TP53INP2-dependent activation of muscle autophagy ameliorates sarcopenia and promotes healthy aging.

Sarcopenia is a major contributor to disability in older adults, and thus, it is key to elucidate the mechanisms underlying its development. Increasing evidence suggests that impaired macroautophagy/autophagy contributes to the development of sarcopenia. However, the mechanisms leading to reduced autophagy during aging remain largely unexplored, and whether autophagy activation protects from sarcopenia has not been fully addressed. Here we show that the autophagy regulator TP53INP2/TRP53INP2 is decreased during aging in mouse and human skeletal muscle. Importantly, chronic activation of autophagy by muscle-specific overexpression of TRP53INP2 prevents sarcopenia and the decline of muscle function in mice. Acute re-expression of TRP53INP2 in aged mice also improves muscle atrophy, enhances mitophagy, and reduces ROS production. In humans, high levels of TP53INP2 in muscle are associated with increased muscle strength and healthy aging. Our findings highlight the relevance of an active muscle autophagy in the maintenance of muscle mass and prevention of sarcopenia.Abbreviation: ATG7: autophagy related 7; BMI: body mass index; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ROS: reactive oxygen species; TP53INP2: tumor protein p53 inducible nuclear protein 2; WT: wild type.

Splice variants of mitofusin 2 shape the endoplasmic reticulum and tether it to mitochondria.

In eukaryotic cells, different organelles interact at membrane contact sites stabilized by tethers. Mitochondrial mitofusin 2 (MFN2) acts as a membrane tether that interacts with an unknown partner on the endoplasmic reticulum (ER). In this work, we identified the MFN2 splice variant ERMIT2 as the ER tethering partner of MFN2. Splicing of MFN2 produced ERMIT2 and ERMIN2, two ER-specific variants. ERMIN2 regulated ER morphology, whereas ERMIT2 localized at the ER-mitochondria interface and interacted with mitochondrial mitofusins to tether ER and mitochondria. This tethering allowed efficient mitochondrial calcium ion uptake and phospholipid transfer. Expression of ERMIT2 ameliorated the ER stress, inflammation, and fibrosis typical of liver-specific Mfn2 knockout mice. Thus, ER-specific MFN2 variants display entirely extramitochondrial MFN2 functions involved in interorganellar tethering and liver metabolic activities.

[Takayasu's disease: an underdiagnosed entity in Sub-Saharan Africa. Report of five Gabonese cases]. / Maladie de Takayasu : une entité sous-diagnostiquée en Afrique Subsaharienne. À propos de cinq observations gabonaises.

Background: Takayasu's disease (TM) is a vasculitis of the aorta and its main branches, Infectious diseases, especially Mycobacterium tuberculosis, can be a trigger for the development of TM by a hypersensitivity reaction, but paradoxically very few cases of the disease are reported in the literature review. Materials and methods: Through a retrospective study carried out in the departments of internal medicine and cardiology of the Centre hospitalier universitaire de Libreville (CHUL) in Gabon, we identified all the observations of TM diagnosed in the said departments from 03/2014 to 05/2022, and rediscussed them on the basis of the criteria of Sharma et al. of 1996. Results: Five patients (3 men, 2 women), with an average age of 38.4 years were found. 2/5 patients reported a history of pulmonary tuberculosis. There was a change in general condition (n=4), fever (n=2), arterial hypertension (n=4), a decrease in the radial pulse (n=2), rheumatological manifestations (n=3), involvement of the serous membranes (n=3). CRP was positive (n=4), and HIV1,2 serology negative (n=5). Echocardiography found pulmonary arterial hypertension (n=1), constrictive pericarditis (n=1) and valvular involvement (minimal aortic insufficiency) (n=1), and typing of aortic involvement by computed tomography or CT angiography staged Takayasu's disease as type IIa (n=2), IIb (n=2) and IV (n=1). The patients were treated with oral corticosteroid therapy (n=5) combined with methotrexate (n=4) and azathioprine (n=1). Discussion: The criteria of Sharma et al. from 1996, suggest a high probability of TM with a sensitivity of 92.5% and a specificity of 95%. In sub-Saharan Africa, TM requires the elimination of certain differential diagnoses, particularly syphillis, tuberculosis, salmonellosis, and atherosclerosis. Corticosteroid therapy (coupled with immunosuppressive treatment) remains effective, allowing significant remission of the disease, but comes up against the risk of opportunistic infections. Conclusion: There is a contrast between the involvement of Mycobacterium tuberculosis in the etiopathogenesis of TM on the one hand and the endemic nature of tuberculosis on the African continent on the other hand; which contrasts with the few cases reported in sub-Saharan Africa.

Coordination of mitochondrial and lysosomal homeostasis mitigates inflammation and muscle atrophy during aging.

Sarcopenia is one of the main factors contributing to the disability of aged people. Among the possible molecular determinants of sarcopenia, increasing evidences suggest that chronic inflammation contributes to its development. However, a key unresolved question is the nature of the factors that drive inflammation during aging and that participate in the development of sarcopenia. In this regard, mitochondrial dysfunction and alterations in mitophagy induce inflammatory responses in a wide range of cells and tissues. However, whether accumulation of damaged mitochondria (MIT) in muscle could trigger inflammation in the context of aging is still unknown. Here, we demonstrate that BCL2 interacting protein 3 (BNIP3) plays a key role in the control of mitochondrial and lysosomal homeostasis, and mitigates muscle inflammation and atrophy during aging. We show that muscle BNIP3 expression increases during aging in mice and in some humans. BNIP3 deficiency alters mitochondrial function, decreases mitophagic flux and, surprisingly, induces lysosomal dysfunction, leading to an upregulation of Toll-like receptor 9 (TLR9)-dependent inflammation and activation of the NLRP3 (nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)-, and pyrin domain-containing protein 3) inflammasome in muscle cells and mouse muscle. Importantly, downregulation of muscle BNIP3 in aged mice exacerbates inflammation and muscle atrophy, and high BNIP3 expression in aged human subjects associates with a low inflammatory profile, suggesting a protective role for BNIP3 against age-induced muscle inflammation in mice and humans. Taken together, our data allow us to propose a new adaptive mechanism involving the mitophagy protein BNIP3, which links mitochondrial and lysosomal homeostasis with inflammation and is key to maintaining muscle health during aging.

Prevalence of smoking in a psychiatric hospital and its relationship with respiratory symptoms and the prevalence of COPD.

Purpose: Psychiatric patients present an elevated rate of smoking, and the smoking habit is related to a high morbidity and mortality in this collective. The aim of this study was to determine the prevalence of smoking in patients admitted for psychiatric disorders and its relationship with respiratory disease, the prevalence of COPD, and alterations in the quality of life. Patients and methods: A cross-sectional, observational study was conducted and detailed information on smoking and respiratory symptomatology was obtained. The study participants underwent the following tests: spirometry with bronchodilator test, Fagerström test, determination of physical activity using the LCADL questionnaire, and evaluation of quality of life with the EuroQoL-5 Dimensions EQ-5D questionnaire. Results: Two hundred seventy-six patients (mean age 56.8 years) were included: 155 with schizophrenia (87.7% smokers), 46 with depressive or anxiety disorders (54.3% smokers), and 49 and 25 with intellectual disability and dementia (43.2% smokers), respectively. The mean Fagerström test score was 5.75 points. Smokers presented with cough (47.6%), expectoration (41.4%), and chronic bronchitis (36.6%). The prevalence of COPD in the total population was 28.9%. The EQ-5D and LCADL scores were better in smokers because of their younger age and lesser psychiatric involvement. A high prevalence of smoking was observed in the psychiatric population studied, and 28.9% were diagnosed with COPD. Conclusion: Smokers presented many more respiratory symptoms and chronic bronchitis but did not present a worse quality of life or physical activity due to their younger age and milder psychiatric involvement.

Value of procalcitonin, C-reactive protein, and neopterin in exacerbations of chronic obstructive pulmonary disease.

OBJECTIVE: The identification of biological markers in order to assess different aspects of COPD is an area of growing interest. The objective of this study was to investigate whether levels of procalcitonin (PCT), C-reactive protein (CRP), and neopterin in COPD patients could be useful in identifying the etiological origin of the exacerbation and assessing its prognosis. METHODS: We included 318 consecutive COPD patients: 46 in a stable phase, 217 undergoing an exacerbation, and 55 with pneumonia. A serum sample was collected from each patient at the time of being included in the study. A second sample was also collected 1 month later from 23 patients in the exacerbation group. We compared the characteristics, biomarker levels, microbiological findings, and prognosis in each patient group. PCT and CRP were measured using an immunofluorescence assay. Neopterin levels were measured using a competitive immunoassay. RESULTS: PCT and CRP showed significant differences among the three patient groups, being higher in patients with pneumonia, followed by patients with exacerbation (P < 0.0001). For the 23 patients with paired samples, PCT and CRP levels decreased 1 month after the exacerbation episode, while neopterin increased. Neopterin showed significantly lower levels in exacerbations with isolation of pathogenic bacteria, but no differences were found for PCT and CRP. No significant differences were found when comparing biomarker levels according to the Gram result: PCT (P = 0.191), CRP (P = 0.080), and neopterin (P = 0.109). However, median values of PCT and CRP were high for Streptococcus pneumoniae, Staphylococcus aureus, and enterobacteria. All biomarkers were higher in patients who died within 1 month after the sample collection than in patients who died later on. CONCLUSIONS: According to our results, biomarker levels vary depending on the clinical status. However, the identification of the etiology of infectious exacerbation by means of circulating biomarkers is encouraging, but its main disadvantage is the absence of a microbiological gold standard, to definitively demonstrate their value. High biomarker levels during an exacerbation episode correlate with the short-term prognosis, and therefore their measurement can be useful for COPD management.

Usefulness of mid regional pro-atrial natriuretic peptide in the exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: A recent approach for the management of chronic obstructive pulmonary disease (COPD) is the measurement of systemic biomarkers. The aim of this study was to evaluate the usefulness of mid regional pro-atrial natriuretic peptide (MR-proANP) to predict short and long term prognosis. METHODS: We included 318 COPD patients: 46 in a stable phase, 217 undergoing an exacerbation and 55 with pneumonia. Serum samples were collected at admission. For 20 exacerbated patients, we also collected a second sample one month later. MR-proANP was measured by an inmunofluorescent assay. RESULTS: Statistically higher levels of MR-proANP were found in patients with pneumonia when comparing to patients in the stable state (p=0.031). For those patients with paired samples, MR-proANP decreased statistically one month later (p=0.027). MR-proANP showed significant lower levels in exacerbations with isolation of pathogenic bacteria (p=0.011). MR-proANP levels were higher in patients that died within one month, decreasing as long as the moment of death occurred later on (p=0.163). CONCLUSIONS: The identification of exacerbation etiology by means of MR-proANP is not clinically reliable. Levels of MR-proANP vary depending on the clinical status, being higher during pneumonia in comparison to the stable state. MR-proANP levels were higher in patients that died within one month after the exacerbation episode.

Impacto de la implementación de medidas de gestión hospitalaria para aumentar la eficiencia en la gestión de camas y disminuir la saturación del servicio de urgencias / Impact of hospital management measures on improving the efficiency of bed allocation and reducing emergency department overcrowding

Objetivo: Analizar el impacto de la implementación de medidas para reducir el número de pacientes ubicados en urgencias en es pera de cama de hospitalización. Método: Tipo de estudio: comparativo con un análisis retrospectivo. Se compararon dos periodos: periodo 1 (nov 06-oct 07) y periodo 2 (nov 07-oct 08). Ámbito: Hospitalde Sant Boi, hospital general de 126 camas, en Sant Boi de Llobregat (Barcelona). Medidas implementadas: disminución de la estancia prequirúrgica, incremento de la cirugía mayor ambulatoria (CMA) y potenciación del ingreso en una unidad de corta estancia médica (UCE). Variables estudiadas: admisiones en el SUH, ingresos hospitalarios, ingresos de CMA, el número de días en que hay al menos 1 paciente pendiente de cama hospitalaria en el SUH a las 8:00 horas, estancia promedio hospitalaria, actividad y estancia promedio en la UCE. Resultados: El total de admisiones en el SUH fue de 57.140 en el periodo 1, y 71.280 en el periodo 2, con 4.840 (8,4%) y 5.385 (7,5%) ingresos, respectivamente. La estancia media de hospitalización disminuyó de 5,2 días a 4,5 días (p < 0,001). En 86 días del periodo 1, uno o más pacientes permanecían en el SUH pendientes de cama (307 pacientes/año), frente a 11 días en el período 2 (26 pacientes/año). Conclusiones: En nuestra experiencia, las medidas de gestión aplicadas fueron eficaces en la disminución del número de pacientes pendientes de cama en urgencias (AU)

Objective: To analyze the impact of hospital management measures to reduce the number of patients held in an emergency department while awaiting admission. Methods: Type of study: retrospective, comparing 2 periods, November 2006 to October 2007 and November 2007 to October 2008. Setting: Hospital de Sant Boi, a 126-bed general hospital in Sant Boi de Llobregat in the province of Barcelona. Management measures: decreased presurgical stay, increased use of ambulatory surgical procedures, and increased use of a medical short-stay unit. Variables studied: emergency department admissions, hospital ward admissions, admissions for ambulatory surgical procedures, number of days in which at least 1 patient was in the emergency department at 8 A.M. while waiting for a bed, mean hospital stay, and admissions and average time spent in the short-stay unit. Results: A total of 57140 patients were admitted to the emergency department in the first period and 71280 in the second period; 4840 (8.4%) were admitted to hospital in the first period and 5385 (7.5%) in the second. The average length of stay was 5.19 days in the first period and 4.54 days in the second (P<.001). At least 1 patient was waiting in the emergency department for a hospital bed to become available on 86 days in the first period (307 patients/year) and11 days in the second period (26 patients/year). Conclusions: The management measures applied in this case were effective in reducing the number of patients held in the emergency department while waiting for admission (AU)

Utility of pneumococcal urinary antigen detection in diagnosing exacerbations in COPD patients.

The aim of this study was to evaluate the utility of pneumococcal urinary antigen detection (Binax Now Streptococcus pneumoniae Antigen Test) in diagnosing pneumococcal exacerbation of chronic obstructive pulmonary disease (COPD). Forty-six patients with S. pneumoniae isolation in sputum culture were studied (29 collected in stable period and 17 collected during exacerbation). In the 29 patients with samples collected in a stable period the antigen was detected in 3 cases (10.3%) using nonconcentrated urine (NCU), and in 12 cases (41.4%) using concentrated urine (CU). Regarding patients recruited during an exacerbation period, the antigen was detected in 3 cases (17.6%) using NCU, and in 13 cases (76.5%) when CU was used. For the evaluation of the specificity of the ICT test we also tested 72 cases in which pneumococcus was not isolated in the sputum sample. ICT was positive in 1NCU and 9CU of these patients. To have had at least one previous exacerbation (P=0.024), at least one exacerbation that required hospitalization (P=0.027), and a pneumonia episode in the year before (P=0.010) had statistically significant associated with the detection of specific antigen in CU. Using NCU, the only significant association was found when a previous pneumonia in the year before had occurred (P=0.006). In summary, a positive result of pneumococcal urinary antigen from a COPD patient, in both bronchial exacerbation and pneumonia, should be evaluated with caution because the antigen detected could be related with previous infectious episode.

Comunicación interventricular y estenosis subaórtica: presentación de caso / Intraventricular shunt and subaortic stenosis: a case report

Se presenta un paciente en edad pediátrica con el diagnóstico de comunicación interventricular y estenosis subaortica, se reportan pocos casos en la literatura mundial de la asociación de estas dos anomalías congénitas cardiovasculares. La ecocardiografía se ha convertido en la herramienta principal en el diagnostico de las cardiopatías desde la etapa prenatal, es un método accesible, seguro y especifico para el estudio de estas entidades. Se realiza esta revisión haciendo énfasis en el diagnóstico ecocardiografico de ambas entidades y de su asociación, para poner a consideración del personal especializado que valora esta temática toda la información teórica sobre el tema en cuestión(AU)

Fibrosarcoma de partesblandas: diagnóstico imagenológico: presentación de caso / Fibrosarcoma of soft parts: imagenological diagnosis: a case report

Los tumores de partes blandas son aquellos procesos tumorales mesenquimales malignos que se originan en los tejidos no epiteliales extraesqueléticos, aunque se excluye el sistema reticuloendotelial, la glía y los tejidos de soporte de algunos órganos parenquimatosos. Son localmente agresivos, con capacidad invasiva o de crecimiento destructivo, de recurrencia y de metástasis a distancia, por lo que requieren de una cirugía radical para asegurar una exéresis completa.La rareza de estos tumores en su incidencia clínica hace que la experiencia en este campo sea muy limitada. Actualmente permanece siendo una enfermedad muy difícil de vencer. Tomando como base la agresividad de este tumor y la demora en el diagnóstico, se justifica entonces nuestro interés en proponer a continuación la presentación de un caso que precisó de la realización de varios estudios imagenológicos, con un diagnóstico tardío y un desenlace fatal(AU)

Eventración Diafragmática: presentación de caso / Diaphragmatic eventration: a case report

Se presenta un paciente adulto con el diagnóstico de eventración diafragmática, existen varios casos reportados en la literatura mundial de esta patología y se considera una de las patologías diafragmáticas mas frecuentes, además de las Hernias Diafragmáticas. Aparece como resultado de una elevación permanente del hemidiafragma sin solución de continuidad y sin modificaciones de las inserciones o revestimientos serosos Se realiza esta revisión haciendo énfasis en el diagnóstico imagenologico de esta entidad para poner a consideración del personal especializado que valora esta temática toda la información teórica sobre el tema en cuestión(AU)