Connecting genomic and proteomic signatures of amyloid burden in the brain.

Background: Alzheimer's disease (AD) has a high heritable component characteristic of complex diseases, yet many of the genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may be helpful to understand the underlying biology of the disease. Methods: We performed a meta-analysis of GWAS of CSF Aß42 and PET measures combining six independent cohorts (n=2,076). Due to the opposite effect direction of Aß phenotypes in CSF and PET measures, only genetic signals in the opposite direction were considered for analysis (n=376,599). Polygenic risk scores (PRS) were calculated and evaluated for AD status and amyloid endophenotypes. We then searched the CSF proteome signature of brain amyloidosis using SOMAscan proteomic data (Ace cohort, n=1,008) and connected it with GWAS results of loci modulating amyloidosis. Finally, we compared our results with a large meta-analysis using publicly available datasets in CSF (n=13,409) and PET (n=13,116). This combined approach enabled the identification of overlapping genes and proteins associated with amyloid burden and the assessment of their biological significance using enrichment analyses. Results: After filtering the meta-GWAS, we observed genome-wide significance in the rs429358-APOE locus and nine suggestive hits were annotated. We replicated the APOE loci using the large CSF-PET meta-GWAS and identified multiple AD-associated genes as well as the novel GADL1 locus. Additionally, we found a significant association between the AD PRS and amyloid levels, whereas no significant association was found between any Aß PRS with AD risk. CSF SOMAscan analysis identified 1,387 FDR-significant proteins associated with CSF Aß42 levels. The overlap among GWAS loci and proteins associated with amyloid burden was very poor (n=35). The enrichment analysis of overlapping hits strongly suggested several signalling pathways connecting amyloidosis with the anchored component of the plasma membrane, synapse physiology and mental disorders that were replicated in the large CSF-PET meta-analysis. Conclusions: The strategy of combining CSF and PET amyloid endophenotypes GWAS with CSF proteome analyses might be effective for identifying signals associated with the AD pathological process and elucidate causative molecular mechanisms behind the amyloid mobilization in AD.

A Case Series and Literature Review of Subacute Infective Endocarditis: A Clinical Challenge.

Endocarditis is a life-threatening, relatively rare disease caused by an infection of the endocardial epithelium of the heart. Its clinical presentation is highly variable, depending on whether it presents acutely, subacutely, or chronically. Also, the wide array of causal etiologies and pathogens makes its diagnosis and treatment complex and challenging. The main etiological agents are Staphylococci and Streptococci, while fastidious microorganisms are infrequent agents of this pathology. Advancements in the identification of microorganisms with novel molecular techniques have revealed new previously unidentified pathogens. Despite their low frequency, these fastidious pathogens are highly relevant, as they have been associated with a higher rate of complications and mortality. Therefore, it is necessary to be aware of the wide array of clinical presentations and important considerations for the management of patients with subacute endocarditis with atypical microorganisms. In this article, we present a case series involving three different clinical presentations of subacute endocarditis with fastidious microorganisms, which required extensive medical management and surgical valve repair with favorable and unfavorable outcomes. We also engage in a review of the literature on their microbiology, diagnosis, and treatment.

Impacto de la rehabilitación cardiopulmonar en paciente con secuelas poscovid-19 Reporte de caso clínico

El SARS-CoV-2 es un virus de la familia Coronaviridae que posee un ácido ribonucleico envuelto y monocatenario positivo. Este virus ha sido el responsable de una suma considerable de muertes a nivel mundial, y produce la enfermedad llamada covid-19, esta ocasiona compromisos multisistémicos en los pacientes, de los cuales la gran mayoría resulta con secuelas en el músculo esquelético, cardiocirculatorias, y pulmonares. La rehabilitación cardiopulmonar es un programa con múltiples componentes que pueden revertir las condiciones fisiopatológicas que sean consecuencias por el virus SARS-CoV-2. Los autores describen su experiencia con un caso clínico, con un paciente de 53 años, que ameritó internamiento por más de un mes, con diagnóstico de covid-19 -neumonía de focos múltiples con sobreinfección bacteriana-, y que durante su estadía requirió ventilación mecánica asistida, eventualmente, con traqueostomía, y que a su egreso se mantenía con dependencia de oxígeno suplementario, así como marcada disnea y sarcopenia. El paciente fue referido para rehabilitación pulmonar poscovid-19, y tras 12 semanas de rehabilitación el paciente es egresado del programa en aire ambiente, con capacidad para realizar ejercicio de moderada a alta intensidad, con saturación superior a 95 %, además de una marcada mejoría en los resultados de capacidad funcional. La rehabilitación cardiopulmonar es un programa multifacético, con diferentes componentes que logran una atención integral, capaz de recuperar al paciente para que logre su adherencia, no solo en su estado físico, sino también en su entorno psicosocial, de tal manera que se reintegra a la sociedad y se disminuyen los costos por atención y tratamientos médicos.

Summary SARS-CoV-2 is a virus of the Coronaviridae family, which has a positive single-stranded, enveloped ribonucleic acid. This virus has been responsible for a considerable number of deaths worldwide, and produces the disease called covid-19, which causes multisystemic compromise in patients, resulting in a vast majority with skeletal muscle, cardiocirculatory, and pulmonary sequelae. Cardiopulmonary rehabilitation is a program with multiple components that can reverse the pshysiopathological conditions that are consequences of the SARS-CoV-2 virus. The authors describe their experience with a clinical case, a 53-year-old patient, who required hospitalization for more than a month, diagnosed with covid-19 -Multiple focus of pneumonia with bacterial infection-, and who required ventilation during hospitalization. mechanically assisted, eventually with tracheostomy, and that at discharge remained dependent on supplemental oxygen, as well as marked dyspnea and sarcopenia. The patient was referred for postcovid-19 pulmonary rehabilitation, and after 12 weeks of rehabilitation the patient is discharged from the program in room air, with the ability to perform moderate to high intensity exercise, saturation greater than 95%, and with marked improvement. in VO2 max and 6MWT results. Cardiopulmonary rehabilitation is a multifaceted program, with different components that achieve comprehensive care, capable of recovering the patient so that he achieves his adherence, not only in his physical state but also in his psychosocial environment, reintegrating him into society and reducing the costs for medical care and treatment.

Laparoscopic Roux-en-Y gastric bypass as a revision procedure after restrictive bariatric surgery.

BACKGROUND: Adjustable gastric banding (AGB) and vertical banded gastroplasty (VBG) have been extensively used to treat morbid obesity. Patients with insufficient weight loss or complications may require surgical revision. The laparoscopic Roux-en-Y gastric bypass (LRYGBP) is one of the most common procedures currently used for revision. The aim of the study was to analyze surgical outcomes of 30 consecutive patients who underwent revision to LRYGBP in a 2-year period. METHODS: The prospectively constructed database and the medical records of all patients undergoing revision to LRYGBP were reviewed. Demographics, surgical details, results, and complications were analyzed. RESULTS: There were 23 women and seven men with a mean age of 41.1+/-9.7 years (r=25-61). Mean body mass index (BMI) was 40.0+/-7.5 kg/m(2) (r=27.2-65.2). Initial operation was AGB in 24, VBG in five, and both in one patient. In ten patients, the band had been removed before revision, in 13 cases, band removal and LRYGBP were performed in one surgical intervention, and in two patients, it was performed in a two-step surgery. There were two conversions to open surgery. Five patients presented major surgical complications. Hospital stay averaged 5.1 days (r=3-25). Mean percent excess body weight loss at 6 and 12 months was 61.7+/-27.5 and 81.2+/-20.5 kg/m(2), respectively. Mean percent low body mass index at 6 and 12 months was 22.5+/-9.1 and 29.1+/-11.4 kg/m(2), respectively. CONCLUSIONS: LRYGBP as a revision procedure is feasible in most patients. Surgical complications are more frequent.

Fortalecimiento del comité popular de salud en el Distrito I / Strengthening of the peopleïs health committee in the district I

A más de cinco años de vigencia, el Comité Popular de Salud (CPS) del Distrito Nro. 1, reinicia sus actividades, aunando esfuerzos e incrementando acciones para su fortalecimiento