Innate IRE1α-XBP1 activation by viral single-stranded RNA and its influence on lung cytokine production during SARS-CoV-2 pneumonia.

The utilization of host-cell machinery during SARS-CoV-2 infection can overwhelm the protein-folding capacity of the endoplasmic reticulum and activate the unfolded protein response (UPR). The IRE1α-XBP1 arm of the UPR could also be activated by viral RNA via Toll-like receptors. Based on these premises, a study to gain insight into the pathogenesis of COVID-19 disease was conducted using nasopharyngeal exudates and bronchioloalveolar aspirates. The presence of the mRNA of spliced XBP1 and a high expression of cytokine mRNAs were observed during active infection. TLR8 mRNA showed an overwhelming expression in comparison with TLR7 mRNA in bronchioloalveolar aspirates of COVID-19 patients, thus suggesting the presence of monocytes and monocyte-derived dendritic cells (MDDCs). In vitro experiments in MDDCs activated with ssRNA40, a synthetic mimic of SARS-CoV-2 RNA, showed induction of XBP1 splicing and the expression of proinflammatory cytokines. These responses were blunted by the IRE1α inhibitor MKC8866, the TLR8 antagonist CU-CPT9a, and knockdown of TLR8 receptor. In contrast, the IRE1α-XBP1 activator IXA4 enhanced these responses. Based on these findings, the TLR8/IRE1α system seems to play a significant role in the induction of the proinflammatory cytokines associated with severe COVID-19 disease and might be a druggable target to control cytokine storm.

Episodios de salmonelosis no tifoidea en pacientes adultos del Área Valladolid Oeste en 2017: evaluación de la idoneidad de la petición del cultivo microbiológico y del tratamiento pautado / Episodes of nontyphoidal salmonellosis in adult patients of the Valladolid West Area in 2017: evaluation of the suitability of the microbiological culture request and the prescribed treatment

INTRODUCCIÓN: Las salmonelosis gastroenteríticas suponen aún la segunda causa diagnosticada de diarrea infecciosa en nuestro medio, la mayoría de estos cuadros clínicos son leves y autolimitados y por eso el uso de antibióticos está circunscrito a pocos supuestos. El objetivo del trabajo fue describir los episodios de diarrea por Salmonella enterica subsp. enterica, valorando la idoneidad de la petición y del uso de antibióticos de acuerdo a los criterios que figuran en la metodología. MATERIAL Y MÉTODOS: Se realizó un estudio observacional descriptivo retrospectivo recabando datos de la historia clínica. RESULTADOS: Se incluyeron 122 episodios. El motivo guía de consulta fue la diarrea, que generó una mayor demanda en los Servicios de Urgencia Hospitalaria (42,6%). Se aislaron sobre todo el serotipo Enteritidis (53,3%) y Typhimurium (40,2%). La adecuación de la petición del coprocultivo fue alta, 90,2%. Se prescribió antibiótico en el 64,6% (79) de los episodios, la mayoría en pacientes menores de 65 años (58 episodios), con una media de edad de 48,43 años. Los episodios se trataron principalmente con ciprofloxacino y azitromicina, en 57 y 14 episodios respectivamente. La duración media de la antibioterapia fue de 6 días. Existió un adecuado uso de los antibióticos en un 49,1%. Cuando el origen de la petición fue el Servicio de Urgencias hospitalario resultó inadecuado en el 63,5% (33) de ellos. Fue inadecuado en un 60,0% (39) de episodios cuando se aisló Salmonella serotipo Enteriditis. En casi la mitad, el 48,85% (42) de los 58 episodios en que se prescribió antibiótico entre los menores de 65 años (86), no estaba indicado. CONCLUSIONES: Se deberían implementar acciones formativas enfocadas a optimizar el manejo de antibióticos en esta entidad así como promover contribuciones que describan esta realidad

INTRODUCTION: Gastroenteritic salmonellosis is still the second cause diagnosed of infectious diarrhea, most of these clinical pictures are mild and self-limited and therefore the use of antibiotics is limited to few cases. The aim of the study was to describe the episodes of diarrhea caused by Salmonella enterica subsp. enterica, assessing the suitability of the request and the use of antibiotics according to the criteria included in the methodology. MATERIAL AND METHODS: A retrospective, descriptive, observational study was conducted, collecting data from the clinical history. RESULTS: A total of 122 episodes were included. The reason for consultation was diarrhea, which generated a greater demand in the Hospital Emergency Services (42.6%). The most frequent serotypes isolated were Enteritidis (53.3%), and Typhimurium (40.2%). The adequate request of the stool was 90.2%. Antibiotic was prescribed in 64.6% (79) of the episodes, most patients under 65 years (58 episodes), the average age was 48.43 years. They were treated mainly with ciprofloxacin and azithromycin, in 57 and 14 episodes, respectively. The average duration of antibiotic treatment was 6 days. There was an adequate use of antibiotics in 49.1% of episodes. When the origin of the request was the Hospital Emergency Service, it was inadequate in 63.5% (33) of them. It was inadequate in 60.0% (39) of episodes when ser. Enteritidis was isolated. Almost half, 48.85% (42) of the 58 episodes in which antibiotics were prescribed among those under 65 (86), were treated without being indicated. CONCLUSIONS: Training actions should be implemented focused on optimizing the management of antibiotics in this entity

Descriptivo de Hafnia alvei aisladas en coprocultivo: aproximación a su valoración en clínica / A descriptive study of Hafnia alvei isolated from stool samples: an approach to its clinical assessment

Introducción. El papel de Hafnia alvei en la etiología de diarrea en humanos es todavía muy controvertido; el objetivo del estudio fue describir la población en cuyos coprocultivos se aisló H. alvei y el manejo terapéutico de estos casos en nuestro Área de Salud. Material y métodos. Para ello se realizó un estudio descriptivo retrospectivo de 2014 y 2015. Se recogieron en la historia clínica informatizada, variables epidemiológicas, clínicas, tratamiento y evolución. Resultados. Se procesaron 7.290 coprocultivos, 3.321 en 2014, 58 (1,7%) en los que se aisló H. alvei y 3.969 en 2015, 53 (1,3%) positivos. El 60,4% de las muestras fueron aisladas en mujeres. La edad media fue de 38,68 años. El 68,5% provenían de Atención Primaria. En el 71,2% se recogió clínica asociada, siendo el más frecuente la diarrea en el 57,7%. En el 75,7% de los casos no existía patología de base asociada. El 43,2% de los casos recibió tratamiento de los cuales el 66,7% de los pacientes procedían de Atención Primaria. La duración media del tratamiento fue de 8 días. En el 85,4% de los casos tratados, la evolución fue favorable. Todas las cepas fueron sensibles a ciprofloxacino y trimetoprim/sulfametoxazol. Conclusiones. Faltan estudios que establezcan de forma concluyente la enteropatogenicidad o no de H. alvei (AU)

Introduction. The importance in human diarrhoeal disease of Hafnia alvei is unclear. The objective of the study was to describe the population which was isolated H. alvei in stool cultures and the therapeutic management of these cases in our Health Area. Material and methods. A descriptive retrospective study was carried out in 2014 and 2015. Epidemiological, clinical, treatment and evolution variables were collected in the computerized clinical history. Result. A collection of 7,290 stool specimens were processed, 3,321 in 2014 and 3,969 in 2015, of which 58 (1.7%) and 53 (1.3%) were positive for H. alvei, respectively. A 60.4% of samples were isolated in women. The mean age was 38.68 years. A 68.5% of samples were from primary care. In 71.2% there was related clinic, diarrhoea in 57.7%. In 75.7% of the cases there was not associated underlying disease. A 43.2% of the cases received treatment. A 66.7% of treated patients came from Primary Care. The mean duration of treatment was 8 days. The evolution was favourable in 85.4% of the cases treated. All strains were susceptible to ciprofloxacin and trimethoprim/sulfamethoxazole. Conclusions. More evidence is needed to support H. alvei as a cause of gastroenteritis (AU)

[Seroprevalence of viral hepatitis in a representative general population of an urban public health area in Castilla y León (Spain)]. / Seroprevalencia de las hepatitis virales en población general representativa de una zona básica de salud urbana en Castilla y León.

INTRODUCTION: Viral hepatitis is a major social, health and economic problem worldwide, requiring strict epidemiological control. METHODS: This study presents the viral hepatitis seroprevalence in a representative sample from an urban health care area in Valladolid (Spain). RESULTS: Antibody prevalence was as follows: anti-HAV 52%; anti-HBc, 8.2%; anti-HCV, 1.1%; anti-HEV, 0.8%; and anti-HGV 5.8%. Prevalence of anti-HAV, anti-HBc and anti-HGV increased significantly with age (P < 0.005 in all cases). In individuals younger than 20, prevalence of anti-HAV was 3.8%, anti-HBc < 0.28% and anti-HGV 1.3%. In the 20-39 year-old group, seroprevalence against HAV was associated with low educational levels (P = 0.009) and with birth in other provinces (P = 0.016). Anti-HBc seroprevalence was mainly associated with three factors: prior hospitalization before 1990 (P = 0.002; OR 3.32 [1.48-7.42]); compulsory military service before 1990 (P < 0.0001; OR 37.33 [3.68-378.03]); and acupuncture treatments (P = 0.018; OR 57.75 [26.17-127.42]). Seroprevalence against HGV was associated with hospitalizations before 1990 (P = 0.019; OR = 2.969 [1.154-7.639]). Seropositive status to HCV revealed a transfusion history (2 cases), hospitalization (1 case) or drug addiction (1 case). Only one case among those seropositive to HEV had a history of a prior trip to a HEV-endemic area. CONCLUSIONS: Our study shows that the seroprevalences of viral hepatitis in a representative sample of urban population of Castille and Leon are similar to the seroprevalences observed in the rest of Spain and other developed countries, lower than the ones observed in the studies performed in Spain in the last 20 years due to the measures of prophylaxis that were taken.

Seroprevalencia de las hepatitis virales en población general representativa de una zona básica de salud urbana en Castilla y León / Seroprevalence of viral hepatitis in a representative general population of an urban public health area in Castilla y León (Spain)

Introducción. Las hepatitis virales constituyen uno de los principales problemas sociosanitarios y económicos a nivel mundial por lo que precisan un estrecho control epidemiológico. Métodos. En el presente trabajo estudiamos la seroprevalencia de las hepatitis virales una muestra representativa de la población de una zona básica de salud urbana en Valladolid (España). Resultados. La prevalencia de anticuerpos anti-VHA (AcVHA) fue del 52%, de HBcAc del 8,2%, de AcVHC del 1,1%, de AcVHE 0,8% y AcVHG 5,8%. La prevalencia de AcVHA, HBcAc y AcVHG aumenta significativamente con la edad (p < 0,005 en todos los casos). En menores de 20 años la prevalencia de AcVHA es del 3,8%, HBcAc < 0,28% y AcVHG 1,3%. En el grupo de edad de 20-39 años, la seroprevalencia frente al VHA se asocia con niveles educativos bajos (p 5 0,009) y con el nacimiento en otras provincias (p 5 0,016). La seroprevalencia de HBcAc se asocia principalmente con hospitalizaciones anteriores a 1990 (p 5 0,002; OR: 3,32 [1,48-7,42]), realización del servicio militar obligatorio anterior a 1990 (p < 0,0001; OR: 37,33 [3,68-378,03]) y prácticas de acupuntura (p 5 0,018; OR: 57,75 [26,17-127,42]). La seroprevalencia frente a VHG se asocia con hospitalizaciones antes de 1990 (p 5 0,019; OR: 2,969 [1,154-7,639]). Los seropositivos frente a VHC tenían antecedentes de transfusiones (2 casos) hospitalización (1 caso) o drogadicción (1 caso). De los seropositivos frente a VHE sólo un caso tenía antecedentes de viaje a zona endémica para VHE. Conclusiones. Nuestro estudio muestra que las seroprevalencias de las hepatitis virales en una muestra representativa de población urbana de Castilla y León son similares a las seroprevalencias obtenidas en el resto de España y de los países desarrollados, inferior a la observada en los estudios realizados en España en los últimos 20 años consecuencia de las medidas profilácticas adoptadas (AU)

Introduction. Viral hepatitis is a major social, health and economic problem worldwide, requiring strict epidemiological control. Methods. This study presents the viral hepatitis seroprevalence in a representative sample from an urban health care area in Valladolid (Spain). Results. Antibody prevalence was as follows: anti-HAV 52%; anti-HBc, 8.2%; anti-HCV, 1.1%; anti-HEV, 0.8%; and anti-HGV 5.8%. Prevalence of anti-HAV, anti-HBc and anti-HGV increased significantly with age (P < 0.005 in all cases). In individuals younger than 20, prevalence of anti-HAV was 3.8%, anti-HBc < 0.28% and anti-HGV 1.3%. In the 20-39 year-old group, seroprevalence against HAV was associated with low educational levels (P 5 0.009) and with birth in other provinces (P 5 0.016). Anti-HBc seroprevalence was mainly associated with three factors: prior hospitalization before 1990 (P 5 0.002; OR 3.32 [1.48-7.42]); compulsory military service before 1990 (P < 0.0001; OR 37.33 [3.68-378.03]); and acupuncture treatments (P 5 0.018; OR 57.75 [26.17-127.42]). Seroprevalence against HGV was associated with hospitalizations before 1990 (P 5 0.019; OR 5 2.969 [1.154-7.639]). Seropositive status to HCV revealed a transfusion history (2 cases), hospitalization (1 case) or drug addiction (1 case). Only one case among those seropositive to HEV had a history of a prior trip to a HEV-endemic area. Conclusions. Our study shows that the seroprevalences of viral hepatitis in a representative sample of urban population of Castille and Leon are similar to the seroprevalences observed in the rest of Spain and other developed countries, lower than the ones observed in the studies performed in Spain in the last 20 years due to the measures of prophylaxis that werw taken (AU)