The effects of diabetes self-management programs on clinical and patient reported outcomes in older adults: a systematic review and meta-analysis.

Objectives: With diabetes self-management continuing to become more complex for older adults, self-management programs have been shown to support this population in meeting their multifaceted medical needs. Building on our previous systematic review and meta-analysis, we aimed to update the literature on the effectiveness of diabetes self-management programs and investigate the impact of specific self-management interventions on clinical and patient-reported outcomes. Methods: We updated our literature search in the following databases: Medline, EMBASE, PsychINFO, CINAHL and Cochrane Database of Randomized Controlled Trials from November 2013 to July 2023 for studies that may fit our inclusion criteria. Two independent reviewers screened and extracted data from the included group of studies. Results: A total of 17 studies with 21 comparison arms met the inclusion criteria, totalling 5976 older adults (3510 individuals randomized to self-management programming and 2466 to usual care). The pooled effectiveness of diabetes self-management programs in older adults on glycemic control (hemoglobin A1C) was a reduction of -0.32 (95% CI -0.44, -0.19). Specifically, the most effective approach on glycemic control (A1C) was the use of feedback (-0.52%; 95% CI -0.68, -0.36). Overall, self-management programs improved behaviour change outcomes, with feedback interventions being most effective (standardized mean difference [SMD] 0.91; 95% CI 0.39, 1.43). The effect of self-management programs on body mass index, weight and lipids were statistically and clinically significant. Conclusions: The evidence for diabetes self-management programs for older adults demonstrates a small but clinically meaningful reduction in A1C, improvement in patient-reported outcomes (behaviour, self-efficacy, knowledge), and other clinical outcomes (BMI, weight and lipids). The specific strategy used in diabetes self-management programs for older adults should be considered to achieve optimal results on outcomes.

Spatial distribution of physicochemical parameters and drinking and irrigation water quality indices in the Jhelum River, Pakistan.

Sustainable management of river systems is a serious concern, requiring vigilant monitoring of water contamination levels that could potentially threaten the ecological community. This study focused on the evaluation of water quality in the Jhelum River (JR), Azad Jammu and Kashmir, and northern Punjab, Pakistan. To achieve this, 60 water samples were collected from various points within the JR Basin (JRB) and subjected to a comprehensive analysis of their physicochemical parameters. The study findings indicated that the concentrations of physicochemical parameters in the JRB water remained within safety thresholds for both drinking and irrigation water, as established by the World Health Organization and Pakistan Environmental Protection Agency. These physicochemical parameters refer to various chemical and physical characteristics of the water that can have implications for both human health (drinking water) and agricultural practices (irrigation water). The spatial variations throughout the river course distinguished between the upstream, midstream, and downstream sections. Specifically, the downstream section exhibited significantly higher values for physicochemical parameters and a broader range, highlighting a substantial decline in its quality. Significant disparities in mean values and ranges were evident, particularly in the case of nitrates and total dissolved solids, when the downstream section was compared with its upstream and midstream counterparts. These variations indicated a deteriorating downstream water quality profile, which is likely attributable to a combination of geological and anthropogenic influences. Despite the observed deterioration in the downstream water quality, this study underscores that the JRB within the upper Indus Basin remains safe and suitable for domestic and agricultural purposes. The JRB was evaluated for various irrigation water quality indices. The principal component analysis conducted in this study revealed distinct covariance patterns among water quality variables, with the first five components explaining approximately 79% of the total variance. Recommending the continued utilization of the JRB for irrigation, we advocate for the preservation and enhancement of water quality in the downstream regions.

Exploring the therapeutic potential of Caralluma fimbriata for antioxidant and diabetes management: a 28-day rat model study.

This study evaluated the anti-oxidant and anti-diabetic potential of Caralluma fimbriata (CF) in 28-days rat modelling trial. Diabetes is a chronic disorder characterized by elevated blood glucose levels and insulin resistance and cause microvascular and macrovascular issues. Caralluma fimbriata was evaluated for its nutritional composition along with anti-oxidant potential of CF powder (CFP) and CF extract (CFE) using total phenolic contents (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) assays. Furthermore, anti-diabetic potential was computed by dividing rats into four groups of 5 individuals each. Rats of Group I was non-diabetic and no supplementation was given while rats of group II were diabetic and no supplementation was given. While group III and group IV rats were diabetic and received CFP and CFE supplementation respectively. CF powder's TPC, and DPPH and FRAP activity were observed maximum at 44.17 ± 0.006 (µgFe/g) in water, 68.75 ± 0.49 (µgFe/g) in acetone and 800.81 ± 0.99 (µgFe/g) in hexane. Supplementation of CFP and CFE reduced blood glucose effectively i.e. (125.00 ± 4.04 and 121.00 ± 4.49 mg/dL, respectively). Moreover, the consumption of C. fimbriata can be helpful in the management of diabetes mellitus due to its glucose lowering potential, anorexic effects, anti-oxidant potential and α-amylase inhibition.

Implications of von Willebrand Factor in Inflammatory Bowel Diseases: Beyond Bleeding and Thrombosis.

Inflammatory bowel disease (IBD) displays an increased venous and arterial thrombotic risk despite the common occurrence of intestinal bleeding. While some of the mechanisms leading to these thrombotic complications have been studied, other specific changes in the hemostasis profile of IBD patients have been less explored. One such example relates to von Willebrand factor (VWF) whose plasma levels have been reported to be modulated in IBD. Von Willebrand factor is a plasma glycoprotein crucial for hemostatic functions via roles both in platelet function and coagulation. High plasma VWF is a known risk factor for venous thromboembolism. In addition to its canonical roles in hemostasis, VWF is known to be directly or indirectly involved in other vascular processes such as maintenance of endothelial barrier integrity or proliferation of vascular smooth muscle cells. The purpose of this review is to recapitulate and update the existing data about VWF biology in IBD and to highlight its role both in the existing procoagulant phenotype and in vascular alterations that may occur in IBD.

Inflammatory bowel disease (IBD) displays an increased thrombotic risk. Von Willebrand factor (VWF) is increased in IBD and is a risk factor for venous thromboembolism. This review purposes to recapitulate and update the existing data about VWF biology in IBD.

Investigating the potential of monocyclic B9N9 and C18 rings for the electrochemical sensing, and adsorption of carbazole-based anti-cancer drug derivatives: DFT-based first-principle study.

CONTEXT: For the first time, the use of monocyclic rings C18 and B9N9 as sensors for the sensing of carbazole-based anti-cancer drugs, such as tetrahydrocarbazole (THC), mukonal (MKN), murrayanine (MRY), and ellipticine (EPT), is described using DFT simulations and computational characterization. The geometries, electronic properties, stability studies, sensitivity, and adsorption capabilities of C18 and B9N9 counterparts towards the selected compounds confirm that the analytes interact through active cavities of the C18 and B9N9 rings of the complexes. METHODS: Based on the interaction energies, the sensitivity of surfaces towards EPT, MKN, MRY, and THC analytes is observed. The interaction energy of EPT@B9N9, MKN@B9N9, MRY@B9N9, and THC@B9N9 complexes are observed - 20.40, - 19.49, - 20.07, and - 18.27 kcal/mol respectively which is more exothermic than EPT@C18, MKN@C18, MRY@C18, and THC@C18 complexes are - 16.37, - 13.97, - 13.96, and - 11.39 kcal/mol respectively. According to findings from the quantum theory of atoms in molecules (QTAIM) and the reduced density gradient (RDG), dispersion forces play a significant role in maintaining the stability of these complexes. The electronic properties including FMOs, density of states (DOS), natural bond orbitals (NBO), charge transfer, and absorption studies are carried out. In comparison of B9N9 and C18, the analyte recovery time for C18 is much shorter (9.91 × 10-11 for THC@C18) than that for B9N9 shorter recovery time value of 3.75 × 10-9 for EPT@B9N9. These results suggest that our reported sensors B9N9 and C18 make it faster to detect adsorbed molecules at room temperature. The sensor response is more prominent in B9N9 due to its fine energy gap and high adsorption energy. Consequently, it is possible to think of these monocyclic systems as a potential material for sensor applications.

Evaluating Spectral Performance for Quantitative Contrast-Enhanced Breast CT with a GaAs based Photon Counting Detector: A Simulation Approach.

Quantitative contrast-enhanced breastcomputed tomography (CT) has the potential to improve the diagnosis and management of breast cancer. Traditional methods using energy-integrated detectors and dual-exposure images with different incident spectra for material discrimination can increase patient radiation dose and be susceptible to motion artifacts and spectral resolution loss. Photon Counting Detectors (PCDs) offer a promising alternative approach, enabling acquisition of multiple energy levels in a single exposure and potentially better energy resolution. Gallium arsenide (GaAs) is particularly promisingfor breast PCD-CT due to its high quantum efficiency and reduction of fluorescence X-rays escaping the pixel within the breast imaging energy range. In this study, the spectral performance of a GaAs PCD for quantitative iodine contrast-enhanced breast CT was evaluated. A GaAs detector with a pixel size of 100 µm, a thickness of 500 µm was simulated. Simulations were performed using cylindrical phantoms of varying diameters (10 cm, 12 cm, and 16 cm) with different concentrations and locations of iodine inserts, using incident spectra of 50, 55, and 60 kVp with 2 mm of added aluminum filtration and one exposure level corresponding to a Mean Glandular Doses (MGD) of approximately 10 mGy. We accounted for the effects of beam hardening and energy detector response using TIGRE CT open-source software and the publicly available Photon Counting Toolkit (PcTK). Material-specific images of the breast were produced using both projection and image-based material decomposition methods, and iodine component images were used to estimate iodine intake. Accuracy and precision of the proposed methods forestimating iodine concentration in breast CT images were assessed for different material decomposition methods, incident spectra, and breastphantom thicknesses. The results showed that both the beam hardening effect and imperfection in the detector response had a significant impact on performance in terms of Root Mean Squared Error (RMSE), precision, and accuracy of estimati.

Transcobalamin deficiency - a rare genetic defect in transportation of cobalamin; case report.

BACKGROUND: Vitamin B12 is primarily transported from plasma to cells by Transcobalamin. Deficiency of Transcobalamin is a rare autosomal recessive disorder that results in unavailability of cobalamin in cells and accumulation of homocysteine and methylmalonic acid. CASE REPORT: We report a case of a 2-year-old male child with persistent pancytopenia, recurrent infections, and megaloblastic anemia. Next-generation sequencing identified a novel variant in exon 8 of TCN2 gene. Substantial improvement has been observed following administration of high doses of parenteral methylcobalamin. CONCLUSION: In patients with unresolved pancytopenia and megaloblastic anemia, Transcobalamin deficiency should be investigated and treated promptly to prevent any irreversible and harmful outcome.

Changes in complacency to adherence to COVID-19 preventive behavioral measures and mental health after COVID-19 vaccination among medical and dental healthcare professionals.

Medical and dental professionals should continue to adhere to preventive measures after COVID-19 vaccination due to their increased risk of exposure to the virus, particularly as new variants emerge that may heighten their risk perception and susceptibility. Therefore, this study aimed to explore the effects of COVID-19 vaccination on complacency to adherence to COVID-19 preventive behavioral measures and mental health among medical and dental professionals. In this cross-sectional study 410 medical and dental professionals were recruited from different medical and dental hospitals in Islamabad, Pakistan. The data was collected using a valid and reliable questionnaire comprising of three sections (socio-demographic, information of preventive behaviors performance against COVID-19 after vaccination, mental health status). A chi-square test and ordinal logistic regression were used for analysis. Post COVID-19 vaccination there was decrease in the frequency of use of hand washing, sanitizers (70.2%), and social distancing (60.5%), however greeting with a handshake (58.8%) and use of public transport (45.9%) seen upward trend among participants. Only face mask usage post-vaccination was statistically significant (p < .05) in association with age, marital status, and years of working Experience. The greatest decrease in the usage of masks after COVID-19 vaccination was seen in age group of 10-30 (41.7%) and working experience group of 0-5 years (39.7%). All the preventive behaviors are statistically significant (p < .05) associated with the mental status of the participants except online shopping and use of public transport. These results indicate the presence of vaccination-induced complacency in adherence to COVID-19 preventive behavioral measures among healthcare professionals.

pH-Sensitive Hydrogels Fabricated with Hyaluronic Acid as a Polymer for Site-Specific Delivery of Mesalamine.

Hydrogels with the main objective of releasing mesalamine (5-aminosalicylic acid) in the colon in a modified manner were formulated in the present work using a free-radical polymerization approach. Different ratios of hyaluronic acid were cross-linked with methacrylic and acrylic acids using methylenebis(acrylamide). The development of a new polymeric network and the successful loading of drug were revealed by Fourier transform infrared spectroscopy. Thermogravimetric analysis demonstrated that the hydrogel was more thermally stable than the pure polymer and drug. Scanning electron microscopy (SEM) revealed a rough and hard surface which was relatively suitable for efficient loading of drug and significant penetration of dissolution medium inside the polymeric system. Studies on swelling and drug release were conducted at 37 °C in acidic and basic conditions (pH 1.2, 4.5, 6.8, and 7.4, respectively). Significant swelling and drug release occurred at pH 7.4. Swelling, drug loading, drug release, and gel fraction of the hydrogels increased with increasing hyaluronic acid, methacrylic acid, and acrylic acid concentrations, while the sol fraction decreased. Results obtained from the toxicity study proved the formulated system to be safe for biological systems. The pH-sensitive hydrogels have the potential to be beneficial for colon targeting due to their pH sensitivity and biodegradability. Inflammatory bowel disease may respond better to hydrogel treatment as compared to conventional dosage forms. Specific amount of drug is released from hydrogels at specific intervals to maintain its therapeutic concentration at the required level.

Recent progress in electro-Fenton technology for the remediation of pharmaceutical compounds in aqueous environments.

The global focus on wastewater treatment has intensified in the contemporary era due to its significant environmental and human health impacts. Pharmaceutical compounds (PCs) have become an emerging concern among various pollutants, as they resist conventional treatment methods and pose a severe environmental threat. Advanced oxidation processes (AOPs) emerge as a potent and environmentally benign approach for treating recalcitrant pharmaceuticals. To address the shortcomings of traditional treatment methods, a technology known as the electro-Fenton (EF) method has been developed more recently as an electrochemical advanced oxidation process (EAOP) that connects electrochemistry to the chemical Fenton process. It has shown effective in treating a variety of pharmaceutically active compounds and actual wastewaters. By producing H2O2 in situ through a two-electron reduction of dissolved O2 on an appropriate cathode, the EF process maximizes the benefits of electrochemistry. Herein, we have critically reviewed the application of the EF process, encompassing diverse reactor types and configurations, the underlying mechanisms involved in the degradation of pharmaceuticals and other emerging contaminants (ECs), and the impact of electrode materials on the process. The review also addresses the factors influencing the efficiency of the EF process, such as (i) pH, (ii) current density, (iii) H2O2 concentration, (iv) and others, while providing insight into the scalability potential of EF technology and its commercialization on a global scale. The review delves into future perspectives and implications concerning the ongoing challenges encountered in the operation of the electro-Fenton process for the treatment of PCs and other ECs.

Diagnostic utility of anti-thyroid peroxidase immunohistochemistry in the identification of papillary thyroid carcinoma.

The routine histomorphological assessment of follicular thyroid neoplasms has been subject to interobserver or intraobserver variability among histopathologists. Anti-thyroid peroxidase (anti-TPO) has emerged as a useful immunohistochemical (IHC) marker, with its expression lost in papillary thyroid carcinoma (PTC). Our study aims to determine the diagnostic accuracy of anti-TPO IHC expression in the identifying PTC and its variants, particularly the Follicular variant of papillary thyroid carcinoma (FVPTC), with H&E assessment as the gold standard. Anti-TPO IHC (DAKO-MoAb47) was performed on 110 cases, including 76 malignant tumors (classic PTC, FVPTC, follicular carcinoma (FC), and oncocytic carcinoma (OC)) and 34 benign tumors (non-invasive follicular tumor with papillary-like nuclear features (NIFTP) and follicular adenoma (FA)). The loss of expression in more than or equal to 51 % of thyrocytes was considered suggestive of a PTC profile. The sensitivity of the loss of anti-TPO expression for identifying PTC among all carcinomas was 61.7 %, specificity was 75 %, positive predictive value was 90.2 %, negative predictive value was 34.2 %, and accuracy was 64.4 %. The loss of anti-TPO IHC expression combined with routine H&E assessment, supports the identification of PTC and its variants.

Comparative Neurological and Behavioral Assessment of Central and Peripheral Stimulation Technologies for Induced Pain and Cognitive Tasks.

Pain is a multifaceted, multisystem disorder that adversely affects neuro-psychological processes. This study compares the effectiveness of central stimulation (transcranial direct current stimulation-tDCS over F3/F4) and peripheral stimulation (transcutaneous electrical nerve stimulation-TENS over the median nerve) in pain inhibition during a cognitive task in healthy volunteers and to observe potential neuro-cognitive improvements. Eighty healthy participants underwent a comprehensive experimental protocol, including cognitive assessments, the Cold Pressor Test (CPT) for pain induction, and tDCS/TENS administration. EEG recordings were conducted pre- and post-intervention across all conditions. The protocol for this study was categorized into four groups: G1 (control), G2 (TENS), G3 (anodal-tDCS), and G4 (cathodal-tDCS). Paired t-tests (p < 0.05) were conducted to compare Pre-Stage, Post-Stage, and neuromodulation conditions, with t-values providing insights into effect magnitudes. The result showed a reduction in pain intensity with TENS (p = 0.002, t-value = -5.34) and cathodal-tDCS (p = 0.023, t-value = -5.08) and increased pain tolerance with TENS (p = 0.009, t-value = 4.98) and cathodal-tDCS (p = 0.001, t-value = 5.78). Anodal-tDCS (p = 0.041, t-value = 4.86) improved cognitive performance. The EEG analysis revealed distinct neural oscillatory patterns across the groups. Specifically, G2 and G4 showed delta-power reductions, while G3 observed an increase. Moreover, G2 exhibited increased theta-power in the occipital region during CPT and Post-Stages. In the alpha-band, G2, G3, and G4 had reductions Post-Stage, while G1 and G3 increased. Additionally, beta-power increased in the frontal region for G2 and G3, contrasting with a reduction in G4. Furthermore, gamma-power globally increased during CPT1, with G1, G2, and G3 showing reductions Post-Stage, while G4 displayed a global decrease. The findings confirm the efficacy of TENS and tDCS as possible non-drug therapeutic alternatives for cognition with alleviation from pain.

The Rising Tide of Antibiotic Resistance: A Study on Extended-Spectrum Beta-Lactamase and Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae.

BACKGROUND: The global spread of extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacterales (CRE) poses a significant concern. Acquisition of antimicrobial resistance genes leads to resistance against several antibiotics, limiting treatment options. We aimed to study ESBL-producing and CRE transmission in clinical settings. METHODS: From clinical samples, 227 ESBL-producing and CRE isolates were obtained. The isolates were cultured on bacterial media and confirmed by VITEK 2. Antibiograms were tested against several antibiotics using VITEK 2. The acquired resistance genes were identified by PCR. RESULTS: Of the 227 clinical isolates, 145 (63.8%) were Klebsiella pneumoniae and 82 (36.1%) were Escherichia coli; 76 (33.4%) isolates were detected in urine, 57 (25.1%) in pus swabs, and 53 (23.3%) in blood samples. A total of 58 (70.7%) ESBL-producing E. coli were resistant to beta-lactams, except for carbapenems, and 17.2% were amikacin-resistant; 29.2% of E. coli isolates were resistant to carbapenems. A total of 106 (73.1%) ESBL-producing K. pneumoniae were resistant to all beta-lactams, except for carbapenems, and 66.9% to ciprofloxacin; 38 (26.2%) K. pneumoniae were resistant to carbapenems. Colistin emerged as the most effective antibiotic against both bacterial types. Twelve (20.6%) E. coli isolates were positive for blaCTX-M, 11 (18.9%) for blaTEM, and 8 (33.3%) for blaNDM. Forty-six (52.3%) K. pneumoniae isolates had blaCTX-M, 27 (18.6%) blaTEM, and 26 (68.4%) blaNDM. CONCLUSION: This study found a high prevalence of drug-resistant ESBL-producing and CRE, highlighting the need for targeted antibiotic use to combat resistance.

Is Lipid Metabolism of Value in Cancer Research and Treatment? Part II: Role of Specialized Pro-Resolving Mediators in Inflammation, Infections, and Cancer.

Acute inflammation is the body's first defense in response to pathogens or injury that is partially governed by a novel genus of endogenous lipid mediators that orchestrate the resolution of inflammation, coined specialized pro-resolving mediators (SPMs). SPMs, derived from omega-3-polyunstaturated fatty acids (PUFAs), include the eicosapentaenoic acid-derived and docosahexaenoic acid-derived Resolvins, Protectins, and Maresins. Herein, we review their biosynthesis, structural characteristics, and therapeutic effectiveness in various diseases such as ischemia, viral infections, periodontitis, neuroinflammatory diseases, cystic fibrosis, lung inflammation, herpes virus, and cancer, especially focusing on therapeutic effectiveness in respiratory inflammation and ischemia-related injuries. Resolvins are sub-nanomolar potent agonists that accelerate the resolution of inflammation by reducing excessive neutrophil infiltration, stimulating macrophage functions including phagocytosis, efferocytosis, and tissue repair. In addition to regulating neutrophils and macrophages, Resolvins control dendritic cell migration and T cell responses, and they also reduce the pro-inflammatory cytokines, proliferation, and metastasis of cancer cells. Importantly, several lines of evidence have demonstrated that Resolvins reduce tumor progression in melanoma, oral squamous cell carcinoma, lung cancer, and liver cancer. In addition, Resolvins enhance tumor cell debris clearance by macrophages in the tumor's microenvironment. Resolvins, with their unique stereochemical structure, receptors, and biosynthetic pathways, provide a novel therapeutical approach to activating resolution mechanisms during cancer progression.

Is Lipid Metabolism of Value in Cancer Research and Treatment? Part I- Lipid Metabolism in Cancer.

For either healthy or diseased organisms, lipids are key components for cellular membranes; they play important roles in numerous cellular processes including cell growth, proliferation, differentiation, energy storage and signaling. Exercise and disease development are examples of cellular environment alterations which produce changes in these networks. There are indications that alterations in lipid metabolism contribute to the development and progression of a variety of cancers. Measuring such alterations and understanding the pathways involved is critical to fully understand cellular metabolism. The demands for this information have led to the emergence of lipidomics, which enables the large-scale study of lipids using mass spectrometry (MS) techniques. Mass spectrometry has been widely used in lipidomics and allows us to analyze detailed lipid profiles of cancers. In this article, we discuss emerging strategies for lipidomics by mass spectrometry; targeted, as opposed to global, lipid analysis provides an exciting new alternative method. Additionally, we provide an introduction to lipidomics, lipid categories and their major biological functions, along with lipidomics studies by mass spectrometry in cancer samples. Further, we summarize the importance of lipid metabolism in oncology and tumor microenvironment, some of the challenges for lipodomics, and the potential for targeted approaches for screening pharmaceutical candidates to improve the therapeutic efficacy of treatment in cancer patients.

Comprehensive review on glucose 6 phosphate dehydrogenase: A critical immunometabolic and redox switch in insects.

Mounting an active immune response is energy intensive and demands the reallocation of nutrients to maintain the body's resistance and tolerance against infections. Central to this metabolic adaptation is Glucose-6-phosphate dehydrogenase (G6PDH), a housekeeping enzyme involve in pentose phosphate pathway (PPP). PPP play an essential role in generating ribose, which is critical for nicotinamide adenine dinucleotide phosphate (NADPH). It is vital for physiological and cellular processes such as generating nucleotides, fatty acids and reducing oxidative stress. The G6PDH is extremely conserved enzyme across species in PP shunt. The deficiency of enzymes leads to serious consequences on organism, particularly on adaptation and development. Acute deficiency can lead to impaired cell development, halted embryonic growth, reduce sensitivity to insulin, hypertension and increase inflammation. Historically, research focusing on G6PDH and PPP have primarily targeted diseases on mammalian. However, our review has investigated the unique functions of the G6PDH enzyme in insects and greatly improved mechanistic understanding of its operations. This review explore how G6PDH in insects plays a crucial role in managing the redox balance and immune related metabolism. This study aims to investigate the enzyme's role in different metabolic adaptations.

Improving flood and drought management in transboundary Upper Jhelum Basin-South Asia.

The two contrasting extremes of the hydrological spectrum have substantial and far-reaching impacts on a wide range of sectors including water resources, agriculture and food security, energy, infrastructure, and ecosystem. The compounding factors of climate change, burgeoning population, and rapid economic development create unprecedented challenges in devising effective and sustainable strategies to cope with these natural disasters and minimize their devastating impacts. This study identifies the geographical areas that are prone to meteorological wet-dry extreme events, as drivers of hydrologic floods and droughts, and their temporal compounding in the transboundary Upper Jhelum Basin-South Asia. Additionally, the study provides a comprehensive overview of the existing and proposed water development projects, their coping capacities, and potential impacts that may be positive or negative in hydrologic, social, economic and environment terms. Extensive review and data analysis revealed that the both Pakistan and India, along with state governments, have implemented a significant number of water-related projects across the basin, however significant progress towards achieving their stated goals remains elusive. Currently, Pakistan operates 15 runoff river type hydropower plants, and an additional 11 similar projects are under construction. In contrast, Indian administrative Kashmir has 10 such plants in operation and 4 under construction. The primary factors that impede the realization of expected benefits from these projects are geography, high flow variability across seasons, climate change, insufficient planning, geopolitical disputes, lack of transboundary cooperation, financial limitations, and reservoir operation. Based on these factors, the present study suggests some alternative water management measures that offer flexibility, cost-effectiveness, accessibility, and a low environmental impact. These solutions include implementation of sub-surface floodwater harvesting system in the southwest of the basin, where extreme wet and dry events occur in close succession, augmentation of existing hydropower reservoirs with floating photovoltaic technology, and non-structural measures, including early warning systems, ecosystems-based adaptation, and green infrastructure interventions such as restoring headwater forests, reclaiming floodplains, and wetlands. This will result in reduced flood and drought impacts at local and downstream areas and reduce the reliance of local communities on forest wood.

Chronic pharmacologic manipulation of dopamine transmission ameliorates metabolic disturbance in trappc9-linked brain developmental syndrome.

Loss-of-function mutations of the gene encoding the trafficking protein particle complex subunit 9 (trappc9) cause autosomal recessive intellectual disability and obesity by unknown mechanisms. Genome-wide analysis links trappc9 to non-alcoholic fatty liver disease (NAFLD). Trappc9-deficient mice have been shown to appear overweight shortly after weaning. Here, we analyzed serum biochemistry and histology of adipose and liver tissues to determine the incidence of obesity and NAFLD in trappc9-deficient mice and combined transcriptomic and proteomic analyses, pharmacological studies, and biochemical and histological examinations of postmortem mouse brains to unveil mechanisms involved. We found that trappc9-deficient mice presented with systemic glucose homeostatic disturbance, obesity and NAFLD, which were relieved upon chronic treatment combining dopamine receptor D2 (DRD2) agonist quinpirole and DRD1 antagonist SCH23390. Blood glucose homeostasis in trappc9-deficient mice was restored upon administrating quinpirole alone. RNA-sequencing analysis of DRD2-containing neurons and proteomic study of brain synaptosomes revealed signs of impaired neurotransmitter secretion in trappc9-deficient mice. Biochemical and histological studies of mouse brains showed that trappc9-deficient mice synthesized dopamine normally, but their dopamine-secreting neurons had a lower abundance of structures for releasing dopamine in the striatum. Our study suggests that trappc9 loss-of-function causes obesity and NAFLD by constraining dopamine synapse formation.

Drug-eluting balloon to treat immediate post-coronary artery bypass grafting ST-elevation myocardial infarction: a case report.

Background: Coronary artery bypass graft (CABG) surgery represents a major cardiovascular operation and may be associated with post-operative ST-elevation myocardial infarction (STEMI) due to graft failure. This is challenging to diagnose and treat as the implanted grafts may be prone to complications when treated percutaneously with drug-eluting stents. Case summary: A man in his 60 s underwent CABG and developed new persistent ST elevations of 2 mm in anterior leads with no significant chest pain, although, administered with intravenous opiates post-operatively. Transthoracic echocardiography was non-diagnostic. Invasive angiography performed emergently showed a thrombotic occlusion of the mid-left anterior descending artery at the site of the anastomosis with the left internal mammary artery (LIMA) graft. Intervention via the graft was considered high risk of complications, therefore, native coronary arteries were used to approach the occlusion, which was successfully cleared with a combination balloon angioplasty with a semi-compliant and then a drug-eluting balloon. The LIMA started working again with the resolution of ST elevation and no immediate complications. Discussion: Early post-operative ST elevations in continuous leads should not be ignored as they often may be the only feature of new-onset STEMI. Drug-eluting balloons represent a feasible and possibly safer option than drug-eluting stents to treat these conditions.