Metabolic profiling of tryptophan pathways: Implications for obesity and metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: The rise in obesity highlights the need for improved therapeutic strategies, particularly in addressing metabolic dysfunction-associated steatotic liver disease (MASLD). We aim to assess the role of tryptophan metabolic pathways in the pathogenesis of obesity and in the different histological stages of MASLD. MATERIALS AND METHODS: We used ultra-high performance liquid chromatography to quantify circulating levels of 15 tryptophan-related metabolites from the kynurenine, indole and serotonin pathways. A cohort of 76 subjects was analysed, comprising 18 subjects with normal weight and 58 with morbid obesity, these last being subclassified into normal liver (NL), simple steatosis (SS) and metabolic dysfunction-associated steatohepatitis (MASH). Then, we conducted gene expression analysis of hepatic IDO-1 and kynyrenine-3-monooxygenase (KMO). RESULTS: Key findings in obesity revealed a distinct metabolic signature characterized by a higher concentration of different kynurenine-related metabolites, a decrease in indole-3-acetic acid and indole-3-propionic acid, and an alteration in the serotonin pathway. Elevated tryptophan levels were associated with MASLD presence (37.659 (32.577-39.823) µM of tryptophan in NL subjects; 41.522 (38.803-45.276) µM in patients with MASLD). Overall, pathway fluxes demonstrated an induction of tryptophan catabolism via the serotonin pathway in SS subjects and into the kynurenine pathway in MASH. We found decreased IDO-1 and KMO hepatic expression in NL compared to SS. CONCLUSIONS: We identified a distinctive metabolic signature in obesity marked by changes in tryptophan catabolic pathways, discernible through altered metabolite profiles. We observed stage-specific alterations in tryptophan catabolism fluxes in MASLD, highlighting the potential utility of targeting these pathways in therapeutic interventions.

Untargeted lipidomics analysis in women with morbid obesity and type 2 diabetes mellitus: A comprehensive study.

There is a phenotype of obese individuals termed metabolically healthy obese that present a reduced cardiometabolic risk. This phenotype offers a valuable model for investigating the mechanisms connecting obesity and metabolic alterations such as Type 2 Diabetes Mellitus (T2DM). Previously, in an untargeted metabolomics analysis in a cohort of morbidly obese women, we observed a different lipid metabolite pattern between metabolically healthy morbid obese individuals and those with associated T2DM. To validate these findings, we have performed a complementary study of lipidomics. In this study, we assessed a liquid chromatography coupled to a mass spectrometer untargeted lipidomic analysis on serum samples from 209 women, 73 normal-weight women (control group) and 136 morbid obese women. From those, 65 metabolically healthy morbid obese and 71 with associated T2DM. In this work, we find elevated levels of ceramides, sphingomyelins, diacyl and triacylglycerols, fatty acids, and phosphoethanolamines in morbid obese vs normal weight. Conversely, decreased levels of acylcarnitines, bile acids, lyso-phosphatidylcholines, phosphatidylcholines (PC), phosphatidylinositols, and phosphoethanolamine PE (O-38:4) were noted. Furthermore, comparing morbid obese women with T2DM vs metabolically healthy MO, a distinct lipid profile emerged, featuring increased levels of metabolites: deoxycholic acid, diacylglycerol DG (36:2), triacylglycerols, phosphatidylcholines, phosphoethanolamines, phosphatidylinositols, and lyso-phosphatidylinositol LPI (16:0). To conclude, analysing both comparatives, we observed decreased levels of deoxycholic acid, PC (34:3), and PE (O-38:4) in morbid obese women vs normal-weight. Conversely, we found elevated levels of these lipids in morbid obese women with T2DM vs metabolically healthy MO. These profiles of metabolites could be explored for the research as potential markers of metabolic risk of T2DM in morbid obese women.

Towards understanding post-COVID-19 condition: A systematic meta-analysis of transcriptomic alterations with sex-specific insights.

BACKGROUND: Post COVID-19 Condition (PCC), characterized by lingering symptoms post-acute COVID-19, poses clinical challenges, highlighting the need to understand its underlying molecular mechanisms. This meta-analysis aims to shed light on the transcriptomic landscapes and sex-specific molecular dynamics intrinsic to PCC. METHODS: A systematic review identified three studies suitable for comprehensive meta-analysis, encompassing 135 samples (57 PCC subjects and 78 recovered subjects). We performed meta-analysis on differential gene expression, a gene set enrichment analysis of Reactome pathways, and weighted gene co-expression network analysis (WGCNA). We performed a drug and disease enrichment analysis and also assessed sex-specific differences in expression patterns. KEY FINDINGS: A clear difference was observed in the transcriptomic profiles of PCC subjects, with 530 differentially expressed genes (DEGs) identified. Enrichment analysis revealed that the altered pathways were predominantly implicated in cell cycle processes, immune dysregulation and histone modifications. Antioxidant compounds such as hesperitin were predominantly linked to the hub genes of the DEGs. Sex-specific analyses highlighted disparities in DEGs and altered pathways in male and female PCC patients, revealing a difference in the expression of ribosomal proteins. PCC in men was mostly linked to neuro-cardiovascular disorders, while women exhibited more diverse disorders, with a high index of respiratory conditions. CONCLUSION: Our study reveals the intricate molecular processes underlying PCC, highlighting that the differences in molecular dynamics between males and females could be key to understanding and effectively managing the varied symptomatology of this condition.

SARS-CoV-2 tropism to intestinal but not gastric epithelial cells is defined by limited ACE2 expression.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affects the lung but can also cause gastrointestinal (GI) symptoms. In vitro experiments confirmed that SARS-CoV-2 robustly infects intestinal epithelium. However, data on infection of adult gastric epithelium are sparse and a side-by-side comparison of the infection in the major segments of the GI tract is lacking. We provide this direct comparison in organoid-derived monolayers and demonstrate that SARS-CoV-2 robustly infects intestinal epithelium, while gastric epithelium is resistant to infection. RNA sequencing and proteome analysis pointed to angiotensin-converting enzyme 2 (ACE2) as a critical factor, and, indeed, ectopic expression of ACE2 increased susceptibility of gastric organoid-derived monolayers to SARS-CoV-2. ACE2 expression pattern in GI biopsies of patients mirrors SARS-CoV-2 infection levels in monolayers. Thus, local ACE2 expression limits SARS-CoV-2 expression in the GI tract to the intestine, suggesting that the intestine, but not the stomach, is likely to be important in viral replication and possibly transmission.

Características clínico epidemiológicas de los pacientes con debilidad muscular aguda atendidos en el Instituto Nacional de Salud del Niño desde Enero hasta Diciembre del 2008 / Clinical epidemiological characteristics of patients with acute muscle weakness Unserved in the National Institute of Child Health from January to December 2008

La Debilidad muscular aguda (DMA) constituye la pérdida de fuerza muscular más o menos generalizada que se instaura en el transcurso de pocas horas o días y siempre antes de cuatro semanas. Este síndrome puede ser debido a una larga lista de enfermedades y se presenta con relativa frecuencia, especialmente en las áreas de urgencias, pudiendo llegar a constituir una emergencia médica. El objetivo de este estudio fue determinar la incidencia y las características clínicas y epidemiológicas de los pacientes con diagnóstico de debilidad muscular aguda, que hayan sido atendidos en el servicio de emergencias del Instituto Nacional del Niño, entre enero y diciembre del año 2008. Se realizó un estudio de carácter descriptivo y retrospectivo, consistente en la revisión de historias clínicas de pacientes con diagnóstico de Debilidad Muscular Aguda hospitalizados en el INSN durante el mes de Enero hasta Diciembre del año 2008. Se utilizaron criterios de inclusión (edad hasta 17 años, debilidad muscular progresiva) y exclusión (Astenia, síndromes atáxicos, impotencia funcional y hemiplejia) aguda para la de datos en la ficha diseñada para tal fin. Se realizó un cruce de variables en tablas de doble entrada. El análisis descriptivo se realizó en medidas de tendencia central, de posición y de variabilidad. De un total de 27 pacientes con diagnóstico de DMA, el 47 por ciento tuvo como diagnóstico polirradiculoneuropatía inflamatoria desmielinizante aguda o Síndrome de Guillain Barré(predominando en varones), el síndrome de debilidad muscular fue la segunda enfermedad más frecuente con 14 por ciento y con 11 por ciento otras polineuropatías. La moda calculada en este estudio fue 8 y la mediana resultó de 6,5...

The acute muscular weakness constitutes the loss of muscle strength that is established in the course of a few hours or days and always within four weeks. This syndrome can be due to a several kinds of diseases and appears with relative frequency, especially in urgencies, being able to constitute a medical emergency. The aim of this study was to determine the incidence and clinical and epidemiological characteristics of patients with acute muscle weakness, which have been treated in the emergency department of the National ChildrenÆs Institute, from January to December 2008. There was realized a study of character descriptive and retrospective, consisting of the review of patient's clinical histories by diagnosis of Acute Muscular Weakness hospitalized in the INSN during January until December 2008. There were in use criteria of incorporation (age up to 17 years, muscular progressive weakness) and exclusion (Debility, ataxic syndromes, functional impotence and acute hemiplegic) for that of information in the card designed for such purpose. A crossing variable was realized in tables of double entry, The descriptive analysis was realized in measures of central trend; of position and of variability. 27 patients of al/, with diagnosis of DMA, 47 per cent was diagnose with Guillain Barré's Syndrome as a diagnosis polirradiculoneuropathy (prevailing in males), the syndrome of muscular weakness was the most frequent second disease with 14 per cent an with 11 per cent other polineuropathies: The mode calculated in t. study was 8 and the median ensued from 6,5...

Caracterízación clínica y epidemiológica de la malaria en una comunidad endémica de Honduras / Clinical and epidemiological characterization of malaria in an endemic community of Honduras

Objetivo. Identificar las características clinicas y epidemiológicas asociadas al diagnóstico microscópico de malaria en pacientes febriles atendidos en el Centro de Salud de Palacios, La Mosquitia. METODOLOGIA. Durante 17 semanas (Noviembre 1999-Marzo 2000), se evaluaron 115 individuos en los cuáles se formuló diagnóstico clínico que incluyó tres categorías: paroxismo malárico, malaria probable y malaria improbable. Se obtuvo gota gruesa.RESULTADOS: Se identificaron parásitos en 34 pacientes(29.6%), 28 (82.4%) Plasmidium vivax y 6 (17.6%) P. falciparum. No se encontró diferencia estadísticamente significativa en la distribución de casos gota gruesa positiva y negativa con relación a edad, sexo, procedencia, antecedente de malaria, y evolución de síntomas. Malestar general (p= 0.004) y esplenomegalia (p=0.002) se asociaron significativamente al diagnóstico confirmado de malaria, y la tos sugirió asociación con gota gruesa negativa. El diagnóstico clinico de malaria demostró una tendencia linear significativa de asociación de gota gruesa positiva (p=0.003). La mayoría de los pacientes presentaron parasitemia baja moderada (70.6%). No se encontró asociación entre la intensidad de la parasitemia y edad, sexo, antecedente de malaria y diagnóstico clínico. CONCLUSIONES: Aunque diagnóstico clínico de la malaria es inespecífico, se deben hacer esfuerzos para optimizar los criterios del diagnóstico de acuerdo a la dinámica de transmisión local y con un enfoque esosistemático...

Malaria: infección subclínica entre escolares en la comunidad de Palacios, la Mosquitia / Malaria: subclinical infection among school children in Palacios, Mosquito Coast

Basados en la detección pasiva de casos de malaria en aproximadamente un tercio de los pacientes febriles atendidos en el Centro de Salud de los Palacios, La Mosquitia, en un período de 17 semanas, se propuso realizar una búsqueda activa entre escolares con el objetivo de detectar infecciones subclínicas. Se explicó el propósito del estudio al personal de la Escuela Marco Aurelio Soto y a varios padres de familia. Durante dos días de trabajo, se entrevistaron y se examinaron los niños que asistieron a clases. Se tomó muestra de sangre por pinchazo del dedo para gota gruesa. Se estudiaron 146 niños, 75 (51.4 por ciento) del sexo masculino, distribuidos en proporción similar en los grupos etáreos de 5-9 años y 10-15 años. Ninguno de los niños informó estar enfermo y todos estaban afebriles al momento de examinarlos. Se detectó esplenomegalia leve en 21 casos (14.4 por ciento). Se demostró plasmodium vivax en dos niños para una prevalencia del 1.4 por ciento (IC 95 por ciento 0.2-4.9). Los resultados indican que en esta región del pais la intensidad de transmisión de la malaria es suficiente para producir infecciones subclínicas. Debido a que las actividades de control y prevención están dirigidas a casos febriles, las infecciones subclínicas contribuyen a mantener la transmisión

Enfermedad de Lyme en Chile: estudio de prevalencia en grupos seleccionados / Lyme's disease in Chile: prevalence study in selected groups

The prevalence of Lyme disease in Chile is unknown. To study the existence and epidemiology of Lyme Disease in Chile. One hundred eighteen patients with signs or symptoms suggestive of Lyme disease were studied. Antibodies against Borrelia burgdorferi were measured using ELISA and indirect immunofluorescence screening tests. Positive cases were confirmed with ELISA using a purified antigen and Western Blot analysis. Human biological samples and ticks were cultured in BSK-H medium. Five patients, 3 with dermatological manifestations and two with facial palsy and other neurological symptoms, had antibodies against Borrelia, measured by ELISA and indirect immunofluorescence. However, the presence of IgM antibodies by ELISA using purified antigen, was confirmed in only one case. All sera and cerebrospinal fluids were negative on Western Blot analysis. No plasma, skin, CFS or thick culture yielded Borrelia. We could not confirm the existence of Lyme disease in Chile. Positive screening with negative confirmatory test suggests false positive non-specific reactivity or that local Borrelia are antigenically different compared to North American strains

Influencia de la preparacion sicofisica en la recuperacion postquirurgica de los ninos de cinco a trece anos sometidos a cirugia ambulatoria en el Instituto de Salud de Bucaramanga: propuesta metodologica para el programa educativo / Influenece of psychophysical preparation on postoperative recovering of children from five to thirdteen years submmited to ambulatory surgery in Instituto de Salud, Bucaramanga: methodological proposal for educational program

Basado en un estudio anterior que demostro los beneficios de la educacion preoperatoria para reducir el temor y la ansiedad de los ninos entre 5 y 13 anos sometidos a amigdalectomia, circuncision o herniorrafia ambulatoria se propone un programa de educacion preoperatoria tendiente a lograr la participacion del paciente y de sus padres en el cuidado perioperatorio. El programa contempla los aspectos administrativos y educacionales necesarios para su implementacion en un centro de cirugia ambulatoria. Presenta el diseno de folletos y guiones para titeres en los cuales se explica al nino la anatomia y la fisiologia del cuerpo humano, la relacion medico - paciente y enfermera - paciente, los eventos del proceso diagnostico y la evolucion postoperatoria. Se describen los contenidos de las charlas educativas sobre la necesidad de la operacion, los cuidados perioperatorios en los ambitos institucional y del hogar y los cuidados generales del nino

Influencia de la preparacion sicofisica en la recuperacion postquirurgica de los ninos de cinco a trece anos sometidos a cirugia ambulatoria en el Instituto Quirurgico de Bucaramanga: mayo - julio 1989 / Influence of psychophysiological preparation on postsurgical recovering of children from five to thirdteen years submmited to ambulatory surgery in Instituto Quirurgico, Bucaramanga: May - July 1989

Se realizo un estudio ex[perimental en un grupo de 24 ninos de 5-13 anos sometidos a cirugias ambulatorias en el Instituto Quirurgico de Bucaramanga, durante 3 mese, evaluando la influencia de la preparacion sicofisica en la recuperacion postoperatoria. Por muestreo aleatorio simple se asigno el grupo experimental al cual se dio preparacion especial para cirugia y el grupo de control que recibio la preparacion tradicional. Se hizo seguimiento en el preoperatorio mediato e inmediato y en el postoperatorio mediato y tardio para establecer la variaciones fisicas (infeccion y recuperacion) y sicologicas (temor, ansiedad, ira) presentadas por efecto o no de la preparacion. En el grupo experimental se disminuyeron en alto grado las alteraciones sicofisicas en relacion al grupo de control. Los cambios mas notorios se observaron en el preoperatorio inmediato para la variable ira, pasando de un 100 por ciento a un 16.6 por ciento en el grupo experimental y una disminucion discreta en el grupo de control de 91.6 por ciento a 66.6 por ciento . La ansiedad aumento en el grupo de control pasando de un 50 por ciento a un 91.6 por ciento ; mientras que en el grupo experimental disminuyo de 41.6 por ciento a 8.3 por ciento . En la tercera semana postquirurgica, el 100 por ciento de los pacientes del grupo experimental se recupero a diferencia del grupo control en el cual la recuperacion fue solo de un 75 por ciento , debido posiblemente a la poca informacion del familiar responsable del nino ya que se presento infeccion y limitacion de movimiento en 3 casos. Los resultados y las pruebas estadististicas realizadas, sugieren que la preparacion sicofisica disminuye la presencia de..