Ivermectin reduces in vivo coronavirus infection in a mouse experimental model.

The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.

Cirugía ginecológica en la paciente obesa / Gynaecological surgery in the obese patient

La cirugía en la paciente obesa supone un reto para el cirujano y anestesista puesto que se asocia a un aumento de las complicaciones intra- y postoperatorias. Los efectos adversos como la infección del lecho quirúrgico, los fenómenos tromboembólicos o las complicaciones de la herida quirúrgica son más frecuentes en estas pacientes. La cirugía mínimamente invasiva ha supuesto un avance para el tratamiento quirúrgico de estas pacientes, reduciendo algunas complicaciones asociadas al abordaje laparotómico, especialmente en el manejo del cáncer ginecológico. El desarrollo de la cirugía robótica ha permitido mejorar las limitaciones de la cirugía laparoscópica, gracias a la mayor precisión o la visión 3D. Concretamente en la paciente obesa la cirugía robótica aporta ventajas, como reducción de las complicaciones intra- y postoperatorias, mayor número de ganglios linfáticos, y reducción de la estancia hospitalaria y del sangrado operatorio respecto a las otras vías

Surgery in the obese patient is a challenge for the surgeon and anaesthetist as it is associated with an increase in intra- and post-operative complications. Adverse effects, such as surgical site infection, thromboembolic disease, or surgical wound complications are more frequent in these patients. Minimally invasive surgery has led to an advance in the surgical treatment of these patients, reducing some complications associated with the laparotomy approach, especially in the management of gynaecological cancer. The development of robotic surgery has led to an improvement in the limitations of laparoscopic surgery, due to greater accuracy or 3D vision. Specifically, in the obese patient, robotic surgery provides advantages, such as reduction of intra- and post-operative complications, greater number of lymph nodes, a reduction in hospital stay, as well as less surgical bleeding compared to other approaches

Satisfacción de los usuarios con las intervenciones educativas realizadas por la Liga Chilena contra la Epilepsia (LICHE) entre los años 2017 a 2019 / User Satisfaction with Educational Interventions carried out by the Chilean League against Epilepsy (LICHE) between 2017 and 2019

La epilepsia es una enfermedad neurológica crónica frecuente, que afecta aproximadamente a 50 millones de personas en el mundo. Puede ser definida, desde un punto de vista biológico, como una enfermedad caracterizada por una tendencia sostenida en el tiempo a presentar crisis epilépticas. Pero para comprender el impacto que conlleva para las personas afectadas y su grupo familiar, además del componente biológico, es necesario también prestar atención a las consecuencias psicosociales de la enfermedad: discriminación y estigma. La Liga Chilena contra la Epilepsia, integrante de Anliche (Asociación Nacional de Ligas Chilena contra la Epilepsia), capítulo chileno del IBE, cuenta con una larga experiencia de más de 20 años en lo que se refiere a educación en Epilepsia. El objetivo del presente trabajo es describir el nivel de satisfacción de los participantes sobre las actividades de capacitación realizadas por LICHE, comparando diferentes grupos de usuarios y la evolución temporal entre 2017 y 2019. El 79,3% de los participantes está completamente de acuerdo en que la intervención educativa cumplió satisfactoriamente sus expectativas. Los ítems con mayor porcentaje de nota óptima fueron: Objetivos 88,9%; Aplicabilidad 85,6% y Contenidos 85,5%.

Epilepsy is a common chronic neurological disease, affecting approximately 50 million people worldwide. It can be defined, from a biological point of view, as a disease characterized by a sustained tendency over time to develop epileptic seizures. But to understand the impact it has on people afflicted by it and their family group, in addition to the biological component, it is also necessary to pay attention to the psychosocial consequences of the disease: discrimination and stigma. The Chilean League against Epilepsy, a member of Anliche (Chilean National Association of Leagues against Epilepsy), Chilean chapter of the IBE, has a long experience of more than 20 years in terms of education in Epilepsy. The objective of this work is to describe the level of satisfaction of the participants on the training activities carried out by LICHE, comparing different user groups between 2017 and 2019. 79.3% of participants fully agree that the educational intervention satisfactorily met their expectations. Items with the highest optimal grade percentage were: Objectives 88.9%; Applicability 85.6% and Contents 85.5%.

Hongos anamorfos biodegradan los libros del Área Histórica de la Universidad Central del Ecuador (UCE) / Anamorphous fungi biodegrade the books of the Historical Area from the Central University of Ecuador (CUE)

Determinamos los géneros de hongos anamorfos que contaminan los libros del área de cuarentena y limpieza, dentro del Área Histórica de la Universidad Central del Ecuador (UCE). Realizamos un hisopado aleatorio a una muestra representativa de 50 de estos libros de acuerdo a una Tabla militarizada estándar. También hisopamos como muestra preferencial a 21 libros gravemente contaminados con hongos. Los hisopados tuvieron una superficie de 5x5 cm, friccionando en la pasta, el borde y el interior de estos libros. Las 213 muestras tomadas fueron inoculadas en medio de cultivo Agar Malta. Los medios fueron incubados a una temperatura de 28°C durante 7 días. Realizamos observaciones por microscopía a 40 y 100x además de usar literatura especializada para la identificación hasta el nivel de género de hongos anamorfos. Los géneros más abundantes en este estudio fueron Penicillium (80,2%) y Mucor (8,1%). (AU)

We determined the genera of anamorphic fungi that contaminate the books in the quarantine and cleaning area, within the Historical Area of the Central University of Ecuador (CUE). We performed a random swab on a representative sample of 50 of these books according to a standard militarized Table. We also swabbed as a preferential sample 21 books seriously contaminated with fungi. The swabs had a surface area of 5x5 cm, rubbing on the paste, the edge and the interior of these books. The 213 samples taken were inoculated in Agar Malta culture medium. The media were incubated at a temperature of 28° C for 7 days. We made observations by microscopy at 40 and 100x in addition to using specialized literature for the identification down to the genus level of anamorphic fungi. The most abundant genus in this study were Penicillium(80,2%) and Mucor(8,1%). (AU)

Impacto de un programa educativo sobre epilepsia en los conocimientos generales de la comunidad: Experiencia de la Liga Chilena contra la Epilepsia (LICHE) entre los años 2018 y 2019 / Impact of an Epilepsy Educational Program on the General Knowledge of the Community: Experience of the Chilean League Against Epilepsy (LICHE) between 2018 and 2019

La epilepsia es una enfermedad neurológica crónica, no transmisible, que afecta en la actualidad a cerca de 50 millones de personas en el mundo. Un aspecto particular de esta patología se refiere al impacto psicosocial negativo que la acompaña, específicamente lo que se refiere a estigma y discriminación. Pese a los grandes avances en el conocimiento científico de esta patología dicho impacto psicosocial negativo se mantiene; estudios realizados en diferentes grupos y poblaciones así lo confirman. El objetivo del presente estudio es determinar si los programas educativos realizados por la Liga Chilena contra la Epilepsia que ha desarrollado desde hace varias décadas para toda la comunidad, con diferentes estrategias metodológicas, de manera de contribuir en la labor de mejorar la calidad de vida de las personas con epilepsia, sus familiares y cuidadores, aumentan los conocimientos sobre las Epilepsias en la población que participa. La capacitación mejoró significativamente los conocimientos en todos los ítems. El mayor impacto se produjo en las preguntas sobre las cuales había desconocimiento.

Epilepsy is a chronic, non-communicable neurological disease that currently affects nearly 50 million people worldwide. A particular aspect of this pathology refers to the negative psychosocial impact that accompanies it, specifically regarding stigma and discrimination. Despite great advances in scientific knowledge of this pathology this negative psychosocial impact remains; studies in different groups and populations confirm this. The objective of this study is to determine whether the educational programs carried out by the Chilean League against Epilepsy which it has developed for several decades for the whole community, with different methodological strategies, in order to contribute to the work of improving the quality of life of people with epilepsy, their families and caregivers, increase knowledge about epilepsy in the people that participate in them. The training significantly improved the knowledge in all items. The greatest impact occurred on questions about which there was no prior knowledge.

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Role of inflammasome activation in tumor immunity triggered by immune checkpoint blockers.

Immune checkpoint blockers improve the overall survival of a limited number of patients among different cancers. Identifying pathways that influence the immunological and clinical response to treatment is critical to improve the therapeutic efficacy and predict clinical responses. Recently, a key role has been assigned to innate immune mechanisms in checkpoint blockade-driven anti-tumor responses. However, inflammatory pathways can both improve and impair anti-tumor immunity. In this review, we discuss how different inflammatory pathways, particularly inflammasome activation, can influence the clinical outcome of immune checkpoint blockers. Inflammasome activation may reinforce anti-tumor immunity by boosting CD8+ T cell priming as well as by enhancing T helper type 17 (Th17) responses. In particular, we focus on the modulation of the cation channel transmembrane protein 176B (TMEM176B) and the ectonucleotidase CD39 as potential targets to unleash inflammasome activation leading to reinforced anti-tumor immunity and improved efficacy of immune checkpoint blockers. Future studies should be aimed at investigating the mechanisms and cell subsets involved in inflammasome-driven anti-tumor responses.

Success of benznidazole chemotherapy in chronic Trypanosoma cruzi-infected patients with a sustained negative PCR result.

Cure assessment in chronic Trypanosoma cruzi infection is controversial, mainly because of the lack of reliable tests to ensure parasite elimination. Here, we assess the impact of benznidazole therapy on the conventional serology and parasitaemia in chronic Chagas disease. A total of 455 patients with long-term Trypanosoma cruzi infection underwent specific chemotherapy with benznidazole. Their parasitological status was assessed by polymerase chain reaction (PCR) detection of T. cruzi DNA. Drops in the titres of antibody levels were serially measured by indirect immunofluorescence assay (IFI) and chemiluminescent microparticle immunoassay (CMIA). Patients were monitored during the treatment period and for a further 90, 150 and 240 days. Controls were repeated yearly during the 7-year follow-up. The PCR result was negative in all patients between 60-day (n = 22) and 90-day (n = 294) controls. Treatment failure was detected in 45 patients and was significantly more frequent in those who did not complete the therapy [12 out of 13 (92 %) vs. 33 out of 442 (7 %)] (p = 0.0001). A significant drop in serum titres was detected after the first follow-up year in patients with sustained negative PCR results: 2nd year (p = 0.029 by IFI; p = 0.002 by CMIA), 5th year (p = 0.036 by IFI; p = 0.039 by CMIA) and 6th year (p = 0.028 by IFI; p = 0.019 by CMIA). The results point to a beneficial effect of benznidazole and may be the cure of chronic patients who had a consistently negative PCR result throughout the follow-up period.

Use of Everolimus After Multivisceral Transplantation: A Report of Two Cases.

Inhibitors of mechanistic target of rapamycin are used in solid organ transplant procedures to avoid calcineurin inhibitor complications, including nephrotoxicity and malignancy. We present 2 cases of multivisceral transplantation for neuroendocrine tumor (NET) for which everolimus was implemented for its potential to prevent NET recurrence as well as preserve renal function. The first case was complicated by NET recurrence in the liver before initiation of everolimus. After initiation of everolimus, the patient developed a ventral hernia and elevated aminotransferase levels with nonspecific biopsy findings. The second case was complicated by cytomegalovirus infection with elevated everolimus trough levels as well as acute cellular rejection. Everolimus was reinitiated in both cases in addition to decreasing the dosage of tacrolimus, and there were no further complications. Everolimus was beneficial in stabilizing renal function in both patients and has the theoretical potential to prevent recurrence of NET.

Intestine Transplantation Across a Positive Crossmatch With Preformed Donor-Specific Antibodies.

BACKGROUND: We describe our experience using a modified protocol for immunosuppression for intestine transplantation across a positive crossmatch. Patients who underwent transplantation in 2013 were evaluated over a 12-month period for rejection and infectious events with comparison to procedure-matched controls on our standard protocol of immunosuppression. PATIENTS AND METHODS: We used a modified protocol for intestine and multivisceral transplantation for patients with a positive flow crossmatch. In addition to our standard protocol, patients with positive crossmatch were given rituximab and intravenous immunoglobulin (IVIg) preoperatively. DSA was sent for clinical evaluation at monthly intervals. Patients were screened for rejection by endoscopic evaluation. RESULTS: Four patients underwent transplantation within a single year across a positive crossmatch. Two received isolated intestine transplants and 2 had multivisceral transplantation (MVT). During the 12-month follow-up, 1 patients had an episode of severe acute cellular rejection, which was managed with increased immunosuppression. None of the patients had episodes of cytomegalovirus infection. One patient developed major infection and 3 patients developed minor bacterial infections. Among procedure-matched controls with negative final crossmatch on standard management (no preoperative rituximab or IVIg), 2 developed mild acute cellular rejection and 2 developed minor infections. One developed cytomegalovirus viremia with invasion to the colonic mucosa. CONCLUSIONS: We report our protocol for immunosuppression for IT and MVT across a positive crossmatch. This allowed transplantation despite the presence of a positive crossmatch, with low rejection rates but potentially increased risk for major infections compared to the negative crossmatch controls on our standard protocol.

A Case Report of Acute Cellular Rejection Following Intestinal Transplantation Managed With Adalimumab.

There is a higher incidence of acute cellular rejection (ACR) in small bowel transplantation (SBT) compared with transplantation of other solid organs. Although there are reports on the use of infliximab to successfully treat ACR refractory to other treatments, there are no reports, to our knowledge, regarding the use of adalimumab. We present a case of a female patient with a history of Crohn's disease who underwent an isolated SBT and developed an episode of severe ACR. She was initially treated with methylprednisolone, thymoglobulin, basiliximab, and a dosage adjustment of tacrolimus. Results of repeat endoscopies and biopsies revealed no significant improvement. The patient initiated treatment with adalimumab every 2 weeks for a total of 6 months, in addition to maintenance treatment with prednisone and tacrolimus. Subsequent evaluations showed gradual improvement to normal mucosa and villi without ulceration. A regimen that incorporates adalimumab can thus be used to treat ACR after intestinal transplantation. Larger multicenter studies are needed to show the full efficacy of this therapeutic regimen.

Experiencia del uso de terapia biológica en pacientes con enfermedad inflamatoria intestinal en un hospital público / Experience in the use of biological therapy in IBD patients in a public hospital

Biological therapy plays an important role in the treatment of inflammatory bowel disease (IBD). However, the use of these drugs is limited due to fears about their side effects. Aim: To report the experience with the use of infliximab/adalimumab in IBD patients in a public hospital. Material and Methods: Descriptive study of a historical cohort of IBD patients treated with infliximab and adalimumab between April 2012 and July 2014. The clinical response was considered favourable when general, intestinal and extra intestinal symptoms subsided after the induction therapy. In addition, endoscopic and/or imaging response was evaluated at three and six months of treatment. Results: Fifteen out of 162 patients, aged 17 to 52 years (7 women) were included. Seven had Crohn´s Disease, 7 had ulcerative colitis and one had non-classifiable IBD. Biological therapy was indicated due to conventional refractory disease in all patients. All patients received combined treatment with immunosuppressive medications. A favorable clinical response was observed in 93 percent after induction therapy and 73 percent showed endoscopic/imagining remission after 3-6 months. Only one patient experienced side effects associated to the biological therapy, which did not result in discontinuation or treatment interruption. Conclusions: In this cohort of IBD patients treated in a public hospital, the use of infliximab/adalimumab was associated with favorable clinical and endoscopic evolution, post induction therapy with no major side effects.

La terapia biológica tiene un papel fundamental en el tratamiento de la enfermedad inflamatoria intestinal (EII). Sin embargo, el uso de estos fármacos es escaso debido a los costos y los temores sobre los efectos secundarios. Objetivo: Dar a conocer la experiencia en el uso de infliximab/adalimumab en pacientes con EII atendidos en un hospital público de nuestro país. Material y Métodos: Estudio descriptivo de una cohorte histórica de pacientes con EII tratados con infliximab y adalimumab entre abril de 2012 y julio de 2014. La respuesta clínica fue considerada favorable cuando los síntomas generales, intestinales y extra-intestinales desaparecieron después de la terapia de inducción. Además se evaluó la respuesta endoscópica/radiológica a los 3 y 6 meses de tratamiento. Resultados: De un total de 162 pacientes con EII, 15 fueron tratados con terapia biológica, con edad entre 17-52 años (7 mujeres). Siete presentaban el diagnóstico de enfermedad de Crohn, siete colitis ulcerosa y uno EII no clasificable. En todos se inició terapia biológica debido a la presencia de refractariedad a la terapia convencional. Todos recibieron terapia combinada con inmunosupresores. Se observó una respuesta clínica favorable en 93 por ciento después de la terapia de inducción y 73 por ciento tuvo una mejoría endoscópica después de 3-6 meses. Sólo un paciente presentó un evento adverso a terapia biológica, el cual no motivó la interrupción del tratamiento. Conclusiones: En esta cohorte de pacientes con EII tratados en un hospital público, el uso de infliximab/adalimumab se asoció con mejoría clínica y endoscópica post terapia de inducción, sin mayores efectos secundarios.

Spatial distribution of human asymptomatic Leishmania infantum infection in southeast Spain: a study of environmental, demographic and social risk factors.

Recent PCR studies indicate that asymptomatic L. infantum infection is common in people in southern Europe. Understanding its spatial distribution is a requisite to evaluate the public health implications and to design disease control schemes. We investigated infection in blood samples from 657 donors in southeast Spain using PCR and antibody ELISA. They came from 19 blood centers and were interviewed about their residence, occupation, dog ownership and Leishmaniosis awareness. The percentage of PCR and ELISA positives were 8% (49/618) and 2% (13/657). Donor's residences were spatially clustered around blood donning centers and PCR prevalence was 18% in rural municipalities with 20-1330 inhabitants, 12% in those with 1467-5088 inhabitants and 3% in larger communities, and was associated with dog ownership (p<0.05). Further analysis of data from rural donors indicated that PCR status was strongly related to the climate, altitude and soil type in the donor's residence area and not to other demographic or sociologic variables. Mixed logistic regression analysis predicted PCR prevalence to be greatest in the 200-300m altitude range with a mean spring-summer (time of highest vector activity) temperature of 18.4-19.0°C. A temperature and altitude risk map was generated that will provide the basis for elaborating evidence-based vector surveillance studies.

Determinant factors of repeat sprint sequences in young soccer players.

The aim of this study was to investigate the relationships between repeated explosive effort sequences (20+20 m shuttle sprint with change of direction, kicking and jumping), metabolic response (lactate and ammonia), and fitness qualities (strength and endurance) in under-19 soccer players. 21 players completed: 1) sprint test: 30 m (T30) and 40 m (20+20 m) shuttle sprints; 2) countermovement jumps (CMJ); 3) maximal kicking; and 4) 9 repeated-explosive effort sequences (RES); 4) a progressive isoinertial loading test in full squat to determine the load which subjects achieved ~1 m · s(-1) (V1-load); 6) Yo-Yo Intermittent Recovery Test Level 1 (YYIRT-1). Mean sprint time of the 9 repeated sprints (RSA(mean1-9)) showed correlation with V1-load (r=- 0.52 [- 0.79, - 0.25]) metabolic response (lactate, r=0.67 [0.47, 0.87] and ammonia, r=0.53 [0.27, 0.79]). YYIRT-1 correlated with RSA(mean1-9) (r(w)=- 0.78 [- 0.92, - 0.64]) when the body weight was controlled. Furthermore, the 3 first sprints (RSA(mean1-3)) correlated with RSA(best) (r=0.93 [0.88, 0.98]), V1-load (r=- 0.64 [-0.86, - 0.42]), and T30 (r=0.63 [0.41, 0.85]). These results suggest that the soccer player's lower body strength (V1-load, jumping and sprinting) explains a large part of the performance in the first sequences, whereas the aerobic capacity, estimated through YYIRT-1, becomes more important to performance as the number of sprints is increases.