Global Prevalence Research Articles

Global Incidence and Prevalence of Chronic Rhinosinusitis: A Systematic Review.

Data on the global prevalence of chronic rhinosinusitis (CRS) is significantly varied and limited across countries and over time. Therefore, we aimed to conduct a comprehensive investigation into the global, regional, and national burden of CRS from the years 1980 to 2021, as well as identify those factors that influence levels of such burden. We conducted a systematic review and meta-analysis of general population-based observational studies focusing on CRS. We calculated pooled estimates of CRS prevalence and incidence with 95% confidence intervals (CIs). Subgroup analyses were conducted stratifying by sex, age cohorts, geographic regions, smoking status, obesity, and comorbid conditions. PubMed/MEDLINE, EMBASE, CINAHL, Google Scholar, and Cochrane databases. We included general population-based observational studies on CRS published from database inception through October 20, 2023. A total of 28 eligible studies, encompassing more than 237 million participants and 11,342,923 patients with CRS from 20 countries across four continents, were included in the analysis. Global pooled prevalence of CRS and CRS with nasal polyps (CRSwNP) was found to be 8.71% (95% CI, 6.69-11.33; number of studies, 20) and 0.65% (95% CI, 0.56-0.75; number of studies, 4), respectively. The prevalence of CRS was greater in Europe compared with North America, South America, and Asia; adults compared with children; smokers compared with never-smoker; those with obesity compared with normal weight; and those with comorbidities such as asthma, diabetes mellitus, eczema, and nasal septal deviation. Pooled prevalence of CRS increased from 1980 to 2020 (1980-2000: 4.72%; 95% CI, 2.12-10.49; 2014-2020: 19.40%; 95% CI, 12.12-31.07). Similar patterns were observed in CRS incidence. Our study provides valuable insights into CRS prevalence and incidence across diverse demographic and clinical factors, highlighting its increasing global burden. The reported prevalence of CRS varies internationally, and may be increasing over time. To enhance data quality and comparability, standardization of reporting methodologies is imperative. PROSPERO (registration no. CRD42024527805).

Intercontinental Insights into Autism Spectrum Disorder: A Synthesis of Environmental Influences and DNA Methylation

Abstract Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by a broad range of symptoms. The etiology of ASD is thought to involve complex gene-environment interactions, which are crucial to understanding its various causes and symptoms. DNA methylation is an epigenetic mechanism that potentially links genetic predispositions to environmental factors in the development of ASD. This review provides a global perspective on ASD, focusing on how DNA methylation studies may reveal gene-environment interactions characteristic of specific geographical regions. It delves into the role of DNA methylation in influencing the causes and prevalence of ASD in regions where environmental influences vary significantly. We also address potential explanations for the high ASD prevalence in North America, considering lifestyle factors, environmental toxins, and diagnostic considerations. Asian and European studies offer insights into endocrine-disrupting compounds (EDC), persistent organic pollutants (POP), maternal smoking, and their associations with DNA methylation alterations in ASD. In areas with limited data on DNA methylation and ASD, such as Africa, Oceania, and South America, we discuss prevalent environmental factors based on epidemiological studies. Additionally, the review integrates global and country-specific prevalence data from various studies, providing a comprehensive picture of the variables influencing ASD diagnoses over region and year of assessment. This prevalence data, coupled with regional environmental variables and DNA methylation studies, provides a perspective on the complexities of ASD research. Integrating global prevalence data, we underscore the need for a comprehensive global understanding of ASD’s complex etiology. Expanded research into epigenetic mechanisms of ASD is needed, particularly in underrepresented populations and locations, to enhance biomarker development for diagnosis and intervention strategies for ASD that reflect the varied environmental and genetic landscapes worldwide.

Pork as a Source of Diverse Viral Foodborne Infections: An Escalating Issue

This review synthesizes current knowledge on the risks posed by viral foodborne infections associated with pork, emphasizing their global prevalence and the complexity of managing such pathogens. It covers a range of significant viruses, including hepatitis A and E, norovirus, rotavirus, sapovirus, enterovirus, astrovirus, and enteric adenovirus. The role of pigs as reservoirs for diverse pathogens with zoonotic potential further complicates safety challenges, extending risks to individuals involved in pork production and processing. Various factors influencing viral contamination throughout the meat production chain are explored, from farm-level practices to processing and handling procedures. Emphasis is placed on the critical importance of implementing effective control measures at each stage, including enhanced biosecurity, rigorous hygiene practices, and appropriate thermal processing techniques. Additionally, the need for improved surveillance and detection methods to effectively identify and monitor viral presence in meat products is highlighted. In conclusion, the necessity of adopting a One Health approach that integrates efforts in animal health, food safety, and public health to mitigate the risks of viral foodborne infections associated with meat consumption is underscored. This holistic strategy is essential for safeguarding consumer health and ensuring the safety of the global food supply.

Expert Opinion on the Role of Sacubitril/Valsartan in the Management of Hypertension in India.

Hypertension, a key modifiable risk factor for cardiovascular diseases (CVD), significantly contributes to premature death and morbidity worldwide. Despite stabilization in age-adjusted global prevalence, the absolute number of hypertensive individuals doubled from 2000 to 2010, largely due to increases in low- and middle-income countries. In 2021, only 21% of hypertensive individuals globally had effective blood pressure (BP) control. In India, hypertension is the leading risk factor for death and disability, with prevalence rates of 24% in men and 21% in women, as reported by the 2019-2020 National Family Health Survey (NFHS-5). Alarmingly, just 25% of rural and 38% of urban hypertensive Indians are undergoing treatment, with only 10% and 20% achieving BP control, respectively. This highlights the hypertension paradox, where clinical inertia and hesitancy in intensifying BP-lowering therapy persist despite the availability of antihypertensive drugs. This expert opinion paper aims to provide a comprehensive evaluation of sacubitril/valsartan in hypertension management, leveraging insights from its approved use in heart failure and examining its benefits and challenges across diverse hypertensive populations. The formulation of this expert opinion involved employing evidence-based methodologies and utilizing all available data. The document underwent scrutiny by expert cardiologists, whose clinical experiences and examination of the evidence and guidelines informed the formation of the expert opinion. This expert opinion paper provides a thorough and informed evaluation of sacubitril/valsartan, highlighting its potential to address unmet needs in BP control, particularly in challenging cases such as resistant hypertension and chronic kidney disease.

Electroencephalography-Based Brain-Computer Interfaces in Rehabilitation: A Bibliometric Analysis (2013–2023)

EEG-based Brain-Computer Interfaces (BCIs) have gained significant attention in rehabilitation due to their non-invasive, accessible ability to capture brain activity and restore neurological functions in patients with conditions such as stroke and spinal cord injuries. This study offers a comprehensive bibliometric analysis of global EEG-based BCI research in rehabilitation from 2013 to 2023. It focuses on primary research and review articles addressing technological innovations, effectiveness, and system advancements in clinical rehabilitation. Data were sourced from databases like Web of Science, and bibliometric tools (bibliometrix R) were used to analyze publication trends, geographic distribution, keyword co-occurrences, and collaboration networks. The results reveal a rapid increase in EEG-BCI research, peaking in 2022, with a primary focus on motor and sensory rehabilitation. EEG remains the most commonly used method, with significant contributions from Asia, Europe, and North America. Additionally, there is growing interest in applying BCIs to mental health, as well as integrating artificial intelligence (AI), particularly machine learning, to enhance system accuracy and adaptability. However, challenges remain, such as system inefficiencies and slow learning curves. These could be addressed by incorporating multi-modal approaches and advanced neuroimaging technologies. Further research is needed to validate the applicability of EEG-BCI advancements in both cognitive and motor rehabilitation, especially considering the high global prevalence of cerebrovascular diseases. To advance the field, expanding global participation, particularly in underrepresented regions like Latin America, is essential. Improving system efficiency through multi-modal approaches and AI integration is also critical. Ethical considerations, including data privacy, transparency, and equitable access to BCI technologies, must be prioritized to ensure the inclusive development and use of these technologies across diverse socioeconomic groups.

Innovative Approaches to Managing Postoperative Complications in Laparoscopic Sleeve Gastrectomy: A Scoping Review.

Background: Laparoscopic sleeve gastrectomy (LSG) is an effective surgical intervention for obesity, but managing complications post LSG remains crucial. Given the global prevalence of obesity, innovative approaches are needed to improve patient outcomes. Objective: This scoping review aimed to comprehensively map the existing literature on innovative approaches for managing complications in adult patients undergoing LSG to treat morbid obesity. This management strategy may include surgical techniques, perioperative care, nutritional support, or other relevant strategies. Methods: A systematic search of PubMed and Scopus databases was conducted to identify relevant studies. The prespecified inclusion criteria were applied through a two-stage screening process. Studies involving adult patients who underwent LSG for morbid obesity (body mass index > 35) and those investigating interventions related to complications were included. The scoping review process adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. The results were summarized using a narrative approach. Results: This review included 31 studies with 4547 participants, showing diverse study designs, patient demographics, and surgical locations. Among them, 6 were case reports, 18 were randomized controlled trials, and 7 were retrospective studies. Complications of LSG include staple-line leaks, stenosis, hemorrhage, infection, gastric volvulus, and nutrient malabsorption. Innovative interventions, such as staple-line reinforcement, plication methods, and the Over-the-Scope Clip system, have been investigated for effective management. Conclusion: This scoping review provides valuable insights into innovative interventions for managing complications post LSG. This review highlights the need for further research to explore long-term outcomes, compare different interventions, and address the existing gaps in the literature.

Knowledge on Complications of Recurrent Tonsillitis and its Surgical Management among Parents/Guardian of Paediatric Patients Receiving Services at the Otorhinolaryngology Department at BMC Mwanza Tanzania

Background: Tonsillitis refers to inflammation of the palatine tonsil and most often occurs in children. Recurrent tonsillitis is defined as more than seven attacks within one year, more than five attacks a year within a two-year period, or more than three attacks a year within a three-year period. The global incidence and prevalence of tonsillitis are not completely known, the research indicates that 15-30% of sore throats in children and 5-10% of sore throats in adults are bacterial tonsillitis. Method: This is a cross-sectional descriptive study with span from May 2024 to August 2024. Results: 385 participants were enrolled in the study; 60.8%of the participants were aged from 21 years to 30 years which was the majority. About 317(82.3%) parents/guardians responded that recurrent tonsillitis has an effect on the child's health, whereas 68 (17.7%) reported that recurrent tonsillitis has no effect on the child's health. Complications of recurrent tonsilitis reported to be known by parent /guardian were snoring (sleep apnoea) 111 (28.8%), ear problems like otitis media 2(0.5%), hearing loss 1(0.3%) heart problem (0.8%), renal problem 3(0.8%), affect the growth of the child 6 (1.6%), missing school 11 (2.9%). 183(47.5%) of the study participants reported that they don’t know about any complications that their child may get after surgery, while other parents/guardians reported that the child can suffer pain after surgery 99(25.7%), intraoperative or postoperative bleeding 3(0.8%) others reported that the child can get pain during eating 8(2.1%)

Quercetin’s Potential in MASLD: Investigating the Role of Autophagy and Key Molecular Pathways in Liver Steatosis and Inflammation

Metabolic dysfunction-associated fatty liver disease (MASLD) is a widespread liver disorder characterized by excessive fat accumulation in the liver, commonly associated with metabolic syndrome components such as obesity, diabetes, and dyslipidemia. With a global prevalence of up to 30%, MASLD is projected to affect over 100 million people in the U.S. and 20 million in Europe by 2030. The disease ranges from Steatotic Lived Disease (SLD) to more severe forms like metabolic dysfunction-associated steatohepatitis (MASH), which can progress to cirrhosis and hepatocellular carcinoma. Autophagy, a cellular process crucial for lipid metabolism and homeostasis, is often impaired in MASLD, leading to increased hepatic lipid accumulation and inflammation. Key autophagy-related proteins, such as Beclin1, LC3A, SQSTM1 (p62), CD36, and Perilipin 3, play significant roles in regulating this process. Disruption in these proteins contributes to the pathogenesis of MASLD. Quercetin, a natural polyphenolic flavonoid with antioxidant and anti-inflammatory properties, has promising results in mitigating MASLD. It may reduce hepatic lipid accumulation, improve mitochondrial function, and enhance autophagy. However, further research is needed to elucidate its mechanisms and validate its therapeutic potential in clinical settings. This underscores the need for continued investigation into autophagy and novel treatments for MASLD.

Genomic epidemiology and immune escape of SARS-CoV-2 recombinant strains circulating in Botswana

Background: SARS-CoV-2 continues to evolve and evade host immunity. We characterized the molecular and mutational landscape of SARS-CoV-2 recombinant strains in Botswana.Methods: We performed genomic, phylogenetic, and immunoinformatic analyses of 5,254 near-complete genomes from 2020 to 2023. We assessed the presence of mutations of interested (MutOI) that may be associated with immune escape in silico.Results: We observed a few recombinant strains in Botswana, with the majority being descendants of Omicron (XBB*), except for XV and XM. Most recombinant sequences corresponded to transmission clusters. Most recombination events occurred within the Receptor Binding Domain (RBD) of the Spike (S) protein. We identified 17 MutOI among different proteins, with the majority occurring at a very low (<4.8 × 10⁻⁵) global prevalence. We also observed S:Q474K, a MutOI in the RBD, that was predicted to escape HLA class I-mediated immune responses. Molecular surveillance is vital to inform early detection and response to potential variants with heightened immune and vaccine breakthrough properties.Conclusions: These results underscore the need for continued molecular surveillance to map the evolutionary landscape of SARS-CoV-2.

Trends in epidemiological characteristics and etiologies of diarrheal disease in children under five: an ecological study based on Global Burden of Disease study 2021

BackgroundDiarrhea remains a significant health threat to children under five years of age. The study aims to systematically elucidate the global burden of diarrhea in children, providing scientific insights for effective prevention and control strategies. MethodsThe data from the Global Burden of Disease (GBD) 2021 study was analyzed to assess the trends in incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of diarrhea in children under five years across the globe, 21 geographical region, and 204 countries and territories, stratified by age group, sex, and socio-demographic index (SDI) levels. The trend of the disease burden for childhood diarrhea from 1990 to 2021 was described and estimated using the average annual percentage change (AAPC), and a Bayesian age-period-cohort (BAPC) model was employed to predict the future burden of diarrhea in children. ResultsFrom 1990 to 2021, there was a significant decline in the global burden of diarrhea among children under five years of age. The AAPC for incidence (－4092.18, 95% confidence interval [CI]: －4224.60 – －3959.76), prevalence (－70.98, 95% CI: －72.67 – －69.28), mortality (－6.89, 95% CI: －6.95 – －6.83), and DALYs rate (－621.79, 95% CI: －627.20 – －616.38) of diarrhea in children all showed a marked downward trend. Diarrheal incidence (r = －0.782, P < 0.001), prevalence (r = －0.777, P < 0.001), mortality (r = －0.908, P < 0.001), and DALYs rate (r = －0.904, P < 0.001) were negatively correlated with the SDI. Between 2022 and 2035, the global incidence, prevalence, and mortality rates of diarrhea in children under five years are projected to continue declining. The leading causes of diarrheal mortality in children include wasting, underweight, and non-exclusive breastfeeding. Rotavirus remains the predominant pathogen associated with diarrhea-related mortality rate and DALY rate. ConclusionAlthough the global burden of diarrhea in children under five has steadily declined, it remains a significant health threat. Rotavirus is the leading pathogen, highlighting the importance of expanding rotavirus vaccination. Additionally, improving nutritional status, increasing exclusive breastfeeding rates, and enhancing access to sanitation and clean drinking water are crucial measures that, when widely implemented, can effectively reduce the health risks posed by diarrhea in children.

Global, regional, and national prevalence of HIV-1 drug resistance in treatment-naive and treatment-experienced children and adolescents: a systematic review and meta-analysis

Despite significant reductions in mother-to-child HIV-1 transmission risks due to the advancements and scale-up of antiretroviral therapy (ART), the global burden of HIV-1 drug resistance (HIVDR) in treatment-naive and treatment-experienced children and adolescents remains poorly understood. In this study, we conducted a systematic review and meta-analysis to estimate the prevalence of HIVDR in these populations globally, regionally, and at the country level. We systematically searched PubMed, Embase, and Web of Science for studies reporting HIVDR in treatment-naive and treatment-experienced children and adolescents from inception to June 28, 2024. Eligible studies reported at least ten successfully genotyped cases. We excluded studies where drug resistance was not reported separately for children and adults or for treatment-naive and treatment-experienced populations. The methodological quality of eligible studies was assessed, and random-effect models were used for meta-analysis to determine the pooled overall and regimen-specific prevalence of one or more HIVDR mutations in these populations globally, regionally, or at the country level. This study is registered with PROSPERO under the number CRD42023424483. Of 2282 records identified, 136 studies (28,539 HIV-1-infected children from 52 countries) were included for analysis. The overall prevalence of HIVDR is 26.31% (95% CI, 20.76-32.25) among treatment-naive children and 74.16% (95% CI, 67.74-80.13) among treatment-experienced children (p<0.0001). HIVDR varied widely across subregion with the highest prevalence in Southern Africa (37.80% [95% CI, 26.24-50.08]) and lowest in South America (11.79% [95% CI, 4.91-20.84]) for treatment-naive children while highest in Asia (80.85% [95% CI, 63.76-93.55]) and lowest in Europe (54.39% [95% CI, 28.61-79.03]) for treatment-experienced children. The proportion of viral failure (VF) presented positive correlation with DR prevalence for treatment-experienced children, which increased from 61.23% (95% CI, 47.98-73.72) in proportion of VF<50%-81.17% (95% CI, 71.57-89.28) in proportion of 100%. Meta-regression analysis for both groups showed that only age (naive: p=0.0005; treated: p<0.0001) was the sources of heterogeneity. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistances were the most seen mutations among the treatment-naive group, with the HIVDR prevalence more than 10% in Southern Africa, Western and Central Africa, Eastern Africa, Asia, and North America. Both nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI resistances were commonly seen among the treatment-experienced group, varying from 36.33% (95% CI, 11.96-64.93) in North America to 77.54% (95% CI, 62.70-89.58) in South America for NRTI and from 39.98% (95% CI, 13.47-69.97) in Europe to 68.86 (95% CI, 43.91-89.17) in Asia for NNRTI, respectively. This study underscores the significant burden of HIVDR among children and adolescents worldwide, particularly pronounced in sub-Saharan Africa and low-income countries. It emphasizes the critical importance of surveillance in all HIV-1-infected children and advocates for the adoption of dolutegravir (DTG) or other optimal formulations as first-line ART in settings where NNRTI resistance exceeds the WHO's 10% threshold. DTG's high resistance barrier, potent antiviral efficacy, and favorable safety profile makes it a superior choice for managing drug-resistant HIV-1, surpassing traditional antiretroviral therapies. This work was supported by the Science and Technology Innovation Committee of Shenzhen Municipality (No. JCYJ20220531102202005) and the Natural Science Foundation of Guangdong Province (No. 2024A1515012118).

Research Progress of Natural Products with the Activity of Anti-nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH), a multi-target disease, is becoming a global epidemic. Although several anti-NASH drug candidates are being evaluated in late-stage clinical trials, none have been approved by the FDA to date. Given the global prevalence of the disease, the lack of effective drugs, and the very limited therapeutic efficacy of most of the existing synthetic drugs focusing on a single target, there is an urgent need to continue to develop new therapeutic agents. In contrast, many natural products, including pure compounds and crude extracts, possess hepatoprotective activities. Usually, these natural components are characterized by multi-targeting and low side effects. Therefore, natural products are important resources for the development of new anti- NASH drugs. In this paper, we focus on reviewing the anti-NASH potential, structure, and some of the side effects of natural products based on structural classification. We hope this mini-review will help researchers design and develop new anti-NASH drugs, especially based on the structure of natural products.

Coexisting parathyroid adenoma, thyroid carcinoma, and tuberculosis of thyroid: a case report

BackgroundCoexisting parathyroid adenoma, thyroid carcinoma, and tuberculosis of thyroid is a very rare phenomenon. Primary thyroid tuberculosis is itself very rare despite high global prevalence of tuberculosis in developing countries. Majority of thyroid tuberculosis identified in postoperative histopathology or cytopathology. The coexistence of thyroid cancer with tuberculosis or parathyroid adenoma has been reported in the literature but not a single case of the three pathologies coexisting together has been found in the literature published. We are presenting a rare case of a constellation of synchronous parathyroid adenoma, thyroid carcinoma, and thyroid tuberculosis. This case report will provoke researchers to work on understanding the association of hypercalcemia or chronic inflammation leading to development of malignancy or parathyroid adenoma in the presence of hypothyroidism will give future perspective in managing such patients.Case presentationA Islam lady aged 45 years old, diagnosed with hypothyroidism, was evaluated for pregnancy loss and rapid weight gain from 13 years back and started on tablets of levothyroxine 25 µg once daily. She was doing well until the past 2 years; there after she noticed insidious onset of a swelling over anterior aspect of right side of the neck and bone pain in back and lower limbs. Patient underwent routine investigations and was found to have raised serum calcium (11.4 mg/dl) and parathyroid hormone (253 pg/ml). Anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg) level were normal. Ultrasounds showed multiple nodules in both lobe of thyroid and left inferior parathyroid adenoma. The patient underwent total thyroidectomy with left inferior parathyroidectomy, and final histopathology showed features of subacute granulomatous thyroiditis along with hurthle cell change in right lobe of thyroid. The left lobe additionally showed necrotizing epitheloid cell granulomas, which on Zeihl–Neelson staining revealed presence of acid-fast bacilli. Sections from the isthmus show a focus of papillary thyroid microcarcinoma. The left inferior parathyroid gland sent as a frozen sample was found to be parathyroid adenoma. On 6-month follow-up, the patient was feeling much relief in bone pain and tolerating antitubercular drugs uneventfully.ConclusionCoexistence of parathyroid adenoma, nonmedullary thyroid carcinoma, and thyroid tuberculosis is extremely rare. Surgery is curative for hyper parathyroidism and thyroid carcinoma. Thyroid tuberculosis responds well to current antitubercular drugs. Its etiology needs to be explored more; the probable hypothesis is chronic inflammation due to latent tuberculosis might leads to development of thyroid carcinoma and parathyroid adenoma. Further studies need to be done for better understanding of underlying mechanism and better management options for such patients. To the best of our knowledge, similar cases have not been reported.

Prevalence of human Schistosoma mansoni infection in endemic regions (2010–2024): a systematic review and meta-analysis

Schistosoma mansoni infection poses a substantial public health challenge globally, and the World Health Organization (WHO) aims for the elimination of schistosomiasis by 2030. This study aimed to assess the current prevalence of human S.mansoni infection in endemic regions worldwide between 2010 and2024. We conducted a comprehensive search in PubMed/Medline and Scopus databases as well as other public sources from 1 January 2010 to 15 July 2024. Population-based studies reporting the prevalence of S.mansoni infection were eligible. We undertook a random-effects meta-analysis to estimate pooled prevalences with 95% confidence intervals (CIs) in WHO-defined regions and assessed potential risk factors associated with S.mansoni infection. The protocol for this study was registered on PROSPERO (CRD42023438455). We identified a total of 542 eligible studies involving 1,163,866 individuals who had been tested for S.mansoni infection in 38 countries. The overall, pooled global prevalence of S.mansoni infection in endemic region was 14.8% (95% CI, 13.5%-16.1%). The pooled prevalences (95% CI) in specific regions were: 15.3% (13.9-16.8%) in sub-Saharan Africa, 12.4% (8.9-16.4%) in South America and 9.5% (5.4-14.6%) in the Eastern Mediterranean region. There was a 52.6% decrease in prevalence of S.mansoni infection and a 37% decrease in high-intensity infection for studies conducted between 2010 and 2014 compared to those conducted between 2020 and 2023. The present analysis revealed that factors including male gender, bathing or swimming in natural water bodies, crossing rivers or lakes, and engaging in water irrigation activities such as fishing, working in rice paddies or maintaining irrigation canals were significantly associated with S.mansoni infection. The findings of this investigation revealed that, despite a decline in prevalence and high-intensity infection, 7-12% of people in endemic regions, notably in sub-Saharan Africa, remained affected by schistosomiasis mansoni between 2020 and 2024. This study provides data of relevance to policymakers to support efforts to eliminate this disease. This study received no funding.

Machine-Learning Approach to Identify Potential Dengue Virus Protease Inhibitors: A Computational Perspective.

The global prevalence of dengue virus (DENV), a widespread flavivirus, has led to varied epidemiological impacts, economic burdens, and health consequences. The alarming increase in infections is exacerbated by the absence of approved antiviral agents against the DENV. Within flaviviruses, the NS3/NS2B serine protease plays a pivotal role in processing the viral polyprotein into distinct components, making it an attractive target for antiviral drug development. In this study, machine-learning (ML) techniques were employed to build predictive models for the screening of a library containing 32,000 protease inhibitors. Utilizing GNINA for structure-based virtual screening, the top potential candidates underwent a subsequent evaluation of their absorption, distribution, metabolism, excretion, and toxicity properties. Selected compounds were subjected to molecular dynamics simulations and binding free energy calculations via MM/GBSA. The results suggest that comp530 possesses binding potential to DENV protease as a noncovalent inhibitor with multiple positions for chemical substitutions, presenting opportunities for optimizing their selectivity and specificity. However, other compounds predicted via ML models may still provide a promising start for covalent inhibitors.

Engineered FnCas9 mediated mutation profiling for clarithromycin resistance in Helicobacter pylori strains isolated from Indian patients with gastrointestinal disorders

Helicobacter pylori is a highly prevalent gut pathogen with reported implications in a wide range of gastrointestinal disorders. Antibiotic based therapy, especially with clarithromycin is one of most effective treatment strategies against H. pylori. However, rising global prevalence of clarithromycin resistance in certain H. pylori strains, primarily attributed to point mutations in the 23 s ribosomal RNA coding gene, pose a major challenge in the effective eradication of this pathogen. There are a number of established methodologies devised for H. pylori mutation detection, so as to provide a tailored treatment plan to the patients and resist further transmissions of antibiotic resistant strains. However, there is no ‘gold standard’ method available to detect mutation status in clinical isolates of H. pylori from infected patients. CRISPR-Cas9 based technologies have revolutionized the field of mutation detection in biological samples, particularly during the recent COVID-19 pandemic. Although multiple assays have been reported for detection of H. pylori in clinical samples including CRISPR diagnostics (CRISPRDx) platforms, there is no such assay reported till date to detect specific mutations that confer antibiotic resistance to this pathogen. In this study, we have developed an assay using engineered FnCas9 (en31-FnCas9) protein to effectively detect the A2142G and A2143G mutations in the 23 s rDNA of H. pylori strains isolated from gastric biopsy samples. The data from in vitro cleavage assays and strip-based lateral flow tests using en31-FnCas9 and guide RNAs targeting the conserved and mutated loci of H. pylori 23 s rDNA are in perfect congruence with the data from Sanger sequencing and restriction fragment length polymorphism (RFLP) analysis. Our results indicate that en31-FnCas9 based mutation analysis can be deployed as an efficient diagnostic methodology to detect clarithromycin susceptibility in patients with suspected H. pylori infections.

Global burden of dementia in younger people: an analysis of data from the 2021 Global Burden of Disease Study

Dementia among younger people is rapidly emerging as a global health concern; however, comprehensive research on its shifting burden trends remains insufficient. Data on the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) associated with dementia occurring in individuals <70 years were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021. Average annual percentage changes (AAPCs) were calculated to assess trends in age-specific rates (ASRs), including age-specific prevalence rates (ASPRs), age-specific incidence rates (ASIRs), age-specific mortality rates (ASMRs), and age-specific DALY rates (ASDRs) while young-onset dementia (YOD) burden trends were analyzed. The correlation between ASR/AAPC and the sociodemographic index (SDI) was evaluated. In 2021, the global prevalence of dementia in individuals <70 years increased by 122.33%, with a 128% increase in new cases since 1990. Concurrently, deaths and DALYs of individuals <70 years with dementia rose by 119.28% and 119.77%, respectively. The AAPCs of YOD ASRs during 1990-2021 initially increased and then decreased with increasing SDI levels, with the highest AAPCs of ASPR (2.20 [95%CI: 2.08-2.32] per 100,000), ASIR (2.25 [95%CI: 2.06-2.45] per 100,000), ASMR (2.04 [95%CI: 1.93-2.15] per 100,000), and ASDR (2.06 [95%CI: 1.99-2.13] per 100,000) observed in middle-SDI levels. Additionally, females <70 years bore a higher burden of dementia globally, and gender differences are still widening. The growth rate of YOD is accelerating, particularly in the middle to high SDI region with females bearing a disproportionately higher burden of YOD. This work was supported by grants from the National High level Hospital Clinical Research Funding, CAMS Innovation Fund for Medical Sciences, and the National Natural Science Foundation of China.

Is it necessary to diagnose and correct vitamin D deficiency in malignant neoplasms? Analytical review

BACKGROUND: Although the critical role of vitamin D in mineral homeostasis regulation is widely recognized, the global prevalence of vitamin D deficiency is exceedingly high. The substantial number of population-based studies that examine the correlation between the concentration of circulating vitamin D levels and the risk of developing cancer may be attributed to the growing interest of researchers in this vitamin as a suppressor of proliferating epithelial cells. However, the data collected are contradictory. AIM: To ascertain the necessity of diagnosing and rectifying vitamin D deficiency in cancer patients. MATERIALS AND METHODS: The keywords “vitamin D,” “vitamin D deficiency,” “cancer,” and “survival” were employed to identify publications in the e-Library, PubMed, and ScienceDirect databases from January 2014 to January 2024. Based on the data obtained, an analytical review of the literature was conducted. RESULTS: The global prevalence of vitamin D deficiency, including among cancer patients, is exceedingly high and does not vary by sex, age, or ethnicity. Decreased serum vitamin D levels are linked to an elevated incidence of colorectal cancer, breast cancer, melanoma, prostate, and pancreatic cancer. Addressing vitamin D deficiency helped mitigate the risk of developing breast cancer. Data on the effect of vitamin D deficiency and its correction on patient survival are inconsistent. CONCLUSION: Currently, there is no consensus regarding the impact of vitamin D supplementation on the incidence of diverse malignancies, as well as tumor-specific and overall survival. Additional research is required to address the necessity of diagnosing and correcting vitamin D deficiency.

The Dominant Personality Trait in Type 2 Diabetes Mellitus Patients at Dr. Soetomo General Hospital Surabaya

Introduction: Diabetes mellitus (DM) is a chronic disease characterized by elevated blood sugar levels above the normal range. The global prevalence of DM increased, with over 90% of cases being Type 2 Diabetes Mellitus (T2DM). People attempted various physical therapies, including adopting a healthy lifestyle through dietary adjustments, physical activity, and pharmacological interventions. However, we have not extensively explored non-physical therapies related to personality traits, and the incidence of DM remains high. The Big Five Personality Theory encompasses openness, conscientiousness, extraversion, agreeableness, and neuroticism. Each personality trait is believed to have specific tendencies toward diseases, emphasizing the importance of identifying the dominant personality traits in T2DM patients. This study aims to identify the dominant personality type in T2DM patients based on the Big Five Personality Theory at Dr. Soetomo General Hospital Surabaya. Methods: We employed a cross-sectional approach for data collection, using Big Five personality questionnaires as the primary data sources. Results: Among the 68 T2DM patients who participated in this study at Dr. Soetomo General Hospital Surabaya, from October 2022 to May 2023, the mean age of patients was 51-60 years, with a majority of female participants (63.2%) and male participants (37.8%). The questionnaire results indicated that the dominant personality trait was agreeableness (85.3%). Conclusion: The dominant personality type in T2DM patients, according to the Big Five Personality Theory at Dr. Soetomo General Academic Hospital Surabaya, was agreeableness (85.3%).

An Insight into the Repurposing of Phytoconstituents obtained from Delhi's Aravalli Biodiversity Park as Antifungal Agents.

The global prevalence of fungal infections is alarming in both the pre- and post- COVID period. Due to a limited number of antifungal drugs, there are hurdles in treatment strategies for fungal infections due to toxic potential, drug interactions, and the development of fungal resistance. All the antifungal targets (existing and newer) and pipeline molecules showing promise against these targets are reviewed. The objective was to predict or repurpose phyto-based antifungal compounds based on a dual target inhibition approach (Sterol-14-α- demethylase and HSP-90) using a case study. In pursuit of repurposing the phytochemicals as antifungal agents, a team of researchers visited Aravalli Biodiversity Park (ABP), Delhi, India, to collect information on available medicinal plants. From 45 plants, a total of 1149 ligands were collected, and virtual screening was performed using Schrodinger Suite 2016 software to get 83 hits against both the target proteins: Sterol-14-α-demethylase and HSP-90. After analysis of docking results, ligands were selected based on their interaction against both the target proteins and comparison with respective standard ligands (fluconazole and ganetespib). We have selected Isocarthamidin, Quercetin and Boeravinone B based on their docking score and binding interaction against the HSP-90 (Docking Score -9.65, -9.22 and -9.21, respectively) and 14-α-demethylase (Docking Score -9.19, -10.76 and -9.74 respectively). The docking protocol was validated and MM/GBSA studies depicted better stability of selected three ligands (Isocarthamidin, Quercetin, Boeravinone B) complex as compared to standard complex. Further, MD simulation studies were performed using the Desmond (67) software package version 2018-4. All the findings are presented as a case study for the prediction of dual targets for the repurposing of certain phytochemicals as antifungal agents.