Dulaglutide reduces oxidative DNA damage and hypermethylation in the somatic cells of mice fed a high-energy diet by restoring redox balance, inflammatory responses, and DNA repair gene expressions.

Obesity is an established risk factor for numerous malignancies, although it remains uncertain whether the disease itself or weight-loss drugs are responsible for a greater predisposition to cancer. The objective of the current study was to determine the impact of dulaglutide on genetic and epigenetic DNA damage caused by obesity, which is a crucial factor in the development of cancer. Mice were administered a low-fat or high-fat diet for 12 weeks, followed by a 5-week treatment with dulaglutide. Following that, modifications of the DNA bases were examined using the comet assay. To clarify the underlying molecular mechanisms, oxidized and methylated DNA bases, changes in the redox status, levels of inflammatory cytokines, and the expression levels of some DNA repair genes were evaluated. Animals fed a high-fat diet exhibited increased body weights, elevated DNA damage, oxidation of DNA bases, and DNA hypermethylation. In addition, obese mice showed altered inflammatory responses, redox imbalances, and repair gene expressions. The findings demonstrated that dulaglutide does not exhibit genotoxicity in the investigated conditions. Following dulaglutide administration, animals fed a high-fat diet demonstrated low DNA damage, less oxidation and methylation of DNA bases, restored redox balance, and improved inflammatory responses. In addition, dulaglutide treatment restored the upregulated DNMT1, Ogg1, and p53 gene expression. Overall, dulaglutide effectively maintains DNA integrity in obese animals. It reduces oxidative DNA damage and hypermethylation by restoring redox balance, modulating inflammatory responses, and recovering altered gene expressions. These findings demonstrate dulaglutide's expediency in treating obesity and its associated complications.

Aetiologies of Leg Pain among Patients Presenting to a Vascular Surgery Clinic.

OBJECTIVE: To determine the frequency and pattern of different aetiologies of leg pain among patients visiting vascular surgery clinics. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Vascular Surgery Clinics of the Aga Khan University Hospital, Karachi, Pakistan, between February 2021 and June 2023. METHODOLOGY: This study examined patients presenting with leg pain for the first time at vascular surgery clinics. The socio-demographic and clinical data including the clinical symptoms, physical examination findings, and management of leg pain were noted using a specially designed proforma. RESULTS: In a total of 142 patients (200 limbs), 82 (57.7%) were females and 60 (42.3%) were males, with a mean age of 46.8 ± 15.1 years. The patients' mean body mass index (BMI) was 30.2 ± 7.9 kg/m2. Ninety-one (64.1%) patients had a predominantly standing job compared to 51 (35.9%) patients who had a predominantly sitting job. The most common aetiology of leg pain was chronic venous insufficiency (CVI), diagnosed in 107 (53.5%) patients, followed by neurogenic pain [41 (20.5%)], musculoskeletal pain including knee osteoarthritis [30 (15.0%)], and arterial insufficiency [22 (11.0%)].  Conclusion: CVI followed by neuropathic pain was the leading cause of leg pain in vascular surgery clinics at a tertiary care hospital. KEY WORDS: Chronic venous insufficiency, Arterial insufficiency, Vascular surgery, Leg pain, Musculoskeletal pain, Neuralgia.

Lymphocytic Colitis With Enterocolic Lymphocytic Phlebitis.

Enterocolic lymphocytic phlebitis is a rare lymphocytic vasculitis afflicting the gastrointestinal veins without involving the arterial system. Lymphocytic colitis is a more common pathology described as lymphocytic inflammation of the colonic epithelium. Concurrence of both these pathologies is extremely rare. We describe a 53-year-old man presenting with chronic watery diarrhea, abdominal pain, and weight loss. Colonoscopic examination revealed normal-appearing mucosa, but biopsy findings revealed lymphocytic colitis with coexisting enterocolic lymphocytic phlebitis. The patient was started on oral budesonide and responded to the treatment with symptomatic and histopathological resolution.

DNMT inhibitor, 5-aza-2'-deoxycytidine mitigates di(2-ethylhexyl) phthalate-induced aggravation of psoriasiform inflammation in mice via reduction in global DNA methylation in dermal and peripheral compartments.

Psoriasis is classified as an autoimmune disorder characterized by abnormal immune response leading to the development of chronic dermal inflammation. Most individuals have a genetic vulnerability that may be further influenced by epigenetic changes occurring due to multiple variables such as pollutant exposure. Epigenetic modifications such as DNA methylation possess a dynamic nature, enabling cellular differentiation and adaptation by controlling gene expression. Di(2-ethylhexyl) phthalate (DEHP) and psoriatic inflammation are known to cause modification of DNA methylation via DNA methyltransferase (DNMT). However, it is not known whether DEHP, a ubiquitous plasticizer affects psoriatic inflammation via DNMT modulation. Therefore, this study investigated the effect of DNMT inhibitor, 5-aza-2'-deoxycytidine (AZA) on DEHP-induced changes in the expression of DNMT1, global DNA methylation, and anti-/inflammatory parameters (p-STAT3, IL-17A, IL-6, iNOS, IL-10, Foxp3, Nrf2, HO-1) in the skin and the peripheral adaptive/ myeloid immune cells (CD4+ T cells/CD11b+ cells) in imiquimod (IMQ) model of psoriasiform inflammation. Further, psoriasis-associated clinical/histopathological features (ear thickness, ear weight, ear PASI score, MPO activity, and H&E staining of the ear and the back skin) were also analyzed in IMQ model. Our data show that IMQ-treated mice with DEHP exposure had increased DNMT1 expression and DNA methylation which was associated with elevated inflammatory (p-STAT3, IL-17A, IL-6, iNOS) and downregulated anti-inflammatory mediators (IL-10, Foxp3, Nrf2, HO-1) in the peripheral immune cells (CD4+ T cells/CD11b+ cells) and the skin as compared to IMQ-treated mice. Treatment with DNMT1 inhibitor caused reduction in inflammatory and elevation in anti-inflammatory parameters with significant improvement in clinical/histopathological symptoms in both IMQ-treated and DEHP-exposed IMQ-treated mice. In conclusion, our study shows strong evidence indicating that DNMT1 plays an important role in DEHP-induced exacerbation of psoriasiform inflammation in mice through hypermethylation of DNA.

Novel dihydropyrimidines as promising EGFR & HER2 inhibitors: Insights from experimental and computational studies.

Dihydropyrimidines are widely recognized for their diverse biological properties and are often synthesized by the Biginelli reactions. In this backdrop, a novel series of Biginelli dihydropyrimidines were designed, synthesized, purified, and analyzed by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. Anticancer activity against MCF-7 breast cancer cells was evaluated as part of their cytotoxicity in comparison with the normal Vero cells. The cytotoxicity of dihydropyrimidines ranges from moderate to significant. Among the 38 dihydropyrimidines screened, compounds 16, 21, and 39 exhibited significant cytotoxicity. These 3 compounds were subjected to flow cytometry studies and EGFRwt Kinase inhibition assay using lapatinib as a standard. The study included evaluation for the inhibition of EGFR and HER2 expression at five different concentrations. At a concentration of 1000 nM compound 21 showed 98.51 % and 96.79 % inhibition of EGFR and HER2 expression. Moreover, compounds 16, 21 and 39 significantly inhibited EGFRwt activity with IC50 = 69.83, 37.21 and 76.79 nM, respectively. In addition, 3D-QSAR experiments were conducted to elucidate Structure activity relationships in a 3D grid space by comparing the experimental and predicted cytotoxic activities. Molecular docking studies were performed to validate the results by in silico method. All together, we developed a new series of Biginelli dihydropyrimidines as dual EGFR/HER2 inhibitors.

Improving Water-Based Drilling Mud Performance Using Biopolymer Gum: Integrating Experimental and Machine Learning Techniques.

Drilling through shale formations can be expensive and time-consuming due to the instability of the wellbore. Further, there is a need to develop inhibitors that are environmentally friendly. Our study discovered a cost-effective solution to this problem using Gum Arabic (ArG). We evaluated the inhibition potential of an ArG clay swelling inhibitor and fluid loss controller in water-based mud (WBM) by conducting a linear swelling test, capillary suction timer test, and zeta potential, fluid loss, and rheology tests. Our results displayed a significant reduction in linear swelling of bentonite clay (Na-Ben) by up to 36.1% at a concentration of 1.0 wt. % ArG. The capillary suction timer (CST) showed that capillary suction time also increased with the increase in the concentration of ArG, which indicates the fluid-loss-controlling potential of ArG. Adding ArG to the drilling mud prominently decreased fluid loss by up to 50%. Further, ArG reduced the shear stresses of the base mud, showing its inhibition and friction-reducing effect. These findings suggest that ArG is a strong candidate for an alternate green swelling inhibitor and fluid loss controller in WBM. Introducing this new green additive could significantly reduce non-productive time and costs associated with wellbore instability while drilling. Further, a dynamic linear swelling model, based on machine learning (ML), was created to forecast the linear swelling capacity of clay samples treated with ArG. The ML model proposed demonstrates exceptional accuracy (R2 score = 0.998 on testing) in predicting the swelling properties of ArG in drilling mud.

Racial Disparities in Cardiovascular and Cerebrovascular Adverse Events in Patients with Non-Hodgkin Lymphoma: A Nationwide Analysis.

Background and Objectives: Non-Hodgkin lymphoma (NHL) has the sixth-highest malignancy-related mortality in the United States (US). However, inequalities exist in access to advanced care in specific patient populations. We aim to study the racial disparities in major adverse cardiovascular and cerebrovascular events (MACCEs) in NHL patients. Materials and Methods: Using ICD-10 codes, patients with NHL were identified from the US National Inpatient Sample 2016-2019 database. Baseline characteristics, comorbidities, and MACCE outcomes were studied, and results were stratified based on the patient's race. Results: Of the 777,740 patients with a diagnosis of NHL, 74.22% (577,215) were White, 9.15% (71,180) were Black, 9.39% (73,000) were Hispanic, 3.33% (25,935) were Asian/Pacific Islander, 0.36% (2855) were Native American, and 3.54% (27,555) belonged to other races. When compared to White patients, all-cause mortality (ACM) was significantly higher in Black patients (aOR 1.27, 95% CI 1.17-1.38, p < 0.001) and in Asian/Pacific Islander patients (aOR 1.27, 95% CI 1.12-1.45, p < 0.001). Sudden cardiac death was found to have a higher aOR in all racial sub-groups as compared to White patients; however, it was statistically significant in Black patients only (aOR 1.81, 95% CI 1.52-2.16, p < 0.001). Atrial fibrillation (AF) risk was significantly lower in patients who were Black, Hispanic, and of other races compared to White patients. Acute myocardial infarction (AMI) was noted to have a statistically significantly lower aOR in Black patients (0.70, 95% CI 0.60-0.81, p < 0.001), Hispanic patients (0.69, 95% CI 0.59-0.80, p < 0.001), and patients of other races (0.57, 95% CI 0.43-0.75, p < 0.001) as compared to White patients. Conclusions: Racial disparities are found in MACCEs among NHL patients, which is likely multifactorial, highlighting the need for healthcare strategies stratified by race to mitigate the increased risk of MACCEs. Further research involving possible epigenomic influences and social determinants of health contributing to poorer outcomes in Black and Asian/Pacific Islander patients with NHL is imperative.

Coombs-Negative Hemolytic Anemia in an Elderly COVID-19 Patient.

COVID-19 infections are known to cause multi-organ complications. Hematological complications like autoimmune hemolytic anemia with a positive direct antiglobulin test (DAT), are commonly encountered. However, Coombs-negative hemolytic anemia is extremely rare. We report an interesting case of an elderly female with moderate-severe acute respiratory distress syndrome in the setting of COVID-19 pneumonia-causing Coombs-negative hemolytic anemia. This patient initially presented with sudden onset abdominal pain and vomiting, found to have an incarcerated inguinal hernia with small bowel obstruction (SBO) on imaging. Additionally, labs revealed positive COVID-19 antigen test and normocytic anemia. The hospital course was complicated by worsening hemolytic anemia and thrombocytopenia requiring blood products. Extensive workup for hemolysis in this patient with no prior hematological abnormalities, was negative for DAT and other conditions associated with or causative of hemolysis. At discharge, hemolytic parameters improved and on follow-up, hemoglobin returned to baseline, and repeat hemolytic parameters were normal. This case emphasizes the importance of considering SARS-CoV-2 along with other viral infections as one of the differentials for Coombs-negative hemolytic anemia.

A short report on the current landscape of Artificial Intelligence (AI) in vascular surgery in Pakistan.

This study focuses on the current applications, potential, and challenges to Artificial Intelligence (AI) integration in vascular surgery with specific emphasis on its relevance in Pakistan. Despite the benefits of AI in vascular surgery, there is a substantial gap in its adoption in Pakistan compared to global standards. In our context with limited resources and a scarcity of vascular surgeons, AI can serve as a promising solution. It can enhance healthcare accessibility, improve diagnostic accuracy, and alleviate the workload on vascular surgeons. However, hurdles including the absence of a comprehensive vascular surgery database, a shortage of AI experts, and potential algorithmic biases pose significant challenges to AI implementation. Despite these obstacles, the study underscores the imperative for continued research, collaborative efforts, and investments to unlock the full potential of AI and elevate vascular healthcare standards in Pakistan.

Dapagliflozin suppresses diabetes-induced oxidative DNA damage and hypermethylation in mouse somatic cells.

Diabetes mellitus is a complex metabolic disorder resulting from the interplay of environmental, genetic, and epigenetic factors that increase the risk of cancer development. However, it is unclear whether the increased cancer risk is due to poor glycemic control or the use of some antidiabetic medications. Therefore, we investigated the genetic and epigenetic changes in somatic cells in a mouse model of diabetes and studied whether multiple exposures to the antidiabetic medication dapagliflozin influence these changes. We also elucidated the mechanism(s) of these ameliorations. The micronucleus test and modified comet assay were used to investigate bone marrow DNA damage and methylation changes. These assays revealed that dapagliflozin is non-genotoxic in the tested regimen, and oxidative DNA damage and hypermethylation were significantly higher in diabetic mice. Spectrophotometry also evaluated oxidative DNA damage and global DNA methylation, revealing similar significant alterations induced by diabetes. Conversely, the dapagliflozin-treated diabetic animals significantly reduced these changes. The expression of some genes involved in DNA repair and DNA methylation was disrupted considerably in the somatic cells of diabetic animals. In contrast, dapagliflozin treatment significantly restored these disruptions and enhanced DNA repair. The simultaneous effects of decreased oxidative DNA damage and hypermethylation levels suggest that dapagliflozin can be used as a safe antidiabetic drug to reduce DNA damage and hypermethylation in diabetes, demonstrating its usefulness in patients with diabetes to control hyperglycemia and decrease the development of its subsequent complications.

Highly efficient mica-incorporated graphene oxide-based membranes for water purification and desalination.

Graphene oxide (GO) has become the most attractive material for membrane technology owing to its potential application as a nanofiller in water treatment, purification, and desalination. In this study, we incorporated mica as a cross-linking reagent to increase the interlayer spacing and stability of GO sheets and fabricated a mica/GO (MGO) membrane for the first time. The MGO membrane (260 ± 10 nm) exhibits 100% rejection for biomolecules such as tannic acid (TA) and bovine serum albumin (BSA) and >99% rejection for multiple probe molecules, such as methylene blue, methyl orange, congo red, and rhodamine B. The high rejection of membranes can be attributed to the surface interaction of mica with GO nanosheets through covalent interaction, which enhances the stability and separation efficiency of the membranes for probe ions and molecules. This ultrathin MGO membrane also exhibits much better water permeability at 870 ± 5 L m-2 h-1 bar-1, which is 10-100 times greater than that reported for pure GO and GO-based composite membranes. Additionally, the membrane shows high rejection for salt ions (70%). Furthermore, the stability of the MGO membranes was evaluated under various conditions, and the membranes demonstrated remarkable stability for up to 60 days in a neutral environment.

Aflatoxin B1 exposure deteriorates immune abnormalities in a BTBR T+ Itpr3tf/J mouse model of autism by increasing inflammatory mediators' production in CD19-expressing cells.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficiencies in communication, repetitive and stereotyped behavioral patterns, and difficulties in reciprocal social engagement. The presence of immunological dysfunction in ASD has been well established. Aflatoxin B1 (AFB1) is a prevalent mycotoxin found in food and feed, causing immune toxicity and hepatotoxicity. AFB1 is significantly elevated in several regions around the globe. Existing research indicates that prolonged exposure to AFB1 results in neurological problems. The BTBR T+ Itpr3tf/J (BTBR) mice, which were used as an autism model, exhibit the primary behavioral traits that define ASD, such as repeated, stereotyped behaviors and impaired social interactions. The main objective of this work was to assess the toxic impact of AFB1 in BTBR mice. This work aimed to examine the effects of AFB1 on the expression of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 by CD19+ B cells in the spleen of the BTBR using flow cytometry. We also verified the impact of AFB1 exposure on the mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain of BTBR mice using real-time PCR. The findings of our study showed that the mice treated with AFB1 in the BTBR group exhibited a substantial increase in the presence of CD19+Notch-1+, CD19+IL-6+, CD19+MCP-1+, CD19+iNOS+, CD19+GM-CSF+, and CD19+NF-κB p65+ compared to the mice in the BTBR group that were treated with saline. Our findings also confirmed that administering AFB1 to BTBR mice leads to elevated mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain, in comparison to BTBR mice treated with saline. The data highlight that exposure to AFB1 worsens immunological abnormalities by increasing the expression of inflammatory mediators in BTBR mice.

Biochemical Investigation of Therapeutic Efficacy of Berberine-Enriched Extract in Streptozotocin-Induced Metabolic Impairment.

Metabolic disorders pose significant global health challenges, necessitating innovative therapeutic approaches. This study focused on the multifaceted therapeutic potential of berberine-enriched extract (BEE) in mitigating metabolic impairment induced by streptozotocin (STZ) in a rat model and compared the effects of BEE with berberine (BBR) and metformin (MET) to comprehensively evaluate their impact on various biochemical parameters. Our investigation reveals that BEE surpasses the effects of BBR and MET in ameliorating metabolic impairment, making it a promising candidate for managing metabolic disorders. For this, 30 male Wistar rats were divided into five groups (n = 6): control (CN), STZ, STZ + MET, STZ + BBR, and STZ + BEE. The treatment duration was extended over 4 weeks, during which various biochemical parameters were monitored, including fasting blood glucose (FBG), lipid profiles, inflammation, liver and kidney function biomarkers, and gene expressions of various metabolizing enzymes. The induction of metabolic impairment by STZ was evident through an elevated FBG level and disrupted lipid profiles. The enriched extract effectively regulated glucose homeostasis, as evidenced by the restoration of FBG levels, superior to both BBR and MET. Furthermore, BEE demonstrated potent effects on insulin sensitivity, upregulating the key genes involved in carbohydrate metabolism: GCK, IGF-1, and GLUT2. This highlights its potential in enhancing glucose utilization and insulin responsiveness. Dyslipidemia, a common occurrence in metabolic disorders, was effectively managed by BEE. The extract exhibited superior efficacy in regulating lipid profiles. Additionally, BEE exhibited significant anti-inflammatory properties, surpassing the effects of BBR and MET in lowering the levels of inflammatory biomarkers (IL-6 and TNF-α), thereby ameliorating insulin resistance and systemic inflammation. The extract's superior hepatoprotective and nephroprotective effects, indicated by the restoration of liver and kidney function biomarkers, further highlight its potential in maintaining organ health. Moreover, BEE demonstrated potent antioxidant properties, reducing oxidative stress and lipid peroxidation in liver tissue homogenates. Histopathological examination of the pancreas underscored the protective effects of BEE, preserving and recovering pancreatic ß-cells damaged by STZ. This collective evidence positions BEE as a promising therapeutic candidate for managing metabolic disorders and offers potential benefits beyond current treatments. In conclusion, our findings emphasize the remarkable therapeutic efficacy of BEE and provide a foundation for further research into its mechanisms, long-term safety, and clinical translation.

Biosynthesis and Multifaceted Characterization of Breynia nivosa-Derived Silver Nanoparticles: An Eco-Friendly Approach for Biomedical Applications.

This study presents an environmentally friendly synthesis of stable silver nanoparticles (Ag-NPs) using the methanolic extract of Breynia nivosa. Initial phytochemical analysis of the extract revealed the presence of alkaloids, flavonoids, glycosides, saponins, and tannins. Further characterization through high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analyses identified a diverse array of bioactive compounds, including hydroquinone, stearic acid, neophytadiene, 9,12-octadecadienoic acid (Z,Z), methyl ester, and others. The addition of B. nivosa methanolic extract to an AgNO3 solution resulted in a color change, confirming the green synthesis of Ag-NPs through the reduction of AgNO3, as made evident by ultraviolet-visible (UV-vis) spectroscopy. X-ray diffraction (XRD) analysis provided valuable insights into the crystal structure, and scanning electron microscopy (SEM) analysis visualized the predominantly spherical shape of the Ag-NPs. However, the zeta (ζ)-potential and dynamic light scattering (DLS) analyses confirmed the stability and nanoscale dimensions of the synthesized Ag-NPs. Meanwhile, Fourier transform infrared (FT-IR) spectra exhibited peaks indicative of various functional groups, including carboxylic acids, phenols, alkanes, and isocyanates. These functional groups played a crucial role in both the reduction and capping processes of the Ag-NPs. The study further explored the antioxidant activity, cytotoxicity, acetylcholinesterase inhibition, and α-amylase inhibition activities of the Ag-NPs of the B. nivosa extract, demonstrating their potential for biomedical and therapeutic applications. In conclusion, this environmentally sustainable synthesis of Ag-NPs from the B. nivosa extract, enriched with bioactive secondary metabolites detected through HPLC and GC-MS analysis, holds promise for diverse applications in the burgeoning field of green nanotechnology.

Prediction of deleterious non-synonymous SNPs of TMPRSS2 protein combined with Molecular Dynamics Simulations and free energy analysis to identify the potential peptide substrates against SARS-CoV-2.

Globally the SARS-CoV-2 viral infection demands for the new drugs, the TMPRSS2 target plays a vital role in facilitating the virus entry. The aim of the present study is to identify the potential peptide substrate from the Anti-viral database against TMPRSS2 of SARS-CoV-2. The compound screening and variation analysis were performed using molecular docking analysis and online tools such as PROVEAN and SNAP2 server, respectively. The re-docked crystal structure peptide substrate exhibits -128.151 kcal/mol whereas the RRKK peptide substrate shows -134.158 kcal/mol. Further, the selected compounds were proceeded with Molecular Dynamics Simulation, it explores the stability of the complex by revealing the hotspot residues (His296 and Ser441) were active for nucleophilic attack against TMPRSS2. The average Binding Free Energy values computed through MM/GBSA for RRKK, Camostat, and Crystal Structure were shown -69.9278 kcal/mol, -64.5983 kcal/mol, and -63.9755 kcal/mol, respectively against TMPRSS2. The 'rate of acylation' emerges as an indicator for RRKK's efficacy, it maintains the distance of 3.2 Å with Ser441 resembles, whilst its -NH backbone stabilizes at 2.5 Å 'Michaelis Complex' which leads to prevent the entry of SARS-CoV-2 to human cells. The sequence variation analysis explores that the V160 and G6 substitutions are essential to emphasize the uncover possibilities for the ongoing drug discovery research. Therefore, the identified peptide substrate found to be potent against SARS-CoV-2 and these results will be valuable for ongoing drug discovery research.Communicated by Ramaswamy H. Sarma.

Aflatoxin B1 exposure exacerbates chemokine receptor expression in the BTBR T+ Itpr3tf/J Mouse Model, unveiling insights into autism spectrum disorder: A focus on brain and spleen.

OBJECTIVE: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by significant difficulties in social interaction, communication, and repeated stereotypic behaviour. Aflatoxin B1 (AFB1) is the most potent and well-known mycotoxin in various food sources. Despite its propensity to generate significant biochemical and structural changes in human and animal tissues, the influence of AFB1 on ASD has yet to be thoroughly studied. Mounting evidence indicates that chemokine receptors play a crucial function in the central nervous system and are implicated in developing several neuroinflammatory disorders. Chemokine receptors in individuals with ASD were elevated in the anterior cingulate gyrus astrocytes, cerebellum, and brain. METHODS: The BTBR T+Itpr3tf/J (BTBR) mice are inbred strains that exhibit strong and consistently observed deficits in social interactions, characterized by excessive self-grooming and limited vocalization in social contexts. We examined the impact of AFB1 on CCR3-, CCR7-, CCR9-, CXCR3-, CXCR4-, and CXCR6-expressing I-A/I-E+ cells in the spleen of the BTBR mouse model of autism. We evaluated the mRNA levels of CCR3, CCR7, CCR9, CXCR3, CXCR4, and CXCR6 chemokine receptors in the brain. RESULTS: The exposure to AFB1 in BTBR mice resulted in a significant rise in the number of I-A/I-E+CCR3+, I-A/I-E+CCR7+, I-A/I-E+CCR9+, I-A/I-E+CXCR3+, I-A/I-E+CXCR4+, and I-A/I-E+CXCR6+ cells. Furthermore, exposure to AFB1 increased mRNA expression levels of CCR3, CCR7, CCR9, CXCR3, CXCR4, and CXCR6 in the brain. CONCLUSIONS: These findings highlight that AFB1 exposure increases the expression of chemokine receptors in BTBR mice, indicating the necessity for further research into AFB1's role in the development of ASD.

Development and content validation of a financial and functional outcomes tool for diabetes-related foot disease in patients undergoing major lower limb amputation: a prospective observational study from Pakistan.

OBJECTIVE: To develop and content validate a questionnaire to assess the financial and functional impact of major lower limb amputation in patients with diabetes-related foot disease. DESIGN: Prospective observational study. SETTING: This study was conducted at a tertiary care centre in Pakistan. PARTICIPANTS: We conducted a thorough literature review and a group interview with 10 participants, resulting in domain identification and item generation. The group included seven patients with diabetes-related foot disease who underwent major lower limb amputation and three caregivers. Subsequently, a focused group discussion was held to assess overlap and duplication among the items, and two rounds of content validation were carried out by five content and five lay experts in both English and Urdu. Question items with a Content Validity Index (CVI) score of >0.79 were retained, items with a CVI score between 0.70 and 0.79 were revised and items with a CVI score of <0.70 were excluded. RESULTS: The initial literature review and group interview resulted in 61 items in the financial and functional domains. After the focused group discussion, the questionnaire was reduced to 37 items. Following two rounds of content validation, the English questionnaire achieved the Scale-Content Validity Index/Average (S-CVI/Ave) of 0.92 and 0.89 on relevance and clarity, respectively. Similarly, the Urdu questionnaire achieved the S-CVI-Ave of 0.92 and 0.95, respectively. CONCLUSION: A 37-item multidimensional questionnaire was developed and rigorously content-validated to assess the financial and functional impact of major lower limb amputation in patients with diabetes-related foot disease. The questionnaire used in this study has shown robust content validity specifically for our population.

Peri-Operative Optimization of Patients with Crohn's Disease.

PURPOSE OF REVIEW: The management of patients with Crohn's disease (CD) undergoing surgery is complex and optimization of modifiable factors perioperatively can improve outcomes. This review focuses on the perioperative management of CD patients undergoing surgery, emphasizing the need for a multi-disciplinary approach. RECENT FINDINGS: Research highlights the benefits of a comprehensive strategy, involving nutritional optimization, psychological assessment, and addressing septic complications before surgery. Despite many CD patients being on immune-suppressing medications, studies indicate that most of these medications are safe to use and should not delay surgery. However, a personalized approach for each case is needed. This review underscores the importance of multi-disciplinary team led peri-operative management of CD patients. We suggest that this can be done at a dedicated perioperative clinic for prehabilitation, with the potential to enhance outcomes for CD patients undergoing surgery.

A novel concept and design for highly efficient photoelectrocatalytic materials with high performance, stability, and charge transport properties: development of an innovative next-generation green technology.

In semiconductors, generating charges via catalysis is a highly challenging task and characteristic of heterojunction photoanodes. A dithiophene-4,8-dione spin-coated film layer has a positive effect on the holes (positive charge carriers) for a long time in BHJ films in the solid state of materials. The photoexcited holes created in the BHJ film can persist for long periods of time, which is beneficial for catalytic reactions. In this study, a photoanode is electrically coupled to a hydrogen gas-evolving platinum cathode. When the photoanode is electrically coupled to a H2 gas evolving Pt cathode, curiously long-lived hole polaron states are observed on the timescale of seconds under operational conditions. These long-lived holes play a crucial role in enhancing the hydrogen peroxide oxidation performance of the film overlayer spin-coated onto the photoanode. The spin-coated film overlayer on the photoanode achieves the best oxidation performance for hydrogen peroxide of approximately 6.5 mA cm-2 at 1.23 VRHE without the need of a catalyst. This demonstrates the effectiveness of the overlayer in improving the catalytic performance of the photoanode with a better efficiency of 17.5% when using 851 nm excitation. This indicates that a relatively high percentage of incident photons at that specific wavelength is converted into photocurrent by the photoanode. This approach can lead to more efficient oxidation catalysis as demonstrated in the case of hydrogen peroxide oxidation.