72 research outputs found
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Genetics of Gland- in-situ or Hypoplastic Congenital Hypothyroidism in Macedonia
Neonatal screening in Macedonia detects congenital hypothyroidism (CH) with an incidence of 1 in 1,585, and more than 50% of cases exhibit a normally located gland-in-situ (GIS). Monogenic mutations causing dyshormonogenesis may underlie GIS CH; additionally, a small proportion of thyroid hypoplasia has a monogenic cause, such as TSHR and PAX8 defects. The genetic architecture of Macedonian CH cases has not previously been studied. We recruited screening-detected, non-syndromic GIS CH or thyroid hypoplasia cases (n = 40) exhibiting a spectrum of biochemical thyroid dysfunction ranging from severe permanent to mild transient CH and including 11 familial cases. Cases were born at term, with birth weight >3,000 g, and thyroid morphologies included goiter (n = 11), thyroid hypoplasia (n = 6), and apparently normal-sized thyroid. A comprehensive, phenotype-driven, Sanger sequencing approach was used to identify genetic mutations underlying CH, by sequentially screening known dyshormonogenesis-associated genes and TSHR in GIS cases and TSHR and PAX8 in cases with thyroid hypoplasia. Potentially pathogenic variants were identified in 14 cases, of which four were definitively causative; we also detected digenic variants in three cases. Seventeen variants (nine novel) were identified in TPO (n = 4), TG (n = 3), TSHR (n = 4), DUOX2 (n = 4), and PAX8 (n = 2). No mutations were detected in DUOXA2, NIS, IYD, and SLC26A7. The relatively low mutation frequency suggests that factors other than recognized monogenic causes (oligogenic variants, environmental factors, or novel genes) may contribute to GIS CH in this region. Future non–hypothesis-driven, next-generation sequencing studies are required to confirm these findings
Ekonomika prava industrijskog vlasništva: primjena geografskog podrijetla kao marketinške strategije za konkurentnost u podsektoru vinarstva u Republici Makedoniji
We analyze the importance of the industrial property rights and the competitiveness of wine sub-sector in four wine-producing countries in order to present geographical indications as a powerful marketing strategy for competitiveness. In the Macedonian agricultural sector, there is a low level of awareness for the economic benefits of industrial property rights. Macedonia has a competitive wine sector, as result of the factor conditions, particularly in tradition, geographic and climate conditions (Balassa index 3.83), but unfortunately the bulk wine has the largest share in export of 87%. The consequences of neglecting the legal protection of industrial property rights could lead to losing the market position of the producers or unsuccessful promotion and export orientation of the products.U radu se analizira značenje prava industrijskog vlasništva i konkurentnosti podsektora vinarstva u četiri regije koje se koje se bave proizvodnjom vina, kako bi se prikazalo geografsko podrijetlo kao snažna marketinška strategija za konkurentnost. U makedonskom poljoprivrednom sektoru vrlo je niska svijest o ekonomskim pogodnostima koje donosi pravo industrijskog vlasništva. Makedonija ima konkurentan vinarski sektor, što proizlazi iz čimbenika uvjeta, posebice tradicije, geografskih i klimatskih uvjeta (Balassa index 3.83). Nažalost, glavnina vina se izvozi (87%). Posljedice zanemarivanja pravne zaštite u smislu prava industrijskog vlasništva mogle bi dovesti proizvođače do gubljenja pozicija na tržištu ili neuspješne promocije i izvozne orijentacije proizvoda
Социјалните медиуми и дигиталната дипломатија
Употребата на социјалните платформи во функција на модерната дипломатија означи длабока промена во пејзажот на меѓународните односи. Како што се движиме по дигиталната граница, станува сè поочигледно дека социјалните медиуми и другите онлајн алатки станаа незаменливи инструменти во дипломатската работа. Овој труд има за цел да ги претстави социјалните платформи кои во поново време, особено за време на Ковид пандемијата станаа актуелни и применливи. Трудот како основна хипотеза го поставува тврдењето дека “во дигиталната ера, социјалните платформи наоѓаат голема примена во современата дипломатија”. Истражувачките прашања кои се однесуваат на видот на социјалните платформи кои се користат во работата на дипломатите, авторите ги проучуваат преку методот на компарација, како и преку теоретско-дескриптивниот метод, за да наративно ги прикажат достапните податоци и сознанија поврзани со социјалните платформи кои наоѓаат примена во современата дипломатија, заштедувајќи им време на дипломатите за брзо пренесување на ставови во глобални рамки
Clinical, Laboratory and Radiographic Features of Patients with Pneumonia and Parapneumonic Effusions
BACKGROUND: Parapneumonic effusions complicating pneumonia are associated with increased morbidity and mortality.AIM: To determine the role of the clinical, laboratory and radiographic features to the differential diagnosis of patients with community- acquired pneumonia (CAP) without effusion, uncomplicated parapneumonic effusion (UCPPE) and complicated parapneumonic effusion (CPPE).MATERIAL AND METHODS: We analysed 148 patients with CAP without effusion, 50 with UCPPE and 44 with CPPE. In three groups of patients, the majority was male patients (58.11%, 58%, 61.36%) consequently.RESULTS: The chronic heart failure was the most common comorbidity in a group with CAP (28; 18.92%) and UCPPE (7; 14%), alcoholism (12;12.77%) in a group with CPPE. Patients with CPPE had significantly longer fever compared to patients with CAP without effusion (p = 0.003). Pleuritic chest pain (86.36%) and dyspnea (88.64%) were the most common symptoms in CPPE, then to group with UCPPE (60%; 52%), and in CAP without effusion (25.68%; 47,97%). Diffuse pulmonary changes were detected more frequently in the group with CAP without effusion compared with the group with CPPE (64.86 % vs. 27.27 %), while the segment lung changes were more common in patients with CPPE (50% vs. 20.27%). Patients with CPPE were significant with higher erythrocytes sedimentation rate (ESR), white blood cells (WBC) and serum C- reactive protein (CRP) than it the other two groups (p = 0.00090, p = 0.01, p= 0.000065).CONCLUSION:Proper analysis of clinical, laboratory and radiographic features of patients with CAP and parapneumonic effusion can prevent mismanagement in these patients and will reduce morbidity and mortality.Â
Human Rights in Patient Care: A Practitioner Guide - Macedonia
Health systems can too often be places of punishment, coercion, and violations of basic rights—rather than places of treatment and care. In many cases, existing laws and tools that provide remedies are not adequately used to protect rights.This Practitioner Guide series presents practical how-to manuals for lawyers interested in taking cases around human rights in patient care. The manuals examine patient and provider rights and responsibilities, as well as procedures for protection through both the formal court system and alternative mechanisms in 10 countries.Each Practitioner Guide is country-specific, supplementing coverage of the international and regional framework with national standards and procedures in the following:ArmeniaGeorgiaKazakhstanKyrgyzstanMacedoniaMoldova (forthcoming)RomaniaRussia (forthcoming)SerbiaUkraineThis series is the first to systematically examine the application of constitutional, civil, and criminal laws; categorize them by right; and provide examples and practical tips. As such, the guides are useful for medical professionals, public health mangers, Ministries of Health and Justice personnel, patient advocacy groups, and patients themselves.Advancing Human Rights in Patient Care: The Law in Seven Transitional Countries is a compendium that supplements the practitioner guides. It provides the first comparative overview of legal norms, practice cannons, and procedures for addressing rights in health care in Armenia, Georgia, Kazakhstan, Kyrgyzstan, Macedonia, Russia, and Ukraine.A Legal Fellow in Human Rights in each country is undertaking the updating of each guide and building the field of human rights in patient care through trainings and the development of materials, networks, and jurisprudence. Fellows are recent law graduates based at a local organization with expertise and an interest in expanding work in law, human rights, and patient care. To learn more about the fellowships, please visit health-rights.org
Fermentable carbohydrate stimulates FFAR2-dependent colonic PYY cell expansion to increase satiety
Objective: Dietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is
important in regulating the beneficial effects of fermentable carbohydrate on body weight and to understand the role of gut hormones PYY and GLP-1.
Methods: Wild-type or Ffar2/ mice were fed an inulin supplemented or control diet. Mice were metabolically characterized and gut hormone concentrations, enteroendocrine cell density measurements were carried out. Intestinal organoids and colonic cultures were utilized to substantiate
the in vivo findings.
Results: We provide new mechanistic insight into how fermentable carbohydrate regulates metabolism. Using mice that lack FFAR2, we demonstrate that the fermentable carbohydrate inulin acts via this receptor to drive an 87% increase in the density of cells that produce the
appetite-suppressing hormone peptide YY (PYY), reduce food intake, and prevent diet-induced obesity.
Conclusion: Our results demonstrate that FFAR2 is predominantly involved in regulating the effects of fermentable carbohydrate on metabolism and does so, in part, by enhancing PYY cell density and release. This highlights the potential for targeting enteroendocrine cell differentiation to treat obesity
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The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism
Increased intake of dietary carbohydrate that is fermented in the colon by the microbiota has been reported to decrease body weight, although the mechanism remains unclear. Here we use in vivo11C-acetate and PET-CT scanning to show that colonic acetate crosses the blood–brain barrier and is taken up by the brain. Intraperitoneal acetate results in appetite suppression and hypothalamic neuronal activation patterning. We also show that acetate administration is associated with activation of acetyl-CoA carboxylase and changes in the expression profiles of regulatory neuropeptides that favour appetite suppression. Furthermore, we demonstrate through 13C high-resolution magic-angle-spinning that 13C acetate from fermentation of 13C-labelled carbohydrate in the colon increases hypothalamic 13C acetate above baseline levels. Hypothalamic 13C acetate regionally increases the 13C labelling of the glutamate–glutamine and GABA neuroglial cycles, with hypothalamic 13C lactate reaching higher levels than the ‘remaining brain’. These observations suggest that acetate has a direct role in central appetite regulation
Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight.
The obesity epidemic is a significant global health issue. Improved understanding of the mechanisms that regulate appetite and body weight will provide the rationale for the design of anti-obesity therapies. Thyroid hormones play a key role in metabolic homeostasis through their interaction with thyroid hormone receptors (TRs), which function as ligand-inducible transcription factors. The TR-beta isoform (TRβ) is expressed in the ventromedial hypothalamus (VMH), a brain area important for control of energy homeostasis. Here, we report that selective knockdown of TRβ in the VMH of adult mice results in severe obesity due to hyperphagia and reduced energy expenditure. The observed increase in body weight is of a similar magnitude to murine models of the most extreme forms of monogenic obesity. These data identify TRβ in the VMH as a major physiological regulator of food intake and energy homeostasis
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