Explore the vast range of titles available.

Epigenetic modifications, particularly histone acetylation-deacetylation and its related enzymes, such as sirtuin 1 (SIRT1) deacetylase, may have substantial roles in the pathogenesis of obesity and its associated health issues. This study aimed to evaluate global histone acetylation status and SIRT1 gene expression in children and adolescents with obesity and their association with metabolic and anthropometric parameters. This study included 60 children and adolescents, 30 with obesity and 30 normal-weight. The evaluation consisted of the analysis of global histone acetylation levels and the expression of the SIRT1 gene in peripheral blood mononuclear cells, by specific antibody and real-time PCR, respectively. Additionally, insulin, fasting plasma glucose, lipid profile and tumor necrosis factor [alpha] (TNF-[alpha]) levels were measured. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). Metabolic syndrome was determined based on the diagnostic criteria established by IDF. Individuals with obesity, particularly those with insulin resistance, had significantly higher histone acetylation levels compared to control group. Histone acetylation was positively correlated with obesity indices, TNF-[alpha], insulin, and HOMA-IR. Additionally, a significant decrease in SIRT1 gene expression was found among obese individuals, which was negatively correlated with the histone acetylation level. Furthermore, SIRT1 expression levels showed a negative correlation with various anthropometric and metabolic parameters. Histone acetylation was enhanced in children and adolescents with obesity, potentially resulting from down-regulation of SIRT1, and could play a role in the obesity-associated metabolic abnormalities and insulin resistance. Targeting global histone acetylation modulation might be considered as an epigenetic approach for early obesity management.

Background Lower lip squamous cell carcinoma is a significant subtype of head and neck cancer, constituting about 25–30% of cases. Traditional surgical methods, like primary closure, have limitations in managing large resections of lip tumors. Recent advancements in surgical techniques, particularly free flaps, have shown promising results in addressing these challenges. The Y-shaped anastomosis is an innovative approach aimed at enhancing the efficiency of microvascular free flap surgeries for improved lip cancer reconstruction outcomes. Case presentation A 77-year-old Persian male with lower lip squamous cell carcinoma underwent tumor resection with a 2 cm safety margin, bilateral neck dissection, and lip reconstruction using the right radial forearm free flap. The surgery incorporated a Y-shaped anastomosis to improve venous pedicle outcomes. Conclusion In this case, it was decided not to open the first anastomosis but to add the second end to the side one to provide two vascular supports for the venous anastomosis. Y anastomosis makes the surgery easier and decreases complications resulting from vascular size mismatch.

Background Severe combined immunodeficiencies (SCIDs) are hereditary disorders characterized by impaired T and B cell function, resulting in significant immune system dysfunction. Recombination-activating gene ( RAG ) mutations account for a substantial proportion of SCID cases. Here, we present two sibling cases of SCID caused by a novel RAG2 gene mutation. Case Presentation The index case was an 8-year-old boy who had a history of recurring infections. After a comprehensive immunological workup, the initial diagnosis of agammaglobulinemia was revised to combined immunodeficiency (CID). The patient underwent hematopoietic stem cell transplantation (HSCT) but succumbed to cytomegalovirus (CMV) infection. His brother, a 4-month-old boy, presented with CMV chorioretinitis. Leaky SCID was diagnosed based on genetic tests and immunological findings. The patient received appropriate treatment and was considered for HSCT. Both siblings had a homozygous RAG2 gene variant, with the first case classified as a variant of uncertain significance (VUS). The presence of the same mutation in the second brother, and the clinical phenotype, supports considering the mutation as likely pathogenic. Conclusions This case report highlights a novel RAG2 gene mutation associated with CID. The classification of a VUS may evolve with accumulating evidence, and additional studies are warranted to establish its pathogenicity. Proper communication between genetic counselors and immunologists, accurate documentation of patient information, increased public awareness, and precise utilization of genetic techniques are essential for optimal patient management.

Background Patients with atrial fibrillation are at risk for various complications, including thromboembolic events. This study involves developing and evaluating a Clinical Decision Support System (CDSS) to select appropriate anticoagulant drug, considering comorbidities, laboratory data, and concurrent medications. The system is based on a streamlined interpretation of the most recent globally accepted clinical guidelines. Methods Primarily a semi-structured interview regarding the challenges in the field of thromboprophylaxis for AF and clinical pharmacists and cardiologists’ needs in practice was conducted. Then the required data were extracted from the latest guidelines and confirmed by the expert panel. Using Microsoft Visio software each scenario and its corresponding rules were modeled. Dart programming language, the Flutter framework, and the Visual Studio editor were used to develop the application. Finally, the uMARS questionnaire was used to evaluate the application quality. Results The selection of the anticoagulants was reported to be the most challenging domain by 78.6% of the participants in the interview. According to the designed algorithms, the application was developed using Asp.net with the Microsoft SQL Server database platform. This CDSS is called ACAFiB-APP, which stands for Anticoagulant in AF Application. The user goes through various calculators and obtains the required data, moreover, the user will choose one or more comorbidities/clinical scenarios. Finally, ACAFiB-APP will represent the proper anticoagulant options with dosing and related considerations. All of the sections in the uMARS questionnaire received acceptable scores. Conclusions The CDSS will facilitate the informed selection of anticoagulants for complicated AF cases by considering the patient clinical scenario. Clinical trial number Not applicable.

Vancomycin is a glycopeptide antibiotic of choice for treating serious Gram-positive bacterial infections, including methicillin-resistant (MRSA). However, its therapeutic efficacy and risk of nephrotoxicity are closely related to maintaining specific serum concentration levels. Liver transplant recipients (LTRs) require precise therapeutic drug monitoring (TDM) due to altered pharmacokinetics. This study compares the accuracy and precision of two vancomycin measurement methods-chemiluminescent microparticle immunoassay (CMIA) and high-performance liquid chromatography (HPLC) in LTRs. The cross-sectional study was conducted over 11 months at the Abu-Ali Sina Solid Organ Transplant Hospital in Shiraz, Iran. The study included 34 adult LTRs on vancomycin treatment, excluding those with hypersensitivity, chronic kidney disease, burn injuries, or receiving phenytoin. Blood samples were collected at different intervals post-vancomycin administration and analyzed using both CMIA and HPLC methods. HPLC demonstrated superior accuracy and precision in measuring vancomycin concentrations, particularly in identifying patients with vancomycin-induced nephrotoxicity. Significantly higher trough (p-value: 0.026) and intermediate (p-value: 0.49) concentrations were detected by HPLC in patients experiencing nephrotoxicity, whereas CMIA did not show significant differences between groups. Pharmacokinetic variables such as half-life (p-value: 0.024) and AUC (p-value:0.037), measured by HPLC, were significantly different between LTRs with and without nephrotoxicity, which was not observed with CMIA. HPLC is more sensitive and reliable than CMIA for measuring vancomycin levels in LTRs, which is critical for optimizing vancomycin therapy and preventing adverse effects. The research suggests that HPLC should be the preferred method for vancomycin TDM in LTRs and further multicenter studies are recommended to validate these results.

The main challenges in using stem cells (SCs) are cellular survivability, undifferentiated cells, their dose-dependent effects, or age-related deteriorating functions. In this study, it was first focused on designing a bio-substrate with suitable physicomechanical properties to provide a cell-to-cell interactive microenvironment and then on studying the role of extracellular vesicle (EV), as an alternative biologic agent to overcome the SCs limitations, and its dosage, to induce bone formation. To this end, an optimized volume ratio of polyvinyl alcohol (PVA)/chitosan (CS) solution was first selected and mixed with hyaluronic acid (HA). Accordingly, adding HA to the PVA/CS structure resulted in a more coherent network (~ 5% decrease in fiber diameter, ~ 25% and 1.28-fold increase in porosity and modulus) and better cellular adhesion. The results of loading EV with different dosages (low and high) on the PVA/CS/HA scaffold network and implantation in the rat skull–defect model also indicated that this scaffold provides a burst release of EV; however, the higher dosage possesses the slower release with the gentler gradient in the release profile. Moreover, the in vivo studies exhibited that the high-dose treatment group possesses more ossification in line of the defect with more numerous, active osteoblasts and ossification in the osteoid, along with more symmetrical restoration (after 8 weeks) than the empty scaffold and the low-dose treatment group.

Background. Besides lipid-lowering effect of statins, they have been shown to have nonlipid lowering effects, such as improving bone health. An improvement in bone mineral density (BMD) has been indicated in some studies after the use of statins, in addition to an increase in 25-hydroxyvitamin D (25OHD) level. The aim of this study is to explore the association between statins and bone health taking into consideration 25OHD level and BMD. Methods. This is a randomized, cross-sectional comparative study. Subjects were divided into two groups, hypercholesterolemic participants taking simvastatin or atorvastatin as the study group and a matched control group not taking statins. All participants were assessed for serum 25OHD and BMD at lumbar spine and femoral neck. Results. A total of 114 participants were included in the study, 57 participants in each group. Results of serum 25OHD showed no significant difference between study and control groups ( P = 0.47 ), while BMD results of lumbar spine and femoral neck showed significant difference ( P = 0.05 and 0.03, resp.). Conclusion. Simvastatin and atorvastatin, at any dose for duration of more than one year, have no additive effect on 25OHD level but have a positive effect on the BMD.