Structural determinants of dual incretin receptor agonism by tirzepatide.

SignificanceTirzepatide is a dual agonist of the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R), which are incretin receptors that regulate carbohydrate metabolism. This investigational agent has proven superior to selective GLP-1R agonists in clinical trials in subjects with type 2 diabetes mellitus. Intriguingly, although tirzepatide closely resembles native GIP in how it activates the GIPR, it differs markedly from GLP-1 in its activation of the GLP-1R, resulting in less agonist-induced receptor desensitization. We report how cryogenic electron microscopy and molecular dynamics simulations inform the structural basis for the unique pharmacology of tirzepatide. These studies reveal the extent to which fatty acid modification, combined with amino acid sequence, determines the mode of action of a multireceptor agonist.

Nunavimmi puvakkut kaggutimik aanniaqarniq: Qanuilirqitaa? Lung cancer in Nunavik: How are we doing? A retrospective matched cohort study.

BACKGROUND: Whether Inuit in Canada experience disparities in lung cancer survival remains unknown. When requiring investigation and treatment for lung cancer, all residents of Nunavik, the Inuit homeland in Quebec, are sent to the McGill University Health Centre (MUHC), in Montréal. We sought to compare survival among patients with lung cancer at the MUHC, who were residents of Nunavik and Montréal, Quebec, respectively. METHODS: We conducted a retrospective cohort study. Using lung cancer registry data, we identified Nunavik residents with histologically confirmed lung cancer diagnosed between 2005 and 2017. We aimed to match 2 Montréal residents to each Nunavik resident on sex, age, calendar year of diagnosis, and histology (non-small cell lung cancer v. small cell lung cancer). We reviewed medical records for data on additional patient characteristics and treatment, and obtained vital status from a provincial registry. We compared survival using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: We included 95 residents of Nunavik and 185 residents of Montréal. For non-small cell lung cancer, median survival times were 321 (95% confidence interval [CI] 184-626) days for Nunavik (n = 71) and 720 (95% CI 536-1208) days for Montréal residents (n = 141). For small cell lung cancer, median survival times were 190 (95% CI 159-308) days for Nunavik (n = 24) and 270 (95% CI 194-766) days for Montréal residents (n = 44). Adjusting for matching variables, stage, performance status, and comorbidity, Nunavik residents had a higher hazard of death (hazard ratio 1.68, 95% CI 1.17-2.41). INTERPRETATION: Nunavik residents experience disparities in survival after lung cancer diagnosis. Although studies in other Inuit Nunangat regions are needed, our findings point to an urgent need to ensure that interventions aimed at improving lung cancer survival, including lung cancer screening, are accessible to Inuit Nunangat residents.

Re-vitalizing wastewater: Nutrient recovery and carbon capture through microbe-algae synergy using omics-biology.

Increasing amounts of wastewater is the most pervasive and challenging environmental problem globally. Conventional treatment methods are costly and entail huge energy, carbon consumption and greenhouse gas emissions. Owing to their unique ability of carbon capturing and resource recovery, microalgae-microbiome based treatment is a potential approach and is widely used for carbon-neutral wastewater treatment. Microalgae-bacteria synergy (i.e., the functionally beneficial microbial synthetic communities) performs better and enhances carbon-sequestration and nutrient recovery from wastewater treatment plants. This review presents a comprehensive information regarding the potential of microalgae-microbiome as a sustainable agent for wastewater and discusses synergistic approaches for effective nutrient removal. Moreover, this review discusses, the role of omics-biology and Insilco approaches in unravelling and understanding the algae-microbe synergism and their response toward wastewater treatment. Finally, it discusses various microbiome engineering approaches for developing the effective microalgae-bacteria partners for carbon sequestration and nutrient recovery from wastewater, and summarizes future research perspectives on microalgae-microbiome based bioremediation.

Engineering of insecticidal hybrid gene into potato chloroplast genome exhibits promising control of Colorado potato beetle, Leptinotarsa decemlineata (Coleoptera: Chrysomelidae).

The potato chloroplast was transformed with codon optimized synthetic hybrid cry gene (SN19) to mitigate crop losses by Colorado potato beetle (CPB). The bombarded explants (leaves and internode) were cultured on MS medium supplemented with BAP (2.0 mg/l), NAA (0.2 mg/l), TDZ (2.0 mg/l) and GA3 (0.1 mg/l); spectinomycin 50 mg/l was used as a selection agent in the medium. Leaf explants of cultivar Kuroda induced highest percentage (92%) of callus where cultivar Santae produced the highest percentage (85.7%) of transplastomic shoots. Sante and Challenger showed 9.6% shoot regeneration efficiency followed by cultivar Simply Red (8.8%). PCR amplification yielded 16 postive transplastomic plantlets out of 21 spectinomycin resistant ones. Target gene integration was confirmed by PCR and Southern blot, whereas RT-qPCR was used to assess the expression level of transgene. The localization of visual marker gene gfp was tracked by laser scanning confocal microscopy which confirmed its expression in chloroplasts of leaf cells. The transplastomic plants ensured high mortality to both larvae and adult CPB. Foliage consumption and weight gain of CPB fed on transplastomic leaves were lower compared to the control plants. Sucessful implementation of current research findings can lead to a viable solution to CPB mediated potato losses globally.

In Vivo Mechanism of Action of Sodium Caprate for Improving the Intestinal Absorption of a GLP1/GIP Coagonist Peptide.

Sodium caprate (C10) has been widely evaluated as an intestinal permeation enhancer for the oral delivery of macromolecules. However, the effect of C10 on the intestinal absorption of peptides with different physicochemical properties and its permeation-enhancing effect in vivo remains to be understood. Here, we evaluated the effects of C10 on intestinal absorption in rats with a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GIP-GLP1) dual agonist peptide (LY) and semaglutide with different enzymatic stabilities and self-association behaviors as well as the oral exposure of the LY peptide in minipigs. Furthermore, we investigated the mechanism of action (MoA) of C10 for improving the intestinal absorption of the LY peptide in vivo via live imaging of the rat intestinal epithelium and tissue distribution of the LY peptide in minipigs. The LY peptide showed higher proteolytic stability in pancreatin and was a monomer in solution compared to that in semaglutide. C10 increased in vitro permeability in the minipig intestinal organoid monolayer to a greater extent for the LY peptide than for semaglutide. In the rat jejunal closed-loop model, C10 increased the absorption of LY peptide better than that of semaglutide, which might be attributed to higher in vitro proteolytic stability and permeability of the LY peptide. Using confocal live imaging, we observed that C10 enabled the rapid oral absorption of a model macromolecule (FD4) in the rat intestine. In the duodenum tissues of minipigs, C10 was found to qualitatively reduce the tight junction protein level and allow peptide uptake to the intestinal cells. C10 decreased the transition temperature of the artificial lipid membrane, indicating an increase in membrane fluidity, which is consistent with the above in vivo imaging results. These data indicated that the LY's favorable physicochemical properties combined with the effects of C10 on the intestinal mucosa resulted in an ∼2% relative bioavailability in minipigs.

The prevalence of tuberculosis infection among foreign-born Canadians: a modelling study.

BACKGROUND: The prevalence of tuberculosis infection is critical to the design of tuberculosis prevention strategies, yet is unknown in Canada. We estimated the prevalence of tuberculosis infection among Canadian residents born abroad. METHODS: We estimated the prevalence of tuberculosis infection by age and year of migration to Canada for people from each of 168 countries by constructing country-specific and calendar year-specific trends for annual risk of infection using a previously developed model. We combined country-specific prevalence estimates with Canadian Census data from 2001, 2006, 2011, 2016 and 2021 to estimate the overall prevalence of tuberculosis infection among foreign-born Canadian residents. RESULTS: The estimated overall prevalence of tuberculosis infection among foreign-born people in Canada was 25% (95% uncertainty interval [UI] 20%-35%) for census year 2001, 24% (95% UI 20%-33%) for 2006, 23% (95% UI 19%-30%) for 2011, 22% (95% UI 19%-28%) for 2016 and 22% (95% UI 19%-27%) for 2021. The prevalence increased with age at migration and incidence of tuberculosis in the country of origin. In 2021, the estimated prevalence of infection among foreign-born residents was lowest in Quebec (19%, 95% UI 16%-24%) and highest in Alberta (24%, 95% UI 21%-28%) and British Columbia (24%, 95% UI 20%-30%). Among all foreign-born Canadian residents with tuberculosis infection in 2021, we estimated that only 1 in 488 (95% UI 185-1039) had become infected within the 2 preceding years. INTERPRETATION: About 1 in 4 foreign-born Canadian residents has tuberculosis infection, but very few were infected within the 2 preceding years (the highest risk period for progression to tuberculosis disease). These data may inform future tuberculosis infection screening policies.

Active screening for tuberculosis in high-incidence Inuit communities in Canada: a cost-effectiveness analysis.

BACKGROUND: Active screening for tuberculosis (TB) involves systematic detection of previously undiagnosed TB disease or latent TB infection (LTBI). It may be an important step toward elimination of TB among Inuit in Canada. We aimed to evaluate the cost-effectiveness of community-wide active screening for TB infection and disease in 2 Inuit communities in Nunavik. METHODS: We incorporated screening data from the 2 communities into a decision analysis model. We predicted TB-related health outcomes over a 20-year time frame, beginning in 2019. We assessed the cost-effectiveness of active screening in the presence of varying outbreak frequency and intensity. We also considered scenarios involving variation in timing, impact and uptake of screening programs. RESULTS: Given a single large outbreak in 2019, we estimated that 1 round of active screening reduced TB disease by 13% (95% uncertainty range -3% to 27%) and was cost saving compared with no screening, over 20 years. In the presence of simulated large outbreaks every 3 years thereafter, a single round of active screening was cost saving, as was biennial active screening. Compared with a single round, we also determined that biennial active screening reduced TB disease by 59% (95% uncertainty range 52% to 63%) and was estimated to cost Can$6430 (95% uncertainty range -$29 131 to $13 658 in 2019 Can$) per additional active TB case prevented. With smaller outbreaks or improved rates of treatment initiation and completion for people with LTBI, we determined that biennial active screening remained reasonably cost-effective compared with no active screening. INTERPRETATION: Active screening is a potentially cost-saving approach to reducing disease burden in Inuit communities that have frequent TB outbreaks.

Microbial lipase production: A deep insight into the recent advances of lipase production and purification techniques.

Importance of enzymes is ever-rising particularly microbial lipases holding great industrial worth owing to their potential to catalyze a diverse array of chemical reactions in aqueous as well as nonaqueous settings. International lipase market is anticipated to cross USD 797.7 million till 2025, rising at a 6.2% compound annual growth rate from 2017 to 2025. The recent breakthrough in the field of lipase research is the generation of new and upgraded versions of lipases via molecular strategies. For example, integration of rational enzyme design and directed enzyme evolution to attain desired properties in lipases. Normally, purification of lipase with significant purity is achieved through a multistep procedure. Such multiple step approach of lipase purification entails both conventional and novel techniques. The present review attempts to provide an overview of different aspects of lipase production including fermentation techniques, factors affecting lipase production, and purification strategies, with the aim to assist researchers to pick a suitable technique for the production and purification of lipase.

Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis.

BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Modern Trends in Plant Genome Editing: An Inclusive Review of the CRISPR/Cas9 Toolbox.

Increasing agricultural productivity via modern breeding strategies is of prime interest to attain global food security. An array of biotic and abiotic stressors affect productivity as well as the quality of crop plants, and it is a primary need to develop crops with improved adaptability, high productivity, and resilience against these biotic/abiotic stressors. Conventional approaches to genetic engineering involve tedious procedures. State-of-the-art OMICS approaches reinforced with next-generation sequencing and the latest developments in genome editing tools have paved the way for targeted mutagenesis, opening new horizons for precise genome engineering. Various genome editing tools such as transcription activator-like effector nucleases (TALENs), zinc-finger nucleases (ZFNs), and meganucleases (MNs) have enabled plant scientists to manipulate desired genes in crop plants. However, these approaches are expensive and laborious involving complex procedures for successful editing. Conversely, CRISPR/Cas9 is an entrancing, easy-to-design, cost-effective, and versatile tool for precise and efficient plant genome editing. In recent years, the CRISPR/Cas9 system has emerged as a powerful tool for targeted mutagenesis, including single base substitution, multiplex gene editing, gene knockouts, and regulation of gene transcription in plants. Thus, CRISPR/Cas9-based genome editing has demonstrated great potential for crop improvement but regulation of genome-edited crops is still in its infancy. Here, we extensively reviewed the availability of CRISPR/Cas9 genome editing tools for plant biotechnologists to target desired genes and its vast applications in crop breeding research.

Techno-economic estimation of wastewater phycoremediation and environmental benefits using Scenedesmus obliquus microalgae.

This study investigated the dual application of Scenedesmus obliquus for wastewater phycoremediation and biochemical component accumulation in microalgal cells. The microalgae grown in wastewater showed micro-elements uptake and removal efficiencies of 71.2 ±â€¯3.5% COD, 81.9 ±â€¯3.8% NH4+, ∼100.0% NO3-, and 94.1 ±â€¯4.7% PO43-. The growth profile of Scenedesmus obliquus indicated a specific growth rate of 0.42 ±â€¯0.02 1·d-1 and carrying capacity of 0.88 ±â€¯0.04 g L-1. The lipid, protein, and carbohydrate yields (w·w-1 of dry weight) were 26.5 ±â€¯1.5%, 28.5 ±â€¯1.5%, and 27.5 ±â€¯1.6%, respectively. The de-oiled biomass was subjected to biochemical extraction, achieving protein and carbohydrate yields of 25.3 ±â€¯1.4% and 21.4 ±â€¯1.2%, respectively. Fourier transform infrared spectroscopy showed several functional groups (e.g., NH, CH3, CH2, CO, CN, PO, and SiO) on the biomass surface, confirming the accumulation of biochemical elements in microalgae. The thermal analysis of microalgal biomass depicted sequential stages of dehydration (60-190 °C), devolatilization (200-490 °C), and solid residue decomposition (490-600 °C). The cost-benefit analysis of microalgae cultivated in wastewater was derived regarding amortization and operating costs and energy and environmental benefits. The net profit of phycoremediation was 16885 US$·y-1, resulting in a payback period of 14.8 years (i.e., shorter than the project lifetime). Accordingly, the proposed phycoremediation process was economically viable.

Enhanced production of streptokinase from Streptococcus agalactiae EBL-31 by response surface methodology.

Streptokinase (SK) is a fibrinolytic protein used for the treatment of cardiovascular disorders. In the present study, enhanced production of SK was achieved by determining the optimum fermentation conditions for the maximum growth of Streptococcus agalactiae EBL-31 using response surface methodology (RSM). Four process variables (pH, temperature, incubation time and inoculum size) with five levels were evaluated in 30 experimental runs. Central composite rotatable design (CCRD) was employed to predict the effect of independent variables on SK activity. The statistical evaluation by ANOVA showed that the model was fit as the effect of single factors, quadratic effects and most of the interactions among variables. The value ofR2 (0.9988) indicated the satisfactory interaction between the experimental and predicted responses. Furthermore, the model F value (902.67) and coefficient of variation (1.92) clearly showed that the model is significant (p =>0.0001). The functional activity of SK was determined by spectrophotometric analysis and maximum SK production was obtained at pH-7.0, temperature- 37.5oC, an incubation time of 36 hours and 2.5 mL inoculum size. Hence it was concluded that the optimization of culture conditions through RSM increases the production of SK by 2.01-fold. Production of SK by fermentation is an economical choice to be used for the treatment of cardiovascular diseases.

Effect of integration of oxalic acid and hot water treatments on postharvest quality of rambutan (Nephelium lappaceum L. cv. Anak Sekolah) under modified atmosphere packaging.

The shelf life of rambutan is often limited due to rapid water loss from the spinterns and browning of the pericarp. An integrated approach, which combined hot water treatment (HWT) (56 °C for 1 min), oxalic acid (OA) dip (10% for 10 min) and modified atmosphere packaging (MAP), was used to study their effectiveness on the quality of rambutan during storage (10 °C, 90-95% relative humidity). Significant differences were observed in rambutan quality with the combination of MAP + HWT + OA after 20 days of storage. This treatment combination resulted into better retention of firmness and colour (L and a* values) than in the control. Change in the total soluble solid content was significantly delayed however the titratable acidity showed no significant change in comparison to the control at the end of storage.

The functions of hydrogen sulfide on the urogenital system of both males and females: from inception to the present.

Hydrogen sulfide (H2S) is known as a chemical gas in nature with both enzymatic and non-enzymatic biosynthesis in different human organs. A couple of studies have demonstrated the function of H2S in regulating the homeostasis of the human body. Additionally, they have shown its synthesis, measurement, chemistry, protective effects, and interaction in various aspects of scientific evidence. Furthermore, many researches have demonstrated the beneficial impacts of H2S on genital organs and systems. According to various studies, it is recognized that H2S-producing enzymes and the endogenous production of H2S are expressed in male and female reproductive systems in different mammalian species. The main goal of this comprehensive review is to assess the potential therapeutic impacts of this gasotransmitter in the male and female urogenital system and find underlying mechanisms of this agent. This narrative review investigated the articles that were published from the 1970s to 2022. The review's primary focus is the impacts of H2S on the male and female urogenital system. Medline, CINAHL, PubMed, and Google scholar databases were searched. Keywords used in this review were "Hydrogen sulfide," "H2S," "urogenital system," and "urogenital tract". Numerous studies have demonstrated the therapeutic and protective effects of sodium hydrosulfide (Na-HS) as an H2S donor on male and female infertility disorders. Furthermore, it has been observed that H2S plays a significant role in improving different diseases such as ameliorating sperm parameters. The specific localization of H2S enzymes in the urogenital system provides an excellent opportunity to comprehend its function and role in various disorders related to this system. It is noteworthy that H2S has been demonstrated to be produced in endocrine organs and exhibit diverse activities. Moreover, it is important to recognize that alterations in H2S biosynthesis are closely linked to endocrine disorders. Therefore, hormones can be pivotal in regulating H2S production, and H2S synthesis pathways may aid in establishing novel therapeutic strategies. H2S possesses pharmacological effects on essential disorders, such as anti-inflammation, anti-apoptosis, and anti-oxidant activities, which render it a valuable therapeutic agent for human urogenital disease. Furthermore, this agent shows promise in ameliorating the detrimental effects of various male and female diseases. Despite the limited clinical research, studies have demonstrated that applying H2S as an anti-oxidant source could ameliorate adverse effects of different conditions in the urogenital system. More clinical studies are required to confirm the role of this component in clinical settings.

Assessment of gastroesophageal reflux disease signs, symptoms, and food behaviors concerning mental health in Herat, Afghanistan: A descriptive study.

Background and Aims: Gastroesophageal reflux disease (GERD) is a highly prevalent gastrointestinal disorder with modifiable risk factors that are associated with considerable health and economic burdens. The current study was conducted to assess the signs and symptoms, food behaviors, depression, anxiety, and stress related to GERD in Herat, Afghanistan. Methods: A descriptive study was conducted between August 29 and October 20, 2020, among patients with GERD symptoms, who provided informed verbal consent at the Mowaffaq Clinic and Sehat Hospital in Herat, Afghanistan. The minimum sample size was 384. Data were collected using a three-domain questionnaire and Depression, Anxiety, and Stress Scale 42 standard questionnaire. SPSS version 27 was used to perform descriptive statistics and χ 2 tests. Results: The sample consisted of 396 patients, with the majority being female (67.9%), married (78.5%), and illiterate (34.8%). Heartburn (88.1%) and regurgitation (84.3%) were the most common symptoms reported by participants. Tomato consumption (60.1%) was the most frequent type of eating behavior. Most patients reported severe anxiety (45.9%) and showed statistically significant differences in age, sex, education level, and cigarette usage. This study also found that certain demographic status, eating behaviors, and symptoms were associated with significantly different depression, anxiety, and stress scores among patients with GERD. Conclusion: Our study demonstrates the association between GERD and various modifiable risk factors in Herat, Afghanistan. Public health initiatives focusing on preventive measures and raising awareness can potentially alleviate the burden of GERD. Moreover, further research and targeted interventions are essential to improve health outcomes, particularly among patients with GERD, who may experience psychological comorbidities.

Efficacy of massage versus massage with post isometric relaxation in temporomandibular disorders: a randomized controlled trial.

BACKGROUND: Temporomandibular joint disorder (TMD) is a common condition affecting the masticatory muscles and joint mobility. OBJECTIVES: The primary objective was to compare the effects of massage therapy alone and massage therapy combined with post-isometric relaxation exercises in patients with TMD for pain and maximal mouth opening. DESIGN: Assessor-blinded randomized controlled trial. SETTING: Sir Ganga Ram Hospital, Chaudhry Muhammad Akram Dental Hospital, Lahore Medical and Dental Hospital. SUBJECTS: Temporomandibular joint disorder patients. INTERVENTION: Group A (n = 23) received conventional treatment including massage and therapeutic exercises consecutively for 2 weeks. Group B (n = 23) received post-isometric relaxation technique along with conventional treatment for consecutive 2 weeks. MAIN MEASURES: The main outcome measures were pain and maximal mouth opening. Pain was measured using the Visual Analogue Scale (VAS) and maximal mouth opening (MMO) was measured using the TheraBite Scale. RESULTS: Both groups demonstrated significant improvements in pain and MMO scores post-treatment. However, Group B (massage with post-isometric relaxation exercises) showed significantly better outcomes compared to Group A (massage alone). There was a statistically significant difference in post-treatment pain scores (P = 0.000) and MMO scores (P = 0.000) between the two groups. CONCLUSION: The results suggest that massage therapy combined with post-isometric relaxation is more effective than massage therapy alone in managing pain and improving mouth opening in TMD patients. The study provides evidence supporting the use of these therapies in TMD management. TRIAL REGISTRY NUMBER: NCT05810831. Date of registration/First submission: 15 March 2023.

Senescence Defines a Distinct Subset of Myofibroblasts That Orchestrates Immunosuppression in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) therapeutic resistance is largely attributed to a unique tumor microenvironment embedded with an abundance of cancer-associated fibroblasts (CAF). Distinct CAF populations were recently identified, but the phenotypic drivers and specific impact of CAF heterogeneity remain unclear. In this study, we identify a subpopulation of senescent myofibroblastic CAFs (SenCAF) in mouse and human PDAC. These SenCAFs are a phenotypically distinct subset of myofibroblastic CAFs that localize near tumor ducts and accumulate with PDAC progression. To assess the impact of endogenous SenCAFs in PDAC, we used an LSL-KRASG12D;p53flox;p48-CRE;INK-ATTAC (KPPC-IA) mouse model of spontaneous PDAC with inducible senescent cell depletion. Depletion of senescent stromal cells in genetic and pharmacologic PDAC models relieved immune suppression by macrophages, delayed tumor progression, and increased responsiveness to chemotherapy. Collectively, our findings demonstrate that SenCAFs promote PDAC progression and immune cell dysfunction. Significance: CAF heterogeneity in PDAC remains poorly understood. In this study, we identify a novel subpopulation of senescent CAFs that promotes PDAC progression and immunosuppression. Targeting CAF senescence in combination therapies could increase tumor vulnerability to chemo or immunotherapy. See related article by Ye et al., p. 1302.

Symptoms and Prevalence of Constipation among Adult Population of Bangladesh.

Background: Constipation is one of the most common gastrointestinal disorders. The prevalence of constipation is rapidly increasing globally. It has adverse effects on the patient's quality of life including productivity and results in a high financial hardship on the healthcare system. The aim of the study was to estimate the symptoms and prevalence of constipation among the adult population of Bangladesh. Materials and methods: It was a cross-sectional observational study based on a structured questionnaire and a checklist. In this study, three criteria were used for the diagnosis of chronic constipation (self-reported perception, Rome III criteria, and Bristol's criteria). The study was conducted among 1,550 population between July 2019 and December 2019. Result: The study population consisted of 1,550 respondents, among them 41.61% male and 58.39% female, and the mean age was 32.71 ± 9.72 years. In the study, 12.2% of the population was categorized to have constipation according to self-reported perception, 11.2% according to Rome III, and 10.3% reported to have been suffering from constipation according to Bristol chart.Female gender tends to have a greater prevalence than male. In multivariate analysis for constipation, betel nut chewer, alcohol consumer, diabetes mellitus, hypertension, GI surgery, and bronchial asthma were significantly (p < 0.001) associated with constipation. According to Bristol's criteria, the most common stool form was Type III (sausage-shaped with cracked surface) among the Bangladeshi population in this study. Conclusion: Chronic constipation is a common problem worldwide. The findings of this study suggest that there is a high prevalence of constipation among the general population of Bangladesh. Decreasing modifiable risk factors of constipation can reduce its prevalence and burden of the disease. Bangladesh is markedly deficient in literature citing constipation prevalence and determinants. These findings may commence a call for setting priority as one of the major public health problems and demanding attention for both at the clinical and community levels. How to cite this article: Ghosh DK, Sarkar DK, Nath M, et al. Symptoms and Prevalence of Constipation among Adult Population of Bangladesh. Euroasian J Hepato-Gastroenterol 2023;13(2):45-49.

Recent Dengue Infection in Bangladesh: A Seasonal Endemic Progressing to Year-long Serious Health Concern.

Dengue represents one of the most dangerous mosquito-borne viral diseases. Although the disease has been prevalent around the globe over the centuries, recent outbreaks of dengue have devasted the healthcare delivery system of many countries. Being a global infection, dengue virus (DENV) is endemically present mainly in Latin America and Caribbean countries as well as countries in South Asia. The recent outbreak of DENV infection has indicated an exceptional outbreak of DENV in some countries in South Asia. There has been a serious endemic of DENV during 2019. After a heterogeneous pause, another severe outbreak of DENV was reported in some Asian countries in 2023. Among the Asian countries, Bangladesh has reported an acute upsurge of DENV infection in 2023 with record numbers of fatalities. However, this pattern of DENV has not been detected in neighbors of Bangladesh, such as India or other countries in Southeast Asia. This provides an emergent task of dissecting the present DENV infection in Bangladesh from different angles to get insights for future containment of the DENV infection, not only in Bangladesh but also in other DENV endemic areas or DENV-native areas. How to cite this article: Akbar SMF, Khan S, Mahtab M, et al. Recent Dengue Infection in Bangladesh: A Seasonal Endemic Progressing to Year-long Serious Health Concern. Euroasian J Hepato-Gastroenterol 2023;13(2):145-151.