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Neuropathy is a disturbance of function or a pathological change in nerves causing poor health and quality of life. A proportion of chronic pain patients in the community suffer persistent neuropathic pain symptoms because current drug therapies may be suboptimal so there is a need for new therapeutic modalities. This study investigated the neuroprotective flavonoid, 6-methoxyflavone (6MF), as a potential therapeutic agent and gabapentin as the standard comparator, against neuropathic models. Thus, neuropathic-like states were induced in Sprague-Dawley rats using sciatic nerve chronic constriction injury (CCI) mononeuropathy and systemic administration of streptozotocin (STZ) to induce polyneuropathy. Subsequent behaviors reflecting allodynia, hyperalgesia, and vulvodynia were assessed and any possible motoric side-effects were evaluated including locomotor activity, as well as rotarod discoordination and gait disruption. 6MF (25-75 mg/kg) antagonized neuropathic-like nociceptive behaviors including static- (pressure) and dynamic- (light brushing) hindpaw allodynia plus heat/cold and pressure hyperalgesia in the CCI and STZ models. 6MF also reduced static and dynamic components of vulvodynia in the STZ induced polyneuropathy model. Additionally, 6MF reversed CCI and STZ suppression of locomotor activity and rotarod discoordination, suggesting a beneficial activity on motor side effects, in contrast to gabapentin. Hence, 6MF possesses anti-neuropathic-like activity not only against different nociceptive modalities but also impairment of motoric side effects., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The objective of this review was to conduct a systematic review and meta-analysis on the efficacy of ICG (indocyanine green) for sentinel lymph node (SLN) detection in head and neck melanoma. The Preferred Reporting Items for Systematic reviews and Meta-Analyses statement standards (PRISMA) were followed when conducting this review with a comprehensive search of the following online databases; Google Scholar, PubMed, MEDLINE, CINAHL, and CENTRAL, World Health Organization International Clinical Trials Registry (http://apps.who.int/trialsearch/), ClinicalTrials.gov (http://clinical-trials.gov/), and the ISRCTN registry (http://www.isrctn.com/). Nine studies met the inclusion criteria and results were reported with forest plots at 95% confidence intervals. Primary outcomes of interest included the localisation rate for sentinel node biopsies in head and neck melanoma using ICG and compared with other adjunct modalities. Secondary outcome measures included false negative rates as well as sensitivity rates for nodal detection with radiocolloid as well as blue dye. ICG reported an overall sensitivity rate of 95% with an untransformed proportion metric analysis (0.950, 0.922, 0.978 (95% CI)). It demonstrated a superior detection rate to blue dye (Odds ratio 15.417, 95% CI, 4.652 to 51.091, p < 0.001) and a comparable localisation efficacy to radiocolloid (Odds ratio 1.425, 95% CI, 0.535 to 3.794, p = 0.478). The sensitivity rate for radiocolloid utilisation in isolation was 90.6% (untransformed proportion metric, 0.906, 0.855, 0.957) and blue dye was 48.7% (untransformed proportion metric, 0.487, 0.364, 0.610). This is the first meta-analysis on the efficacy of ICG for sentinel node detection in head and neck melanoma. The authors advocate for a dual modality approach with ICG and radiocolloid to mitigate the inherent limitations of both methods when conducting sentinel node retrieval for head and neck melanoma. Further high-quality randomised trials are needed to improve the current evidence base., (Copyright © 2024. Published by Elsevier Ltd.)

In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable α-amylase inhibitory activity having IC 50 values from 3.51 ± 2.13 to 11.92 ± 2.30 µM. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent α-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent anti-glycating activity with IC 50 values from 6.91 ± 2.66 to 15.80 ± 1.87 µM when compared them with the standard rutin (IC 50  = 22.5 ± 0.90 µM). Molecular docking was carried out to predict the binding modes of all the compounds with α-amylase and α-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with α-amylase and α-glucosidase. All compounds fitted well into the binding pockets of α-amylase and α-glucosidase. Among all compounds 2a and 2f were most potent based on docking score -8.2515 and -7.3949 against α-amylase and α-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The internet has become a common means by which many older adults seek out health information. The prevalence of misinformation on the internet makes the search for accurate online health information a more complex and evaluative process. This study examined the role of age and neurocognition in credibility evaluations of credible and non-credible health websites. Forty-one older adults and fifty younger adults completed a structured credibility rating task in which they evaluated a series of webpages displaying health information about migraine treatments. Participants also completed measures of neurocognition, internet use, and health literacy. Results suggested that older adults rated non-credible health websites as more credible than younger adults, but the age groups did not differ in their ratings of credible sites. Within the full sample, neurocognition was associated with credibility ratings for non-credible health websites, whereas health literacy was related to the ratings of credible sites. Findings indicate that older adults may be more likely to trust non-credible health websites than younger adults, which may be related to differences in higher-order neurocognitive functions. Future work might examine whether cognitive-based supports for credibility training in older adults can be used to improve the accuracy with which they evaluate online health information.

Introduction: The discovery and development of new phytomedicines can be greatly aided by plants because of their tremendous therapeutic benefits, efficiency, cost-effectiveness, lack of side effects, and cheaper therapies. In this regard, Quercus baloot, generally known as oak, is used in folkloric medicine for treating and preventing various human disorders, including diabetes., Aim: For this purpose, the present study aimed to evaluate crude methanolic extract and various fractions of Quercus baloot for antihyperlipidemic and antihyperglycemic potential followed by the analysis of active compounds., Method: The hypoglycemic and hypolipidemic activity was evaluated in Swiss male Albino mice by administering an oral dose of 150-300 mg/kg of Q. baloot extracts in alloxan induced diabetic mice for 14 days., Results: The results revealed that crude methanolic extract at a dose of 300 mg/kg exhibited a significant reduction in the blood glucose level (198.50 ± 1.99 mg/dl) at day 14 and the same treatment significantly increased the body weight (31.26 ± 0.27g) at day 14 in comparison to the control group. Moreover, the biochemical parameters were investigated which presented an increase in high-density lipids (HDL) (30.33 ± 0.33 mg/dl), whereas Low-Density Lipids (LDL) showed a significant decrease (105.66 ± 0.26 mg/dl). Additionally, triglyceride levels 104.83 ± 0.70 mg/dl, and total cholesterol 185.50 ± 0.76 mg/dl are significantly decreased. In serum biochemical analysis creatinine and hepatic enzyme markers, like serum glutamate pyruvate transaminase (32.00 ± 0.36 U/mg), serum glutamate oxaloacetate transaminase (34.33 ± 0.61 U/mg), and alkaline phosphatase (157.00 ± 0.73 U/mg), were significantly reduced by the crude methanolic extract at a dose of 300 mg/kg as compared to the control group. The antioxidant enzymes like Superoxide dismutase (4.57 ± 0.011), peroxidases dismutase (6.53 ± 0.014, and catalase (8.38 ± 0.014) at a dosage of 300 mg/kg of methanolic extract exhibited a significant increase. The histopathological study of the diabetic heart, liver, and pancreas showed substantial restoration of damaged tissues in the methanolic extract 150 and 300 mg/kg treated group, which supports the effectiveness of Q. baloot seeds. The gas chromatography-mass spectrometry analysis of methanolic extract identified 10 antidiabetic active compounds in the Q. baloot seeds, validating the antihyperglycemic activity. Thus, methanolic crude extract at the doses 150 and 300 mg/kg of Q. baloot showed significant antihyperlipidemic and antihyperglycemic activities, which validate the folkloric utilization of Q. baloot as a remedy in diabetes., Conclusion: In conclusion, the 300 mg/kg methanolic extract of Q. baloot has notable hypoglycemic and hypolipidemic potential, supporting the plant's traditional medicinal usage in the treatment of diabetes and its complications. Further studies are needed for the purification, characterization, and structural clarification of bioactive compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The scarcity of donors coupled with the improvements in left ventricular assist devices (LVAD) technology has led to the use of LVAD as a bridge to transplantation (BTT)., Areas Covered: The authors provide an overview of the current status of LVAD BTT implantation with special focus ranging from patient selection and pre-implantation optimization to post-transplant outcomes., Expert Opinion: The United Network for Organ Sharing 2018 policy amendment resulted in a significant reduction in the number of LVADs used for BTT in the US. To overcome this issue, modifications in the US allocation policy to consider factors such as days on device support, age, and type of complications may be necessary to potentially increase implantation rates.

Objective: To understand how Long COVID is impacting the health and social conditions of the Black and Latinx communities., Background: Emerging research on Long COVID has identified three distinct characteristics, including multi-organ damage, persistent symptoms, and post-hospitalization complications. Given Black and Latinx communities experienced significantly higher COVID rates in the first phase of the pandemic they may be disproportionately impacted by Long COVID., Methods: Eleven focus groups were conducted in four languages with diverse Black and Latinx individuals (n = 99) experiencing prolonged symptoms of COVID-19 or caring for family members with prolonged COVID-19 symptoms. Data was analyzed thematically., Results: Most participants in non-English language groups reported they were unfamiliar with the diagnosis of long COVID, despite experiencing symptoms. Long COVID impacts spanned financial and housing stability to physical and mental health impacts. Participants reported challenging encounters with health care providers, a lack of support managing symptoms and difficulty performing activities of daily living including work., Conclusions: There is a need for multilingual, accessible information about Long COVID symptoms, improved outreach and healthcare delivery, and increased ease of enrollment in long-term disability and economic support programs., (© 2024. The Author(s).)

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population ( n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059-0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group ( n = 36). We established an association of MUC5AC expression with treatment response and outcomes.

Monoubiquitination of histones H2B-K120 (H2BK120ub) and H2A-K119 (H2AK119ub) play opposing roles in regulating transcription and chromatin compaction. H2BK120ub is a hallmark of actively transcribed euchromatin, while H2AK119ub is highly enriched in transcriptionally repressed heterochromatin. Whereas H2BK120ub is known to stimulate the binding or activity of various chromatin-modifying enzymes, this post-translational modification (PTM) also interferes with the binding of several proteins to the nucleosome H2A/H2B acidic patch via an unknown mechanism. Here, we report cryoEM structures of an H2BK120ub nucleosome showing that ubiquitin adopts discrete positions that occlude the acidic patch. Molecular dynamics simulations show that ubiquitin remains stably positioned over this nucleosome region. By contrast, our cryoEM structures of H2AK119ub nucleosomes show ubiquitin adopting discrete positions that minimally occlude the acidic patch. Consistent with these observations, H2BK120ub, but not H2AK119ub, abrogates nucleosome interactions with acidic patch-binding proteins RCC1 and LANA, and single-domain antibodies specific to this region. Our results suggest a mechanism by which H2BK120ub serves as a gatekeeper to the acidic patch and point to distinct roles for histone H2AK119 and H2BK120 ubiquitination in regulating protein binding to nucleosomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Dysmenorrhea is the most common pathology women of childbearing age face. It is defined as painful uterine cramping associated with menstruation. Primary dysmenorrhea occurs in the absence of an organic cause, whereas secondary dysmenorrhea is pelvic pain associated with an underlying pelvic pathology. The purpose of this review is to discuss the pathophysiology of dysmenorrhea and provide a discussion of pharmacologic and non-pharmacologic treatment options. Prostaglandins play a large role in the pathophysiology of dysmenorrhea by causing myometrial contraction and vasoconstriction. The first-line treatment for dysmenorrhea is with nonsteroidal anti-inflammatory drugs due to the inhibition of cyclooxygenase enzymes, thereby blocking prostaglandin formation, as well as hormonal contraception. Other pharmacologic treatment options include Paracetamol, as well as Gonadotrophic Release Hormone Analogs, which are typically used in the treatment for endometriosis. Non-pharmacologic treatments with strong evidence include heat therapy and physical exercise. There are less evidence-based data behind other modalities for treating dysmenorrhea, such as dietary supplements, acupuncture, and transcutaneous nerve stimulation, and these methods should be used in conjunction with first-line therapy after a discussion of risks and benefits. Lastly, for women who fail medical management, surgical options include endometrial ablation, presacral neurectomy, and laparoscopic uterosacral nerve ablation. Further research is needed to measure the socioeconomic burden of dysmenorrhea on the healthcare system and to evaluate the efficacy of treatment combinations, as a multi-modal approach likely provides the most benefit for women who suffer from this condition., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Kirsch et al.)

Belief and plausibility functions based on evidence theory (ET) have been widely used in managing uncertainty. Various generalizations of ET to fuzzy sets (FSs) have been reported in the literature, but no generalization of ET to q-rung orthopair fuzzy sets (q-ROFSs) has been made yet. Therefore, this paper proposes a novel, simple, and intuitive approach to distance and similarity measures for q-ROFSs based on belief and plausibility functions within the framework of ET. This research addresses a significant research gap by introducing a comprehensive framework for handling uncertainty in q-ROFSs using ET. Furthermore, it acknowledges the limitations inherent in the current state of research, notably the absence of generalizations of ET to q-ROFSs and the challenges in extending belief and plausibility measures to certain aggregation operators and other generalizations including Hesitant fuzzy sets, Bipolar fuzzy sets, Fuzzy soft sets etc. Our contribution lies in the proposal of a novel approach to distance and similarity measures for q-ROFSs under ET, utilizing Orthopairian belief and plausibility intervals (OBPIs). We establish new similarity measures within the generalized ET framework and demonstrate the reasonability of our method through useful numerical examples. Additionally, we construct Orthopairian belief and plausibility GRA (OBP-GRA) for managing daily life complex issues, particularly in multicriteria decision-making scenarios. Numerical simulations and results confirm the usability and practical applicability of our proposed method in the framework of ET., (© 2024. The Author(s).)

In recent decades, analytical techniques have increasingly focused on the precise quantification. Achieving this goal has been accomplished with conventional analytical approaches that typically require extensive pretreatment methods, significant reagent usage, and expensive instruments. The need for rapid, simple, and highly selective identification platforms has become increasingly pronounced. Molecularly imprinted polymer (MIP) has emerged as a promising avenue for developing advanced sensors that can potentially surpass the limitations of conventional detection methods. In recent years, the application of MIP-silica materials-based sensors has garnered significant attention owing to their distinctive characteristics. These types of probes hold a distinct advantage in their remarkable stability and durability, all of which provide a suitable sensing platform in severe environments. Moreover, the substrate composed of silica materials offers a vast surface area for binding, thereby facilitating the efficient detection of even minuscule concentrations of targets. As a result, sensors based on MIP-silica materials have the potential to be widely applied in various industries, including medical diagnosis, and food safety. In the present review, we have conducted an in-depth analysis of the latest research developments in the field of MIPs-silica materials based sensors, with a focus on succinctly summarizing and elucidating the most crucial findings. This is the first comprehensive review of integration MIPs with silica materials in electrochemical (EC) and optical probes for biomedical analysis and food safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Transient embryonic carotid-vertebrobasilar anastomoses can intermittently persist beyond the embryonic period. These vascular anomalies are often serendipitously identified during evaluation for unrelated disease states and pathologies. The persistent proatlantal intersegmental artery is one such recognized rare fetal anastomotic connection, often arising unilaterally. Bilateral persistence of the proatlantal anastomosis is a rarer occurrence, seldom described in the literature. We report a case of bilateral concurrent type I and type II proatlantal arteries, describe the embryology of persistent carotid-vertebrobasilar anastomoses, and consider pertinent clinical implications., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Objective: Historically, mid-upper arm circumference (MUAC) has been instrumental to identifying malnutrition in children under 5 years living in resource restricted settings. Less attention is directed to at-risk, school-aged youth. Updated and validated pediatric age- and gender-specific MUAC growth curves expand malnutrition screening opportunities (2 months-18 years) including overweight/obesity. An innovative partnership was created to integrate MUAC z -score measurement trainings and screenings in the Real Madrid Foundation's (RMF) Social Sports Schools (S 3 ) program, which provide sports and wellness programming to under-resourced communities. This work aimed to investigate the feasibility of leveraging non-healthcare professionals (non-HCPs) to identify malnutrition risk as part of RMF S 3 ., Methods: This global, two-part program on malnutrition risk identification included training adult facilitators and screening children attending RMF S 3 . RMF facilitators were trained with didactic lectures on malnutrition, and practical hands-on learning of proper MUAC z -score tape measurement. Aggregate data on facilitators and the number of times to correctly administer the MUAC z -tape were recorded. Aggregate data on child malnutrition risk screenings were collected., Results: Nine countries participated representing Europe, Pacific Asia, Africa, Latin America, and North America. In total, 143 RMF facilitators were trained, and 318 children were screened across 11 sites. More than half of facilitators were male (56%, n = 80), and majority were coaches (41.3%, n = 59), followed by staff (25.2%, n = 36), and volunteers (16.1%, n = 23). Facilitator attempts ranged from 1 to 4 times for proper MUAC z -score administration with mean 2.12 (± 0.86). There were no significant differences for attempts among RMF facilitator types ( p = 0.10). Sixteen percent ( n = 51) of children screened were recommended for HCP referral, with concentrations in Pacific Asia (68%, n = 35), Latin America (24%, n = 12), and Africa (8%, n = 4)., Conclusions: Findings from our sample demonstrate that integration of MUAC z -score based malnutrition risk screening within community sports and wellness programming among non-HCPs is feasible, and that some regions with less frequent access to routine health care may experience greater benefit from these programs. Equipping non-HCP facilitators in community sports and wellness programs with training on malnutrition screening provides a means to meet under-resourced families where they live to begin conversations around malnutrition risk with the hope of establishing additional pathways to care., Competing Interests: ARS, EM-M, and SS were employees of Abbott Nutrition at the time the work was conducted. MV-RG declares speaker honoraria from Abbott Nutrition. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sharn, Sorgho, Sulo, Molina-Molina, Rojas Montenegro, Villa-Real Guno and Abdel-Rahman.)

Urban residential and industrial growth development affects sustainable and healthful indoor environments. Environmental issues are a global problem. The deterioration of indoor air quality has prompted the creation of several air cleansing techniques. This review explains how carbon-based materials have influenced the development of air purification systems using photocatalysis. These carbon-based materials offer unique properties and advantages in VOC removal processes. Biochar, produced from biomass pyrolysis, provides an environmentally sustainable solution with its porous structure and carbon-rich composition. Carbon quantum dots, with their quantum confinement effects and tunable surface properties, show promise in VOC sensing and removal applications. Polymers incorporating reduced graphene oxide demonstrate enhanced adsorption capabilities owing to the synergistic effects of graphene and polymer matrices. Activated carbon fibers, characterized by their high aspect ratio and interconnected porosity, provide efficient VOC removal with rapid kinetics. With their unique electronic and structural properties, graphitic carbon nitrides offer opportunities for photocatalytic degradation of VOCs under visible light. Catalysts integrated with MXene, a two-dimensional nanomaterial, exhibit enhanced catalytic activity for VOC oxidation reactions. Using various carbon-based materials in VOC removal showcases the versatility and effectiveness of carbon-based approaches in addressing environmental challenges associated with indoor air pollution. Metal-organic-framework materials are carbon-based compounds. It examines the correlation between VOC mineralization and specific characteristics of carbon materials, including surface area, adsorption capability, surface functional groups, and optoelectronic properties. Discussions include the basics of PCO, variables influencing how well catalysts degrade, and degradation mechanisms. It explores how technology will improve in the future to advance studies on healthy and sustainable indoor air quality., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Nisar Ali reports financial support was provided by Huaiyin Institute of Technology. Yong Yang reports financial support was provided by Huaiyin Institute of Technology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Urinary bladder cancer, is the 10th most common global cancer, diagnosed in over 600,000 people causing 200,000 deaths annually. Artemisinin and its derivatives are safe compounds that have recently been proven to possess potent anti-tumor effects in vivo, through inhibition of cancer cell growth. The aim of this study is to assess the efficiency of artemisinin as a cancer treatment alone and as a pre-treatment fore cisplatin therapy for high grade urothelial carcinoma., Methods: Sixty male albino mice were divided into six groups, and BBN was used to induce urinary bladder cancer. Blood samples were tested for renal functions and complete blood counts, kidney and urinary bladder tissues were harvested for histopathological examination. Total RNAs from urinary bladder tissues was collected, and gene expression of FGFR3, HRAS, P53, and KDM6A was quantified using qRT-PCR., Results: Compared to the induced cancer group, the results revealed that FGFR3 expression levels were down-regulated in the induced cancer group treated by artemisinin only and the induced cancer group pre-treated with artemisinin prior to cisplatin by ~ 0.86-fold and 0.4-folds, respectively, aligning with HRAS down-regulation by ~ 9.54-fold and 9.05-fold, respectively. Whereas, P53 expression levels were up-regulated by ~ 0.68-fold and 0.84-fold, respectively, in parallel with KDM6A expression, which is up-regulated by ~ 0.95-folds and 5.27-folds, respectively. Also, serum creatinine and urea levels decreased significantly in the induced cancer group treated by artemisinin alone and the induced cancer group pre-treated with artemisinin prior to cisplatin, whereas the induced cancer group treated by cisplatin their levels increased significantly. Moreover, Hb, PLT, RBC, and WBC counts improved in both cancer groups treated by artemisinin alone and pre-treated with artemisinin prior to cisplatin. Histologically, in kidney tissues, artemisinin pre-treatment significantly reduced renal injury caused by cisplatin. While Artemisinin treatment for cancer in bladder tissues reverted invasive urothelial carcinoma to moderate urothelial dysplasia., Conclusions: This study indicates that artemisinin demonstrated a significant effect in reversal of the multi-step carcinogenesis process of high grade urothelial carcinoma and could enhance the effect of cisplatin therapy using artemisinin pre-treatment., (© 2024. The Author(s).)

The first case of COVID-19 was detected in Bangladesh on 8 March 2020. Since then, the Government of Bangladesh (GoB) has implemented various measures to limit the transmission of COVID-19, including widespread testing facilities across the nation through a laboratory network for COVID-19 molecular testing. This study aimed to analyze the dynamics of SARS-CoV-2 in Bangladesh by conducting COVID-19 testing and genomic surveillance of the virus variants throughout the pandemic. Nasopharyngeal swabs were collected from authorized GoB collection centers between April 2020 and June 2023. The viral RNA was extracted and subjected to real-time PCR analysis in icddr,b's Virology laboratory. A subset of positive samples underwent whole-genome sequencing to track the evolutionary footprint of SARS-CoV-2 variants. We tested 149,270 suspected COVID-19 cases from Dhaka (n = 81,782) and other districts (n = 67,488). Of these, 63% were male. The highest positivity rate, 27%, was found in the >60 years age group, followed by 26%, 51-60 years, 25% in 41-50 years, and the lowest, 9% in under five children. Notably, the sequencing of 2742 SARS-CoV-2 genomes displayed a pattern of globally circulating variants, Alpha, Beta, Delta, and Omicron, successively replacing each other over time and causing peaks of COVID-19 infection. Regarding the risk of SARS-CoV-2 infection, it was observed that the positivity rate increased with age compared to the under-5 age group in 2020 and 2021. However, these trends did not remain consistent in 2022, where older age groups, particularly those over 60, had a lower positivity rate compared to other age groups due to vaccination. The study findings generated data on the real-time circulation of different SARS-CoV-2 variants and the upsurge of COVID-19 cases in Bangladesh, which impacted identifying hotspots and restricting the virus from further transmission. Even though there is currently a low circulation of SARS-CoV-2 in Bangladesh, similar approaches of genomic surveillance remain essential for monitoring the emergence of new SARS-CoV-2 variants or other potential pathogens that could lead to future pandemics.

Anthocyanins are known as an antioxidant, and their water-soluble purple-colored pigments are very nutritive. Therefore, the present study investigated the antioxidant activity of black rice anthocyanins nano-composite against infertility induced by AlCl3 in rats. Anthocyanin silver nanoparticles (An-AgNPs) were prepared by reducing black rice anthocyanin with the metallic ions. Antioxidant activity (DPPH %) of anthocyanin was determined. Also, the morphology of (An-AgNPs) was examined by scanning electron microscopy (SEM). Albino rats were divided into five groups (negative control (NC): fed on basel diet, positive control (PC): treated with AlCl3 (34 mg/kg bw) for seventy days, and three other groups treated with AlCl3 (34 mg/kg bw) + An-AgNPs at 10, 15, and 20 mg/kg, b.w/ day, respectively for seventy days. Serum testosterone, LH, FSH, and estradiol were measured. Additionally, Sperm motility, Sperm count (Testicular and Epididymal), fructose in semen, and semen quality were determined. The values of the anthocyanin component and DPPH radical scavenging activity obtained were 3603.82±6.11 mg CCE/g and 84.62±1.98, respectively. An-AgNPs shows tend to agglomerate, particles are uniform in size and shape, and the diameter of the particles ranges between 70nm to 130nm. LH, estradiol and testosterone levels increased significantly in rats treated with An-AgNPs 10, 15, 20 mg/kg b.w+ AlCl3 (34 mg/kg bw) also exhibited significantly higher sperm motility, sperm count, and daily sperm production, and decreased sperm transit rate than G2. In comparison to G2, animals treated with AlCl3 (34 mg/kg bw) + An-AgNPs 10, 15, 20 mg/kg b.w(G3 to G5) had significantly higher semen and semen quality (P 0.05). We can conclude that the An-AgNPs showed a strong effect against infertility induced by AlCl3; this represents a suitable natural supply of biological substances for medicine and anthocyanins could be considered the ideal ingredients against oxidative stress-induced infertility.

Purpose: Hypertension is one of the major causes of cardiovascular morbidity and mortality in the USA and disproportionately affects Black women. Endothelial-derived nitric oxide (eNO) substantially regulates blood pressure in humans, and impaired NO-mediated vasodilation has been reported in the Black population. Previous studies using an NO synthase inhibitor, N G -monomethyl-L-arginine (L-NMMA) did not fully determine the NO contribution to blood pressure because of baroreflex buffering. Therefore, in the present study we used trimethaphan, a ganglionic blocker, to inhibit baroreflex buffering and study NO modulation of blood pressure in Black women during L-NMMA infusion., Methods: L-NMMA at doses of 250 μg/kg per minute was infused in combination with trimethaphan at doses of 4 mg/min to eliminate baroreflex mechanisms. Heart rate (HR) was obtained with continuous electrocardiogram monitoring, and continuous blood pressure was measured with the volume clamp method. The increase in systolic blood pressure (SBP) during both infusions was used to estimate the contribution of NO to blood pressure., Results: Ten Black (age range 30-50 years, body mass index [BMI] 30-45 kg/m 2 ), and nine White women (age range 30-50 years, body mass index 30-45 kg/m 2 ) were enrolled in this study. During autonomic blockade, there was no difference in the decrease in SBP between Black and White women (- 20 ± 16.45 vs. - 24 ± 15.49 mm Hg, respectively; P = 0.659). When autonomic blockade was combined with L-NMMA, Black women had a significant increase in SBP compared to White women (54 ± 13.62 vs. 39 ± 09.64 mm Hg, respectively; P = 0.022, respectively)., Conclusion: Autonomic blood pressure regulation was similar between Black and White women. However, NO contribution to blood pressure was significantly greater in Black women compared to White women., Registration: ClinicalTrials.gov: NCT01122407., (© 2024. The Author(s).)

Receptor for advanced glycation endproducts (RAGE) and toll-like receptor 4 (TLR4) are pattern-recognition receptors that bind to molecular patterns associated with pathogens, stress, and cellular damage. Diffusion plays an important role in receptor functionality in the cell membrane. However, there has been no prior investigation of the reciprocal effect of RAGE and TLR4 diffusion properties in the presence and absence of each receptor. This study reports how RAGE and TLR4 affect the mobility of each other in the human embryonic kidney (HEK) 293 cell membrane. Diffusion properties were measured using single-particle tracking (SPT) with quantum dots (QDs) that are selectively attached to RAGE or TLR4. The Brownian diffusion coefficients of RAGE and TLR4 are affected by the presence of the other receptor, leading to similar diffusion coefficients when both receptors coexist in the cell. When TLR4 is present, the average Brownian diffusion coefficient of RAGE increases by 40%, while the presence of RAGE decreases the average Brownian diffusion coefficient of TLR4 by 32%. Diffusion in confined membrane domains is not altered by the presence of the other receptor. The mobility of the cell membrane lipid remains constant whether one or both receptors are present. Overall, this work shows that the presence of each receptor can affect a subset of diffusion properties of the other receptor without affecting the mobility of the membrane., (© 2024. European Biophysical Societies' Association.)

Circadian rhythms are biological rhythms that originate from the "master circadian clock," called the suprachiasmatic nucleus (SCN). SCN orchestrates the circadian rhythms using light as a chief zeitgeber, enabling humans to synchronize their daily physio-behavioral activities with the Earth's light-dark cycle. However, chronic/ irregular photic disturbances from the retina via the retinohypothalamic tract (RHT) can disrupt the amplitude and the expression of clock genes, such as the period circadian clock 2, causing circadian rhythm disruption (CRd) and associated neuropathologies. The present review discusses neuromodulation across the RHT originating from retinal photic inputs and modulation offered by endocannabinoids as a function of mitigation of the CRd and associated neuro-dysfunction. Literature indicates that cannabinoid agonists alleviate the SCN's ability to get entrained to light by modulating the activity of its chief neurotransmitter, i.e., γ-aminobutyric acid, thus preventing light-induced disruption of activity rhythms in laboratory animals. In the retina, endocannabinoid signaling modulates the overall gain of the retinal ganglion cells by regulating the membrane currents (Ca 2+ , K + , and Cl - channels) and glutamatergic neurotransmission of photoreceptors and bipolar cells. Additionally, endocannabinoids signalling also regulate the high-voltage-activated Ca 2+ channels to mitigate the retinal ganglion cells and intrinsically photosensitive retinal ganglion cells-mediated glutamate release in the SCN, thus regulating the RHT-mediated light stimulation of SCN neurons to prevent excitotoxicity. As per the literature, cannabinoid receptors 1 and 2 are becoming newer targets in drug discovery paradigms, and the involvement of endocannabinoids in light-induced CRd through the RHT may possibly mitigate severe neuropathologies., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The study aimed to evaluate the profitability, meat quality, and carcass parameters of fast-, medium-, and slow-growing meat-type chicken genotypes of Bangladesh. Nine hundred DOCs were randomly allocated to 6 treatments: T 1  = commercial broilers, T 2  = CPF-3 (central poultry farm-3), T 3  = cockerel, T 4  =  sonali , T 5  = NDD (non-descriptive desi ), and T 6  =  hilly , having 5 replications of 30 chicks each. Birds were reared under complete confinement until their respective market ages (commercial broilers = 35 d; CPF-3 = 45 d; cockerel = 56 d, and hilly  = 77 d; sonali  = 63 d and NDD = 77 d) and fed commercial broiler diets. Net returns, meat quality, growth, and carcass yield were measured. NDD and hilly showed significantly the highest profitability and superior meat quality. Commercial broilers exhibited the highest final body weight (2355.59 g/b) followed by hilly (1241 g/b) and NDD (1006 g/b), while CPF-3 (860.21 g/b), cockerel (915.49 g/b), and sonali (788.43 g/b) had lower final body weights at their respective market ages. Commercial broilers had the highest carcass weight and dressing yields, followed by hilly and cockerel, and lower in sonali , CPF-3, and NDD. The study concluded that rearing slow- or medium-growing NDD and hilly is superior to fast-growing commercial broilers or CPF-3 regarding profitability, and meat quality. The results of current findings help small-scale farmers in choosing a suitable meat-type chicken that yields better profitability and also for the consumers who wish to pay a fair price for the birds, considering the meat quality specific to each chicken genotype., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Thirteen novel hydrazone-Schiff bases (3-15) of fexofenadine were succesfully synthesized, structurally deduced and finally assessed their capability to inhibit urease enzyme (in vitro). In the series, six compounds 12 (IC 50 =10.19±0.16 μM), 11 (IC 50 =15.05±1.11 μM), 10 (IC 50 =17.01±1.23 μM), 9 (IC 50 =17.22±0.81 μM), 13 (IC 50 =19.31±0.18 μM), and 14 (IC 50 =19.62±0.21 μM) displayed strong inhibitory action better than the standard thiourea (IC 50 =21.14±0.24 μM), while the remaining compounds displayed significant to less inhibition. LUMO and HOMO showed the transferring of charges from molecules to biological transfer and MEP map showed the chemically reactive zone appropriate for drug action are calculated using DFT. AIM charges, non-bonding orbitals, and ELF are also computed. The urease protein binding analysis benefited from the docking studies., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

We aimed to provide a detailed phenotypic description of status epilepticus (SE) in a large cohort of patients with POLG disease and identify prognostic biomarkers to improve the management of this life-threatening condition. In a multinational, retrospective study with data on patients with POLG disease from seven European countries, we identified those who had SE. The age of SE onset, accompanying clinical, laboratory, imaging and genetic findings were analysed. One hundred and ninety-five patients with genetically confirmed POLG disease were recruited, of whom 67% (130/194) had epilepsy. SE was identified in 77% (97/126), with a median age of SE onset of 7 years. SE was the presenting symptom of the disease in 43% (40/93) of those with SE, while 57% (53/93) developed SE during the disease course. Convulsive SE was reported in 97% (91/94) followed by epilepsia partialis continua in 67% (56/84). Liver impairment 78% (74/95), ataxia 69% (60/87), stroke-like episodes 57% (50/88), were the major comorbidities. In the majority (66%; 57/86) with SE this became refractory or super-refractory. The presence of seizures was associated with significantly higher mortality compared to those without (P ≤ 0.001). The median time from SE debut to death was 5 months. SE is a major clinical feature of POLG disease in early and juvenile to adult-onset disease and can be the presenting feature or arise as part of a multisystem disease. It is associated with high morbidity and mortality, with the majority of patients with SE going on to develop refractory or super-refractory SE., (© 2024. The Author(s).)

Background and Objective: Automatic electrocardiogram (ECG) signal analysis for heart disease detection has gained significant attention due to busy lifestyles. However, ECG signals are susceptible to noise, which adversely affects the performance of ECG signal analysers. Traditional blind filtering methods use predefined noise frequency and filter order, but they alter ECG biomarkers. Several Deep Learning-based ECG noise detection and classification methods exist, but no study compares recurrent neural network (RNN) and convolutional neural network (CNN) architectures and their complexity., Methods: This paper introduces a knowledge-based ECG filtering system using Deep Learning to classify ECG noise types and compare popular computer vision model architectures in a practical Internet of Medical Things (IoMT) framework. Experimental results demonstrate that the CNN-based ECG noise classifier outperforms the RNN-based model in terms of performance and training time., Results: The study shows that AlexNet, visual geometry group (VGG), and residual network (ResNet) achieved over 70% accuracy, specificity, sensitivity, and F1 score across six datasets. VGG and ResNet performances were comparable, but VGG was more complex than ResNet, with only a 4.57% less F1 score., Conclusions: This paper introduces a Deep Learning (DL) based ECG noise classifier for a knowledge-driven ECG filtering system, offering selective filtering to reduce signal distortion. Evaluation of various CNN and RNN-based models reveals VGG and Resnet outperform. Further, the VGG model is superior in terms of performance. But Resnet performs comparably to VGG with less model complexity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Rohingya refugees residing in Bangladesh have been exposed to profound trauma in addition to ongoing daily stressors of living in the refugee camps. Accurate assessments of mental health burden and their impact among this population require culturally sensitive tools that remain lacking in this context. The purpose of this study was to characterize salient cultural concepts of distress (CCDs), their causes, consequences, and approaches to treatment, among Rohingya refugees living in Cox's Bazar, Bangladesh, to help inform future measurement and intervention design., Methods: Between December 2020 and March 2022, 106 free-listing interviews and 10 key informant interviews were conducted with community members to identify and better understand common CCDs. Rohingya research staff analyzed the interview transcripts by tabulating the frequency of unique CCDs in the free-listing interviews and the unique attributed causes, signs, consequences, and treatment strategies for each CCD in the key informant interviews., Results: In total, five CCDs were identified: tenshon (tension), bishi sinta (excessive thinking), feshar (pressure), gum zai nofara (unable to sleep), and shoit-shoit lagon (feeling restless and/or trapped). Although the five CCDs had overlapping symptoms, they also had unique presentation, consequences, and preferred strategies for treatment that may impact service-seeking behavior. Three out of the five CCDs were considered life-threatening, if severe and left untreated., Conclusion: The five CCDs identified are culturally salient ways of experiencing and communicating distress within this community but are not adequately captured in existing mental health assessments for this population. This may negatively impact programmatic efforts among the group., (© 2024. The Author(s).)

Heavy metal ions pose significant risks to human health, pelagic, and several other life forms due to perniciousness, tendency to accumulate, and resistance to biodegradation. Waste bio-materials extend a budding alternative as low-cost adsorbent to address the removal of noxious pollutants from wastewater on account of being cost-effective and exhibiting exceptional adsorption capacities. The current exploration was accomplished to gauge the performance of raw and modified human hair concerning lead scavenging in a down-flow fixed bed column. The appraisal of column performance under varying operational parameters encompassing bed height (15-45 cm), influent metal ion concentration (60-140 mg L -1 ), and a solution flow rate (20-40 mL min -1 ) was performed by breakthrough curve analysis. The consequences acquired were evaluated using the Yoon Nelson, Thomas, Adam-Bohart, and Bed Depth Service Time (BDST) model. Among these employed models, Bed Depth Service Time (BDST) and Thomas models exhibited the highest R-squared value compared to the Yoon Nelson and Adam-Bohart's model for most cases. In addition, the optimization of lead adsorption was followed using the Box-Behnken design of response surface methodology (RSM). The optimal conditions (desirability-1.00) for achieving a goal of maximum percent removal of lead ions were marked to be a bed height of 42.79 cm, solution flow rate of 20.92 mL min -1, and an initial metal concentration of 139.51 mg L -1 . Under these optimized conditions, the percent amputation of lead in a fixed bed was observed to be 82.31 %, while the results of the experiment performed approximately under these optimized conditions revealed a percent removal of 85.05 %, reflecting a reasonable conformity with values acquired through Box-Behnken design., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Overactive or dysregulated cytokine expression is a hallmark of many acute and chronic inflammatory diseases. This is true for acute or chronic infections, neurodegenerative diseases, autoimmune diseases, cardiovascular diseases, cancer, and others. Cytokines such as interleukin-6 (IL-6) are known therapeutic targets and biomarkers for such inflammatory diseases. Platforms for cytokine detection are, therefore, desirable tools for both research and clinical applications. Single-walled carbon nanotubes (SWCNT) are versatile nanomaterials with near-infrared fluorescence that can serve as transducers for optical sensors. When functionalized with an analyte-specific recognition element, SWCNT emission may become sensitive and selective toward the desired target. SWCNT-aptamer sensors are easily assembled, inexpensive, and biocompatible. In this work, we introduced a nanosensor design based on SWCNT and a DNA aptamer specific to IL-6. We first evaluated several SWCNT-aptamer constructs based on this simple direct complexation method, wherein the aptamer both solubilizes the SWCNT and confers sensitivity to IL-6. The sensor limit of detection, 105 ng/mL, lies in the relevant range for pathological IL-6 levels. Upon investigation of sensor kinetics, we found rapid response within seconds of antigen addition which continued over the course of 3 h. We found that this sensor construct is stable and the aptamer is not displaced from the nanotube surface during IL-6 detection. Finally, we investigated the ability of this sensor construct to detect macrophage activation caused by bacterial lipopolysaccharides (LPS) in an in vitro model of disease, finding rapid and sensitive detection of macrophage-expressed IL-6. We are confident that further development of this sensor will have novel implications for diagnosis of acute and chronic inflammatory diseases, in addition to contributing to the understanding of the role of cytokines in these diseases.

Background and Objectives: Deoxyguanosine kinase deficiency is one genetic cause of mtDNA depletion syndrome. Its major phenotypes include neonatal/infantile-onset hepatocerebral disease, isolated hepatic disease and myopathic disease. In this retrospective study, we seek to describe the natural history of deoxyguanosine kinase deficiency and identify any genotype-phenotype correlations., Methods: Retrospective literature search and collation of data from genetically confirmed cases of deoxyguanosine kinase deficiency., Results: 173 cases of DGUOK deficiency were identified. Neonatal/infantile-onset hepatocerebral disease accounted for 128 (74%) of cases. Isolated liver disease was seen in 36 (21%) and myopathic disease in 9 (5%) of cases. The most frequently involved systems were liver (98%), brain (75%), growth (46%) and gastrointestinal tract (26%). Infantile-onset disease typically presented with cholestatic jaundice and lactic acidosis. Neurological involvement included hypotonia, nystagmus and developmental delay with MRI brain abnormalities in about half of cases. Missense variants accounted for 48% of all pathogenic variants while variants resulting in truncated transcripts accounted for 39%. Prognosis was poor, especially for neonatal/ infantile-onset hepatocerebral disease for which 1 year survival was 11%. Twenty-three patients received liver transplants, of whom 12 died within 2 years of transplant. Patients with two truncating variants had a higher risk of death and were more likely to have the neonatal/infantile-onset hepatocerebral disease phenotype. No blood biomarker predictive of neurological involvement was identified. Earlier onset correlated with increased mortality., Conclusions: There is a narrow window for therapeutic intervention. For the hepatocerebral disease phenotype, median age of onset was 1 month while the median age of death was 6.5 months implying rapid disease progression., Competing Interests: Declaration of competing interest NK declares no competing interests. SR declares that she has provided consultancy on primary mitochondrial diseases for pharmaceutical companies as listed in the IJCME conflict of interest form., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: The objective of this study was to evaluate the effect of acidic beverages on the surface topography and elemental composition of human teeth., Methods: A total of five highly acidic beverages (Red Bull, Pepsi, Apple Cidra, Tang Mosambi, and Tang Orange) were investigated. The tooth specimens of experimental groups were submerged in each beverage and incubated at 37 °C for 7 days, whereas, the tooth specimens of control groups were placed in distilled water. Afterwards, tooth specimens were analyzed using scanning electron microscopic (SEM), stereomicroscopic, and energy dispersive x-ray (EDX) techniques., Results: All experimental groups revealed a decline in the tooth elements compared to controls, however, such decline was not statistically significant. Nevertheless, comparing the experimental groups, the Red Bull beverage caused a marked reduction in the percentage of both calcium and phosphorus elements compared to the Pepsi, Apple Cidra, Tang Mosambi, and Tang Orange beverages but it was insignificant as well in contrast to its control counterpart. All five acidic beverages demonstrated erosive potential under SEM analysis; however, each group of specimens showed a diverse amount of demineralization. In addition, all experimental groups exhibited significant discoloration of tooth specimens compared to their respective control counterparts., Conclusions: Within the limitations of study, all five acidic beverages demonstrated erosive potential in the simulated in vitro conditions under SEM analysis; however, each group of specimens exhibited a different extent of demineralization. In addition, the overall effect of all beverages was insignificant under EDX analysis as no substantial difference was revealed between the elemental composition of experimental and control group specimens., (© 2024. The Author(s).)

Sickle cell retinopathy (SCR) is a progressive, sight-threatening ophthalmic complication of sickle cell disease (SCD). Current SCR screening focuses on the detection of pathologic sea fan neovascularization, the first sign of proliferative sickle cell retinopathy (PSR). If untreated, PSR can lead to severe visual impairment and blindness through progression to vitreous hemorrhage and/or retinal detachment. SCR screening with dilated fundus examination (DFE) is recommended every 1-2 years starting at age 10, but data underlying this recommendation are of poor quality and based upon expert consensus. We performed a systematic review to characterize imaging techniques, laboratory-based tests, and clinical practices for SCR screening. This PROSPERO-registered systematic review included relevant texts identified through predetermined searches in online databases. Collected test accuracy data facilitated the calculation of likelihood ratios. Forty-four studies evaluating 4928 patients were included. DFE demonstrated moderate test accuracy (LR+ of 8.0, LR- of 0.3). Ultra-widefield-fundus photography demonstrated superior accuracy (LR+ 32.5, LR- 0.03). Optical coherence tomography angiography applications were highly accurate for PSR identification (machine learning LR+ 32.5, LR- 0.03; human grader LR+ 2.8-213.1, LR- 0.1-0.2). Most techniques and tests were more accurate at detecting PSR than staging SCR or detecting lower-grade SCR. Our findings support the integration of advanced image-based approaches, such as computer-based image analysis and ultra-wide-field fundus imaging, for SCR screening in SCD patients given the superior accuracy in PSR detection compared with the current standard of care. Rigorous SCR screening implementation studies are needed to support evidence-based SCR screening recommendations., (© 2024 Wiley Periodicals LLC.)

[This corrects the article DOI: 10.1039/D0RA09970H.]., (This journal is © The Royal Society of Chemistry.)

The functional significance of the interactions between proteins in living cells to form short-lived quaternary structures cannot be overemphasized. Yet, quaternary structure information is not captured by current methods, neither can those methods determine structure within living cells. The dynamic versatility, abundance, and functional diversity of G protein-coupled receptors (GPCRs) pose myriad challenges to existing technologies but also present these proteins as the ideal testbed for new technologies to investigate the complex inter-regulation of receptor-ligand, receptor-receptor, and receptor-downstream effector interfaces in living cells. Here, we present development and use of a novel method capable of overcoming existing challenges by combining distributions (or spectrograms) of FRET efficiencies from populations of fluorescently tagged proteins associating into oligomeric complexes in live cells with diffusion-like trajectories of FRET donors and acceptors obtained from molecular dynamics (MD) simulations. Our approach provides an atom-level picture of the binding interfaces within oligomers of the human secretin receptor (hSecR) in live cells and allows for extraction of mechanistic insights into the function of GPCRs oligomerization. This FRET-MD spectrometry approach is a robust platform for investigating protein-protein binding mechanisms and opens a new avenue for investigating stable as well as fleeting quaternary structures of any membrane proteins in living cells.

Background: In the USA, multiple organizations rate hospitals based on quality and patient safety data, but few studies have analyzed and compared the rating results., Objective: Compare the results of different US hospital-rating organizations., Design: Observational data analysis of US acute care hospital ratings., Participants: Four rating organizations: Hospital Compare® (HC), Healthgrades® (HG), The Leapfrog Group® (Leapfrog), and US News and World Report® (USN)., Main Measures: We analyzed the level of concordance (similar ranking), discordance (difference of 1 or more rankings), and severe discordance (difference of two or more rankings), as well as differences and correlations between the scores., Key Results: From Feb 1 to Oct 3, 2023, we analyzed data from 2,384 hospitals. In Leapfrog, there were 688 hospitals (29%) with Grade A, 652 (27.3%) with B, 885 (37.1%) with C, 153 (6.4%) with D, and 6 (0.3%) with F. For HC, 333 hospitals (14%) had five stars, 676 (28.4%) four, 695 (29.2%) three, 502 (21.4%) two, and 171 (7.2%) one-star. In ratings between HC and Leapfrog, discordance was 70%, and severe discordance was 25.1%. USN ranked 469 hospitals (19.7%). Within the USN-ranked hospital group, there was a 62% discordance and 19.8% severe discordance between HC and Leapfrog. The analysis of orthopedic procedures from HG and USN showed discordance ranging from 48 to 61.2%., Conclusion: The rating organizations' reported metrics were highly discordant. A hospital's ranking by one organization frequently did not correspond to a similar ranking by another. The methodology and included timeline and patient population can help explain the differences. However, the discordant ratings may confuse patients and customers., (© 2024. The Author(s).)

Background: Women in the fisher communities in coastal regions of Bangladesh are engaged in a wide range of fishery activities. However, there is limited evidence available on the occupational hazards and risks experienced by them., Method: The study was conducted among fishing colonies in Cox's Bazar and Chattogram districts in Bangladesh. This was a cross-sectional study blending qualitative and quantitative approaches. The qualitative component comprised five focus group discussions to understand the occupational context, hazards, and risks faced by the fisherwomen, informing the questionnaire design for the subsequent survey. The quantitative survey involved a sample of 207 women from fisher communities, gathering socio-demographic information, occupational hazards, risks, and health and safety practices., Findings: The study found a high occurrence of occupational hazards, health risks and limited availability of preventive measures among the women in fisher communities. Occupational hazards include physical safety hazards such as slippery surfaces and fish cutting instruments, and physical hazards like prolonged sun exposure and noise. Chemical hazards like pesticides and saltwater, ergonomic hazards such as prolonged uncomfortable posture and heavy lifting, and biological hazards including inadequate sanitation facilities were prevalent. The study also identified the potential occupational risks, and the outcomes resulting from the hazards, including injuries (87.44%), musculoskeletal conditions (69.08%), skin diseases/conditions (56.52%), eye complaints (33.82%), severe respiratory distress (24.15%) and high incidence of self-reported communicable diseases. Most women (78.26%) did not use personal protective equipment, and the majority (93.72%) lacked a workplace first aid kit., Conclusion: The study revealed a high prevalence of occupational hazards and health risks, including injuries and diseases, among Bangladeshi women in fisher communities with insufficient safety measures. Collaboration among government, NGOs, development partners, fisheries stakeholders, and the community is imperative for targeted training, innovative procedures, ergonomic solutions, provision of protective equipment, and advocacy to enhance the well-being of these women., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Halder et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Magnetic resonance enterography (MRE) interpretation of Crohn's disease (CD) is subjective and uses 2D analysis. We evaluated the feasibility of volumetric measurement of terminal ileal CD on MRE compared to endoscopy and sMARIA, and the responsiveness of volumetric changes to biologics., Methods: CD patients with MRE and contemporaneous CD endoscopic index of severity-scored ileocolonoscopy were included. A centreline was placed through the terminal ileum (TI) lumen defining the diseased bowel length on the T2-weighted non-fat saturated sequence, used by two radiologists to independently segment the bowel wall to measure volume (phase 1). In phase 2, we measured disease volume in patients treated with biologics, who had undergone pre- and post-treatment MRE, with treatment response classified via global physician assessment., Results: Phase 1 comprised 30 patients (median age 29 (IQR 24, 34) years). Phase 2 included 12 patients (25 years (22, 38)). In phase 1, the mean of the radiologist-measured volumes was used for analysis. The median disease volume in those with endoscopically active CD was 20.9 cm 3 (IQR 11.3, 44.0) compared to 5.7 cm 3 (2.9, 9.8) with normal endoscopy. The mean difference in disease volume between the radiologists was 3.0 cm 3 (limits of agreement -21.8, 15.9). The median disease volume of patients with active CD by sMARIA was 15.0 cm 3 (8.7, 44.0) compared to 2.85 cm 3 (2.6, 3.1) for those with inactive CD. Pre- and post-treatment median disease volumes were 28.5 cm 3 (26.4, 31.2), 11 cm 3 (4.8, 16.6), respectively in biological responders, vs 26.8 cm 3 (12.3, 48.7), 40.1 cm 3 (10, 56.7) in non-responders., Conclusion: Volumetric measurement of terminal ileal CD by MRE is feasible, related to endoscopy and sMARIA activity, and responsive to biologics., Clinical Relevance Statement: Measuring the whole volume of diseased bowel on MRE in CD is feasible, related to how biologically active the disease is when assessed by endoscopy and by existing MRE activity scores, and is sensitive to treatment response., Key Points: MRE reporting for CD is subjective and uses 2D images rather than assessing the full disease volume. Volumetric measurement of CD relates to endoscopic activity and shows reduced disease volumes in treatment responders. This technique is an objective biomarker that can assess disease activity and treatment response, warranting validation., (© 2024. The Author(s).)

MXenes with their wide range of tunability and good surface chemistry provide unique and distinctive characteristics offering potential employment in various aspects of energy management applications. These high-performance materials have attracted considerable attention in recent decades due to their outstanding characteristics. In the literature, most of the work is related to specific methods for the preparation of MXenes. In this Review, we present a detailed discussion on the synthesis of MXenes through different etching routes involving acids, such as hydrochloric acid, hydrofluoric acid, and lithium fluoride, and non-acidic alkaline solution, electrochemical, and molten salt methods. Furthermore, a concise overview of the different structural, optical, electronic, and magnetic properties of MXenes is provided corresponding to their role in supporting high thermal, chemical, mechanical, environmental, and electrochemical stability. Additionally, the role of MXenes in maintaining the thermal management performance of photovoltaic thermal systems (PV/T), wearable light heaters, solar water desalination, batteries, and supercapacitors is also briefly discussed. A techno-economic and life cycle analysis of MXenes is provided to analyze their sustainability, scalability, and commercialization to facilitate a comprehensive array of energy management systems. Lastly, the technology readiness level of MXenes is defined, and future recommendations for MXenes are provided for their further utilization in niche applications. The present work strives to link the chemistry of MXenes to process economics for energy management applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Microproteins, known as micropeptides, are small protein molecules encoded by short open reading frames. These recently identified molecules have been proven to be an essential part of the human proteome that participates in multiple processes, such as DNA repair, mitochondrial respiration, and regulating different signaling pathways. A growing body of studies has evidenced that microproteins exhibit dysregulated expression levels in various malignancies and contribute to tumor progression. It has been reported that microproteins interact with many proteins, such as enzymes (e.g., adenosine triphosphate synthase) and signal transducers (e.g., c-Jun), and regulate malignant cell metabolism, proliferation, and metastasis. Moreover, microproteins have been found to play a significant role in multidrug resistance in vitro and in vivo by their activity in DNA repair pathways. Considering that, this review intended to summarize the roles of microproteins in different aspects of tumorigenesis with diagnostic and therapeutic perspectives., (© 2024 International Federation for Cell Biology.)

Protein-based ultrafine fibrous scaffolds can mimic the native extracellular matrices (ECMs) with regard to the morphology and chemical composition but suffer from poor mechanical and wet stability. As a result, cells cannot get a true three-dimensional (3D) environment as they find in native ECMs. In this study, an epoxide, ethylene glycol diglycidylether (EGDE), with high reactivity to active hydrogen is introduced to gelatin solution, serving as an effective cross-linker. The gelatin/EGDE 3D-ultrafine (∼500 nm in diameter) fibrous composite scaffolds are made by an ultralow-concentration phase separation technique (ULCPS). The effects of the polymer content and modification conditions on the morphology and wet stability of the constructs are investigated. It is revealed that ultrafine fibers with 3D random orientation could be formed at low concentrations (0.01, 0.05, and 0.1 wt %, respectively). The wet stability of the constructs could be effectively improved by introducing EGDE into the gelatin system. The shrinkage is reduced to merely 2.14% after the modification at 120 °C for 2 h and could be maintained for up to 3 days. In order to improve the compression properties, the same technique is utilized with the presence of a poly(lactic acid) (PLA) spacer fabric to produce a bicomponent scaffold. The mechanical property and cell viability of the bicomponent scaffolds are investigated, and it is found that cells could enter deep inside and orient themselves randomly at the central area of the bicomponent scaffold. The modification and design approach presented in this study has the potential to provide various protein-based ultrafine fibrous biomaterials for a variety of biomedical applications.

Background: Preterm birth (PTB) and its complications are important public health problems. Its aetiology is multifactorial and involves both modifiable and non-modifiable factors. Among the modifiable risk factors, micronutrient deficiencies, including maternal folate deficiency, are increasingly being studied in PTB. In this study, we estimated the prevalence of folate deficiency during pregnancy and examined its association with PTB among rural Bangladeshi women., Methods: We conducted a nested case-control study using data from a population-based cohort of 3000 pregnant women who were enrolled between 8 and 19 weeks of gestation following ultrasound confirmation of gestational age. Sociodemographic, epidemiologic, clinical, and pregnancy outcomes data were collected through home visits, while blood samples were collected at enrolment and 24-28 weeks of gestation during pregnancy. We included all women who delivered preterm (defined as live births <37 weeks of gestation) as cases (n = 235) and a random sample of women having a term birth as controls (n = 658). The main exposure was folate concentrations in maternal serum during 24-28 weeks of pregnancy. We categorised women into folate deficient (<3 ng/mL) and not deficient (≥3 ng/mL). We then performed multivariable logistic regression analysis to examine the association between maternal folate levels and PTB, adjusting for relevant covariates., Results: Thirty-eight per cent of the enrolled pregnant women were folate deficient. Maternal serum folate deficiency was significantly associated with PTB (adjusted OR (aOR) = 1.73; 95% confidence interval (CI) = 1.27-2.36). The risk of PTB was also higher among women who were of short stature (aOR = 1.83; 95% CI = 1.27-2.63), primiparous (aOR = 1.60; 95% CI = 1.15-2.22), and had exposure to passive smoking (aOR = 1.54; 95% CI = 1.02-2.31)., Conclusions: The prevalence of folate deficiency was high among pregnant women in rural Bangladesh, and folate deficiency was significantly associated with an increased risk of preterm birth., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Background: This study aimed to identify factors that influence the mortality rate of patients with coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA)., Methods: In this cross-sectional study, data from 23 centers across 15 countries, spanning the period of March 2020 to December 2021, were retrospectively collected. The study population comprised patients who developed invasive pulmonary aspergillosis while being treated for COVID-19 in the intensive care unit. Cox regression and decision tree analyses were used to identify factors associated with mortality in patients with CAPA., Results: A total of 162 patients (males, 65.4 %; median age: 64 [25th-75th: 54.0-73.8] years) were included in the study, of whom 113 died during the 90-day follow-up period. The median duration from CAPA diagnosis to death was 12 (25th-75th: 7-19) days. In the multivariable Cox regression model, an age of ≥65 years (hazard ratio [HR]: 2.05, 95 % confidence interval [CI]: 1.37-3.07), requiring vasopressor therapy at the time of CAPA diagnosis (HR: 1.80, 95 % CI: 1.17-2.76), and receiving renal replacement therapy at the time of CAPA diagnosis (HR: 2.27, 95 % CI: 1.35-3.82) were identified as predictors of mortality. Decision tree analysis revealed that patients with CAPA aged ≥65 years who received corticosteroid treatment for COVID-19 displayed higher mortality rates (estimated rate: 1.6, observed in 46 % of patients)., Conclusion: This study concluded that elderly patients with CAPA who receive corticosteroids are at a significantly higher risk of mortality, particularly if they experience multiorgan failure., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

The present study describes the development and validation of a simple and rapid HPLC method for the simultaneous quantification of exemestane and thymoquinone. The separation of both compounds was performed on a 5 μ C-18 column utilizing phase A as water/methanol (45:5 v/v) and phase B as acetonitrile (50 v/v) (total ratio of A/B = 40:60 v/v) in isocratic elution mode as the mobile phase at a flow rate of 0.8 mL/min. Further, the Box-Behnken design was used for optimizing the analytical method. The proposed method was validated for various parameters, and all parameters were found to be within an acceptable range. The simultaneous detection of both drugs was monitored at 243 nm with a retention time of 5.73 and 6.93 min, respectively. Moreover, the forced degradation studies were conducted under various stress conditions, and the relevance of the validated RP-HPLC method was further explored for the estimation of drugs from lipid-based nanoformulation. Taken together, the study construed the development of an efficient and robust method that could be used for the quantification of these agents in various in vitro as well as in vivo models., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Postoperative cognitive dysfunction (POCD) is a significant concern, with incidences reported up to 70% following cardiac surgery. Therefore, we aim to evaluate the incidence of POCD after elective coronary artery bypass graft (CABG) surgery at our single centre over a one-year period from August 2021 to July 2022. We included 34 patients in the study and conducted serial cognitive assessments up to three months post-surgery. Interestingly, our findings indicated an absence of POCD among patients who underwent elective CABG. Reasons contributing to this outcome are multifactorial, which may include the patients' younger age, higher educational levels, lack of pre-existing neurological disorders, meticulous intraoperative cerebral saturation monitoring, and the duration of aortic crossclamp and cardiopulmonary bypass time.

Stroke is one of the most common neurological disorder and third most common cause of death in the world. Low vitamin D concentrations have been shown to predict risk of cardiovascular disease and all-cause of mortality. The aim of this study was to estimate serum vitamin D level in acute ischemic stroke patients. This comparative cross-sectional type of study was conducted in the Department of Neurology and Department of Medicine at Mymensingh Medical College and Hospital, Bangladesh from November 2017 to June 2019 with a total number of 100 study subjects. Total fifty patients with acute ischemic stroke were enrolled in Group A and another fifty age and sex matched volunteer subjects were enrolled in Group B with no prior history of stroke or transient ischemic attacks. Serum vitamin D levels, fasting plasma glucose and lipid profile were assessed in both groups and compared with each other. P value <0.05 was considered as significant in the study. Mean fasting blood sugar, serum fasting total cholesterol (TC), serum fasting triglycerides, serum fasting Low density lipoprotein (LDL) were significantly higher in Group A than Group B (p<0.05). Serum vitamin D level in Group A was 25.28±8.47ng/ml and in Group B was 30.90±5.80, (p=0.001). Insufficient vitamin D level was found in 52.0% of ischemic stroke patients and in 30% of healthy controls (p=0.0002). Vitamin D deficiency was found in 20.0% ischemic stroke patients and 10.0% in healthy controls. This study demonstrates a positive association between low serum vitamin D level and acute ischemic stroke. Further studies are required to determine whether vitamin D supplementation could improve functional outcome in patients with ischemic stroke.

Obesity and hypothyroidism are interlinked. In this prospective study, 142 children and adolescents (mean age 140±34 months, girls 54.2%) either with obesity or overweight were included from the patients attending at the Endocrine out-patient clinic of Dhaka Shishu (Children) Hospital during a period from March, 2017 to February, 2020 and were assessed for thyroid function. Among them, 85 were obese (Body mass index, BMI >95th percentile), 29 were overweight (BMI between 85th to 95th percentile) and 28 had normal weight (BMI <85th percentile). Girls were more frequent in obese (57.6%) and overweight (51.7%) groups than boys. Mean TSH was not significantly different among the three groups (3.39 vs. 4.01 vs. 4.06mIU/L; p=0.248). Subclinical hypothyroidism was present in 22 cases (15.5%); the frequencies were 3.6% in Group 1, 17.2% in Group 2 and 18.8% in Group 3. Both overweight and obese groups had significantly (p<0.005) higher prevalence of SCH than the normal-weight group. Girls were more frequently affected than boys (72.7% vs. 27.3%, p=0.047). Among the 22 children who had SCH, 2(9.1%) had a mild goiter and higher serum levels of anti-TPO and anti-TG. Serum TSH had no correlations with age, body weight, height, BMI and serum FT₄. The findings indicate that a substantial portion of over weight and obese children and adolescents have SCH and the causes other than thyroid autoimmunity are more prevalent in them.

Objectives: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome., Study Design: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified., Results: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes., Conclusions: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objective: Mast cells have been implicated in abdominal pain-associated disorders of gut-brain interaction, such as functional dyspepsia. As such, ketotifen, a second-generation antihistamine and mast cell stabilizer, could represent a viable treatment option in these conditions. The primary aim of the current pilot study was to assess clinical response to ketotifen and assess pharmacokinetics in youth with functional dyspepsia., Methods: We conducted a pilot randomized, double-blind, placebo-controlled, cross-over trial of ketotifen in 11 youth with functional dyspepsia and duodenal mucosal eosinophilia with 4 weeks of active treatment at a dose of 1 mg twice daily. Global clinical response was graded on a 5-point Likert Scale. A single plasma sample was obtained at steady state for pharmacokinetic analysis., Results: Ketotifen was not superior to placebo with regard to global clinical response. Only 18% of patients demonstrated a complete or near-complete clinical response. The estimated half-life was 3.3 h., Conclusions: While ketotifen was not superior to placebo, this study highlights several important challenges for developing drug trials for youth with chronic abdominal pain. Recommendations are made for designing a larger treatment trial for ketotifen in this patient group., Clinical Trial Registration: This study was registered at ClinicalTrials.gov: NCT02484248., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The tumor immune microenvironment is distinct between early-onset and late-onset colorectal cancer, which facilitates tumor progression. We previously identified several genes, including complement factor D, as having increased expression in patients with early-onset colorectal cancer., Objective: This study aimed to assess and validate the differential expression of immune genes in early-onset and late-onset colorectal cancer. We also aimed to test known drugs targeting genes increased in early-onset colorectal cancer in preclinical mouse models., Design: A retrospective cohort study with analysis was performed using tumor RNA from formalin-fixed paraffin-embedded cell culture and immunohistochemistry to validate gene expression and function and in vivo preclinical tumor study to assess drug efficacy., Settings: The Oregon Colorectal Cancer Registry was queried to identify patients with colorectal cancer., Patients: The study included 67 patients with early-onset colorectal cancer and 54 patients with late-onset colorectal cancer., Interventions: Preclinical animal models using the HCT-116 colon cancer cell line were treated with the complement factor D inhibitor danicopan and the BCL2 inhibitor venetoclax, or with vehicle controls., Main Outcome Measures: Elevated RNA signatures using NanoString data were evaluated by the retrospective cohort. When inhibiting these markers in the mouse preclinical model, tumor volume and weight were the main outcome measures., Results: After updating our sample size from our previously published data, we found that complement factor D and BCL2, genes with known function and small molecule inhibitors, are elevated in patients with early-onset colorectal cancer. When inhibiting these markers with the drugs danicopan and venetoclax in a mouse model, we found that the combination of these drugs decreased tumor burden but also resulted in toxicity., Limitations: This study is limited by a small sample size and a subcutaneous tumor model., Conclusions: Combinatorial inhibition of early-onset associated genes complement factor D and BCL2 slows the growth of early-onset colorectal cancer in a mouse preclinical model. See Video Abstract ., Inhibicin Combinada Del Factor Dcomplementario Y Del Bcl En Casos De Cncer Colorrectal De Aparicin Temprana: ANTECEDENTES:El microambiente inmunológico del tumor es distinto entre el cáncer colorrectal de aparición temprana y el de aparición tardía, lo que facilita la progresión de dicho tumor. Anteriormente identificamos varios genes, incluidos el factor D-Complementario, con una mayor expresión en pacientes con cáncer colorrectal de aparición temprana.OBJETIVO:El presente estudio tuvo como objetivo el evaluar y validar la expresión diferenciada de genes inmunes en casos de cáncer colorrectal de aparición temprana y tardía. También nos propusimos evaluar los fármacos conocidos dirigidos sobre los genes aumentados en el cáncer colorrectal de aparición temprana en modelos pre-clínicos en ratones.DISEÑO:Estudio de cohortes con análisis retrospectivo utilizando el ARN tumoral procedente de cultivos celulares fijados con formalina e incluidos en parafina, y el analisis por inmunohistoquímica para validar la expresión y la función genética. Se realizó el estudio pre-clínico de los tumores in vivo para evaluar la eficacia de los fármacos.AJUSTES:Se consultó el Registro de Oregon de casos de Cáncer Colorrectal para encontrar los pacientes afectados.SUJETOS:67 pacientes con cáncer colorrectal de aparición temprana y 54 pacientes con cáncer colorrectal de aparición tardía.INTERVENCIONES (SI LAS HUBIESE):Los modelos animales pre-clínicos que utilizaron la línea celular de cáncer de colon HCT-116 se trataron con el inhibidor del factor D-Complementario o Danicopan y con el inhibidor de BCL-2 o Venetoclax, ambos con control del transportador.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron las firmas de ARN elevadas utilizando los datos del NanoString a partir de la cohorte retrospectiva. Al inhibir estos marcadores del modelo pre-clínico en los ratones, el volumen y el peso del tumor fueron las principales medidas de resultado.RESULTADOS:Después de actualizar el tamaño de nuestra muestra a partir de datos publicados con anterioridad, encontramos que el factor D-Complementario y BCL-2, genes con función conocida e inhibidores de moléculas pequeñas, se encuentran elevados en aquellos pacientes con cáncer colorrectal de aparición temprana. Al inhibir estos marcadores con los medicamentos Danicopan y Venetoclax en el modelo de ratones vivos, encontramos que la combinación de estos dos farmacos disminuyó la carga tumoral pero también produjo toxicidad.LIMITACIONES:Estudio limitado por un tamaño de muestra pequeño y el modelo de tumor subcutáneo.CONCLUSIONES:La inhibición combinada de genes asociados de aparición temprana, el factor D-Complementario y el BCL-2, enlentecen el crecimiento del cáncer colorrectal de aparición temprana del modelo preclínico en ratones. (Traducción-Dr. Xavier Delgadillo )., (Copyright © The ASCRS 2024.)

Objective: To investigate the prevalence and natural history of POLG disease in the Norwegian population., Methods: A national, population-based, retrospective study using demographic, clinical, and genetic data of patients with genetically confirmed POLG disease. The patients were diagnosed between 2002 and 2022, and were included into the Norwegian POLG Patient Registry. Patients were stratified according to age at disease onset (early <12 years, juvenile to adult 12-40 years, late ≥40 years) and resident region., Results: Ninety-one patients were included. The point prevalence of POLG disease was 1:149,253. Birth prevalence was 1:48,780. Median age at clinical onset was 16 years (range: 2 months to 70 years). Onset occurred early in 35% (32 out of 91), juvenile-adult in 55% (50 out of 91) and late in 10% (9 out of 91). A distinct seasonal pattern in disease onset was observed, with 57% (52 out of 91) presenting between May and August. Forty-five patients (49%) had acute exacerbations that required intensive care, and this affected 72% of those in the early-onset group. The mortality rate was 54% (49 out of 91), with a median time from disease onset to death of 3 years (range: 1 month to 36 years)., Interpretation: We provide the point prevalence and birth prevalence of POLG disease in the first nationwide study in which epidemiological and clinical data were integrated. Seasonal variations in clinical onset may offer valuable insights into disease mechanisms and modifying factors. The findings from this study are crucial for quantifying the disease burden, and contribute to evidence-based healthcare planning., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)