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1.
BMC Med ; 22(1): 386, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267052

RESUMEN

BACKGROUND: Long-term deterioration in the mental health of healthcare workers (HCWs) has been reported during and after the COVID-19 pandemic. Determining the impact of COVID-19 incidence and mortality rates on the mental health of HCWs is essential to prepare for potential new pandemics. This study aimed to investigate the association of COVID-19 incidence and mortality rates with depressive symptoms over 2 years among HCWs in 20 countries during and after the COVID-19 pandemic. METHODS: This was a multi-country serial cross-sectional study using data from the first and second survey waves of the COVID-19 HEalth caRe wOrkErS (HEROES) global study. The HEROES study prospectively collected data from HCWs at various health facilities. The target population included HCWs with both clinical and non-clinical roles. In most countries, healthcare centers were recruited based on convenience sampling. As an independent variable, daily COVID-19 incidence and mortality rates were calculated using confirmed cases and deaths reported by Johns Hopkins University. These rates represent the average for the 7 days preceding the participants' response date. The primary outcome was depressive symptoms, assessed by the Patient Health Questionnaire-9. A multilevel linear mixed model (LMM) was conducted to investigate the association of depressive symptoms with the average incidence and mortality rates. RESULTS: A total of 32,223 responses from the participants who responded to all measures used in this study on either the first or second survey, and on both the first and second surveys in 20 countries were included in the analysis. The mean age was 40.1 (SD = 11.1), and 23,619 responses (73.3%) were from females. The 9323 responses (28.9%) were nurses and 9119 (28.3%) were physicians. LMM showed that the incidence rate was significantly and positively associated with depressive symptoms (coefficient = 0.008, standard error 0.003, p = 0.003). The mortality rate was significantly and positively associated with depressive symptoms (coefficient = 0.049, se = 0.020, p = 0.017). CONCLUSIONS: This is the first study to show an association between COVID-19 incidence and mortality rates with depressive symptoms among HCWs during the first 2 years of the outbreak in multiple countries. This study's findings indicate that additional mental health support for HCWs was needed when the COVID-19 incidence and mortality rates increase during and after the early phase of the pandemic, and these findings may apply to future pandemics. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04352634.


Asunto(s)
COVID-19 , Depresión , Personal de Salud , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , COVID-19/psicología , Estudios Transversales , Personal de Salud/psicología , Depresión/epidemiología , Masculino , Femenino , Incidencia , Adulto , Persona de Mediana Edad , SARS-CoV-2
2.
Ecol Evol ; 14(8): e70065, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39108564

RESUMEN

Most ecological studies attempting to understand causes of population dynamics and community structure disregard intraspecific trait variation. We quantified the importance of natural intra-cohort variation in body size and density of juveniles for recruitment of a sessile marine organism, the barnacle Semibalanus balanoides. Barnacles are representative of species organised in metapopulations, that is, as open local populations connected by larval dispersal. We tracked the individual growth and survival of a cohort of juvenile barnacles from two shores of North Wales. Barnacles settled as larvae in spring of 2002 on previously cleared rock. The density of these new recruits was experimentally manipulated in June and randomly selected individuals were monitored from June to October to evaluate the role of barnacle size and density in predicting survival. In doing so we characterised density at three spatial scales (quadrat: 25 cm2, cells within quadrats: 25 mm2 and neighbourhood: number of neighbours in physical contact with the target barnacle). At all scales, variations in juvenile body size exacerbated the effect of density-dependent mortality on population size. While density-dependent mortality was very intense in the small-sized individuals, large-sized individuals experienced very weak density-dependent mortality and showed high survival rates. Using the concept of 'Jensen inequality', we show that important biases in estimations of survival, based on population size only, occur at high barnacle densities, where survival is low. Our study highlights the role of body size variation in understanding dynamics of open populations.

3.
J Anim Ecol ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39180253

RESUMEN

Marine heatwaves (MHWs) are extreme weather events that have major impacts on the structure and functioning of marine ecosystems worldwide. Due to anthropogenic climate change, the occurrence of MHWs is predicted to increase in future. There is already evidence linking MHWs with reductions in biodiversity and incidence of mass mortality events in coastal ecosystems. However, because MHWs are unpredictable, the quantification of their effects on communities is challenging. Here, we use the Helgoland Roads long-term time series (German Bight, North Sea), one of the richest marine time series in the world, and implement a modified before-after control-impact (BACI) design to evaluate MHW effect on mesozooplankton communities. Mesozooplankton play an essential role in connecting primary producers to higher trophic levels, and any changes in their community structure could have far-reaching impacts on the entire ecosystem. The responses of mesozooplankton community to MHWs in terms of community structure and densities occurred mainly in spring and autumn. Abundances of seven taxa, including some of the most abundant groups (e.g. copepods), were affected either positively or negatively in response to MHWs. In contrast, we observed no clear evidence of an impact of summer and winter MHWs; instead, the density of the most common taxa remained unchanged. Our results highlight the seasonally dependent impacts of MHWs on mesozooplankton communities and the challenges in evaluating those impacts. Long-term monitoring is an important contributor to the quantification of effects of MHWs on natural populations.

4.
J Cell Biol ; 223(9)2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-38990714

RESUMEN

Dermal fibroblasts deposit type I collagen, the dominant extracellular matrix molecule found in skin, during early postnatal development. Coincident with this biosynthetic program, fibroblasts proteolytically remodel pericellular collagen fibrils by mobilizing the membrane-anchored matrix metalloproteinase, Mmp14. Unexpectedly, dermal fibroblasts in Mmp14-/- mice commit to a large-scale apoptotic program that leaves skin tissues replete with dying cells. A requirement for Mmp14 in dermal fibroblast survival is recapitulated in vitro when cells are embedded within, but not cultured atop, three-dimensional hydrogels of crosslinked type I collagen. In the absence of Mmp14-dependent pericellular proteolysis, dermal fibroblasts fail to trigger ß1 integrin activation and instead actuate a TGF-ß1/phospho-JNK stress response that leads to apoptotic cell death in vitro as well as in vivo. Taken together, these studies identify Mmp14 as a requisite cell survival factor that maintains dermal fibroblast viability in postnatal dermal tissues.


Asunto(s)
Apoptosis , Supervivencia Celular , Fibroblastos , Metaloproteinasa 14 de la Matriz , Animales , Metaloproteinasa 14 de la Matriz/metabolismo , Metaloproteinasa 14 de la Matriz/genética , Fibroblastos/metabolismo , Ratones , Ratones Noqueados , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Integrina beta1/metabolismo , Integrina beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Dermis/metabolismo , Dermis/citología , Células Cultivadas , Matriz Extracelular/metabolismo , Ratones Endogámicos C57BL , Piel/metabolismo
5.
Mar Environ Res ; 200: 106646, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39048495

RESUMEN

Rocky shore communities are shaped by complex interactions among environmental drivers and a range of biological processes. Here, we investigated the importance of abiotic and biotic drivers on the population structure of key rocky intertidal species at 62 sites, spanning ∼50% of the Brazilian rocky shoreline (i.e., ∼500 km). Large-scale population patterns were generally explained by differences in ocean temperature and wave exposure. For the gastropod species Lottia subrugosa, differences at smaller scales (i.e., 0.1-1 km) were better explained by other abiotic influences such as freshwater discharge and substrate roughness. Based on the general population patterns of intertidal species identified, three main oceanographic groups were observed: a cold-oligotrophic grouping at northern sites (Lakes sub-region), a eutrophic group associated with large estuaries and urban zones (Santos and Guanabara bays); and a transitional warm-water group found between the two more productive areas. Larger individuals of Stramonita brasiliensis, L. subrugosa and Echinolittorina lineolata were generally found in the cold-oligotrophic system (i.e., upwelling region), while small suspension feeders dominate the warm-eutrophic systems. Evidence of bottom-up regulation was not observed, and top-down regulation effects were only observed between the whelk S. brasiliensis and its mussel prey Pernaperna. Environmental drivers as compared to biotic interactions, therefore, play a key role determining the population structure of multiple intertidal species, across a range of spatial scales along the SW Atlantic shores.


Asunto(s)
Ecosistema , Brasil , Animales , Monitoreo del Ambiente , Gastrópodos/fisiología , Dinámica Poblacional , Biodiversidad , Temperatura
6.
J Clin Invest ; 134(14)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39007271

RESUMEN

The melanocortin-3 receptor (MC3R) regulates GABA release from agouti-related protein (AgRP) nerve terminals and thus tonically suppresses multiple circuits involved in feeding behavior and energy homeostasis. Here, we examined the role of the MC3R and the melanocortin system in regulating the response to various anorexigenic agents. The genetic deletion or pharmacological inhibition of the MC3R, or subthreshold doses of an MC4R agonist, improved the dose responsiveness to glucagon-like peptide 1 (GLP1) agonists, as assayed by inhibition of food intake and weight loss. An enhanced anorectic response to the acute satiety factors peptide YY (PYY3-36) and cholecystokinin (CCK) and the long-term adipostatic factor leptin demonstrated that increased sensitivity to anorectic agents was a generalized result of MC3R antagonism. We observed enhanced neuronal activation in multiple hypothalamic nuclei using Fos IHC following low-dose liraglutide in MC3R-KO mice (Mc3r-/-), supporting the hypothesis that the MC3R is a negative regulator of circuits that control multiple aspects of feeding behavior. The enhanced anorectic response in Mc3r-/- mice after administration of GLP1 analogs was also independent of the incretin effects and malaise induced by GLP1 receptor (GLP1R) analogs, suggesting that MC3R antagonists or MC4R agonists may have value in enhancing the dose-response range of obesity therapeutics.


Asunto(s)
Liraglutida , Receptor de Melanocortina Tipo 3 , Receptor de Melanocortina Tipo 4 , Animales , Masculino , Ratones , Depresores del Apetito/farmacología , Colecistoquinina/metabolismo , Ingestión de Alimentos/efectos de los fármacos , Péptido 1 Similar al Glucagón/metabolismo , Hipotálamo/metabolismo , Leptina/metabolismo , Liraglutida/farmacología , Ratones Endogámicos C57BL , Ratones Noqueados , Péptido YY/metabolismo , Péptido YY/genética , Receptor de Melanocortina Tipo 3/genética , Receptor de Melanocortina Tipo 3/metabolismo , Receptor de Melanocortina Tipo 3/agonistas , Receptor de Melanocortina Tipo 4/metabolismo , Receptor de Melanocortina Tipo 4/genética , Receptor de Melanocortina Tipo 4/agonistas
7.
bioRxiv ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38895206

RESUMEN

Most antipsychotic drugs (APDs) induce hyperphagia and weight gain. However, the neural mechanisms are poorly understood, partly due to challenges replicating their metabolic effects in rodents. Here, we report a new mouse model that recapitulates overeating induced by clozapine, a widely prescribed APD. Our study shows that clozapine boosts food intake by inhibiting melanocortin 4 receptor (MC4R) expressing neurons in the paraventricular nucleus of the hypothalamus. Interestingly, neither clozapine nor risperidone, another commonly used APD, affects receptor-ligand binding or the canonical Gαs signaling of MC4R. Instead, they inhibit neuronal activity by enhancing the coupling between MC4R and Kir7.1, leading to the open state of the inwardly rectifying potassium channel. Deletion of Kir7.1 in Mc4r-Cre neurons prevents clozapine-induced weight gain, while treatment with a selective Kir7.1 blocker mitigates overeating in clozapine-fed mice. Our findings unveil a molecular pathway underlying the effect of APDs on feeding behavior and suggest its potential as a therapeutic target.

8.
bioRxiv ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38895219

RESUMEN

Hereditary defects in the function of the Kir7.1 in the retinal pigment epithelium are associated with the ocular diseases retinitis pigmentosa, Leber congenital amaurosis, and snowflake vitreal degeneration. Studies also suggest that Kir7.1 may be regulated by a GPCR, the melanocortin-4 receptor, in certain hypothalamic neurons. We present the first structures of human Kir7.1 and describe the conformational bias displayed by two pathogenic mutations, R162Q and E276A, to provide an explanation for the basis of disease and illuminate the gating pathway. We also demonstrate the structural basis for the blockade of the channel by a small molecule ML418 and demonstrate that channel blockade in vivo activates MC4R neurons in the paraventricular nucleus of the hypothalamus (PVH), inhibiting food intake and inducing weight loss. Preliminary purification, and structural and pharmacological characterization of an in tandem construct of MC4R and Kir7.1 suggests that the fusion protein forms a homotetrameric channel that retains regulation by liganded MC4R molecules.

9.
Methods Mol Biol ; 2796: 229-248, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38856905

RESUMEN

Automated patch clamp recording is a valuable technique in drug discovery and the study of ion channels. It allows for the precise measurement and manipulation of channel currents, providing insights into their function and modulation by drugs or other compounds. The melanocortin 4 receptor (MC4-R) is a G protein-coupled receptor (GPCR) crucial to appetite regulation, energy balance, and body weight. MC4-R signaling is complex and involves interactions with other receptors and neuropeptides in the appetite-regulating circuitry. MC4-Rs, like other GPCRs, are known to modulate ion channels such as Kir7.1, an inward rectifier potassium channel, in response to ligand binding. This modulation is critical for controlling ion flow across the cell membrane, which can influence membrane potential, excitability, and neurotransmission. The MC4-R is the target for the anti-obesity drug Imcivree. However, this drug is known to lack optimal potency and also has side effects. Using high-throughput techniques for studying the MC4-R/Kir7.1 complex allows researchers to rapidly screen many compounds or conditions, aiding the development of drugs that target this system. Additionally, automated patch clamp recording of this receptor-channel complex and its ligands can provide valuable functional and pharmacological insights supporting the development of novel therapeutic strategies. This approach can be generalized to other GPCR-gated ion channel functional complexes, potentially accelerating the pace of research in different fields with the promise to uncover previously unknown aspects of receptor-ion channel interactions.


Asunto(s)
Técnicas de Placa-Clamp , Canales de Potasio de Rectificación Interna , Receptor de Melanocortina Tipo 4 , Técnicas de Placa-Clamp/métodos , Animales , Humanos , Receptor de Melanocortina Tipo 4/metabolismo , Canales de Potasio de Rectificación Interna/metabolismo , Activación del Canal Iónico/efectos de los fármacos , Receptores Acoplados a Proteínas G/metabolismo , Células HEK293
11.
J Med Chem ; 67(4): 2690-2711, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38345933

RESUMEN

Melanocortin 4 receptor (MC4-R) antagonists are actively sought for treating cancer cachexia. We determined the structures of complexes with PG-934 and SBL-MC-31. These peptides differ from SHU9119 by substituting His6 with Pro6 and inserting Gly10 or Arg10. The structures revealed two subpockets at the TM7-TM1-TM2 domains, separated by N2857.36. Two peptide series based on the complexed peptides led to an antagonist activity and selectivity SAR study. Most ligands retained the SHU9119 potency, but several SBL-MC-31-derived peptides significantly enhanced MC4-R selectivity over MC1-R by 60- to 132-fold. We also investigated MC4-R coupling to the K+ channel, Kir7.1. Some peptides activated the channel, whereas others induced channel closure independently of G protein coupling. In cell culture studies, channel activation correlated with increased feeding, while a peptide with Kir7.1 inhibitory activity reduced eating. These results highlight the potential for targeting the MC4-R:Kir7.1 complex for treating positive and restrictive eating disorders.


Asunto(s)
Péptidos , Receptor de Melanocortina Tipo 4 , Humanos , Péptidos/farmacología , Ligandos , Diseño de Fármacos , Receptor de Melanocortina Tipo 3 , Receptores de Melanocortina
12.
bioRxiv ; 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38106197

RESUMEN

The melanocortin-3 receptor (MC3R) acts presynaptically to regulate GABA release from agouti-related protein (AgRP) nerve terminals and thus may be a negative regulator of multiple circuits involved in feeding behavior and energy homeostasis. Here, we examined the role of MC3R in regulating the response to various anorexigenic agents. Our findings reveal that genetic deletion or pharmacological inhibition of MC3R improves the dose responsiveness to Glucagon-like peptide 1 (GLP1) agonists, as assayed by inhibition of food intake and weight loss. An enhanced anorectic response to other agents, including the acute satiety factors peptide YY (PYY3-36) and cholecystokinin (CCK) and the long-term adipostatic factor, leptin, demonstrated that increased sensitivity to anorectic agents is a generalized result of MC3R antagonism. Enhanced neuronal activation in multiple nuclei, including ARH, VMH, and DMH, was observed using Fos immunohistochemistry following low-dose liraglutide in MC3R knockout mice (Mc3r-/-), supporting the hypothesis that the MC3R is a negative regulator of circuits regulating multiple aspects of feeding behavior. The enhanced anorectic response in Mc3r -/- mice after administration of GLP1 analogs was also independent of the incretin effects and malaise induced by GLP1R analogs, suggesting that MC3R antagonists may have value in enhancing the dose-response range of obesity therapeutics.

13.
Front Cell Neurosci ; 17: 1263591, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37920203

RESUMEN

Introduction: At the cellular level, acute temperature changes alter ionic conductances, ion channel kinetics, and the activity of entire neuronal circuits. This can result in severe consequences for neural function, animal behavior and survival. In poikilothermic animals, and particularly in aquatic species whose core temperature equals the surrounding water temperature, neurons experience rather rapid and wide-ranging temperature fluctuations. Recent work on pattern generating neural circuits in the crustacean stomatogastric nervous system have demonstrated that neuronal circuits can exhibit an intrinsic robustness to temperature fluctuations. However, considering the increased warming of the oceans and recurring heatwaves due to climate change, the question arises whether this intrinsic robustness can acclimate to changing environmental conditions, and whether it differs between species and ocean habitats. Methods: We address these questions using the pyloric pattern generating circuits in the stomatogastric nervous system of two crab species, Hemigrapsus sanguineus and Carcinus maenas that have seen a worldwide expansion in recent decades. Results and discussion: Consistent with their history as invasive species, we find that pyloric activity showed a broad temperature robustness (>30°C). Moreover, the temperature-robust range was dependent on habitat temperature in both species. Warm-acclimating animals shifted the critical temperature at which circuit activity breaks down to higher temperatures. This came at the cost of robustness against cold stimuli in H. sanguineus, but not in C. maenas. Comparing the temperature responses of C. maenas from a cold latitude (the North Sea) to those from a warm latitude (Spain) demonstrated that similar shifts in robustness occurred in natural environments. Our results thus demonstrate that neuronal temperature robustness correlates with, and responds to, environmental temperature conditions, potentially preparing animals for changing ecological conditions and shifting habitats.

14.
Philos Trans R Soc Lond B Biol Sci ; 378(1892): 20220363, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-37899009

RESUMEN

Sessile marine invertebrates play a vital role as ecosystem engineers and in benthic-pelagic coupling. Most benthic fauna develop through larval stages and the importance of natural light cycles for larval biology and ecology is long-established. Natural light-dark cycles regulate two of the largest ocean-scale processes that are fundamental to larvae's life cycle: the timing of broadcast spawning for successful fertilization and diel vertical migration for foraging and predator avoidance. Given the reliance on light and the ecological role of larvae, surprisingly little is known about the impacts of artificial light at night (ALAN) on the early life history of habitat-forming species. We quantified ALAN impacts on larval performance (survival, growth, development) of two cosmopolitan ecosystem engineers in temperate marine ecosystems, the mussel Mytilus edulis and the barnacle Austrominius modestus. Higher ALAN irradiance reduced survival in both species (57% and 13%, respectively). ALAN effects on development and growth were small overall, and different between species, time-points and parentage. Our results show that ALAN adversely affects larval survival and reiterates the importance of paternal influence on offspring performance. ALAN impacts on the early life stages of ecosystem engineering species have implications not only for population viability but also the ecological communities that these species support. This article is part of the theme issue 'Light pollution in complex ecological systems'.


Asunto(s)
Ecosistema , Contaminación Lumínica , Animales , Larva/fisiología , Estadios del Ciclo de Vida , Organismos Acuáticos , Luz
15.
Nat Rev Endocrinol ; 19(9): 507-519, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37365323

RESUMEN

A large body of preclinical and clinical data shows that the central melanocortin system is a promising therapeutic target for treating various metabolic disorders such as obesity and cachexia, as well as anorexia nervosa. Setmelanotide, which functions by engaging the central melanocortin circuitry, was approved by the FDA in 2020 for use in certain forms of syndromic obesity. Furthermore, the FDA approvals in 2019 of two peptide drugs targeting melanocortin receptors for the treatment of generalized hypoactive sexual desire disorder (bremelanotide) and erythropoietic protoporphyria-associated phototoxicity (afamelanotide) demonstrate the safety of this class of peptides. These approvals have also renewed excitement in the development of therapeutics targeting the melanocortin system. Here, we review the anatomy and function of the melanocortin system, discuss progress and challenges in developing melanocortin receptor-based therapeutics, and outline potential metabolic and behavioural disorders that could be addressed using pharmacological agents targeting these receptors.


Asunto(s)
Enfermedades Metabólicas , Disfunciones Sexuales Psicológicas , Humanos , Melanocortinas/uso terapéutico , Disfunciones Sexuales Psicológicas/tratamiento farmacológico , Disfunciones Sexuales Psicológicas/metabolismo , Obesidad/tratamiento farmacológico , Caquexia , Enfermedades Metabólicas/tratamiento farmacológico
16.
Artículo en Inglés | MEDLINE | ID: mdl-36906064

RESUMEN

INTRODUCTION: This study assessed if the healthcare system overload and the organizational changes made in response to COVID-19 may be having an impact on clinical and epidemiological characteristics of the peritonsillar infection (PTI). MATERIALS AND METHODS: In a retrospective longitudinal and descriptive follow-up, we reviewed the circumstances of the patients attended during 5 years, from 2017 to 2021, in two hospitals, one regional and other tertiary. Variables related to underlying pathology, history of tonsillitis, time of evolution, previous visits to Primary Care, diagnostic findings, abscess/phlegmon ratio, and length of hospital stay were recorded. RESULTS: From 2017 to 2019, the incidence of the disease ranged between 14 and 16 cases/100,000 inhabitants-year, and decreased to 9.3 in 2020, a 43% less. Patients with PTI consulting in pandemic time were visited much less often in Primary Care services. They showed a greater severity of symptoms and the period of time between their appearance and diagnosis was longer. Additionally, there were more abscesses and the need for hospital admission greater than 24h was 66%. There was hardly a causal relationship with acute tonsillitis, although 66% of the patients evidenced history of recurrent tonsillitis, and 71% concomitant pathology. All these findings showed statistically significant differences with the pre-pandemic cases. CONCLUSIONS: The protection of airborne transmission, the social distancing and the lockdown adopted in our country are measures that seem having been able to modify the evolution of PTI, with a much lower incidence, a longer recovery period and a minimal relationship with acute tonsillitis.


Asunto(s)
COVID-19 , Absceso Peritonsilar , Tonsilectomía , Tonsilitis , Humanos , Pandemias/prevención & control , Estudios Retrospectivos , Tonsilectomía/efectos adversos , COVID-19/complicaciones , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Absceso Peritonsilar/epidemiología , Tonsilitis/epidemiología , Tonsilitis/cirugía , Atención a la Salud
17.
Am J Physiol Cell Physiol ; 324(3): C694-C706, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36717105

RESUMEN

The inward rectifier potassium channel Kir7.1, encoded by the KCNJ13 gene, is a tetramer composed of two-transmembrane domain-spanning monomers, closer in homology to Kir channels associated with potassium transport such as Kir1.1, 1.2, and 1.3. Compared with other channels, Kir7.1 exhibits small unitary conductance and low dependence on external potassium. Kir7.1 channels also show a phosphatidylinositol 4,5-bisphosphate (PIP2) dependence for opening. Accordingly, retinopathy-associated Kir7.1 mutations mapped at the binding site for PIP2 resulted in channel gating defects leading to channelopathies such as snowflake vitreoretinal degeneration and Leber congenital amaurosis in blind patients. Lately, this channel's role in energy homeostasis was reported due to the direct interaction with the melanocortin type 4 receptor (MC4R) in the hypothalamus. As this channel seems to play a multipronged role in potassium homeostasis and neuronal excitability, we will discuss what is predicted from a structural viewpoint and its possible implications for hunger control.


Asunto(s)
Canales de Potasio de Rectificación Interna , Humanos , Mutación , Neuronas/metabolismo , Potasio/metabolismo , Canales de Potasio de Rectificación Interna/genética , Canales de Potasio de Rectificación Interna/metabolismo , Dominios Proteicos
18.
J Yeungnam Med Sci ; 40(3): 311-314, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36537175

RESUMEN

Thallium poisoning is usually accidental. We present a case of a 51-year-old woman who was evaluated in June 2018 for myalgia, vertigo, asthenia, and abdominal pain. Physical examination revealed temporal-spatial disorientation, jaundice, and asterixis. The laboratory reported the following: bilirubin, 10.3 mg/dL; aspartate transaminase, 78 U/L; alanine transaminase, 194 U/L; albumin, 2.3 g/dL; prothrombin time, 40%; and platelet count, 60,000/mm3. Serology performed for hepatitis A, B, and C; Epstein-Barr virus; cytomegalovirus; and human immunodeficiency virus was negative, and a collagenogram was negative. Physical reevaluation revealed alopecia on the scalp, armpits, and eyebrows; macules on the face; plantar hyperkeratosis; and ulcers on the lower limbs. Tests for lead, arsenic, copper, and mercury were carried out, which were normal; however, elevated urinary thallium (540 µg/g; range, 0.4-10 µg/g) was observed. The patient was treated with ᴅ-penicillamine 1,000 mg/day and recovered her urinary thallium levels were within normal range at annual follow-up. Thallium poisoning is extremely rare and can be fatal in small doses. An adequate clinical approach can facilitate early diagnosis.

19.
Acta Otorrinolaringol Esp ; 74(2): 108-115, 2023.
Artículo en Español | MEDLINE | ID: mdl-35846592

RESUMEN

Introduction: This study assessed if the healthcare system overload and the organizational changes made in response to COVID-19 may be having an impact on clinical and epidemiological characteristics of the peritonsillar infection (PTI). Materials and methods: In a retrospective longitudinal and descriptive follow-up, we reviewed the circumstances of the patients attended during 5 years, from 2017 to 2021, in two hospitals, one regional and other tertiary. Variables related to underlying pathology, history of tonsillitis, time of evolution, previous visits to Primary Care, diagnostic findings, abscess/phlegmon ratio, and length of hospital stay were recorded. Results: From 2017 to 2019, the incidence of the disease ranged between 14 and 16 cases/100,000 inhabitants-year, and decreased to 9.3 in 2020, a 43% less. Patients with PTI consulting in pandemic time were visited much less often in Primary Care services. They showed a greater severity of symptoms and the period of time between their appearance and diagnosis was longer. Additionally, there were more abscesses and the need for hospital admission greater than 24 h was 66%. There was hardly a causal relationship with acute tonsillitis, although 66% of the patients evidenced history of recurrent tonsillitis, and 71% concomitant pathology. All these findings showed statistically significant differences with the pre-pandemic cases. Conclusions: The protection of airborne transmission, the social distancing and the lockdown adopted in our country are measures that seem having been able to modify the evolution of PTI, with a much lower incidence, a longer recovery period and a minimal relationship with acute tonsillitis.

20.
Artículo en Español | LILACS, UY-BNMED, BNUY | ID: biblio-1520019

RESUMEN

La emergencia sanitaria COVID-19 impactó en los/as trabajadores de salud, dejando en evidencia: el malestar subjetivo y altos índices de ansiedad y depresión. El objetivo del presente trabajo es analizar las experiencias y vivencias de trabajadores/as de la salud durante la pandemia. La misma se realizó a partir del análisis de las respuestas obtenidas en la pregunta abierta del formulario autoadministrado del proyecto Héroes Uruguay. La población objetivo fue el personal de los servicios de salud integrados al Sistema Nacional Integrado de Salud en los tres niveles de atención. Las respuestas fueron agrupadas y categorizadas en base a su frecuencia. La categoría condiciones de trabajo fue la temática más mencionada, seguida de organización del trabajo y vivencias. Realizamos otra categorización sobre los sentidos subjetivos durante la pandemia, nueve categorías son las frecuentes, siendo el 86% de los sentidos subjetivos: ansiedad y estrés, miedo, cansancio, no apoyo social y sobrecarga son los más mencionados. Los resultados muestran que la mayoría de las respuestas remite a las condiciones y a la organización del trabajo, se trata de dimensiones claves en la salud del trabajador, en su entorno, y en los procesos de asistencia al paciente y su familia. Este estudio nos permite afirmar la importancia a nivel organizacional y de políticas de salud, de generar entornos laborales seguros y saludables. La emergencia sanitaria generada por el COVID 19, expuso y agudizó la tensión de los sistemas sanitarios y su impacto en la salud y bienestar del personal.


The COVID-19 health emergency impacted health workers, revealing: subjective discomfort and high rates of anxiety and depression. The objective of this work is to analyze the experiences of health workers during the pandemic. It was carried out from the analysis of the answers obtained in the open question of the self-administered form of the Héroes Uruguay project. The target population was the staff of the health services integrated into the National Integrated Health System at the three levels of care. The responses were grouped and categorized based on recurring themes. The working conditions category was the most mentioned theme, followed by work organization and experiences. We carry out another categorization of the subjective senses during the pandemic, nine categories are the most frequent, with 86% of the subjective senses: anxiety and stress, fear, tiredness, lack of social support and overload are the most mentioned. The results show that most of the answers refer to the conditions and organization of work, these are key dimensions in the worker's health, in his environment, and in the patient assisted and his family. This study allows us to affirm the importance at the organizational and health policy level of generating safe and healthy work environments. The health emergency generated by COVID 19 exposed and exacerbated the tension in health systems and its impact on the health and well-being of personnel.


A emergência sanitária da COVID-19 impactou os trabalhadores da saúde, revelando: desconforto subjetivo e altos índices de ansiedade e depressão. O objetivo deste trabalho é analisar as vivências dos trabalhadores da saúde durante a pandemia. Foi realizada a partir da análise das respostas obtidas na questão aberta do formulário autoaplicável do projeto Héroes Uruguai. A população alvo foram os trabalhadores dos serviços de saúde integrados no Sistema Único de Saúde Integrado nos três níveis de cuidados. As respostas foram agrupadas e categorizadas com base em temas recorrentes. A categoria condições de trabalho foi o tema mais citado, seguido de organização do trabalho e experiências. Realizamos outra categorização dos sentidos subjetivos durante a pandemia, nove categorias são as mais frequentes, com 86% dos sentidos subjetivos: ansiedade e estresse, medo, cansaço, falta de apoio social e sobrecarga são os mais citados. Os resultados mostram que a maioria das respostas se refere às condições e organização do trabalho, dimensões fundamentais na saúde do trabalhador, em seu ambiente, e no paciente assistido e sua família. Este estudo permite afirmar a importância a nível organizacional e da política de saúde de gerar ambientes de trabalho seguros e saudáveis. A emergência de saúde gerada pelo COVID 19 expôs e exacerbou a tensão nos sistemas de saúde e seu impacto na saúde e bem-estar do pessoal.


Asunto(s)
Humanos , Masculino , Femenino , Salud Mental , Personal de Salud/psicología , Estrés Laboral/etiología , Uruguay , Distribución por Sexo , Pandemias , COVID-19/epidemiología
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