Nucleosome remodeler exclusion by histone deacetylation enforces heterochromatic silencing and epigenetic inheritance.

Heterochromatin enforces transcriptional gene silencing and can be epigenetically inherited, but the underlying mechanisms remain unclear. Here, we show that histone deacetylation, a conserved feature of heterochromatin domains, blocks SWI/SNF subfamily remodelers involved in chromatin unraveling, thereby stabilizing modified nucleosomes that preserve gene silencing. Histone hyperacetylation, resulting from either the loss of histone deacetylase (HDAC) activity or the direct targeting of a histone acetyltransferase to heterochromatin, permits remodeler access, leading to silencing defects. The requirement for HDAC in heterochromatin silencing can be bypassed by impeding SWI/SNF activity. Highlighting the crucial role of remodelers, merely targeting SWI/SNF to heterochromatin, even in cells with functional HDAC, increases nucleosome turnover, causing defective gene silencing and compromised epigenetic inheritance. This study elucidates a fundamental mechanism whereby histone hypoacetylation, maintained by high HDAC levels in heterochromatic regions, ensures stable gene silencing and epigenetic inheritance, providing insights into genome regulatory mechanisms relevant to human diseases.

Exploring Phytochemical Profile, Pharmaceutical Activities, and Medicinal and Nutritional Value of Wild Edible Plants in Ethiopia.

In many parts of the world, wild edible plants (WEPs) constitute an essential component of the global food basket, providing an alternative source of wholesome and nourishing food. Ethiopia is one of countries of the world having largest concentrations of WEPs. In the country, various parts of WEPs, such as fruits, stems, leaves, tubers, roots, or entire plant sections, are frequently consumed and used as food sources for famine relief during seasonal food shortages, as well as for commercial purposes. WEPs have been also used in the country as sources of phytochemicals, traditional medicine, and pharmaceutical applications. Approximately 30%-40% of WEPs and over 413 different kinds of WEPs are commonly consumed by Ethiopians regularly. Most plant families utilized as WEPs are Moraceae, Fabaceae, Flacourtiaceae, Myrtaceae, Rosaceae, and Tiliaceae. The most widely used plant parts of WEPs were fruits. WEPs can be used as substitutes for traditional plant-based human diets because of their high nutritional value, which includes proteins, vitamins B2 and C, and low moisture content. This review focuses on using edible wild plants for pharmacological purposes, dietary supplements, and alternative medicine. Many obstacles prevent people from consuming WEPs, even when they are easily accessible and available. The use of WEPs must be encouraged by nutrition policies as one of the pillars of food and nutrition security. To increase yield, diversify the revenue streams of small-scale farmers, and protect the diminishing wild edible fruit resources, it is imperative to domesticate and enhance WEPs.

Automatic pipeline for segmentation of LV myocardium on quantitative MR T1 maps using deep learning model and computation of radial T1 and ECV values.

Native T1 mapping is a non-invasive technique used for early detection of diffused myocardial abnormalities, and it provides baseline tissue characterization. Post-contrast T1 mapping enhances tissue differentiation, enables extracellular volume (ECV) calculation, and improves myocardial viability assessment. Accurate and precise segmenting of the left ventricular (LV) myocardium on T1 maps is crucial for assessing myocardial tissue characteristics and diagnosing cardiovascular diseases (CVD). This study presents a deep learning (DL)-based pipeline for automatically segmenting LV myocardium on T1 maps and automatic computation of radial T1 and ECV values. The study employs a multicentric dataset consisting of retrospective multiparametric MRI data of 332 subjects to develop and assess the performance of the proposed method. The study compared DL architectures U-Net and Deep Res U-Net for LV myocardium segmentation, which achieved a dice similarity coefficient of 0.84 ± 0.43 and 0.85 ± 0.03, respectively. The dice similarity coefficients computed for radial sub-segmentation of the LV myocardium on basal, mid-cavity, and apical slices were 0.77 ± 0.21, 0.81 ± 0.17, and 0.61 ± 0.14, respectively. The t-test performed between ground truth vs. predicted values of native T1, post-contrast T1, and ECV showed no statistically significant difference (p > 0.05) for any of the radial sub-segments. The proposed DL method leverages the use of quantitative T1 maps for automatic LV myocardium segmentation and accurately computing radial T1 and ECV values, highlighting its potential for assisting radiologists in objective cardiac assessment and, hence, in CVD diagnostics.

Global treatment of haemorrhoids-A worldwide snapshot audit conducted by the International Society of University Colon and Rectal Surgeons.

AIM: There is no universally accepted treatment consensus for haemorrhoids, and thus, management has been individualized all over the world. This study was conducted to assess a global view of how surgeons manage haemorrhoids. METHODS: The research panel of the International Society of University Colon and Rectal Surgeons (ISUCRS) developed a voluntary, anonymous questionnaire evaluating surgeons' experience, volume and treatment approaches to haemorrhoids. The 44 multiple-choice questionnaire was available for one month via the ISUCRS email database and the social media platforms Viber and WhatsApp. RESULTS: The survey was completed by 1005 surgeons from 103 countries; 931 (92.6%) were in active practice, 819 (81.5%) were between 30 and 60 years of age, and 822 (81.8%) were male. Detailed patient history (92.9%), perineal inspection (91.2%), and digital rectal examination (91.1%) were the most common assessment methods. For internal haemorrhoids, 924 (91.9%) of participants graded them I-IV, with the degree of haemorrhoids being the most important factor considered to determine the treatment approach (76.3%). The most common nonprocedural/conservative treatment consisted of increased daily fibre intake (86.9%), increased water intake (82.7%), and normalization of bowel habits/toilet training (74.4%). Conservative treatment was the first-line treatment for symptomatic first (92.5%), second (72.4%) and third (47.3%) degree haemorrhoids; however, surgery was the first-line treatment for symptomatic fourth degree haemorrhoids (77.6%). Rubber band ligation was the second-line treatment in first (50.7%) and second (47.2%) degree haemorrhoids, whereas surgery was the second-line treatment in third (82.9%) and fourth (16.7%) degree symptomatic haemorrhoids. Rubber band ligation was performed in the office by 645(64.2%) of the participants. The most common surgical procedure performed for haemorrhoids was an excisional haemorrhoidectomy for both internal (87.1%) and external (89.7%) haemorrhoids - with 716 (71.2%) of participants removing 1, 2 or 3 sectors as necessary. CONCLUSION: Although there is no global haemorrhoidal treatment consensus, there are many practice similarities among the different cultures, resources, volume and experience of surgeons around the world. With additional studies, a consensus statement could potentially be developed.

Extraconal orbital craniopharyngioma.

A female, in her 60s, presented with pain and swelling of the right eye for 3 years. The radiological work-up revealed an extraconal solid-cystic orbital tumour suggestive of an epidermoid cyst. The patient underwent supraorbital craniotomy with a gross total excision of the tumour. An intraoperative diagnosis was sought, which on both squash smear and frozen section showed features of craniopharyngioma (CP), later confirmed on paraffin sections and immunohistochemistry. The orbit is a very rare site for ectopic CP, with only two cases reported in the literature. Many theories have been proposed to explain the occurrence of CP at ectopic sites. This report aims to provide insight into the different hypotheses of the pathogenesis of ectopic CP through a review of the literature.

Leveraging thiol-functionalized biomucoadhesive hybrid nanoliposome for local therapy of ulcerative colitis.

Directly administering medication to inflamed intestinal sites for treating ulcerative colitis (UC), poses significant challenges like retention time, absorption variability, side effects, drug stability, and non-specific delivery. Recent advancements in therapy to treat colitis aim to improve local drug availability that is enema therapy at the site of inflammation, thereby reducing systemic adverse effects. Nevertheless, a key limitation lies in enemas' inability to sustain medication in the colon due to rapid peristaltic movement, diarrhea, and poor local adherence. Therefore, in this work, we have developed site-specific thiolated mucoadhesive anionic nanoliposomes to overcome the limitations of conventional enema therapy. The thiolated delivery system allows prolonged residence of the delivery system at the inflamed site in the colon, confirmed by the adhesion potential of thiolated nanoliposomes using in-vitro and in-vivo models. To further provide therapeutic efficacy thiolated nanoliposomes were loaded with gallic acid (GA), a natural compound known for its antibacterial, antioxidant, and potent anti-inflammatory properties. Consequently, Gallic Acid-loaded Thiolated 2,6 DALP DMPG (GATh@APDL) demonstrates the potential for targeted adhesion to the inflamed colon, facilitated by their small size 100 nm and anionic nature. Therapeutic studies indicate that this formulation offers protective effects by mitigating colonic inflammation, downregulating the expression of NF-κB, HIF-1α, and MMP-9, and demonstrating superior efficacy compared to the free GA enema. The encapsulated GA inhibits the NF-κB expression, leading to enhanced expression of MUC2 protein, thereby promoting mucosal healing in the colon. Furthermore, GATh@APDL effectively reduces neutrophil infiltration and regulates immune cell quantification in colonic lamina propria. Our findings suggest that GATh@APDL holds promise for alleviating UC and addressing the limitations of conventional enema therapy.

PIEZO1 targeting in macrophages boosts phagocytic activity and foam cell apoptosis in atherosclerosis.

The rising incidences of atherosclerosis have necessitated efforts to identify novel targets for therapeutic interventions. In the present study, we observed increased expression of the mechanosensitive calcium channel Piezo1 transcript in mouse and human atherosclerotic plaques, correlating with infiltration of PIEZO1-expressing macrophages. In vitro administration of Yoda1, a specific agonist for PIEZO1, led to increased foam cell apoptosis and enhanced phagocytosis by macrophages. Mechanistically, PIEZO1 activation resulted in intracellular F-actin rearrangement, elevated mitochondrial ROS levels and induction of mitochondrial fragmentation upon PIEZO1 activation, as well as increased expression of anti-inflammatory genes. In vivo, ApoE-/- mice treated with Yoda1 exhibited regression of atherosclerosis, enhanced stability of advanced lesions, reduced plaque size and necrotic core, increased collagen content, and reduced expression levels of inflammatory markers. Our findings propose PIEZO1 as a novel and potential therapeutic target in atherosclerosis.

Cost-effectiveness of portable-automated ABR for universal neonatal hearing screening in India.

The World Health Organization considers Universal Neonatal Hearing Screening (UNHS) essential to global public health. Rashtriya Bal Swasthya Karyakram has included newborn hearing screening in India since 2013. The program faces human, infrastructure, and equipment shortages. First-line hearing screening with improved diagnostic accuracy is needed. The Portable Automated Auditory Brainstem Responses (P-AABR) can be used in remote areas for UNHS due to its low infrastructure needs and diagnostic accuracy. This study evaluated the cost-effectiveness of P-AABR in UNHS. We employed an analytical model based on decision trees to assess the cost-effectiveness of Otoacoustic Emission (OAE) and P-AABR. The total cost to the health system for P-AABR, regardless of true positive cases, is INR 10,535,915, while OAE costs INR 7,256,198. P-AABR detects 262 cases, whereas OAE detects 26 cases. Portable Automated ABR costs INR 97 per case detection, while OAE costs INR 67. The final ICER was 97407.69. The P-AABR device is cost-effective, safe and feasible for UNHS Rashtriya Bal Swasthya Karyakram (RBSK) programs. Beyond reducing false referrals and parent indirect costs, it detects more hearing-impaired infants. Even in shortages of skilled workers, existing staff can be trained. Thus, this study suggests integrating this device into community and primary health centers to expand UNHS coverage.

Therapeutic potential of Nelumbo nucifera Linn. in systemic lupus erythematosus: Network pharmacology and molecular modeling insights.

BACKGROUND: Systemic lupus erythematosus is a chronic autoimmune inflammatory disease characterized by multiple symptoms. The phenolic acids and other flavonoids in Nelumbo nucifera have anti-oxidants, anti-inflammatory, and immunomodulatory activities that are essential for managing SLE through natural sources. This study employs network pharmacology to unveil the multi-target and multi-pathway mechanisms of Nelumbo nucifera as a complementary therapy. The findings are validated through molecular modeling, which includes molecular docking followed by a molecular dynamics study. METHODS: Active compounds and targets of SLE were obtained from IMPPAT, KNApAcKFamily and SwissTargetPrediction databases. SLE-related targets were retrieved from GeneCards and OMIM databases. A protein-protein interaction (PPI) network was built to screen out the core targets using Cytoscape software. ShinyGO was used for GO and KEGG pathway enrichment analyses. Interactions between potential targets and active compounds were assessed by molecular docking and molecular dynamics simulation study. RESULTS: In total, 12 active compounds and 1190 targets of N. nucifera's were identified. A network analysis of the PPI network revealed 10 core targets. GO and KEGG pathway enrichment analyses indicated that the effects of N. nucifera are mediated mainly by AGE-RAGE and other associated signalling pathways. Molecular docking indicated favourable binding affinities, particularly leucocianidol exhibiting less than -4.5 kcal/mol for all 10 targets. Subsequent molecular dynamics simulations of the leucocianidol-ESR1 complex aimed to elucidate the optimal binding complex's stability and flexibility. CONCLUSIONS: Our study unveiled the potential therapeutic mechanism of N. nucifera in managing SLE. These findings provide insights for subsequent experimental validation and open up new avenues for further research in this field.

Emerging Roles of Gossypol in Therapy: Innovations in Prodrug Design and Nanoformulation Frontiers.

Stimuli activatable systems have the potential to deliver drugs to targeted areas by releasing therapeutic agents in response to diseased specific microenvironments such as the acidic environment commonly found in diseased tissues. This review article focuses on gossypol, a bioactive compound with inherent toxicity due to its formyl groups. It highlights the potential of imine-linked gossypol-based prodrugs and nanoparticle formulations for targeted delivery and controlled release. The unique presence of polyphenolic cores on gossypol can be utilized to prepare nanoparticles. This review offers valuable insights into designing safer and more effective drug delivery systems by elucidating the masking effect and stimuli-responsive release mechanisms. Numerous examples demonstrate the conversion of formyl groups to imines, creating prodrugs that mask reactive functionalities and offer pH-responsive release. This insight can guide the design of combination therapeutics, where a second drug with an amine terminal group can form imine-linked prodrugs. Additionally, the second part discusses the use of polyphenolic moieties to create stable nanoparticles from infinite polymeric networks. Through a comprehensive examination of gossypol's properties and applications, this review emphasizes the broader implications of such a masking strategy for optimizing the therapeutic benefits of many similar bioactive compounds while minimizing adverse effects.

Operational feasibility and multi-centric evaluation of 'TBDetect sputum microscopy kit' for the direct detection of Mycobacterium tuberculosis in field settings.

BACKGROUND: India relies primarily on direct smear microscopy for tuberculosis (TB) diagnosis. However, the low sensitivity of smear microscopy emphasizes the need to improve its performance. We recently described the development of 'TBDetect' kit which showed improved performance over direct smear microscopy at National Reference Laboratories (NRLs) in India. METHODS: The present study was aimed to assess the operational feasibility of 'TBDetect' microscopy in field settings. This was evaluated by (i) assessing the performance of 'TBDetect' microscopy vs. LED-fluorescence microscopy (LED-FM) on consecutive presumptive pulmonary TB patients (n = 5300) who attended Designated Microscopy Centres (DMCs, n = 13) under 4 NRLs at Bhubaneswar, Bhopal, Chennai, and New Delhi, and (ii) obtaining feedback from Scientists (n = 10) and laboratory technicians (n = 42) using semi-structured questionnaires under the following parameters: feasibility of initiation of 'TBDetect' microscopy in DMCs, sample preparation and testing, training, time-to-result, logistics, and troubleshooting. A scoring questionnaire was also used to assess 'TBDetect' microscopy vs. LED-FM and statistical significance of the scores was calculated using paired t-test. RESULTS: The overall positivity of 'TBDetect' microscopy was 10.32% (547/5300) vs. 8.96% (475/5300) of LED-FM at all sites and the increment in positivity was significant (p = 0.019). In addition, 'TBDetect' microscopy yielded an increment in smear grade status over LED-FM (p = 0.043). The feedback from the study-in-charge and kit users indicated that 'TBDetect' microscopy was easily adapted in point-of-care settings. An analysis of scoring feedback suggested that it was easy to perform and observe in comparison to LED-FM (p < 0.005). CONCLUSIONS: This study established the feasibility of 'TBDetect' microscopy in field settings.

Quercetin ameliorates neuroinflammatory and neurodegenerative biomarkers in the brain and improves neurobehavioral parameters in a repeated intranasal amyloid-beta exposed model of Alzheimer's disease.

Objectives: The aim of the present study was to study the potential therapeutic effects of quercetin in protection against repeated intranasal exposure of an amyloid-beta-induced mouse model. Methods: Mice received intranasal Aß1-42 (5 µg/10 µL) exposure once daily for seven consecutive days. Quercetin was orally administered to them at 30 mg kg-1 and 100 mg kg-1 doses for one week starting from day five following Aß1-42 peptide administration. Following this, the animals were evaluated for neurobehavioral parameters using a Morris water maze test and a novel object recognition test. Further to this, the biomarkers for neuroinflammation and neurodegeneration were evaluated in the hippocampus and cortex regions of the brain in these animals. Results: Multiple exposures to intranasal Aß led to a significant decline in the learning and cognitive memory of the animals, whereas oral treatment with quercetin at dosages of 30 and 100 mg kg-1 alleviated Aß-induced effects. Quercetin treatment significantly reduced Aß accumulation, oxidative stress and proinflammatory cytokine biomarkers in the brain. In addition, it also alleviated the activation of astrocytic biomarkers, amyloid precursor protein and phosphorylated-tau proteins in the brain. Conclusion: Quercetin was found to be a potent antioxidant, anti-inflammatory compound with protection against neurodegenerative damage and improved learning and cognitive memory in a repeated Aß-exposure model of AD.

Early screening for foot problems in people with diabetes is the need of the hour: 'Save the Feet and Keep Walking Campaign' in India.

INTRODUCTION: Evidence on the prevalence of foot problems among people with diabetes in India at a national level is lacking. Hence, this study was aimed to assess the burden of high-risk (HR) feet in people with diabetes across India. RESEARCH DESIGN AND METHODS: A cross-sectional national-level project 'Save the Feet and Keep Walking' campaign was conducted by the Research Society for the Study of Diabetes in India (RSSDI) from July 10, 2022 to August 10, 2022. A modified version of 3 min foot examination was used to assess the foot problems. Around 10 000 doctors with RSSDI membership were trained online to conduct foot screening and provided a standardised monofilament for detection of loss of protective sensation. People with diabetes aged >18 years who visited the clinics during the study period were examined for foot problems. Data were collected online using the semi-structured questionnaire. A total of 33 259 participants with complete information were included for the final analysis. The foot at risk was categorised based on International Working Group on the Diabetic Foot guidelines 2023. RESULTS: Nearly 75% of the participants were aged above 45 years. Around 49% had diabetes duration >5 years and uncontrolled diabetes (hemoglobin A1c >8%). Presence of history of foot ulcer (20%), lower limb amputation (15.3%), foot deformities (24.5%) and absence of diminished dorsal pedis and posterior tibial pulses (26.4%) was noted in the study participants. Around 25.2% of them had HR feet and highly prevalent among males. Diabetic kidney and retinal complications were present in 70% and 75.5% of people with HR feet. Presence of heel fissures (OR (95% CI) 4.6 (4.2 to 5.1)) and callus or corns (OR (95% CI) 3.6 (3.3 to 4.0)) were significantly associated with HR feet. CONCLUSIONS: One-fourth of people with diabetes were found to have HR feet in India. The findings are suggestive of regular screening of people with diabetes for foot problems and strengthening of primary healthcare.

Evaluating Carcinoembryonic Antigen and Glucose Levels in Pancreatic Cyst Fluid for Mucinous Versus Non-mucinous Differentiation.

BACKGROUND: A more precise identification of mucinous cysts will lower the likelihood of needless pancreatic surgery. Pancreatic cyst fluid (PCF) contains glucose and carcinoembryonic antigen (CEA), which serve as biomarkers to differentiate mucinous from non-mucinous pancreatic cystic neoplasms (PCNs). OBJECTIVE: To evaluate the diagnostic accuracy of combined CEA and glucose levels in PCF for distinguishing mucinous from non-mucinous PCNs preoperatively. METHODS: After receiving approval from the Institutional Ethical Committee of Indira Gandhi Institute of Medical Sciences, Patna, a cross-sectional validation research was carried out. All patients ≥18 years of age who had undergone pancreatic surgery or endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for a pancreatic cystic lesion and for whom PCF was acquired were eligible for inclusion. Patients were excluded if there was no PCF available, if they had been diagnosed with an extrapancreatic illness (such as ampullary adenoma), or if they could not be excluded due to pancreatic cancer generated from PCN. Diagnoses were pathologically confirmed. We performed measurements for CEA and glucose in PCF. CEA and glucose were measured using an Architect i2000SR analyzer (Abbott, Lake County, IL) and AU 5800 Beckman Coulter (Brea, CA), respectively. Diagnostic accuracy was evaluated by receiver operator characteristic (ROC) curves. RESULTS: PCF was obtained from 100 patients, of whom 54 (54%) had mucinous PCN and 46 (46%) had non-mucinous PCN. When CEA (cut-off ≥ 151 ng/ml) and glucose levels (cut-off ≤ 50 mg/dL) were combined, the results showed 46% sensitivity and 92% specificity. However, when CEA (cut-off ≥ 17 ng/ml) or glucose testing (cut-off ≤ 50 mg/dL) was used separately, the results showed 82% sensitivity and 73% specificity. CONCLUSION: The combined CEA and glucose testing in PCF demonstrated high specificity and sensitivity for differentiating mucinous from non-mucinous PCNs, suggesting its potential utility in preoperative diagnosis.

Predictive Value of C-reactive Protein in the Spontaneous Passage of Lower Ureteric Stones: A Prospective Single-Centre Study.

INTRODUCTION: Ureteric stones, characterised by their presence in the ureter, present a common yet often painful urological condition requiring timely intervention. As C-reactive protein (CRP) emerges as a potential biomarker, its correlation with the spontaneous stone passage (SSP) offers valuable insights into patient management and treatment strategies. The present study aimed to assess if CRP levels can predict SSP in symptomatic lower ureteric calculi of size 5 mm-10 mm. MATERIALS AND METHODS: This prospective observational study, conducted at the Indira Gandhi Institute of Medical Sciences in Patna, India, from July 2022 to June 2023, focused on individuals aged 13 to 60 years presenting with ureteric colic and single distal ureteral stones (5 mm-10 mm). Patients underwent comprehensive initial assessment and monitoring, including diagnostic procedures such as a complete blood count, urinalysis, CRP levels, and renal function evaluations. Treatment consisted of hydration encouragement, tamsulosin (0.4 mg) daily administration, and diclofenac (50 mg) as needed. Follow-up assessments at one-month post-treatment involved clinical examination and imaging studies to evaluate treatment efficacy. RESULTS: This study analysed 157 patients with ureteric stones, finding that 76% experienced SSP. Lower CRP levels (≤6 mg/L), along with other laboratory parameters like low white blood cell counts, low neutrophil levels, absence of leukocyturia, absence of hematuria, and lower urine specific gravity, were associated with higher SSP rates. C-reactive protein levels ≤6 mg/L emerged as a strong predictor of SSP in multiple regression analysis. CONCLUSION: The findings underscore the potential utility of CRP as a predictive biomarker in guiding the management and treatment strategies for ureteric stones.

The severity of non-smoking chronic obstructive pulmonary disease is correlated with biomass fuel exposure and COPD assessment test score.

BACKGROUND AND OBJECTIVE: Tobacco smoking is an established risk factor for chronic obstructive pulmonary disease (COPD). Current evidence suggests that non-tobacco-related risk factors vary geographically and are less understood than smoking. This study aims to compare the risk factors, symptoms, and clinical features of smoking (S-COPD) and non-smoking (NS-COPD) in a COPD population. MATERIALS AND METHODS: In this retrospective cross-sectional study, 489 COPD patients were screened. Data on socio-demographics, smoking and medical history, other risk factors, symptoms, and clinical characteristics including COPD Assessment Test (CAT) score, and Modified Medical Research Council (mMRC) Dyspnea Scale were examined. RESULTS: Of the total selected 416 COPD patients, 35.34% were NS-COPD while 64.66% were S-COPD. S-COPD was predominant in males, whereas NS-COPD was predominant in females (P < 0.0001). In NS-COPD, biomass fuel exposure was a major risk factor (P < 0.0001), and 61% of subjects had a biomass fuel exposure index of >60. In bivariate and multivariate analyses, no risk factors were correlated with forced expiratory volume in 1 second (FEV1)% predicted, while among clinical features, duration of illness (P = 0.001) was correlated with lower values of FEV1 in the multivariate table of S-COPD. In the multivariate analysis, biomass fuel exposure (P = 0.039) and CAT score (P < 0.0001) were correlated with FEV1(%) in NS-COPD. CONCLUSION: Biomass fuel exposure is a substantial risk factor for NS-COPD and was correlated with FEV1(%) predicted. In addition, the CAT score correlated with disease severity in patients with NS-COPD. The development of COPD in non-smokers is being recognized as a separate phenotype and it should be managed according to risk factors.

Adverse cardiovascular outcomes associated with proton pump inhibitor use after percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for gastroprotection in patients undergoing percutaneous coronary intervention (PCI), who are at increased risk of gastrointestinal bleeding due to antiplatelet therapy. However, emerging evidence suggests that PPIs may adversely impact cardiovascular outcomes. This systematic review and meta-analysis sought to assess the relationship between using PPIs and cardiovascular outcomes in patients following PCI. METHODS: We searched various databases up to March 15, 2024, for observational studies and randomized controlled trials (RCTs) assessing the cardiovascular effects of PPIs in PCI patients. Data were extracted on study characteristics, patient demographics, PPI use, and cardiovascular outcomes. The Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool 2 assessed study quality. Meta-analyses were conducted using a random-effects model using R software version 4.3. RESULTS: A total of 21 studies involving diverse populations and study designs were included. Observational studies suggested a moderate increase in risk for composite cardiovascular diseases (CVD), myocardial infarction (MI), and major adverse cardiac events (MACE) associated with PPI use, with pooled hazard ratios (HRs) of 1.20 (95% CI: 1.093-1.308) for CVD, 1.186 (95% CI: 1.069-1.303) for MI, and 1.155 (95% CI: 1.001-1.309) for MACE. However, RCTs showed no significant link between PPI therapy and negative cardiovascular events (Relative Risk: 1.016, 95% CI: 0.878-1.175). Substantial heterogeneity was observed among observational studies but not RCTs. CONCLUSION: The findings indicate that while observational studies suggest a potential risk of adverse cardiovascular events with post-PCI use of PPI, RCTs do not support this association. Further large-scale, high-quality studies are required to understand the cardiovascular implications of individual PPIs better and optimize patient management post-PCI. This analysis shows the complexity of PPI use in patients with coronary artery diseases and the necessity to balance gastroprotective benefits against potential cardiovascular risks.

Navigating the future of health care with AI-driven digital therapeutics.

Digital therapeutics (DTx) is a recently conceived idea in health care that aims to cure ailments and modify patient behavior by employing a range of digital technologies. Notably, when traditional medication is not entirely efficacious, DTx offers an innovative avenue for treatments linked to dysfunctional behaviors and lifestyle management. DTx involves extremely adaptable therapeutic devices that empower greater patient engagement in treating illness, using algorithms to collect, transfer and analyze the patient's data. Efficient clinical monitoring and supervision at the individual level by remote access and algorithms for a range of diseases is made possible by integrating machine learning and artificial intelligence with DTx. There is a potentially large worldwide market for DTx owing to its convenient, personalized therapies.

Precision Nanomedicine with Bio-Inspired Nanosystems: Recent Trends and Challenges in Mesenchymal Stem Cells Membrane-Coated Bioengineered Nanocarriers in Targeted Nanotherapeutics.

In the recent past, the formulation and development of nanocarriers has been elaborated into the broader fields and opened various avenues in their preclinical and clinical applications. In particular, the cellular membrane-based nanoformulations have been formulated to surpass and surmount the limitations and restrictions associated with naïve or free forms of therapeutic compounds and circumvent various physicochemical and immunological barriers including but not limited to systemic barriers, microenvironmental roadblocks, and other cellular or subcellular hinderances-which are quite heterogeneous throughout the diseases and patient cohorts. These limitations in drug delivery have been overcome through mesenchymal cells membrane-based precision therapeutics, where these interventions have led to the significant enhancements in therapeutic efficacies. However, the formulation and development of nanocarriers still focuses on optimization of drug delivery paradigms with a one-size-fits-all resolutions. As mesenchymal stem cell membrane-based nanocarriers have been engineered in highly diversified fashions, these are being optimized for delivering the drug payloads in more and better personalized modes, entering the arena of precision as well as personalized nanomedicine. In this Review, we have included some of the advanced nanocarriers which have been designed and been utilized in both the non-personalized as well as precision applicability which can be employed for the improvements in precision nanotherapeutics. In the present report, authors have focused on various other aspects of the advancements in stem cells membrane-based nanoparticle conceptions which can surmount several roadblocks and barriers in drug delivery and nanomedicine. It has been suggested that well-informed designing of these nanocarriers will lead to appreciable improvements in the therapeutic efficacy in therapeutic payload delivery applications. These approaches will also enable the tailored and customized designs of MSC-based nanocarriers for personalized therapeutic applications, and finally amending the patient outcomes.

Deep learning-based segmentation of left ventricular myocardium on dynamic contrast-enhanced MRI: a comprehensive evaluation across temporal frames.

PURPOSE: Cardiac perfusion MRI is vital for disease diagnosis, treatment planning, and risk stratification, with anomalies serving as markers of underlying ischemic pathologies. AI-assisted methods and tools enable accurate and efficient left ventricular (LV) myocardium segmentation on all DCE-MRI timeframes, offering a solution to the challenges posed by the multidimensional nature of the data. This study aims to develop and assess an automated method for LV myocardial segmentation on DCE-MRI data of a local hospital. METHODS: The study consists of retrospective DCE-MRI data from 55 subjects acquired at the local hospital using a 1.5 T MRI scanner. The dataset included subjects with and without cardiac abnormalities. The timepoint for the reference frame (post-contrast LV myocardium) was identified using standard deviation across the temporal sequences. Iterative image registration of other temporal images with respect to this reference image was performed using Maxwell's demons algorithm. The registered stack was fed to the model built using the U-Net framework for predicting the LV myocardium at all timeframes of DCE-MRI. RESULTS: The mean and standard deviation of the dice similarity coefficient (DSC) for myocardial segmentation using pre-trained network Net_cine is 0.78 ± 0.04, and for the fine-tuned network Net_dyn which predicts mask on all timeframes individually, it is 0.78 ± 0.03. The DSC for Net_dyn ranged from 0.71 to 0.93. The average DSC achieved for the reference frame is 0.82 ± 0.06. CONCLUSION: The study proposed a fast and fully automated AI-assisted method to segment LV myocardium on all timeframes of DCE-MRI data. The method is robust, and its performance is independent of the intra-temporal sequence registration and can easily accommodate timeframes with potential registration errors.