Regulation of adipogenesis and fat storage by IRX3 and IRX5

Obesity is a highly prevalent disease underlying several chronic diseases including Type 2 diabetes (T2D) and cardiovascular diseases (CVDs). Thus, increasing levels of obesity is associated with a series of co-morbidities and elevated risk of premature death. Obesity results from a chronic positive energy balance, causing white adipose tissue dysfunction, which in turn promotes dyslipidemia, systemic lipotoxicity and insulin resistance, eventually leading to ectopic fat accumulation and chronic diseases in multiple organs, including the heart, liver, arteries and kidneys. Unlike white adipocytes, beige fat cells are capable of disposing of excess energy by heat dissipation, thus protecting against obesity-related disease. Recently, two developmental transcription factors, IRX3 and IRX5, were shown to inhibit beige adipogenesis via an obesity associated risk genotype-dependent activation in preadipocytes. The aim of this study was therefore to investigate whether reducing IRX3 or IRX5 expression in adipose tissue offers protection from obesity, and if so, by which mechanisms. In paper I, we randomized wild type (WT) and Irx5 knock-out (KO) mice to a control or high-fat diet, and measured body weight, fat mass and global gene expression in adipose tissue. We found Irx5-KO mice to be lean and completely protected from diet-induced obesity. This was found to be partially attributable to increased mitochondrial respiration and thermogenesis due to reduction of Irx5 and App specifically in adipocytes. In papers II and III, we investigated the role of Irx3 in transcriptional regulation of adipogenesis, using WT and CRISPR-Cas9 mediated KO of Irx3 in preadipocytes, followed by RNA-, ATAC- and ChIP-sequencing. We found Irx3 to be critical for adipogenic identity and the ability of precursor cells to differentiate into mature adipocytes. Moreover, this lineage control was found to be mediated by direct transcriptional regulation of chromatin remodeling factors by Irx3. In conclusion, genetic repression of Irx3 or Irx5 offers strong protection against obesity, and reduces adipose tissue mass partially by increasing thermogenesis and improving mitochondrial respiration in existing adipocytes, and partially by preventing the formation of new adipocytes. This work has implications for identifying patients with genetic predisposition to obesity, who could benefit from potential therapeutic intervention targeting IRX3 or IRX5

ROOT CAUSE IDENTIFICATION

Presented herein is a novel machine learning approach that learns the failure patterns of a device and uses this information to drive automatic root case identification. Anomalous events can be associated with potential root causes in order to build intellectual capital for training future predictive automated remediation systems

Cold chain management: Knowledge and practices in primary health care facilities in Niassa, Mozambique

Background: To maintain vaccines perfectly conserved from its manufacture through administration requires an adequate could chain infrastructure. At the end of the chain, primary health care providers must have adequate knowledge to manage the cold chain. Objective: The study describes an observed audit of the Expanded Program on Immunization (EPI) in Niassa province of Mozambique. Methods: Data collection methods included questionnaires, observations and document analysis in 44 health facilities, 12 of which in district capitals, and the remaining 32 in peripheral health facilities in Niassa province. Findings: The results show that the principal explanatory variable for the inadequacies of the system was the location of the health facility as health workers in the peripheral health facilities were in general less educated, had less work experience and their knowledge of cold chain was not as per required levels to support effective cold chain management. Conclusions: The study strongly indicates the need to improve and integrate the knowledge and practices on cold chain management, especially to the peripheral level workers, by providing them with adequate training and supervision, and demonstrating how that can be effectively integrated with practice.The Ethiopian Journal of Health Development Vol. 21 (2) 2007: pp. 130-13

Diagnostic and treatment delay among pulmonary tuberculosis patients in Ethiopia: a cross sectional study

BACKGROUND: Delayed diagnosis and treatment of tuberculosis (TB) results in severe disease and a higher mortality. It also leads to an increased period of infectivity in the community. The objective of this study was to determine the length of delays, and analyze the factors affecting the delay from onset of symptoms of pulmonary tuberculosis (PTB) until the commencement of treatment. METHODS: In randomly selected TB management units (TBMUs), i.e. government health institutions which have diagnosing and treatment facilities for TB in Amhara Region, we conducted a cross sectional study from September 1-December 31/2003. Delay was analyzed from two perspectives, 1. Period between onset of TB symptoms to first visit to any health provider (health seeking period), and from the first health provider visit to initiation of treatment (health providers' delay), and 2. Period between onset of TB symptoms to first visit to a medical provider (patients' delay), and from this visit to commencement of anti-TB treatment (health systems' delay). Patients were interviewed on the same date of diagnosis using a semi-structured questionnaire. Logistics regression analysis was applied to analyze the risk factors of delays. RESULTS: A total of 384 new smear positive PTB patients participated in the study. The median total delay was 80 days. The median health-seeking period and health providers' delays were 15 and 61 days, respectively. Conversely, the median patients' and health systems' delays were 30 and 21 days, respectively. Taking medical providers as a reference point, we found that forty eight percent of the subjects delayed for more than one month. Patients' delays were strongly associated with first visit to non-formal health providers and self treatment (P < 0.0001). Prior attendance to a health post/clinic was associated with increased health systems' delay (p < 0.0001). CONCLUSION: Delay in the diagnosis and treatment of PTB is unacceptably high in Amhara region. Health providers' and health systems' delays represent the major portion of the total delay. Accessing a simple and rapid diagnostic test for TB at the lowest level of health care facility and encouraging a dialogue among all health providers are imperative interventions

Diagnostic and treatment delay among Tuberculosis patients in Afar Region, Ethiopia: A cross-sectional study

BACKGROUND: TB is a major public health problem globally and Ethiopia is 8(th) among the 22 high burden countries. Early detection and effective treatment are pre-requisites for a successful TB control programme. In this regard, early health seeking action from patients’ side and prompt diagnosis as well as initiation of treatment from the health system’s side are essential steps. The aim of this study was to assess delay in the diagnosis and treatment of TB in a predominantly pastoralist area in Ethiopia. METHODS: On a cross-sectional study, two hundred sixteen TB patients who visited DOTS clinics of two health facilities in Afar Region were included consecutively. Time from onset of symptoms till first consultation of formal health providers (patients’ delay) and time from first consultation till initiation of treatment (health system’s delay) were analyzed. RESULTS: The median patients’ and health system’s delay were 20 and 33.5 days, respectively. The median total delay was 70.5 days with a median treatment delay of 1 day. On multivariate logistic regression, self-treatment (aOR. 3.99, CI 1.50-10.59) and first visit to non-formal health providers (aOR. 6.18, CI 1.84-20.76) were observed to be independent predictors of patients’ delay. On the other hand, having extra-pulmonary TB (aOR. 2.08, CI 1.08- 4.04), and a first visit to health posts/clinics (aOR. 19.70, CI 6.18-62.79), health centres (aOR. 4.83, CI 2.23-10.43) and private health facilities (aOR. 2.49, CI 1.07-5.84) were found to be independent predictors of health system’s delay. CONCLUSIONS: There is a long delay in the diagnosis and initiation of treatment and this was mainly attributable to the health system. Health system strengthening towards improved diagnosis of TB could reduce the long health system’s delay in the management of TB in the study area

Time to first consultation, diagnosis and treatment of TB among patients attending a referral hospital in Northwest, Ethiopia

Background Early detection and treatment of TB is essential for the success of TB control program performance. The aim of this study was to determine the length and analyze predictors of patients’, health systems’ and total delays among patients attending a referral hospital in Bahir Dar, Ethiopia. Methods A cross-sectional study was conducted among newly diagnosed TB cases?=?15 years of age. Delay was analyzed at three levels: the periods between 1) onset of TB symptoms and first visit to medical provider, i.e. patients’ delay, 2) the first visit to a medical provider and the initiation of treatment i.e. health systems’ delay and 3) onset of TB symptoms and initiation of treatment i.e. total delay. Uni- and multi-variate logistic regression analyses were performed to investigate predictors of patients’, health systems’ and total delays. Results The median time of patients’ delay was 21 days [(interquartile range (IQR) (7 days, 60 days)]. The median health systems’ delay was 27 days (IQR 8 days, 60 days) and the median total delay was 60 days (IQR 30 days, 121 days). Patients residing in rural areas had a three-fold increase in patients’ delay compared to those from urban areas [Adjusted Odds Ratio (AOR) 3.4; 95% (CI 1.3, 8.9)]. Extra-pulmonary TB (EPTB) cases were more likely to experience delay in seeking treatment compared to pulmonary (PTB) cases [(AOR 2.6; 95% (CI 1.3, 5.4)]. Study subjects who first visited health centres [(AOR) 5.1; 95% (CI 2.1, 12.5)], private facilities [(AOR) 3.5; 95% (CI 1.3, 9.7] and health posts [(AOR) 109; 95% (CI 12, 958], were more likely to experience an increase in health systems’ delay compared to those who visited hospitals. Conclusions The majority of TB patients reported to medical providers within an acceptable time after the onset of symptoms. Rural residence was associated with patients’ and total delays. Providing the population with information about TB symptoms and the importance of early health seeking may be an efficient way to decrease TB transmission, morbidity and mortality. Establishing efficient TB diagnostic and treatment facilities at the periphery level is imperative to reduce diagnostic delay and expedite TB treatment

Two vicious circles contributing to a diagnostic delay for tuberculosis patients in Arkhangelsk

Setting: Delay in tuberculosis (TB) diagnosis increases the infectious pool in the community and the risk of development of resistance of mycobacteria, which results in an increased number of deaths. Objective: To describe patients’ and doctors’ perceptions of diagnostic delay in TB patients in the Arkhangelsk region and to develop a substantive model to better understand the mechanisms of how these delays are linked to each other. Design: A grounded theory approach was used to study the phenomenon of diagnostic delay. Patients with TB diagnostic delay and doctors–phthisiatricians were interviewed. Results: A model named ‘sickness trajectory in health-seeking behaviour among tuberculosis patients’ was developed and included two core categories describing two vicious circles of diagnostic delay in patients with TB: ‘limited awareness of the importance to contact the health system’ and ‘limited resources of the health system’ and the categories: ‘factors influencing health-seeking behaviour’ and ‘factors influencing the health system effectiveness’. Men were more likely to report patient delay, while women were more likely to report health system delay. Conclusions: To involve people in early medical examinations, it is necessary to increase alertness on TB among patients and to improve health systems in the districts

Initial (March 2023) uses and perceptions of ChatGPT in a sample of students and instructors at the University of Bergen (UiB), Norway

The spring semester of 2023 in higher education was impacted by the release of Large Language Models (LLMs) to the general public. OpenAI’s ChatGPT was at the forefront, with Google's Bard, Microsoft’s Bing, and others following suit. In response to the ongoing discussions in higher education, we conducted a survey to examine the use and understanding of LLMs among students and instructors at the Faculty of Mathematics and Natural Sciences at the University of Bergen, Norway. Given that the survey was distributed in February and March 2023 - shortly after ChatGPT was launched and before similar tools from other providers were in wide use - we focused primarily on ChatGPT. Our aim was to gain a deeper understanding of existing perceptions and misconceptions about ChatGPT, enabling us to design more informed implementation strategies for its integration into our courses. Further, by considering usage patterns and perceptions shortly after the launch of ChatGPT, we established a baseline for later comparisons as these tools become increasingly embedded in our routines.bioCEED, SLATEpublishedVersio

Editorial: Teaching palaeosciences to future generations

Sec. Paleoecology This article is part of the Research Topic: Teaching Palaeosciences to Future Generation

Le Kouri : race bovine du lac Tchad. I. Introduction générale à son étude zootechnique et biochimique : origines et écologie de la race

Les auteurs présentent de façon détaillée la race des taurins Kouris, bovins du lac Tchad. Cette première étude est l'introduction pour l'ensemble des travaux qui visent à éclairer les divers aspects zootechniques et biochimiques de cette race, connue depuis longtemps déjà et qui est étroitement liée au milieu aquatique du lac Tchad. Le but poursuivi est de ne pas laisser disparaître un maillon, sans doute essentiel, dans la phylogénie des races bovines et de tirer profit rapidement des propriétés les plus intéressantes de la race : production laitière, production de viande de qualité et propriétés des métis de 1re ou de 2e génération. Après l'étude écologique de l'aire géographique, le type caractéristique est décrit ainsi que ses propriétés économiques. Le mode d'élevage et la pathologie sont largement détaillés. De nombreuses raisons plaident actuellement pour le maintien et la sélection des bovins Kouris purs. (Résumé d'auteur