performed to examine immunologic changes upon treatment. The combination of BRD4 inhibitor and RT significantly suppressed tumor growth compared to RT alone. BRD4 inhibitor reduced the size of the unirradiated tumor indicating that it may induce systemic immune responses. Expression of HIF-1α and PD-L1 in tumor was significantly downregulated by the BRD4 inhibitor. Proportion of M1 tumor-associated macrophages (TAMs) increased, and proportion of M2 TAMs decreased upon BRD4 inhibition. BRD4 inhibitor expanded CD4+ and CD8+ T cell populations and reduced the population of monocytic myeloid-derived suppressor cells (M-MDSCs). RT-induced splenic M-MDSCs decreased upon addition of BRD4 inhibitor. Therefore, addition of BRD4 inhibition significantly enhanced the systemic antitumor responses of local RT.

Hepatocellular carcinoma (HCC) poses a significant global health concern, with its incidence steadily increasing. The development of HCC is a multifaceted, multi-step process involving alterations in various signaling cascades. In recent years, significant progress has been made in understanding the molecular signaling pathways that play central roles in hepatocarcinogenesis. In particular, the EGFR/PI3K/Akt/mTOR signaling pathway in HCC has garnered renewed attention from both basic and clinical researchers. Preclinical studies in vitro and in vivo have shown the effectiveness of targeting the key components of this signaling pathway in human HCC cells. Thus, targeting these signaling pathways with small molecule inhibitors holds promise as a potential therapeutic option for patients with HCC. In this review, we will explore recent advancements in understanding the role of the EGFR/PI3K/Akt/mTOR signaling pathway in HCC and assess the effectiveness of targeting this signaling cascade as a potential strategy for HCC therapy based on preclinical studies

Exposure to particulate matter (PM) causes considerable breathing-related health risks. We assessed the inhibitory effect of Siraitia grosvenorii extract (SGE) on airway inflammation in mice exposed to a fine dust mixture of PM10 (PM diameter &lt; 10 mm) and diesel exhaust particles (DEPs) known as PM10D. SGE attenuated neutrophil infiltration and the number of immune B and T cells in lung tissue and bronchoalveolar lavage fluid (BALF) of PM10D-exposed mice. SGE reduced the secretion of cytokines and chemokines, including interleukin (IL)-1a, tumor necrosis factor (TNF)- a, IL-17, chemokine (C-X-C motif) ligand (CXCL)-1, and macrophage inflammatory protein (MIP)-2 in BALF. Airway inflammation, accumulation of inflammatory cells, and collagen fibrosis in the lung after PM10D exposure were investigated by histopathological analysis, and SGE treatment ameliorated these symptoms. SGE decreased the mRNA expression of mucin 5AC (MUC5AC), CXCL-1, TNF-a, MIP-2, and transient receptor potential vanilloid and ankyrin 1 ion channels in the lung tissues of mice. Furthermore, SGE ameliorated mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling activated by PM10D in mice. We conclude that SGE attenuated PM10D-induced neutrophilic airway inflammation via inhibiting MAPK/NF-κB activation. These results show that SGE may be a candidate for the treatment of inflammatory respiratory diseases.

The alterations of coagulation status in patients with Severe Burn Injury are associated with serious complications, increased morbidity and mortality. This study aims to compare Rotational Thromboelastometry(ROTEM)–a Viscoelastic Coagulation Assays(VCAs) with Conventional Coagulation Assays(CCAs) including Prothrombin time(PT), Activated Partial Thromboplastin time(aPTT), International normalized ratio(INR), Complete Blood Count(CBC) and Coagulation Factors during the early five post- burn days in Survivors and Non- Survivors with Severe Burn Injury in order to correlate these results with Burn Coagulopathy and Prognosis. Seventeen Sur-vivors and ten Non- Survivors, with a mean Total Burn Surface Area(TBSA) of 33,78% were in-cluded in our study. Even though CCAs measurements were abnormal, they were unable to detect overall burn patients’ coagulopathy. On the contrary, VCAs from day 2 to day 5 took pathological values, especially for Non- survivors. Those changes were underlined through pathological values of Coagulation Factors. As a result, CCAs were considered poor indicators of coagulation status in burn injury, whereas VCAs were more accurate in demonstrating coagulation alterations from the early post- burn period and detecting patients in greater risk of mortality. These advantages of VCAs could be used for timely intervention in high risk patients and for the guidance of blood product transfusions.

(1) Background: The study presents an assessment of the psychometric properties of the Polish version the Short Schema Mode Inventory (SMI) adaptation. (2) Methods: First, the original version of the scale was translated. Subsequently, a validity and reliability study was conducted on a sample of 240 patients and 400 non-patients. In particular: the factor structure of the inventory was checked, internal reliability and intercorrelations between subscales were tested, differences between the clinical and non-clinical groups in terms of the severity of each factor were examined, and construct validity was assessed by comparing the association of results with external variables. (3) Results: The results did not conclusively confirm the 14-factor structure postulated in the original scale. Nevertheless, relatively the best fit indices were obtained for such a model. Internal reliability for the 14 subscales was in the acceptable to excellent range. Correlations between subscales took moderate to high values. The existence of differences between the clinical and non-clinical groups and the construct validity were confirmed. (4) Conclusions: The psychometric evaluation performed is mostly similar to the results obtained for other adaptations, and the results entitle the inventory to be used for research and clinical purposes with the knowledge of its limitations.

(1) Introduction: Every two hours, a Romanian woman is diagnosed with cervical cancer [1] as the country ranks second in Europe in terms of mortality and incidence rate [2]. This paper aims to identify the main reasons that have led to this situation, focusing on the measures taken by the Romanian Ministry of Health for the prevention of this type of cancer national - programs for cervical cancer screening and HPV vaccination. (2) Materials and methods: We performed a study based on available secondary data from the National Statistics Institute, World Health Organization and Bucharest Institute of Oncology in order to assess the burden associated with cervical cancer and placing it in the context of known global and European incidence and mortality rates, thus evaluating the importance of this health issue in Romania. The second component of our study was a cross-sectional study, using a 14 questions questionnaire, applied to the women participating in the National Screening Program for Cervical Cancer, aimed to evaluate the women’s level of knowledge about screening and HPV vaccination and their access cervical cancer specific health-care services. (3) Results: The results of the research shows that a high percentage of women postpone the routine checks due to lack of time and financial resources and indicate that low level of knowledge about the disease and the specific preventive methods determines low participation screening and HPV vaccination programs implemented in Romania contributing to the country’s situation of cervical cancer. (4) Conclusions: The national programs have complicated procedures, are underfunded, and do not motivate enough health care workers. This combined with the lack of information adds up to an extremely low number of women screened and vaccinated. Our conclusion is that the Romanian Ministry of Health must take immediate action by conducting major awareness campaigns, implementing measures to make the programs functional and ensuring coherent funding.

Background: This study aimed to develop a highly consumable collagen-containing bar that contributes to enriching the diets of elderly individuals in terms of energy and nutrients. Method: For this purpose, after the development of 5 different bar samples (C, P1, P2, D1, D2) containing different amounts of collagen, date puree, and pumpkin puree, they were evaluated in terms of sensory and nutritional properties. Results: The highest flavor score bars were those with high levels of pumpkin puree (P2) and date puree (D2). By applying the TOPSIS technique, which is used when there are multiple crite-ria among multiple samples, to the snack bar samples with different contents, the most liked sample was found to be the snack bar (D2) with a high level of date puree. One serving of the developed bars contains approximately 300-400 kcal of energy and 6.8-8.8 g of protein. Consid-ering age-related decreased appetite and chewing and swallowing problems in elderly individ-uals, regular consumption of nutrient-rich small meals or snacks with enhanced sensory charac-teristics will contribute to improving their nutritional and functional status.

There exists a variety of studies about tumor-infiltrating lymphocytes (TILs) in cervical cancer, but their prognostic value in correlation to the histopathological subtype was never investigated. Therefore, the aim of this study was to quantify TILs in a panel of 250 sporadic cervical cancers and investigate the correlation with cervical cancer subtype and patient survival. TIL levels were significantly increased in the subgroup of squamous cell carcinomas in comparison to adenocarcinomas. In squamous cell carcinomas, TIL infiltration shows a negative correlation to age, FIGO stage and to the histone protein modification H3K4me3. Moreover, in adenocarcinomas, it was positively correlated to p16 and to the glucocorticoid receptor and inversely correlated to the MDM2 protein and to H3K4me3. Interestingly, immune infiltration was an independent positive prognosticator for disease free survival (DFS) in patients with squamous cell carcinomas, those bearing tumors with the strongest TIL infiltration showing the better DFS. Altogether, the present study provides a differentiated overview of the relations between TIL levels and prognosis in patients with cervix squamous cell carcinomas vs patients with cervix adenocarcinomas.

Enophthalmos is a severe complication of primary reconstruction following orbital floor frac-tures, oncological resections or maxillo-facial syndromes. The goal of secondary reconstruction is to re-store symmetrical globe positions to recover function and aesthetics. In this article we pre-sent a method of computer-assisted orbital floor reconstruction using a mirroring technique and a customized titanium or high-density polyethylene mesh, printed using computer aided manufac-turing techniques. This reconstructive protocol involves 4 steps: mirroring of the healthy orbit at the affected site, vir-tual design of a patient specific orbital floor mesh, computer-assisted manufacturing (CAD) of the implant, and surgical insertion of the device. Using a computed tomography data set, the un-injured side of the craniofacial skeleton was reflected onto the contralateral injured side, and a reconstructive orbital floor prosthesis was virtually designed on the mirrored orbital bone sur-face. The solid-to-layer (.STL) files of the prosthesis were then manufactured using Direct Metal Laser Sintering (DMLS) or Computer Numerical Control (CNC) methods, leading to the produc-tion of 10 titanium meshes and 2 high density polyethylene (HDPE) implants. Clinical outcomes were assessed using 3dMD photogrammetry and computed tomography measures in 14 treated patients. The technique described here appears to be a viable method to correct complex orbital floor de-fects needing delayed reconstruction. This article represents the prosecution of a previous study, which is part of a wider experimental protocol for orbital floor reconstruction using comput-er-assisted design-computer-assisted manufacturing (CAD-CAM) technology

Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut-brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising >2,000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this pa-per presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid, and is expected to continue to evolve with further development.

Background: Asthma is a very prevalent disease with special characteristics during pregnancy, however little is known about its relation to the psychological wellbeing of women in this period; We aimed to know whether depression and anxiety symptoms are more frequent in asthmatic pregnant women. (2) Methods: Family Apgar (week 20), Edinburgh (weeks 20 and 32) and STAI (week 32) tests were administered to 738 pregnant women (81 asthmatics) in the NELA birth cohort; (3) Results: There were no significant differences between asthmatic and non-asthmatic pregnant women in any of the different tests at any of the time points. The mean? scores for the different tests and timepoints between asthmatic and non-asthmatic pregnant women were: Apgar 20, 17.9±2.2 vs. 10.0±2.2; Edinburgh 20, 6.7±4.2 vs. 6.9±4.3; Edinburgh 32, 5.9±4.4 vs. 5.6±4.3; and STAI 32, 16.7±8.4 vs. 15.8±8.3. The proportion of pregnant women out of the normal range score for any of the tests and time points was also similar in both populations. (4) Conclusions: Asthma is not associated with the psychological wellbeing among pregnant women.

Background: Atherosclerotic plaque (AP) vulnerability can be assessed by coronary artery imaging techniques. Modern lipid-lowering therapy (LLT) has a stabilizing effect on the AP and reduces the likelihood of progression of vascular remodeling. Methods: Databases searched comprised PubMed, and the Web of Science up to April 2023. In total, 8 relevant articles were selected, and all of them are original clinical studies. Results Based on the results of ODISSEY-J-IVUS, there was a decrease in the percentage change in the normalized total volume of AP by 3.1% in the monotherapy group and by 4.8% in the combined LLT group (p = 0.23). According to GLACOV study normalized total atheroma volume decreased by 0.9 mm3 in the placebo group and by 5.8 mm3 in the evolocumab group (95% CI -7.3 -2.5; p<0.001). Plaque regression was observed in 64.3% of patients receiving evolocumab versus 47.3% of those on placebo. The dynamics of the minimum thickness of the fibrous cap varied within 18.0-62.67 microns while on combined LLT and 13.2-33.19 microns on monotherapy (PACMAN-AMI, Gao F). In the HUYGENS study, a lipid arc regression of 57.5° was obtained on combined LLT and by 31.4° with the statin alone. Conclusion: significant progress in the development of cardiovascular imaging has made it possible to expand our understanding of the morphology of AP, the features of coronary vessel remodeling, and the development of acute cardiovascular complications.

Ovarian endometriomas have a negative impact on a patient’s reproductive potential and likely cause a reduction in ovarian reserve. The most commonly employed ovarian reserve parameters are anti-mullerian hormone (AMH) and antral follicular count (AFC). Surgical management options of endometrioma include cystectomy, ablative methods, ethanol sclerotherapy and combined techniques. The optimal surgical approach remains a matter of debate. Our review aimed to summarize the literature on the impact of surgical management of endometrioma on AMH, AFC and fertility outcomes. Cystectomy may reduce recurrence rates and increase chances of spontaneous conception. However, a post-operative reduction in AMH is to be anticipated, albeit there is evidence of recovery during follow-up. The reduction in ovarian reserve is likely multi-factorial. Cystectomy does not appear to significantly reduce, and may even increase, AFC. Ablative methods achieve an ovarian tissue-sparing effect and improved ovarian reserve, compared to cystectomy, has been demonstrated. A single study reported on AMH and AFC post- sclerotherapy and both were significantly reduced. AMH levels may be useful in predicting the chances of conception post-operatively. None of the aforementioned approaches has clearly demonstrated a superiority in terms of overall chances of conception. Surgical management of endometrioma may, overall, improve probability of pregnancy. Evidence on its value before medically-assisted reproduction (MAR) is conflicting, however, a combination of surgery followed by MAR may achieve the optimal fertility outcome. In view of the complexity of available evidence, individualisation of care, combined with optimal surgical technique, is highly recommended.

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher exercise frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

Z-ligustilide is a main active ingredient in the volatile oil of Angelica sinensis, a traditional Chinese medicine. Cisplatin is a commonly used chemotherapy drug for the treatment of lung cancer. Efficacy is often limited by the development of drug resistance after long-term treatment. Here, we investigated the effect of the combination of Z-ligustilide and cisplatin (Z-ligustilide+cisplatin) on resistance of cisplatin-resistant lung cancer cells and its action mechanism. Cell viability was analyzed by cell counting kit-8 (CCK-8) assay. Cell cycle and cell apoptosis were examined by flow cytometry assay. mRNA and protein levels of factors related to cell cycle and apoptosis were analyzed by real-time PCR and western blot. Liquid chromatography-mass spectrometry (LC-MS) analysis and RNA sequencing in A549, A549/DDP and A549/DDP cells treated with the Z-ligustilide+cisplatin were performed. The expression of PLPP1 was analyzed by the Cancer Genome Atlas (TCGA). The correlation between PLPP1 and prognosis was evaluated by immunohistochemistry and Kaplan-Meier (KM) plotter analysis. We found that Z-ligustilide+cisplatin could decrease the cell viability of cisplatin-resistant lung cancer cells. Z-ligustilide+cisplatin induced cell cycle arrest, and promoted cell apoptosis of cisplatin-resistant lung cancer cells. Metabolomics combined with transcriptomics revealed that Z-ligustilide+cisplatin inhibited phospholipid synthesis by upregulating the expression of PLPP1. Furthermore, PLPP1 expression was positively correlated with good prognosis. Knockdown of PLPP1 abolished the effects of Z-ligustilide+cisplatin on cell cycle and apoptosis. Z-ligustilide+cisplatin inhibited the activation of AKT by reducing the levels of PIP3 levels. Z-ligustilide+cisplatin induced cell cycle arrest and promoted cell apoptosis of cisplatin-resistant lung cancer cells by inhibiting PLPP1-mediated phospholipid synthesis.

The influence of diet and nutritional status of milk donors on the nutritional composition of donor human milk (DHM) is unknown. The present study aimed to determine the nutritional profile of DHM and the associations of donors’ dietary intake and nutritional status with micronutrient and lipid composition in DHM. For this purpose, 113 donors completed a food frequency questionnaire, provided a 5-day weighed dietary record, and collected milk for 5 consecutive days. Nutrient determinations in donors’ erythrocytes, plasma, urine, and milk were performed. Multiple linear regressions were conducted for the evaluation of the associations. We highlight the following results: DHM docosahexaenoic acid (DHA) was positively associated with donors’ plasma DHA content and donors’ DHA intake (R2 0.45, p < 0.001). For every 1 g/day of DHA intake, the percentage of DHA in DHM increased by 0.38% (% of total fat) and the percentage of total omega-3 in DHM increased by 0.78% (R2 0.29, p < 0.001). DHM saturated fatty acids were positively associated with erythrocyte dimethyl acetals, plasma stearic acid, trans fatty acids intake, and breastfeeding duration, and negatively associated with erythrocyte margaroleic acid (R2 0.34, p < 0.01). DHM cholecalciferol was associated with plasma cholecalciferol levels and dairy intake (R2 0.57, p < 0.01). Other weaker associations were found for free thiamine, free riboflavin, pyridoxal, dehydroascorbic acid, and lipid profile in DHM. In conclusion, the diet and nutritional status of donors influences the fatty acid profile and micronutrient content of DHM.

Osteoarthritis (OA) is the degeneration of cartilage in joints that results in bones rubbing against each other, it causes uncomfortable symptoms such as pain, swelling, stiffness, and can lead to disability. It usually occurs in the elderly and causes a large medical burden. The aim of this study is to evaluate cost-effectiveness between the standard treatment for osteoarthritis and the standard treatment with added crystalline glucosamine sulfate at various stages. The Markov analysis modelling was applied to evaluate the effect of both adding glucosamine compared to standard treatment from a societal perspective during whole patients’ lifetimes. Data input was collected by review in previous studies. The outcome was measured in quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) from a societal perspective was ap-plied with 3%-discounted for all cost and outcome. One-way analysis via Tornado diagram was performed to investigate the change of factors in model. In general, the adding glucosamine into the standard treatment proved to be more cost-effectiveness compared to the standard treatment. Particularly, early stage adding glucosamine in the treatment was cost-effectiveness then post-stage adding glucosamine. The addition of supplementing crystalline glucosamine sulfate to whole regimen at any stage was cost-effectiveness at willingness-to-pay (WTP) threshold

The purpose of this study was to evaluate the outcomes of implants placed in horizontally augmented alveolar ridges using porcine bone grafts and to investigate the long-term stability of the porcine bone grafts. A retrospective analysis was conducted on 55 sites that underwent horizontal ridge augmentation using porcine bone grafts and implant placement with a follow-up period longer than 5 years. Furthermore, additional analysis was conducted on 24 sites where porcine bone grafts were used exclusively and implants were placed simultaneously with horizontal ridge augmentation. The mean follow-up period after prosthesis loading was 67.3 months, with a mean marginal bone loss of 0.18 mm at 1 year and a cumulative mean marginal bone loss of 0.37 mm over the entire follow-up period. Of the 55 implants, 2 were lost and 4 did not meet the success criteria, resulting in a survival rate of 96.4% and a success rate of 89.1%. In 24 sites, the mean marginal bone loss was 0.22 mm at 1 year and 0.40 mm at 65.8 months, with 100% survival and success rates. Porcine bone grafts can be successfully used in horizontal ridge augmentation for implant placement in cases of ridges with insufficient horizontal width.

Objectives: Studies on the association between non-steroidal anti-inflammatory drugs (NSAIDs) and major adverse cardiovascular events (MACE) in the Arabian Gulf are scarce. The aim of this study was to evaluate the association between NSAIDs use and MACE in acute coronary syndrome (ACS) patients in the Arabian Gulf region. Methods: Data was analyzed from 3,007 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 as well as being on prior NSAIDs use during the index admission. MACE included stroke/transient ischemic attacks (TIAs), myocardial infarction (MI), all-cause mortality and readmissions for cardiac reasons. Results: The overall mean age of the cohort was 62 ± 12 years and 9.6% (n = 290) of the patients were on prior NSAID use during the index admission. At 12-months follow-up, after adjusting for confounding factors, those on NSAIDs were significantly more likely to have had MACE (adjusted OR (aOR), 1.89; 95% confidence interval (CI): 1.44-2.48; p < 0.001). Specifically, the higher event rates observed were stroke/TIA (aOR, 2.50; 95% CI: 1.51-4.14; p < 0.001) and readmissions for cardiac reasons (aOR, 2.09; 95% CI: 1.59-2.74; p < 0.001) but not MI (aOR, 1.26; 95% CI: 0.80-1.99; p = 0.320) and all-cause mortality (aOR, 0.79; 95% CI: 0.46-1.34; p = 0.383). Conclusions: NSAIDs use was associated with significant stroke/TIA events as well as readmissions for cardiac reasons. However, NSAIDs were not associated with increased MI or all-cause mortality rates in ACS patients in the Arabian Gulf.

Upper limb paresis is very common after stroke. An important tool to assess motor recovery is to use marker-based motion capture systems to measure the kinematic characteristics of patients’ movements in ecological scenarios. These systems are, however, very expensive and, as such, not readily available for many rehabilitation units. Here, we explored whether the markerless hand motion capabilities of the cost-effective Oculus Quest head-mounted display could be used to provide clinically meaningful measures. 14 stroke patients executed ecologically relevant upper limb tasks in an immersive virtual environment. During task execution, we recorded their hand movements simultaneously by means of the Oculus Quest’s and a marker-based motion capture system. Our results showed that the markerless estimates of the hand position and peak velocity provided by the Oculus Quest were in very close agreement with those provided by a marker-based commercial system with their regression line having a slope close to 1. Furthermore, the Oculus Quest had virtually the same sensitivity as that of a commercial system in distinguishing healthy from pathological kinematic measures. The Oculus Quest was as accurate as a commercial marker-based system in measuring clinically meaningful upper limb kinematic parameters in stroke patients.

The discovery of microRNAs and their role in disease today represents a substantial breakthrough that has inspired and propagating research on microRNAs as targets for diagnosis and therapy. Cardiovascular disease is an area where the limitations of early diagnosis and conventional pharmacotherapy are evident and deserve attention. Thus microRNA-based drugs have substantial potential for development. Research and its application can progress considerably as witnessed in preclinical and clinical trials. The use of miRNAs remains experimental at the time of writing but has a promising role in the diagnosis and prognosis of a variety of acute coronary syndrome presentations. Its use, alone or in combination with currently available biomarkers, could be adopted soon, especially if diagnostic ambiguity exists. In this review, we explore the current state of knowledge about microRNAs as potential targets for diagnosis and therapy in the cardiovascular system. We report recent improvements in the acknowledgment and characterization of microRNAs focusing on clinical translation. The new dares and outlooks toward clinical application are discussed.

Doppler findings of persistent reverse end-diastolic flow (PREDF) in a fetal middle cerebral artery (MCA) are a very rare sonographic finding and are a marker of poor fetal condition. This finding often leads to intrauterine fetal death or early neonatal death. The reverse end-diastolic flow in the middle cerebral artery is the terminal hemodynamic event. Fetal cerebral circulation normally has a high impedance; in the event of fetal hypoxemia, impedance decreases, resulting in the central redistribution of blood flow to vital organs, which maintains the oxygen delivery to the brain. Reverse flow in the middle cerebral arteries describes the loss of this autoregulatory process. PREDF is a sequence happening due to increased extracranial or intracranial pressure. Previous case reports mentioned intracranial hemorrhage, intrauterine growth restriction (IUGR), fetal anemia, and fetal hepatic abnormalities as leading problems to PREDF. This condition presumably arises due to cerebral edema associated with severe hypoxemia. We reported Doppler findings of PREDF MCA in a 33-year-old female at 30 weeks gestation who was referred to the hospital with severe preeclampsia accompanied by IUGR and oligohydramnios. A cesarean section was performed due to severe preeclampsia and a low bishop score. Hypotheses on various etiologies and their association with intrauterine/neonatal death as well as the best management still require further investigation.

Background/Aims: Conflicting results have been reported regarding the interaction between proton pump inhibitors (PPIs) and clopidogrel. We investigated whether concomitant PPI use influenced the risk of recurrence in patients with stroke and myocardial infarction (MI). Methods: This study used two databases for different designs, the Korean National Health Insurance Service (NHIS) database for a self-controlled case series design, and the national sample cohort of the NHIS database converted to the Observational Medical Outcomes Partnership-Common Data Model version for a cohort study. Results: In the PPI co-prescription group, recurrent hospitalization with stroke occurred in 17.6% of the 8,201 patients with history of stroke, and recurrent MI occurred in 17.1% of the 1,216 patients with history of MI during 1 year. According to the self-controlled case series, the overall relative risk (RR) of recurrent stroke was 2.09 [95% confidence interval (CI); 1.83-2.38], and the RR showed an increasing trend with PPI duration. In the cohort study, there was a higher incidence of recurrent stroke in the PPI co-prescription group [Hazard ratio (HR): 1.34, 95% CI: 1.01-1.76, P=0.04]. The overall RR of recurrent MI was 1.47 (95% CI; 1.02-2.11) in the self-controlled case series; however, there was no statistically significant difference in recurrent MI in the cohort study (HR:1.42, 95% CI:0.79-2.49, P=0.23). The impact of individual PPIs on stroke and MI showed different patterns. Conclusions: PPI co-prescription with clopidogrel was associated with recurrent stroke; however, its association with recurrent MI remains inconclusive. The influence of individual PPIs should be clarified in the future.

Background: The heterogeneity of rectal biopsy techniques encourages us to search for a surgical and pathological standardisation of this diagnostic technique to exclude Hirschsprung’s disease. The varying amount of information on the anatomopathology report prompts us to compile a template concerning the anatomopathology report for diagnostic rectal biopsies for colleague surgeons and pathologists working on Hirschsprung’s disease. Methods: We gathered the anonymous biopsy information and its pathology information from five hospitals of all patients in which rectal biopsies were taken to diagnose Hirschsprung’s disease over two years (2020-2021). Results: 82 biopsies: 20 suction (24,4%), 31 punch (37.8%) and 31 open biopsies (37,8%) were taken. Of all biopsies 69 were conclusive (84,2%), 13 were not (15,8%). In the suction biopsy group 60% were conclusive, 40% not, for punch biopsy 87% and 13% respectively and for open biopsy 97% and 3%. Inconclusive results were due to insufficient submucosa in 6/8 suction biopsies, 4/4 punch and 0/1 open biopsies. An insufficient amount of submucosa was the reason for an inconclusive result in 6/20 cases (30%) after suction biopsy, 4/31 (12,9%) after punch biopsy and 0 cases (0%) after open biopsy. We had one case with major postoperative bleeding post suction biopsy; there were no further adverse effects after biopsy. Conclusions: Diagnostic rectal biopsies in children are safe. Non-surgical biopsies are more likely to give inconclusive results, due to less submucosa present in the specimen. Open biopsies are especially useful when previous non-surgical biopsies are inconclusive. An experienced pathologist is a key factor for the result. The anatomopathology report should specify the different layers present in the specimen, the presence of ganglion cells and hypertrophic nerve fibers, their description and a conclusion.

Fexuprazan is a potassium-competitive acid blocker approved for treating gastric acid-related diseases. Herein, we evaluated the pharmacokinetics (PKs) of single-dose and multiple-dose oral administration of fexuprazan 10 mg tablets in healthy subjects (Part 1) and investigated the bioequivalence between fexuprazan 10 mg and 40 mg tablets (Part 2). Part 1 comprised a single- and multiple-dose, 1-sequence, and 2-period design, and Part 2 comprised a single-dose, 2×2 crossover design. Eight and 23 subjects completed Parts 1 and 2, respectively. In Part 1, multiple doses accumulated twice as much as single doses. In Part 2, the geometric mean ratios [90% confidence intervals] for maximum plasma concentration (Cmax) and area under the concentration–time curve from zero to the time of the last quantifiable concentration (AUClast) of four fexuprazan 10 mg tablets to those of one fexuprazan 40 mg tablet were 1.0290 (0.9352–1.1321) and 1.0290 (0.9476–1.1174), respectively, which met bioequivalence criteria. Overall, favorable PK was observed after single and multiple administrations of one fexuprazan 10 mg tablet, and four fexuprazan 10 mg tablets were pharmacokinetically equivalent to one fexuprazan 40 mg tablet.

In the last 20 years, TADs have become one of the topics in orthodontic science, as it becomes one of the effective anchorages in moving teeth in a 3D movement to treat malocclusion and dental-alveolar orthopedic. Problems with the collusion of the roots of the teeth and trauma have hindered the use of these TADs; one of the solutions to keep TADs safe is a step-by-step innovation of procedure to make this anchorage concept using TAD safe. Making surgical guides for single-standing TADs is essential, and in practice, it is virtually possible with the advance of today's CAD/CAM and 3D printers. The content subject in the paper contains two parts: the consideration of why a surgical guide is necessary for the implantation of TADs and the making of the Surgical guide itself.

Background: Community acquired Acinetobacter pneumonia (CAAP) typically presents with rapid progression to fulminant disease, and is complicated by high mortality. Australian epidemiological studies are few. Methods: We conducted a retrospective study on bacteraemic cases of CAAP over twenty years, (2000-2019) in North Queensland. Cases were selected on microbiologic, clinical, and radiographic parameters. Data on patient demographics were obtained, along with microbial, antibiotic, mortality, and climatic data. Results: 28 cases of CAAP were included. Nineteen (67.9%) were male, twenty-three (82.1%) were Indigenous Australians, and mean age was 45.9 years. Most presentations were of moderate to severe pneumonia, 25/28 (89.3%). 90% of cases had two or more risk factors. The strongest risk factors for CAAP were alcohol excess and tobacco use. No statistically significant difference in presenting severity, ICU admission or mortality was seen between dry and wet season disease. Dry season disease accounted for 35.7% of cases. Overall mortality was 28.6%. Early use of meropenem or gentamicin reduced mortality irrespective of presenting severity (mortality 17.6%) Non-targeted antibiotic therapy was associated with a non-significant difference in mortality of 44.4%. Conclusions: Early administration of targeted antibiotics can mitigate a high mortality rate. Choice of antibiotic therapy for community acquired pneumonia should be based upon severity, risk factors and clinical suspicion of CAAP rather than seasonality.

Asthma is a prevalent disease that around 300 million worldwide, resulting in substantial morbidity, mortality, and economic burden on a global scale. New clinical and laboratory research has shed light on the immunology causing asthma. Asthma is now recognized as a heterogeneous disease. A personalized medicine is based on the classification of asthma by endotype by linking observable characteristics to immunological mechanisms. Identifying endotype mechanisms is essential for better characterizing patients and personalizing therapeutic approaches with novel biological agents that target specific immune pathways. This article provides a summary of the major immunological mechanisms involved in the pathogenesis and emergence of the disease's phenotypic features, as well as the individualized treatment for severe asthma subtypes

(1) Background: To identify the association between the presence or absence of raphe and aortic valve dysfunction as well as the presence of aortopathy in patients with bicuspid aortic valve (BAV); (2) Methods: This retrospective study enrolled 312 participants (mean [SD] age, 52.7 [14.3] years; 227 men [72.8%]) with BAV. The BAVs were divided into those with presence (raphe+) or absence (raphe-) of raphe. Valvular function was classified as normal, aortic regurgitation (AR), or aortic stenosis (AS) using TTE. The pattern of BAV aortopathy was determined by the presence of dilatation at the sinus of Valsalva and the middle ascending aorta using CCT.; (3) Results: BAVs with raphe+ had a higher prevalence of AR (148 [79.5%] vs. 48 [37.8%], P < .001) but a lower prevalence of AS (90 [48.6%] vs. 99 [78.0%], P < .001) compared with those with raphe-. The types of BAV aortopathy were significantly different (P = 0.021) according to those with BAV-raphe+ and BAV-raphe-.; (4) Conclusions: The presence of a raphe was significantly associated with a higher prevalence of AR but a lower prevalence of AS and combined dilatation of the aortic root and middle ascending aorta. The presence of raphe was an independent determinant of AR.

Objective: To study the factors affecting the time of umbilical cord shedding in premature infants.Methods: A total of 151 premature infants who were born in the obstetrics department of a Class III hospital in Hefei from November 2020 to June 2021 were selected as subjects. All premature infants and their families met the complete inclusion criteria. A total of 33 related factors from 3 aspects, including the birth situation of premature infants, the condition of premature infants in hospital and the condition of pregnant mothers, were collected for univariate analysis and multiple Logistic regression analysis. The relevant factors affecting the umbilical cord shedding time of premature infants were screened through the univariate analysis results, and the main factors affecting the umbilical cord shedding time of premature infants were screened through the multiple Logistic regression analysis results.it was found that the weight, gestural age, admission age, whether the premature infants were combined with NRDS, the use of antibiotics, the duration in the warm box, the initial temperature in the warm box, the duration of light therapy, the degree of Apgar for 1 minute, the maternal education level had an effect on the time of umbilical cord shedding of premature infants (P < 0.05). Through Logistic multiple regression analysis, it was screened that the duration of premature infants in the incubator was the main factor affecting the umbilical cord shedding time of premature infants (P < 0.05).Conclusion: Factors such as premature infants' weight, gestural age, admission age, whether they are combined with NRDS, antibiotic use, duration in the incubator, initial temperature in the incubator, duration of phototherapy, Apgar level of 1 minute, and maternal education level will affect the umbilical cord shedding time of premature infants. Among them, duration in the incubator is the main factor affecting the umbilical cord shedding time of premature infants.

Purpose: The study aimed to investigate the efficacy of TXA supplemented with local infiltration analgesia (LIA) in reducing blood loss in patients undergoing total knee replacement. Materials: A retrospective study on 530 individuals with a mean age of 71,44 years after posterior stabilized total knee arthroplasty was evaluated. Patients were divided into three groups, corresponding to the method of bleeding control: I - patients without additional bleeding protocol (control group); II - patients with iV TXA administration (TXA group); III - patients with exact TXA protocol combined with intraoperative local infiltration analgesia (TXA + LIA group). Blood loss was measured as a substitute for blood loss by maximal Hb drop compared to preoperative Hb level. Results: The mean hospitalization for patients from the control group was 7.02 (SD 1.34) days, 6.08 (SD 1.06) days for the TXA group, and 5.56 (SD 0.79) for the TXA + LIA group. The most significant hemoglobin drop was found in the control group, which amounted to an average of 30.08% output value. In the TXA group, the decrease in hemoglobin was, on average, 25.17% (p<0.001), and in the TXA + LIA group, it was 23.67% (p<0.001). A decrease in the rate of allogeneic blood transfusions was observed, which was 24.4% in the control group, 9.9% in the TXA group, and 8% in TXA + LIA group (p<0.01). Conclusions: Compared to the separate administration of tranexamic acid, the combination of perioperative administration with local infiltration analgesia statistically significantly reduces blood loss in patients after total knee replacement.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

Purpose: Metastatic spinal cord compression (MSCC) is a severe complication of cancer that can lead to irreversible neurological impairment, necessitating prompt recognition and intervention. This retrospective, single-center study aimed to determine the prognostic factors and survival rates among patients presenting with MSCC secondary to lung cancer. Methods and Materials: We identified 74 patients with epidural metastases-related spinal cord compression and a history of lung cancer, through the electronic database of Medway Maritime Hospital in United Kingdom (UK), spanning the period from April 2016 to September 2021. Among them, 39 were below 55 years old, while 35 were aged 55 years or older, whereas 24 patients were diagnosed with small cell lung cancer (SCLC), and 50 patients had non-small cell lung cancer (NSCLC). Results: The median overall survival (OS) was 5.5 months, with 52 out of 74 patients dying within 6 months of the diagnosis of MSCC. For the entire cohort, the statistically significant variables on multi-variate analysis were: cancer type (NSCLC had improved OS), number of involved vertebrae (one to two vertebrae involvement had improved OS) and time taken to develop motor deficits (≤10 days to develop motor deficits had worsened OS). For the NSCLC cohort, the statistically significant variables on multivariate analysis were: molecular alterations (patients with epidermal growth factor receptor (EGFR) mutation), pre-treatment ambulatory status, Eastern Cooperative Oncology Group (ECOG) performance status, and time taken to develop motor deficits. Conclusions: Within the entire cohort, patients diagnosed with NSCLC and spinal metastases affecting one to two vertebrae exhibited enhanced OS. Within the NSCLC subgroup, those with EGFR mutations, who were ambulatory, and possessed an ECOG performance status of 1-2, demonstrated improved OS. In both the entire cohort and NSCLC subgroup, the development of motor deficits within a period of ≤10 days was associated with poorer OS.

Congenital diseases of the large intestine have scarcely been reported and mostly include fistula, atresia, or colonic duplication. Cases of partial colonic agenesis have rarely been described. The purpose of this study was to report a cohort of dogs and cats diagnosed with partial colonic agenesis. The colon was measured during colonoscopy or contrast-radiography and compared to the average length described in the literature. Six dogs and 17 cats were retrospectively included. Depending on the case, partial colonic agenesis could represent an incidental finding or the likeliest cause of clinical signs. Diarrhea was reported in most cases, and no specific clinical or biological abnormality was observed. Median age of presentation was variable and long asymptomatic periods were common. Abdominal ultrasound was useful and identified a short colon in 14/17 cats but only in one dog. Endoscopy was useful to confirm the diagnosis and to identify associated lesions and complications. Among others, colonic stenosis was reported in 8/9 cases that had lifelong clinical signs and the shortest colon length. This anatomical abnormality could promote chronic inflammation that might generate fibrosis and ultimately stenosis.

Background: Arthroscopic revision rotator cuff repair (ARRCR) is challenging. Biologic strategies seem to be promising. The aim was to evaluate the effectiveness of combination of microfractures of the greater tuberosity, augmentation with collagen patch graft, and platelet concentrate injections in ARRCR. Methods: A retrospective comparative study was conducted on patients that underwent ARRCR with minimum two-years follow-up. Patients in the augmentation group underwent ARRCR combined with microfractures, collagen patch graft, and postoperative subacromial injections of platelet concentrate. A standard rotator cuff repair was performed in the control group. Primary outcome: Constant Murley score (CMS). Secondary outcomes: disease-specific health-related quality of life by using the Disabilities of the Arm, Shoulder and Hand (DASH) score; assessment of tendon integrity with magnetic resonance at least six months after surgery. Significance was set at p < 0.05. Results: Forty patients were included. Mean follow-up was 36.2 + 8.7 months. The mean CMS was greater in the augmentation group (p = 0.022). No differences could be found for DASH score. Healing failure rate was higher in the control group (p = 0.002). Conclusion: Biologic augmentation of ARRCR by combination of microfractures, collagen patch graft and subacromial injections of platelet concentrate is an effective strategy in improving tendon healing rate.

Background and objectivesː Physical examination is the predominant method for evaluating pelvic floor defects. Magnetic Resonance Imaging (MRI) is a radiological technique useful to identify the underlying defects of pelvic floor structures that require surgery. The primary aim was to find correspondence between the clinical and radiological staging of pelvic organ prolapse (POP) before and after vaginal surgery. A secondary endpoint was to investigate, through clinical and MRI findings if surgery influences continence mechanisms. Finally, we reported changes in the quality of life in women who underwent surgery for prolapse. Materials and methodsː Twenty-five women with prolapse stage ≥ 2 POP-Q were recruited in this prospective study. They underwent preoperative clinical examination, MRI at rest and under the Valsalva maneuver, and quality of life questionnaires. Three months after vaginal surgery they repeated clinical and radiological evaluation. Resultsː Twenty women completed the study. Both clinical and MRI evaluations showed an improvement in prolapse and symptoms after surgery. There were some discrepancies between clinical and radiological staging. MRI parameters did not show differences between pre and postoperative at rest; under the Valsalva maneuver instead, the measurements changed after surgery. Continence was not worsening by the widening of the vesicourethral angle. Patients reported improvement in quality of life. Conclusionsː MRI is an accurate and objective method to define the stage of prolapse but the clinical evaluation alone is sufficient to stage prolapse before surgery and evaluate the result at follow-up. It is an accurate method to visualize some pelvic structures that can be compromised because of pelvic organ prolapse. MRI showed that vaginal surgery doesn’t affect continence mechanisms.

Bioactive fractions were isolated from the leaves extract of Kalanchoe pinnata and subjected to scrutiny for their prospective anti-obesity properties. An array of in vitro phytochemical, antioxidant, and enzyme inhibition assays were executed, which dis-cerned fractions F1 and F2 as the most effective fractions. These fractions were sub-sequently studied through in vivo experiments, affirming that F2 as the most potent fraction. Further characterization of F2 was conducted via HPTLC MS-MSn tech-niques. The outcomes demonstrated that F2 produced a notable anti-obesity effect in obese mice, reducing their body weight and lipid metrics, and leading to advanta-geous changes in their organs. An analytical examination of F2 revealed the existence of four principal compounds, which were subsequently subjected to in silco molecular docking and dynamic analysis, confirming their aptitude for binding to selected pro-teins. These findings imply that the utilization of Kalanchoe pinnata leaves could pro-vide a promising therapeutic strategy for the treatment of obesity.

Electrocardigraphy remains as a first-line evaluation method for cardiac function, recording the electrical activity of the heart from the body surface. Since atrial activation is seen on the ECG as P-wave, several factors are known to impact the appearance of the P-wave, such as direction of electric impulse, conduction abnormalities and anatomical characteristics of the atria. The aim of this retrospective study was to find statistically significant associations between anatomy of pulmonary veins (PVs) osberved in cardiac computed tomography (CT) and P-wave appearance during sinus rhythm on resting ECG. For each patient, a resting 12-lead ECG was recorded, the field of analysis was P wave – its’ duration, morphology and axis. The evaluation of the CT scan recordings was performed by creating 3D models of the left atrium and analyzing anatomy of the PVs and left atrial appendage (LAA). Noteworthy correlations were found: anatomy of the left PVs showed an association with LAA volume, LAA morphology and P-wave notching in lead II. The right PVs demonstrated relation with P wave axis and amplitude. Although these correlations cannot be classified as strong, they may play a role in significant scientific discoveries in future research projects.

Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause oxidative stress in metabolic processes. This study aimed to evaluate the relationship between exposure to PAHs, including benzo[a]pyrene (BaP) and 1-nitropyrene (1-NP), in the atmosphere and oxidative stress levels in the human body. This study included 44 Korean adults who lived in Cheongju, South Korea. Atmospheric BaP and 1-NP concentrations and urinary 6-hydroxy-1-nitropyrene (6-OHNP), N-acetyl-1-aminopyrene (1-NAAP), and 1-hydroxypyrene (1-OHP) concentrations were measured. The oxidative stress level was assessed by measuring urinary thiobarbituric acid reactive substances (TBARS) and 8-hydroxydeoxyguanosine (8-OHdG) concentrations. Urinary TBARS and 6-OHNP concentrations significantly differed between winter and summer. BaP exposure was significantly associated with urinary 8-OHdG concentrations in summer. However, atmospheric 1-NP did not show a significant correlation with oxidative stress marker concentrations. Urinary 1-NAAP concentration was a significant determinant for urinary 8-OHdG concentration in summer. Oxidative stress in the body increases in proportion to inhalation exposure to BaP, and more 8-OHdG is produced in the body as the amount of 1-NP, which is metabolized to 1-AP or 1-NAAP, increases.

This study aimed to compare the prognosis and characteristics of patients with advanced hepatocellular carcinoma treated with first-line atezolizumab plus bevacizumab (AB) combination therapy and hepatic artery infusion chemotherapy (HAIC). We retrospectively assessed 179 and 72 patients treated with HAIC and AB combination therapy, respectively, between January 2018 and January 2023. The progression-free survival of patients treated with HAIC was significantly superior than that of patients treated with AB (P&lt;0.05), but there was no significant difference in overall survival and objective response rate (ORR) between the two groups (P=0.1056 and P=0.137, respectively). After propensity score matching (PSM), our data revealed that there was no significant difference in PFS between patients who received AB combination therapy and HAIC therapy (P=0.8888). However, patients who received AB combination therapy had significantly better overall survival than those who received HAIC therapy (P=0.0133). In addition, after PSM, significant differences in ORR and disease control rate were not observed. In conclusion, our propensity score study reveals that patients treated with AB therapy have a significantly longer OS than those treated with HAIC.

Background and Objectives: Angioembolization has emerged as an effective therapeutic approach for pelvic hemorrhages; however, its exact effect size remains uncertain. Therefore, we conducted this systematic review and meta-analysis to investigate the effect size of embolization-related pelvic complications after nonselective angioembolization compared to that after selective angioembolization in patients with pelvic injury accompanying hemorrhage. Materials and Methods Relevant articles were collected by searching the PubMed, EMBASE, and Cochrane databases until June 24, 2023. Meta-analyses were conducted using odds ratios (ORs) for binary outcomes. Quality assessment was conducted using the risk of bias tool in non-randomized studies of interventions. Results: Five studies examining 357 patients were included in the meta-analysis. Embolization-related pelvic complications did not significantly differ between patients with nonselective and selective angioembolization (OR 1.581, 95% confidence interval [CI] 0.592 to 4.225, I2 = 0%). However, in-hospital mortality was more likely to be higher in the nonselective group (OR 2.232, 95% CI 1.014 to 4.913, I2 = 0%) than in the selective group. In the quality assessment, two studies were found to have a moderate risk of bias, whereas two studies exhibited a serious risk of bias. Conclusions: Despite the favorable outcomes observed with nonselective angioembolization concerning embolization-related pelvic complications, determining the exact effect sizes was limited owing to the significant risk of bias and heterogeneity. Nonetheless, the low incidence of ischemic pelvic complications appears to be a promising result.

It is currently unknown whether thrombin generation is associated with venous thromboembolism (VTE) recurrence, major bleeding, and mortality in the elderly. Therefore, our aim was to prospectively study the association between thrombin generation and VTE recurrence, major bleeding and mortality in elderly patients with acute VTE. Consecutive patients aged ≥65years with acute VTE were followed for 2 years starting from 1 year after the index VTE. Primary outcomes were VTE recurrence, major bleeding and mortality. Thrombin generation was assessed in 565 patients 1 year after the index VTE. At this time, 59% of patients were still anticoagulated. Thrombin generation was discriminatory for VTE recurrence, but not for major bleeding and mortality in non-anticoagulated patients. Moreover, peak ratio (adjusted subhazard ratio 4.09, 95% CI, 1.12-14.92) and normalized peak ratio (adjusted subhazard ratio 2.18, 95% CI, 1.28-3.73) in presence/absence of thrombomodulin were associated with VTE recurrence, but not with major bleeding and mortality after adjustment for potential confounding factors. In elderly patients, thrombin generation was associated with VTE recurrence, but not with major bleeding and/or mortality. Therefore, our study suggests the potential usefulness of thrombin generation measurement after anticoagulation completion for VTE to help identifying among elderly patients those at higher risk of VTE recurrence.

(1) Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that poses unique management challenges. This review aims to synthesize the current literature on IBC, focusing on diagnosis, treatment, and prognosis, while highlighting recent advances and ongoing issues in patient management.; (2) Methods: We outline the typical clinical presentation and diagnostic criteria of IBC. Additionally, we detail the main therapeutic strategies, including neoadjuvant chemotherapy, surgery, radiation therapy, targeted therapies, hormonal therapies, and emerging treatments such as immunotherapy. The review is based on a comprehensive analysis of the existing literature.; (3) Results: Despite advancements in systemic therapy and a better understanding of IBC biology, the prognosis for patients with IBC remains poor. The overall survival rate has shown only marginal improvement over the past few decades. Future research directions, including the identification of novel biomarkers for early detection and personalized medicine strategies, are identified. The need for more high-quality clinical trials to address the challenges in IBC management is emphasized.; (4) Conclusions: Managing IBC is a complex task that necessitates multidisciplinary care and patient-centered communication. This review provides clinicians and researchers with a comprehensive overview of the current challenges and future directions in IBC management. The goal is to guide treatment decisions and inform further research, ultimately improving patient outcomes and prognosis.

This work presents patient radiation dose data for pediatric interventional cardiology procedures in a large hospital in Colombia. The data collection period was from April 2020 to July 2022. The local DRLs were calculated as the 3rd quartile of patient dose data distributions for kerma area-product (Pka) values. The sample of collected clinical procedures (255) was divided into diagnostic and therapeutic procedures and grouped into five weight and five age bands. The Pka differences found between diagnostic and therapeutic procedures were statistically in all weight and age bands, except the group between 1-5 years. The local DRLs were 69 Gy/cm2 (< 5 kg), 3.44 Gy/cm2 (5-<15 kg), 8.87 Gy/cm2 (15-<30 kg), 10.51 Gy/cm2 (30-<50 kg) y 22.61 Gy/cm2 (50-<80 kg), respectively. In conclusion, from comparing our results with other existing DRL values, we are similar to other centers and scope to continue optimizing the radiation dose values. This will contribute to setting national diagnostic reference levels (DRLs) for Colombia in the near future.

Bone marrow mononuclear cells (BMMNCs) have emerged as a potential therapeutic strategy for various incurable conditions including autism spectrum disorder (ASD). To study its safety and efficacy, we analyzed 1011 patients who underwent intrathecal administration of autologous BMMNCs along with neurorehabilitation. At mean follow-up of 19.3 months after intervention, 90.6% patients showed overall improvement. Improvements were observed in attention concentration, command following, eye contact, sitting tolerance, social interaction, hyperactivity, communication, speech, aggressiveness, stereotypical and self-injurious behavior. Statistically significant changes were observed in scores of Indian Scale of Autism Assessment and Childhood Autism Rating Scale (p<0.05). On subgroup analysis, improvements were recorded irrespective of age and disease severity and better outcome was observed in patients who took multiple doses of cell therapy compared to single dose. Comparative Brain PET-CT scan of 401 patients showed improved brain metabolism after the intervention. No major adverse events were reported. Only 9 out of 1011 patients experienced seizures which were managed using medications. 4 out of 9 had history of seizures while 5 had normal EEG with no history. However, improvements were still observed in these 9 patients. Thus, intrathecal transplantation of autologous BMMNCs along with neurorehabilitation is safe and efficacious in patients with ASD.

Abstract: Background: The vaccination status of patients with inflammatory bowel disease (IBD) should be investigated before starting any treatment, and patients eventually vaccinated against vaccine preventable diseases (VPDs). Vaccination rates in patients with IBD are known to be suboptimal. The aim of this study was to investigate the vaccination coverage, attitude towards vaccinations and its possible determinants among a national cohort of IBD patients. Methods: An anonymous web-based questionnaire was sent by the Italian IBD patients’ association (AMICI) in February 2021. Previous vaccination status and patients’ attitude towards vaccinations were rec-orded. The factors influencing their attitudes were examined using crude and adjusted odds ratios (AdjORs) with 95% confidence intervals (CIs). Results: Among 4039 patients invited, 1252 patients (including 729 women, median age 47.7 [37–58]) completed the questionnaire, a response rate of 25.3%. Patients declared being vaccinated against: 74.1% tetanus, 67.7% flu (last season), 43.3% MMR, 37.1% HBV, 29.1% pneumococcus, 20% meningitis, 16% HAV, 15.3% VZV, 7.6% HPV. Two hundred and fifty-nine (20.7%) did not remember every previous vaccination. One thousand one hundred and twelve (88.8%) expressed a positive attitude towards vaccination, 91 (7.3%) were indifferent, 49 (3.9%) reported being opposed to vaccinations. The belief of possible return of VPDs with decline of vaccination coverage rates was the factor most strongly related to a positive at-titude towards vaccinations (AdjOR 5.67, 95% CI 3.45-9.30, p-value <0.001). Conclusions: A low vaccination rate against some VPDs was found among a national cohort of patients with IBD, despite a generally positive attitude towards vaccinations.

Vanadium is a well-known essential trace element, which usually exists in oxidation states in form of vanadate cation intracellularly. The pharmacological study of vanadium begins at the discovery of its unexpected inhibitory effect on ATPase. Thereafter, the protective effects on cells and the abilities in glucose metabolism regulation were observed from vanadium compound, leading to the application of vanadium compounds in clinical trials for curing diabetes. Alzheimer’s dis-ease (AD) is the most common dementia disease in elderly people. However, there is still no efficient agents for treating AD safely to date. This is mainly because of the complexity of the pathology, which are characterized by the senile plaques composed by amyloid-beta (Aβ) protein in the parenchyma of brain and the neurofibrillary tangles (NFTs) derived from hyperphosphorylated tau protein in neurocyte, along with mitochondrial damage, and eventually the central nervous system (CNS) atrophy. AD was also illustrated as type-3 diabetes, because of the observations of insulin deficiency and the high level of glucose in cerebrospinal fluid (CSF), as well as the im-paired insulin signaling in brain. In this review, we summarized the advance of applicating vanadium compound on AD treatment in experimental research and pointed out the limitation of the current study on using vanadium compounds in AD treatment. We hope it will help the future study in this field.

Background: The role of NFATC genes expression in BAV progression is not fully understood. Aim of study is to determine the significance of NFATC1 and NFATC4 gene expression for myocardial changes in children with BAV. Methods: In 47 children with BAV the standard Doppler echocar-digraphic characteristics were detected and the expression of the NFATC1 and NFATC4 genes was studied. Results: PWTd, AoPPG, in BAV patients were significantly higher compared to healthy controls (PWTd median(min-max) 9 (7-10) mm vs 7 (6-8) mm), AoPPG median (min-max) 7,79 (2,98-15,09) mm Hg vs 2,94 (2,42-3,72) mm Hg. Expression of NFATC1 gene in BAV children was significantly higher compared to NFATC4 (NFATC1 median (min-max) 70,88 (8,79-106,51) e.u. vs 7,72 (1,74-22,67) e.u., respectively p<0,05). Significant correlation of NFATC1 expression with Ao found (R=+0,53, p<0,05). In BAV patients with PWTd > 8 mm and Ao> 21 mm the NFATC1 expression was significantly higher compare to those with PWTd< =8 mm and Ao<=21 mm NFATC1 median (min-max) 45,49 (5,01-101,52) e.u. vs 15,53 (2,36-44,40) e.u., p<0.05 and 81.11 (20.27-101.10) e.u. mm vs 12.16 (2,40-45.49) e.u., p<0.05, respectively) Conclusion: in children with BAV the high expression of the NFATC1 calcineurin signalling pathway gene is associated with elevated PWTd and Ao.

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis both under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their known proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, proliferation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation of the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving post-stroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.

Psoriasis is considered an immune-mediated disease involving the innate and adaptative immune system triggered by environmental risk factors in genetically susceptible individuals. However, its physiopathology is not fully understood yet. Recent technological advances, specially genome and epigenome-wide studies, have allowed a more sensitive study of the genetic and epigenetic mechanisms, allowing an enhanced understanding of its physiopathology and facilitating the development of new drugs. In this review, we aim to summarize the current evidence on genetic and epigenetic mechanisms of psoriasis.

(1) Background: Melanoma is the most aggressive tumor located at the skin level and the man-agement of this pathology requires a correct staging as well as a modern oncological treatment, adapted to each patient. The main objective of the study is to determine the variability of lymphatic drainage in the case of melanomas located on the trunk; (2) Methods: This retrospective study in-cluded 62 cases of melanoma located on the trunk operated between July 2019 and March 2023 in which SLNB was performed and a total of 84 lymph node were excised; (3) Results: Patients had an average age of 54.5 years old, while melanomas had a mean Breslow index of 2.3 mm. The distri-bution of trunk melanomas was: upper trunk 54 cases, lower trunk 30 cases (64.3 % vs. 35.7%). The type of anesthesia chosen was general anesthesia in 53 cases, respectively spinal anesthesia in 9 cases (85.5% vs. 14.5%, p<0.001). The number of sentinel lymph nodes was 54 for melanomas lo-cated on the upper trunk, 8 cervical and 46 axillary, respectively 30 sentinel lymph nodes in cases of melanomas of the lower trunk, 16 at the axillary level and 14 at the inguinal level; (4) Conclusions: Lymph node involvement in melanoma represents an important prognostic factor and the different lymphatic drainage pathways in relation to the location of the primary tumor represents an im-portant objective in the management of this pathology.

HIV-associated cognitive dysfunction during combination antiretroviral therapy (cART) involves mitochondrial dysfunction, but the impact of contemporary cART on chronic metabolic changes in the brain and in latent HIV infection is unclear. We interrogated mitochondrial function in a human microglia (hμglia) cell line harboring inducible HIV provirus, and in SH-SY5Y cells, after exposure to individual antiretroviral drugs or cART, using the MitoStress assay. cART-induced changes in protein expression, reactive oxygen species (ROS) production, mitochondrial DNA copy number, and cellular iron were also explored. Finally, we evaluated the ability of ROS scavengers or plasmid-mediated overexpression of the antioxidant iron-binding protein, Fth1, to reverse mitochondrial defects. Contemporary antiretroviral drugs, particularly bictegravir, depressed multiple facets of mitochondrial function by 20-30%, with most pronounced effects in latently infected-HIV+ hμglia and SH-SY5Y cells. Latently HIV-infected hμglia exhibited upregulated glycolysis. Increases in total and/or mitochondrial ROS, mitochondrial DNA copy number, and cellular iron accompanied mitochondrial defects in hμglia and SH-SY5Y cells. In SH-SY5Y cells, cART reduced mitochondrial iron-sulfur-cluster-containing supercomplex and subunit expression and increased Nox2 expression. Fth1 overexpression or pre-treatment with N-acetylcysteine prevented cART-induced mitochondrial dysfunction. Contemporary cART impairs mitochondrial bioenergetics in hμglia and SH-SY5Y cells, partly through cellular iron accumulation; some effects differ by HIV latency.

Phosphocalcium metabolism disorders have emerged as potential complications in individuals recovering from COVID-19. This abstract provides a concise summary of the current understanding of phosphocalcium metabolism disturbances post-COVID, their prevalence, clinical manifestations, and underlying mechanisms. The impact of COVID-19 on phosphorus, calcium, and parathyroid hormone levels is discussed, highlighting the importance of regular monitoring and appropriate management strategies. The abstract emphasizes the need for further research to enhance our understanding of these disorders and improve post-COVID patient care.

A diagnosis of typical chronic lymphocytic leukemia (CLL) requires the presence of ≥5000 clonal B-lymphocytes/μL with the coexistence of CD19, CD20, CD5, and CD23 and the restriction of light chain immunoglobulin, and the lack of expression of antigens CD22 and CD79b. Atypical CLL (aCLL) can be distinguished from typical CLL morphologically and immunophenotypically. Atypical CLL cells are defined as prolymphocytes; morphologically, these present as deeply-clefted lymphocytes which are larger than those in typical CLL, with condensed chromatin and without prominent nucleoli. However, current aCLL diagnostics rely more on immunophenotypic characteristics rather than atypical morphology. Immunophenotypically, atypical CLL differs from classic CLL in the lack of expression of one or fewer surface antigens, most commonly CD5 and CD23, and the patient does not meet the criteria for a diagnosis of any other B-cell lymphoid malignancy. Morphologically atypical CLL has more aggressive clinical behavior and worse prognosis than classic CLL. Patients with aCLL are more likely to display markers associated with poor prognosis, including trisomy 12, unmutated IGVH, and CD38 expression compared with classic CLL. However, no standard or commonly-accepted criteria exist for differentiating aCLL from classic CLL and the clinical significance of aCLL is still under debate. This review summarizes the current state of knowledge on the morphological, immunophenotypic and genetic abnormalities of aCLL.

Prostate cancer is a common cancer among men and typically progresses slowly for several decades before becoming aggressive and spreading to other organs, leaving few treatment options. While large animals have been studied, the dog's prostate is anatomically similar to humans and has been used to study spontaneous prostate cancer. However, most research currently focuses on the mouse as a model organism due to the ability to genetically modify their prostatic tissues for molecular analysis. One hallmark in this research was the identification of the prostate-specific promoter Probasin, allowing for prostate-specific expression of transgenes. This has led to generations of mice with aggressive prostatic tumors through overexpression of the SV40 oncogene. The Probasin promoter is also used to drive Cre expression and allow researcher to generated prostate specific loss-of-function studies. Another landmark in the process of modeling prostate cancer in mice was orthoptic delivery of viral particles. This technology allows selective overexpression of oncogenes from lentivirus or the use of CRISPR to generate complex loss of function studies. These genetic modified models are complemented by classical xenografts of human prostate tumor cells in immune deficient mice. Overall, pre-clinical models have provided a portfolio of model systems to study and address complex mechanisms in prostate cancer for improved treatment options. This review will focus on the advances of each technique.