RESUMO
Kisspeptin and γ-amino butyric acid (GABA), synthesized in the central nervous system, are critical for reproduction. Both are also expressed in peripheral organs/tissues critical to metabolic control (liver/pancreas/adipose). Many kisspeptin neurons coexpress GABAB receptors (GABABR) and GABA controls kisspeptin expression and secretion. We developed a unique mouse lacking GABABR exclusively from kisspeptin cells/neurons (Kiss1-GABAB1KO) to evaluate the impact on metabolism/reproduction. We confirmed selective deletion of GABABR from Kiss1 cells in the anteroventral periventricular nucleus/periventricular nucleus continuum (AVPV/PeN; immunofluorescence and PCR) and arcuate nucleus (ARC), medial amygdala (MeA), pituitary, liver, and testes (PCR). Young Kiss1-GABAB1KO males were fertile, with normal LH and testosterone. Kiss1 expression was similar between genotypes in AVPV/PeN, ARC, MeA, bed nucleus of the stria terminalis (BNST), and peripheral organs (testis, liver, pituitary). Kiss1-GABAB1KO males presented higher fasted glycemia and insulin levels, an impaired response to a glucose overload, reduced insulin sensitivity, and marked insulin resistance. Interestingly, when Kiss1-GABAB1KO males got older (9 mo old) their body weight (BW) increased, in part due to an increase in white adipose tissue (WAT). Old Kiss1-GABAB1KO males showed higher fasted insulin, increased pancreatic insulin content, insulin resistance, and significantly decreased pancreatic kisspeptin levels. In sum, lack of GABABR specifically in Kiss1 cells severely impacts glucose homeostasis in male mice, reinforcing kisspeptin involvement in metabolic regulation. These alterations in glucose homeostasis worsened with aging. We highlight the impact of GABA through GABABR in the regulation of the pancreas kisspeptin system in contrast to liver kisspeptin that was not affected.NEW & NOTEWORTHY We developed a unique mouse lacking GABAB receptors specifically in Kiss1 cells to evaluate the impact on reproduction and metabolism. Knockout males showed a severe impact on glucose homeostasis, which worsened with aging. These results reinforce the proposed kisspeptin involvement in metabolic regulation and highlight the impact of GABA through GABABR in the regulation of the peripheral pancreas kisspeptin system.
Assuntos
Resistência à Insulina , Insulinas , Camundongos , Animais , Masculino , Kisspeptinas/genética , Kisspeptinas/metabolismo , Resistência à Insulina/genética , Estradiol/metabolismo , Camundongos Knockout , Reprodução/genética , Homeostase , Ácido gama-Aminobutírico/metabolismoRESUMO
BACKGROUND: The COVID-19 pandemic has led to an unprecedented global health care challenge for both medical institutions and researchers. Recognizing different COVID-19 subphenotypes-the division of populations of patients into more meaningful subgroups driven by clinical features-and their severity characterization may assist clinicians during the clinical course, the vaccination process, research efforts, the surveillance system, and the allocation of limited resources. OBJECTIVE: We aimed to discover age-sex unbiased COVID-19 patient subphenotypes based on easily available phenotypical data before admission, such as pre-existing comorbidities, lifestyle habits, and demographic features, to study the potential early severity stratification capabilities of the discovered subgroups through characterizing their severity patterns, including prognostic, intensive care unit (ICU), and morbimortality outcomes. METHODS: We used the Mexican Government COVID-19 open data, including 778,692 SARS-CoV-2 population-based patient-level data as of September 2020. We applied a meta-clustering technique that consists of a 2-stage clustering approach combining dimensionality reduction (ie, principal components analysis and multiple correspondence analysis) and hierarchical clustering using the Ward minimum variance method with Euclidean squared distance. RESULTS: In the independent age-sex clustering analyses, 56 clusters supported 11 clinically distinguishable meta-clusters (MCs). MCs 1-3 showed high recovery rates (90.27%-95.22%), including healthy patients of all ages, children with comorbidities and priority in receiving medical resources (ie, higher rates of hospitalization, intubation, and ICU admission) compared with other adult subgroups that have similar conditions, and young obese smokers. MCs 4-5 showed moderate recovery rates (81.30%-82.81%), including patients with hypertension or diabetes of all ages and obese patients with pneumonia, hypertension, and diabetes. MCs 6-11 showed low recovery rates (53.96%-66.94%), including immunosuppressed patients with high comorbidity rates, patients with chronic kidney disease with a poor survival length and probability of recovery, older smokers with chronic obstructive pulmonary disease, older adults with severe diabetes and hypertension, and the oldest obese smokers with chronic obstructive pulmonary disease and mild cardiovascular disease. Group outcomes conformed to the recent literature on dedicated age-sex groups. Mexican states and several types of clinical institutions showed relevant heterogeneity regarding severity, potentially linked to socioeconomic or health inequalities. CONCLUSIONS: The proposed 2-stage cluster analysis methodology produced a discriminative characterization of the sample and explainability over age and sex. These results can potentially help in understanding the clinical patient and their stratification for automated early triage before further tests and laboratory results are available and even in locations where additional tests are not available or to help decide resource allocation among vulnerable subgroups such as to prioritize vaccination or treatments.
Assuntos
COVID-19 , Idoso , COVID-19/epidemiologia , Criança , Análise por Conglomerados , Humanos , Unidades de Terapia Intensiva , Pandemias , SARS-CoV-2RESUMO
ANTECEDENTES: El situs inversus totalis (SIT) es una condición congénita infrecuente, en la cual los órganos asimétricos del abdomen y el tórax presentan una disposición en espejo; su asociación con aneurismas de aorta abdominal (AAA) es inusual y supone un reto quirúrgico. CASO CLÍNICO: Presentamos el caso de una paciente con SIT y AAA, por lo que se decide llevar a reparación quirúrgica. El AAA en pacientes con SIT es infrecuente; en la literatura hay pocos casos reportados. A pesar de ser una relación inusual, su tratamiento de forma electiva fue segura en nuestra paciente. BACKGROUND: The situs inversus totalis (SIT) is a rare congenital condition, in which the asymmetric organs of the abdomen and thorax have a mirror ubication; its association with abdominal aortic aneurysms, is unusual. CASE REPORT: We will present the case of a patient with SIT, who has an abdominal aortic aneurysm, taken to open surgical repair. The presentation of abdominal aortic aneurysms in patients with infrequent SIT, with few reported cases in the literature. Despite being an unusual relationship, elective treatment was safe, as we seen in our patient.
Assuntos
Aneurisma da Aorta Abdominal , Situs Inversus , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Situs Inversus/complicaçõesRESUMO
Introducción y objetivos: La hiponatremia es un factor de mal pronóstico en pacientes con insuficiencia cardiaca. Nuestro objetivo fue valorar el impacto de la hiponatremia en la evolución de los pacientes sometidos a implante de desfibrilador en prevención primaria. Método: Se trata de un estudio observacional retrospectivo multicéntrico en el que se valoró la natremia periimplante y los eventos adversos (la mortalidad de cualquier causa y la cardiovascular, el primer ingreso por insuficiencia cardiaca, la primera terapia apropiada e inapropiada del desfibrilador), en una cohorte española sometida a implante de desfibrilador en la prevención primaria. Se comparó la hiponatremia ligera (Na ≤ 135 mEq/l) y la moderada-severa (Na ≤ 131 mEq/l) respecto a la ausencia de la hiponatremia. Resultados: Un total de 725 pacientes, con un valor medio de sodio en la sangre periimplante de 139 ± 3,6 mEq/l y un tiempo medio de seguimiento de 34,1 ± 18,5 meses. En los pacientes con Na ≤ 135 mEq/l (n = 105) se observó una mayor incidencia de primer ingreso por insuficiencia cardiaca (odds ratio: 1,701; p = 0,031). En los pacientes con hiponatremia moderada-severa (n = 18) se observó mayor mortalidad total (hazard ratio; 3,552; p = 0,002) y mayor mortalidad cardiovascular (hazard ratio: 4,24; p = 0,003). Ninguno de los grados de la hiponatremia estudiados se asoció con mayor incidencia de terapias apropiadas o inapropiadas. Conclusiones: La hiponatremia ligera en el momento del implante de un desfibrilador se asocia a una mayor incidencia de ingreso por insuficiencia cardiaca en el seguimiento, mientras que en el caso de una hiponatremia moderada-severa, se asocia a un riesgo de muerte 4 veces mayor.
Introduction and objectives: Hyponatremia is a prognostic factor in patients with heart failure. Our objective was to assess the impact of hyponatremia in the evolution of patients undergoing cardioverter implantation in primary prevention. Method: This is a multicenter retrospective observational study in which serum sodium periimplant and adverse events (all-cause and cardiovascular mortality, first admission for heart failure, first appropriate and inappropriate therapy) were assessed in a Spanish cohort receiving cardioverter in primary prevention. Patients with mild hyponatremia (Na ≤ 135 mEq/L) and those with moderate to severe hyponatremia (Na ≤ 131 mEq/L) were compared to those without hyponatremia. Results: 725 patients, with a mean value of sodium in blood peri-implant of 139 ± 3.6 mEq/L and a mean follow-up was 34.1 ± 18.5 months. In patients with Na ≤ 135 mEq/L (n = 105), an increased incidence of first admission for heart failure was observed (Odds Ratio: 1.701; P = .031). In patients with moderate to severe hyponatremia (n = 18), higher total mortality (Hazard Ratio: 3.552; P = .002) and increased cardiovascular mortality (Hazard Ratio: 4.24; P = .003) were observed. None of those values of hyponatremia were associated with increased incidence of appropriate or inappropriate therapies Conclusions: Mild hyponatremia at the time of cardioverter implantation is related with a higher incidence of hospitalization for heart failure during follow-up, while moderate to severe hyponatremia increases the risk of death during follow-up.
Assuntos
Humanos , Desfibriladores , Hiponatremia , Prevenção Primária , Insuficiência CardíacaRESUMO
The idea of an area of endemism implies that different groups of plants and animals should have largely coincident distributions. This paper analyses an area of 1152 000 km2 , between parallels 21 and 32°S and meridians 70 and 53°W to examine whether a large and taxonomically diverse data set actually displays areas supported by different groups. The data set includes the distribution of 805 species of plants (45 families), mammals (25 families), reptiles (six families), amphibians (five families), birds (18 families), and insects (30 families), and is analysed with the optimality criterion (based on the notion of endemism) implemented in the program NDM/VNDM. Almost 50% of the areas obtained are supported by three or more major groups; areas supported by fewer major groups generally contain species from different genera, families, or orders. © The Willi Hennig Society 2011.
RESUMO
La presión que ejerce el manguito del tubo orotraqueal (TOT) sobre la mucosa al ser insuflado debe mantenerse en un rango de seguridad que evite complicaciones por sobreinflación o por desinsuflación. En nuestro medio, los instrumentos de medición objetiva no son de uso común. Objetivo: evaluar la concordancia de la presión del manguito del TOT estimada por palpación frente al uso de un manómetro manual en pacientes adultos sometidos a anestesia general. Materiales y métodos: se realizó un estudio de corte transversal que incluyó a 40 pacientes, a quienes, una vez intubados, dos anestesiólogos enmascarados, diferentes al que los intubó, palparon el manguito del TOT categorizándolo como sobreinflado, normal o desinflado; posteriormente, uno de los investigadores registró la medida con un manómetro en fase inspiratoria y espiratoria. Se consideró como rango normal de 20 a 30 cm H2O. Resultados: la concordancia de la estimación por palpación entre los dos anestesiólogos fue débil (Kappa = 0,21, ES: 0,11). La concordancia entre la estimación por palpación y la medición con el manómetro manual fue muy débil. Entre el primer anestesiólogo y el investigador en fase inspiratoria, k 0,08 (ES: 0,09), y en espiración, k 0,08 (ES: 0,07). Entre el segundo anestesiólogo y el investigador, k 0,05 (ES: 0,07) y 0,02 (ES: 0,06), respectivamente. Conclusión: el estudio muestra que la concordancia entre los métodos subjetivo y objetivo para determinar si el manguito del TOT está adecuadamente inflado fue débil. Se sugiere el empleo de métodos más objetivos para su determinación.
The pressure exerted by the cuff of endotracheal tube (ETT) on the mucosa to be blown, should be kept in a safe range to avoid complications by on inflation or deflation. In our context, the objective measurement instruments are not commonly used. Objective: To evaluate the correlation between ETT cuff pressure estimated by palpation, and that obtained with a manual gauge in adult patients undergoing general anesthesia. Materials and methods: It was performed a cross-sectional study by obtaining the sample of adult patients undergoing general anesthesia requiring endotracheal intubation. We included forty patients who were intubated and then two blind anesthesiologists, other than the one who intubated, estimated insufflation of ETT cuff by palpation categorizing as over-inflated, normal or deflated. One of the observers subsequently, carried out the measurement of pressure with a manometer, both in inspiration and expiration. It was considered as normal pressure range 20 to 30 cm H2O. Results: The correlation of the estimation by palpation between the two anesthesiologists was weak (Kappa = 0.21, ES: 0.11). The correlation of the estimation by palpation and measurement with manual gauge was very weak. Between the first anesthesiologist and observers, in inspiration the k was 0.08 (ES: 0.09), in expiration was 0.08 (ES: 0.07), also between the second anesthesiologist and the observers, k 0.05 (ES: 0.07) and 0.02 (ES: 0.06) respectively. Conclusion: The study shows that the correlation between subjective and objective methods to determine if the cuff of ETT is properly inflated was weak. It suggests the use of more objective methods for its determination.
A pressão que exerce o manguito do tubo orotraqueal (TOT) sobre a mucosa ao ser insuflado deve manter-se em um rango de segurança que evite complicações por sobre inflação ou por desinsuflação. Em nosso meio, os instrumentos de medição objetiva não são de uso comum. Objetivo: avaliar a concordância da pressão do manguito do TOT estimada por palpação versus o uso de um manômetro manual, em pacientes adultos submetidos à anestesia geral. Materiais e métodos: realizou-se um estudo de corte transversal que incluiu 40 pacientes aos quais, uma vez intubados, dois anestesiologistas mascarados, diferentes ao que intubou, palparam o manguito do TOT categorizando-lhe como super-inflado, normal ou desinflado, posteriormente um dos pesquisadores registrou a medida com um manômetro em fase inspiratória e expiratória. Considerou-se como rango normal de 20 a 30 cmH2O. Resultados: a concordância da estimação por palpação entre os dois anestesiologistas foi fraca (kappa = 0.21, ES: 0.11). A concordância entre a estimação por palpação e s medição com o manômetro manual foi muito fraca. Entre o primeiro anestesiologista e o pesquisador em fase inspiratória, k 0.08 (ES: 0.09) e em expiratória, k 0.08 (ES: 0.07). Entre o segundo anestesiologista e o pesquisador k 0.05 (ES: 0.07) y 0.02 (ES: 0.06) respectivamente. Conclusão: o estudo mostra que a concordância entre os métodos subjetivo e objetivo para determinar se o manguito do TOT está adequadamente inflado foi fraco. Sugere-se o emprego de métodos mais objetivos para sua determinação.
Assuntos
Humanos , Intubação Intratraqueal , Palpação , Pressão , Valores de Referência , Estudos Transversais , Anestesia Geral , MucosaRESUMO
We describe a patient with a history of asthma and remote use of steroids the development of necrotizing fascitis due to Vibrio alginolyticus after an injury from a coral reef during bathing in the Caribbean Sea off Colombia. The patient recovered with aggressive surgical debridement and antibiotics.
Assuntos
Fasciite Necrosante/microbiologia , Imunocompetência , Traumatismos da Perna/complicações , Vibrioses/microbiologia , Vibrio/isolamento & purificação , Antozoários , Desbridamento , Feminino , Humanos , Pessoa de Meia-Idade , Água do Mar , NataçãoRESUMO
Las trisomías y en especial el Síndrome de Down es una anormalidad congénita común, con una serie de síntomas manifestaciones muy características que comprometen varios sistemas, muchos de estos posibles y necesarios de corregir quirúrgicamente durante el transcurso de la vida. El riesgo anestésico es más elevado en estos pacientes, por lo tanto haremos una revisión práctica de las implicaciones anestésicas cuidados perioperatorios requeridos para pacientes con este síndrome