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KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron
2012
Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins tha…
Aspartoacylase-lacZ knockin mice: an engineered model of Canavan disease.
2011
Canavan Disease (CD) is a recessive leukodystrophy caused by loss of function mutations in the gene encoding aspartoacylase (ASPA), an oligodendrocyte-enriched enzyme that hydrolyses N-acetylaspartate (NAA) to acetate and aspartate. The neurological phenotypes of different rodent models of CD vary considerably. Here we report on a novel targeted aspa mouse mutant expressing the bacterial β-Galactosidase (lacZ) gene under the control of the aspa regulatory elements. X-Gal staining in known ASPA expression domains confirms the integrity of the modified locus in heterozygous aspa lacZ-knockin (aspa(lacZ/+)) mice. In addition, abundant ASPA expression was detected in Schwann cells. Homozygous (…
Transcriptional profiling reveals functional links between RasGrf1 and Pttg1 in pancreatic beta cells
2014
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License .
Statins and other drugs: Facing COVID-19 as a vascular disease
2020
Angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and HMG-CoA reductase inhibitors ("statins") have been hypothesized to affect COVID-19 severity. However, up to now, no studies investigating this association have been conducted in the most vulnerable and affected population groups (ie, older adults residing in nursing homes). The objective of this study was to explore the association of ACEi/ARB and/or statins with clinical manifestations in COVID-19-infected older adults residing in nursing homes.We undertook a retrospective multicenter cohort study to analyze the association between ACEi/ARB and/or statin use with clinical outcome of COVID-19. The …
Pain and quality of life among residents of Norwegian nursing homes.
2008
Pain is a major problem in the nursing home population, with a prevalence range of 27% to 84%. Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage (International Association for the Study of Pain, 2008). It has an impact on many aspects of a person's emotional, social, and physical functioning, and on quality of life (QoL) The purpose of this study was to describe pain and QoL in a nursing home population that could self-report pain and to examine the association between QoL and pain in these patients. Pain was measured by a verbal rating scale from "no pain" to "severe pain." Quality of life was measu…
Importance of mitochondrial dynamin-related protein 1 in hypothalamic glucose sensitivity in rats.
2012
International audience; AIMS: Hypothalamic mitochondrial reactive oxygen species (mROS)-mediated signaling has been recently shown to be involved in the regulation of energy homeostasis. However, the upstream signals that control this mechanism have not yet been determined. Here, we hypothesize that glucose-induced mitochondrial fission plays a significant role in mROS-dependent hypothalamic glucose sensing. RESULTS: Glucose-triggered translocation of the fission protein dynamin-related protein 1 (DRP1) to mitochondria was first investigated in vivo in hypothalamus. Thus, we show that intracarotid glucose injection induces the recruitment of DRP1 to VMH mitochondria in vivo. Then, expressio…
Inverse relationship between body mass index and mortality in older nursing home residents: A meta-analysis of 19,538 elderly subjects
2015
Body mass index (BMI) and mortality in old adults from the general population have been related in a U-shaped or J-shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5–24.9, 25–29.9, ≥30 kg/m2), the most adjusted hazard ratios (HRs) according to a pre-defined list of covariates were obtained from authors and pooled by random-effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursin…
Hepatocellular expression of a dominant-negative mutant TGF-β type II receptor accelerates chemically induced hepatocarcinogenesis
2001
The potent growth-inhibitory activity of cytokines of the transforming growth factor-beta (TGF-beta) superfamily and their widespread expression in epithelia suggest that they may play an important role in the maintenance of epithelial homeostasis. To analyse TGF-beta mediated tumor suppressor activity in the liver, we generated transgenic mice overexpressing a dominant negative type II TGF-beta receptor in hepatocytes under control of the regulatory elements of the human C-reactive protein gene promoter. Transgenic animals exhibited constitutive and liver-specific transgene expression. The functional inactivation of the TGF-beta signaling pathway in transgenic hepatocytes was shown by redu…
Use of the Barthel Index to Assess Activities of Daily Living before and after SARS-COVID 19 Infection of Institutionalized Nursing Home Patients
2021
The objective of the present study was to evaluate the activities of daily living (ADLs) using the Barthel Index before and after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and also to determine whether or not the results varied according to gender. The ADLs of 68 cohabiting geriatric patients, 34 men and 34 women, in two nursing homes were measured before and after SARS-CoV-2 (Coronavirus 2019 (COVID-19)) infection. COVID-19 infection was found to affect the performance of ADLs in institutionalized elderly in nursing homes, especially in the more elderly subjects, regardless of sex. The COVID-19 pandemic, in addition to having claimed many victims, espe…
Physical Activity and Related Factors Among Nursing Home Residents
1994
OBJECTIVE: The purpose of this study was to examine physical activity and the predictors of physical activity and exercise among nursing home residents. DESIGN: Population study. PARTICIPANTS: The sample (n = 190) was obtained by selecting every man and every second women from the entire nursing home population (n = 346) in the city of Jyvaskyla, central Finland, in autumn 1989. Information was eventually collected by interview from 158 persons (49 men and 109 women). SETTING: An in-home interview carried out among nursing home populations. MEASUREMENTS: Independent variables were the questions describing physical activity among nursing home populations. Dependent variables were the predict…