Chronic Heart Failure (CHF) is a debilitating illness commonly encountered in primary care. Its prevalence in developing countries is rising as a result of an ageing population, and an escalating epidemic of hypertension, type 2 diabetes and coronary heart disease. CHF can be specifically diagnosed as Heart Failure with Reduced Systolic Function (HF-RSF) or Heart Failure with Preserved Systolic Function (HF-PSF). This paper illustrates a common presentation of HF-PSF in primary care; and critically appraises the evidence in support of its diagnosis, prognosis and management. Regardless of the specific diagnosis, long term management of CHF is intricate as it involves a complex interplay between medical, psychosocial, and behavioural factors. Hence, there is a pressing need for a multidisciplinary team management of CHF in primary care, and this usually takes place within the broader context of an integrated chronic disease management programme. Primary care physicians are ideally suited to lead multidisciplinary teams to ensure better co-ordination, continuity and quality of care is delivered for patients with chronic conditions across time and settings. Given the rising epidemic of cardiovascular risk factors in the Malaysian population, preventive strategies at the primary care level are likely to offer the greatest promise for reducing the growing burden of CHF.

The patient is a 43-year-old male with medical history significant for severe alcoholic cirrhosis who presented with a one-month history of periumbilical pain. The patient did not have any symptoms of bowel obstruction. Physical examination revealed an umbilical defect containing an intra-abdominal structure, mimicking incarcerated umbilical hernia. Computed tomography revealed an engorged, umbilical varix 1.6 cm in diameter, herniating through the umbilical defect. No surgical intervention was offered for this patient and medical management for varix resulted in clinical resolution in three months.
Adult ; Hernia* ; Hernia, Umbilical ; Humans ; Hypertension, Portal ; Liver Cirrhosis, Alcoholic ; Male ; Physical Examination ; Varicose Veins*

The prevalence of canine H3N8 influenza and human H1N1 and H3N2 influenza in dogs in Ohio was estimated by conducting serologic tests on 1,082 canine serum samples. In addition, risk factors, such as health status and age were examined. The prevalences of human H1N1, H3N2, and canine H3N8 influenzas were 4.0%, 2.4%, and 2.3%, respectively. Two samples were seropositive for two subtypes (H1N1 and H3N2; H1N1 and canine influenza virus [CIV] H3N8). Compared to healthy dogs, dogs with respiratory signs were 5.795 times more likely to be seropositive against H1N1 virus (p = 0.042). The prevalence of human flu infection increased with dog age and varied by serum collection month. The commercial enzyme-linked immunosorbent assay used in this study did not detect nucleoprotein-specific antibodies from many hemagglutination inhibition positive sera, which indicates a need for the development and validation of rapid tests for influenza screening in canine populations. In summary, we observed low exposure of dogs to CIV and human influenza viruses in Ohio but identified potential risk factors for consideration in future investigations. Our findings support the need for establishment of reliable diagnostic standards for serologic detection of influenza infection in canine species.
Animals ; Antibodies ; Cross-Sectional Studies ; Dogs* ; Enzyme-Linked Immunosorbent Assay ; Hemagglutination ; Hospitals, Animal* ; Humans ; Influenza A virus* ; Influenza A Virus, H1N1 Subtype ; Influenza, Human* ; Mass Screening ; Ohio* ; Orthomyxoviridae ; Prevalence ; Risk Factors ; Seroepidemiologic Studies* ; Serologic Tests

In mammalian cells, transcribed enhancers (TrEns) play important roles in the initiation of gene expression and maintenance of gene expression levels in a spatiotemporal manner. One of the most challenging questions is how the genomic characteristics of enhancers relate to enhancer activities. To date, only a limited number of enhancer sequence characteristics have been investigated, leaving space for exploring the enhancers' DNA code in a more systematic way. To address this problem, we developed a novel computational framework, Transcribed Enhancer Landscape Search (TELS), aimed at identifying predictive cell type/tissue-specific motif signatures of TrEns. As a case study, we used TELS to compile a comprehensive catalog of motif signatures for all known TrEns identified by the FANTOM5 consortium across 112 human primary cells and tissues. Our results confirm that combinations of different short motifs characterize in an optimized manner cell type/tissue-specific TrEns. Our study is the first to report combinations of motifs that maximize classification performance of TrEns exclusively transcribed in one cell type/tissue from TrEns exclusively transcribed in different cell types/tissues. Moreover, we also report 31 motif signatures predictive of enhancers' broad activity. TELS codes and material are publicly available at http://www.cbrc.kaust.edu.sa/TELS.
Enhancer Elements, Genetic ; Genomics ; methods ; Humans ; Nucleotide Motifs ; Sequence Analysis, DNA ; methods ; Transcription, Genetic

Androgen deprivation in men leads to increased adiposity, but the mechanisms underlying androgen regulation of fat mass have not been fully defined. Androgen receptor (AR) is expressed in monocytes/macrophages, which are resident in key metabolic tissues and influence energy metabolism in surrounding cells. Male mice bearing a cell-specific knockout of the AR in monocytes/macrophages (M-ARKO) were generated to determine whether selective loss of androgen signaling in these cells would lead to altered body composition. Wild-type (WT) and M-ARKO mice (12-22 weeks of age, n = 12 per group) were maintained on a regular chow diet for 8 weeks and then switched to a high-fat diet for 8 additional weeks. At baseline and on both the regular chow and high-fat diets, no differences in lean mass or fat mass were observed between groups. Consistent with the absence of differential body weight or adiposity, no differences in food intake (3.0 ± 0.5 g per day for WT mice vs 2.8 ± 0.4 g per day for M-ARKO mice) or total energy expenditure (0.6 ± 0.1 Kcal h^-1 for WT mice vs 0.5 ± 0.1 Kcal h^-1 for M-ARKO mice) were evident between groups during high-fat feeding. Liver weight was greater in M-ARKO than that in WT mice (1.5 ± 0.1 g vs 1.3 ± 0.0 g, respectively, P = 0.02). Finally, M-ARKO mice did not exhibit impairments in glucose tolerance or insulin sensitivity relative to WT mice at any study time point. In aggregate, these findings suggest that AR signaling specifically in monocytes/macrophages does not contribute to the regulation of systemic energy balance, adiposity, or insulin sensitivity in male mice.
Adiposity/genetics* ; Animals ; Blood Glucose/metabolism* ; Energy Metabolism/genetics* ; Glucose Tolerance Test ; Homeostasis/genetics* ; Liver/anatomy & histology* ; Macrophages/metabolism* ; Male ; Mice ; Mice, Knockout ; Monocytes/metabolism* ; Organ Size ; Receptors, Androgen/metabolism* ; Signal Transduction

Problem: Over 290 million people worldwide suffer from chronic hepatitis B (CHB), with the highest prevalence in the Pacific islands. Mortality attributable to this disease exceeds that from HIV, tuberculosis and malaria combined in this region. Context: CHB is a major health problem in the Pacific island nation of Kiribati. Medical care is complicated by vast expanses of ocean separating population centres in its constituent islands. Birth-dose hepatitis B immunization rates need improvement. High rates of obesity, metabolic syndrome, and co-infection with hepatitis B and hepatitis D in Kiribati make treatment less effective. Staff allocation, training and retention are difficult. Limited infrastructure creates challenges in training, communications, laboratory testing and record-keeping. Action: We have established a CHB treatment programme in Kiribati based on World Health Organization (WHO) guidelines and local needs. It includes direct patient care; laboratory, radiology and pharmacy support; public education; training; and data management. Thousands of individuals have been screened, and 845 hepatitis B-positive patients have had blood sent to Australia for molecular testing. Patient education pamphlets, medical training programmes and treatment protocols have been developed. Seventy-nine patients have started treatment. Regular onsite visits by technical experts are scheduled throughout the year. Lessons learnt and discussion: This is the first national CHB treatment programme established in the Pacific islands region. Unique challenges exist in Kiribati, as they do in each nation affected by CHB. Close engagement with local partners, knowledge of the barriers involved, flexibility, advocacy, and support from WHO and volunteer technical experts are key attributes of a successful treatment programme.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.