[Translated article] Total hip arthroplasty with shelf acetabuloplasty in dysplastic coxarthrosis, mean follow-up of 7 years.

INTRODUCTION: Developmental dysplasia of the hip is the cause of approximately one third of secondary coxarthrosis. Anatomy alterations make it difficult to place a total hip prosthesis in its anatomical position and for it to be stable in the long term; there are several techniques to achieve this goal. In the present work, we used autograft of the femoral head (shelf graft or reinforced roof), to improve the coverage of the acetabular component with favourable results. MATERIALS AND METHODS: Sixteen cases were included in 14 patients with a diagnosis of developmental dysplasia of the hip (13 women and one man), the mean age was 44.3 years (range 35-68 years), with a mean follow-up of 7 years (range 1-15 years). All the cases were evaluated clinically and radiographically, to demonstrate the osseointegration of the graft and the functional results in the medium term. RESULTS: All the acetabular components were placed in anatomical position (Ranawat technique), the mean percentage of host bone coverage was 54.53% (range 43.28-79.05%), obtaining additional coverage with the bone graft of 45.13%. Osseointegration of the graft of 100% at 12 weeks, resorption of the graft from the sixth month, stabilising in the third postoperative year. Only one case of dislocation is reported, no cases of infection, loosening, heterotopic ossification or revision. CONCLUSION: This procedure has shown good functional results in the medium term with 100% osseointegration, despite cases of severe bone resorption of the graft that does not compromise the stability of the prosthesis.

Total hip arthroplasty with shelf acetabuloplasty in dysplastic coxarthrosis, mean follow-up of 7 years. / Artroplastia total de cadera no cementada con techo armado en coxartrosis displásica, seguimiento medio de 7 años.

Developmental dysplasia of the hip is the cause of approximately one third of secondary coxarthrosis. Anatomy alterations make it difficult to place a total hip prosthesis in its anatomical position and for it to be stable in the long term; there are several techniques to achieve this goal. In the present work, we used autograft of the femoral head (shelf graft or reinforced roof), to improve the coverage of the acetabular component with favorable results. MATERIALS AD METHODS: Sixteen cases were included in 14 patients with a diagnosis of developmental dysplasia of the hip (13 women and one man), the mean age was 44.3 years (range 35-68 years), with a mean follow-up of 7 years (range 1-15 years). All the cases were evaluated clinically and radiographically, to demonstrate the osseointegration of the graft and the functional results in the medium term. RESULTS: All the acetabular components were placed in anatomical position (Ranawat technique), the mean percentage of host bone coverage was 54.53% (range 43.28-79.05%), obtaining additional coverage with the bone graft of 45.13%. Osseointegration of the graft of 100% at 12 weeks, resorption of the graft from the sixth month, stabilizing in the third postoperative year. Only one case of dislocation is reported, no cases of infection, loosening, heterotopic ossification or revision. CONCLUSION: This procedure has shown good functional results in the medium term with 100% osseointegration, despite cases of severe bone resorption of the graft that does not compromise the stability of the prosthesis.

Long-term effects of dietary calcium and phosphorus level, and feed form during rearing on egg production, eggshell quality, and bone traits in brown laying hens from 30 to 89 wk of age.

The effects of feeding strategies during rearing (0-16 wk) of brown laying hens on mid and end laying performance (30-89 wk) were studied. The rearing feeding strategies followed a 3 × 2 factorial arrangement with feed form; mash with inclusion of 3% finely ground wheat straw (MWS), crumbles with inclusion of 3% finely ground wheat straw (CWS), and crumbles with inclusion of 3% unground oat hulls as fiber sources (COH) at 2 dietary Ca and P levels (high or low Ca-P). Feed conversion ratio improved with COH and MWS compared with CWS from 30 to 59 wk. Rate of lay and egg mass production showed a feed form × Ca-P interaction from 60 to 89 wk. Low Ca-P led to a higher egg production, but only when COH and MWS were fed. BW at 89 wk was higher with CWS compared to COH and MWS. BW uniformity was better with COH compared to MWS at 51 wk and both CWS and MWS at 67 wk. Tibia characteristics were not clearly affected by treatment, although there was a feed form × Ca-P interaction on compression at 89 wk, where compression was lower with MWS and low vs. high Ca-P. Low Ca-P during rearing led to higher eggshell thickness, compared to high Ca-P at 45 wk of age, but breaking strength was lower with low vs. high Ca-P at 75 wk. Although eggshell quality was affected by Ca-P and there were some interactions with feed form at some ages, the effect was not consistent. There was no clear relationship between eggshell quality and tibia characteristics. It was concluded that feeding low Ca-P in combination with COH and MWS during the rearing period positively affects egg production during late lay. Also, dietary Ca-P levels, compared to commercial practice, can be lowered during rearing, as this will not affect eggshell quality and bone mineralization at later ages.

Evaluación del sangrado, dolor y tiempo quirúrgico del abordaje midvasto versus parapatelar medial en artroplastía total de rodilla primaria por osteoartrosis grado IV / Evaluation of bleeding, pain and operative time of the midvasto versus medial parapatellar approach in primary total knee arthroplasty for grade IV osteoarthrosis

Resumen: Introducción: la artroplastía total de rodilla es un procedimiento común en la cirugía ortopédica de tratamiento para gonartrosis grado IV. Este procedimiento disminuye el dolor y mejora la funcionalidad. Sin embargo, los resultados según el abordaje son distintos, no existe evidencia sobre qué abordaje quirúrgico sea claramente superior. El objetivo de este estudio es evaluar el tiempo y sangrado transquirúrgico, así como el dolor postquirúrgico del abordaje midvasto versus parapatelar medial en artroplastía total de rodilla primaria en gonartrosis grado IV. Material y métodos: se realizó estudio observacional, comparativo, retrospectivo del 01 de Junio de 2020 al 31 de Diciembre de 2020 incluyendo derechohabientes del Instituto Mexicano del Seguro Social, mayores de 18 años con diagnóstico de gonartrosis grado IV, programados para artroplastía total de rodilla primaria en ausencia de otra patología inflamatoria, osteotomías previas o coagulopatías. Resultados: noventa y nueve pacientes que fueron sometidos a abordaje midvasto (grupo M) y 100 pacientes a abordaje parapatelar medial (grupo T) con hemoglobina preoperatoria 14.7 g/l grupo M y 15.2 g/l grupo T, la reducción fue de 5.0 g/l grupo M y 4.6 g/l grupo T. Dolor en ambos grupos sin diferencia significativa; de 6.7 a 3.2 grupo M y de 6.7 a 3.1 grupo T. Tiempo quirúrgico mayor con el abordaje parapatelar medial (98.7 versus 89.2 minutos). Conclusiones: ambos abordajes representan excelente vía de acceso para realizar artroplastía total primaria de rodilla; sin embargo, no se encontraron diferencias significativas en el volumen de sangrado ni en la reducción del dolor, el abordaje midvasto se asoció con menor tiempo quirúrgico y menor afectación de la flexión de la rodilla, por lo que se recomienda el abordaje midvasto en pacientes sometidos a artroplastía total de rodilla primaria.

Abstract: Introduction: total knee arthroplasty is a common procedure in orthopedic surgery for treating grade IV knee osteoarthritis. This procedure reduces pain and improves functionality. However, the results according to the approach are different, it is not clear which surgical approach is clearly superior. The objective of this study is to evaluate the time and post-surgical bleeding, as well as the postoperative pain of the midvasto versus medial parapatellar approach in primary total knee arthroplasty in grade IV gonarthrosis. Material and methods: an observational, comparative, retrospective study was carried out from June 1, 2020 to December 31, 2020, including beneficiaries of the Mexican Social Security Institute over 18 years of age with a diagnosis of grade IV knee osteoarthritis scheduled for primary total knee arthroplasty in the absence of other inflammatory pathology, previous osteotomies or coagulopathies. Results: of 99 patients who underwent the midvasto approach (group M) and 100 patients to the medial parapatellar approach (group T), there was preoperative hemoglobin 14.7 g/l group M and 15.2 g/l group T, reduction was 5.0 g/l group M and 4.6 g/l group T. Significant pain reduction in both groups without significant difference; from 6.7 to 3.2 group M and from 6.7 to 3.1 group T. The surgical time was significantly longer with the medial parapatellar approach (98.7 versus 89.2 minutes). Conclusions: both approaches represent an excellent access route to perform primary total knee arthroplasty; however, no significant differences were found in the volume of bleeding or in the reduction of pain, the midvaste approach was associated with shorter surgical time and less involvement of flexion of the knee. Therefore, the midvasto approach is recommended in patients undergoing primary total knee arthroplasty.

Unresolved issues in the epidemiology and diagnosis of bacteremia: an opinion paper.

Bacteremia is an important cause of morbidity and mortality worldwide and, despite the diagnostic and therapeutic advances of the last decades, the evidence supporting many diagnostic aspects of bacteremia is scarce. Information on the epidemiological evolution of this entity is limited and many methodological aspects of blood culture collection and analysis are under discussion. Furthermore, the recommendations of the main scientific societies on many of these aspects are variable and, in many cases, have not been updated recently. In this scenario, we have arranged a series of questions on different aspects of bacteremia and reviewed the literature trying to find proper answers for them. We offer our opinion on the topics where the evidence was weak. The topics covered include epidemiological aspects of bacteremia, indications for blood culture extraction, methods for obtaining and incubating samples, or ways of transmitting results from the microbiology laboratory. We do not intend to summarize the current clinical practice guidelines, nor will we deal with the therapeutic management of this entity. The aim of this paper is to review the current perspective on the diagnosis of bacteremia with a critical approach, to point out the gaps in the literature, to offer the opinion of a team dedicated to infectious diseases and clinical microbiology, and to identify some areas of knowledge on which future studies should focus.

COVID 19 and Psychological Problems in Mexican Mothers

COVID-19 seriously affected people’s mental health. Possibly symptoms of anxiety, depression and insomnia occur with most frequency in various sectors of the population, especially in mothers. The objective of this research was to evaluate levels of depression, anxiety and insomnia in Mexican mothers who had COVID-19, who care for or cared for patients with COVID-19, or in neither of these two conditions. A sample of 540 Mexican mothers was gathered, a questionnaire was applied to obtain data on sociodemographic variables, as well as instruments to measure depression, anxiety and insomnia. The 70% of the participants had insomnia, 77% had depressive symptoms, while 80.2% showed anxiety. Working mothers presented more severe symptoms of insomnia than housewives. Caring for a COVID-19 patient was significantly associated with the psychological variables evaluated. Mexican mothers who care or cared for COVID-19 patients have high rates of depression, anxiety, and insomnia (AU)

The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.

INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. DISCUSSION: These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.

[Evaluation of bleeding, pain and operative time of the midvasto versus medial parapatellar approach in primary total knee arthroplasty for grade IV osteoarthrosis]. / Evaluación del sangrado, dolor y tiempo quirúrgico del abordaje midvasto versus parapatelar medial en artroplastía total de rodilla primaria por osteoartrosis grado IV.

INTRODUCTION: total knee arthroplasty is a common procedure in orthopedic surgery for treating grade IV knee osteoarthritis. This procedure reduces pain and improves functionality. However, the results according to the approach are different, it is not clear which surgical approach is clearly superior. The objective of this study is to evaluate the time and post-surgical bleeding, as well as the postoperative pain of the midvasto versus medial parapatellar approach in primary total knee arthroplasty in grade IV gonarthrosis. MATERIAL AND METHODS: an observational, comparative, retrospective study was carried out from June 1, 2020 to December 31, 2020, including beneficiaries of the Mexican Social Security Institute over 18 years of age with a diagnosis of grade IV knee osteoarthritis scheduled for primary total knee arthroplasty in the absence of other inflammatory pathology, previous osteotomies or coagulopathies. RESULTS: of 99 patients who underwent the midvasto approach (group M) and 100 patients to the medial parapatellar approach (group T), there was preoperative hemoglobin 14.7 g/l group M and 15.2 g/l group T, reduction was 5.0 g/l group M and 4.6 g/l group T. Significant pain reduction in both groups without significant difference; from 6.7 to 3.2 group M and from 6.7 to 3.1 group T. The surgical time was significantly longer with the medial parapatellar approach (98.7 versus 89.2 minutes). CONCLUSIONS: both approaches represent an excellent access route to perform primary total knee arthroplasty; however, no significant differences were found in the volume of bleeding or in the reduction of pain, the midvaste approach was associated with shorter surgical time and less involvement of flexion of the knee. Therefore, the midvasto approach is recommended in patients undergoing primary total knee arthroplasty.

INTRODUCCIÓN: la artroplastía total de rodilla es un procedimiento común en la cirugía ortopédica de tratamiento para gonartrosis grado IV. Este procedimiento disminuye el dolor y mejora la funcionalidad. Sin embargo, los resultados según el abordaje son distintos, no existe evidencia sobre qué abordaje quirúrgico sea claramente superior. El objetivo de este estudio es evaluar el tiempo y sangrado transquirúrgico, así como el dolor postquirúrgico del abordaje midvasto versus parapatelar medial en artroplastía total de rodilla primaria en gonartrosis grado IV. MATERIAL Y MÉTODOS: se realizó estudio observacional, comparativo, retrospectivo del 01 de Junio de 2020 al 31 de Diciembre de 2020 incluyendo derechohabientes del Instituto Mexicano del Seguro Social, mayores de 18 años con diagnóstico de gonartrosis grado IV, programados para artroplastía total de rodilla primaria en ausencia de otra patología inflamatoria, osteotomías previas o coagulopatías. RESULTADOS: noventa y nueve pacientes que fueron sometidos a abordaje midvasto (grupo M) y 100 pacientes a abordaje parapatelar medial (grupo T) con hemoglobina preoperatoria 14.7 g/l grupo M y 15.2 g/l grupo T, la reducción fue de 5.0 g/l grupo M y 4.6 g/l grupo T. Dolor en ambos grupos sin diferencia significativa; de 6.7 a 3.2 grupo M y de 6.7 a 3.1 grupo T. Tiempo quirúrgico mayor con el abordaje parapatelar medial (98.7 versus 89.2 minutos). CONCLUSIONES: ambos abordajes representan excelente vía de acceso para realizar artroplastía total primaria de rodilla; sin embargo, no se encontraron diferencias significativas en el volumen de sangrado ni en la reducción del dolor, el abordaje midvasto se asoció con menor tiempo quirúrgico y menor afectación de la flexión de la rodilla, por lo que se recomienda el abordaje midvasto en pacientes sometidos a artroplastía total de rodilla primaria.

Increase in the frequency of catheter-related bloodstream infections during the COVID-19 pandemic: a plea for control.

BACKGROUND: The incidence of nosocomial infections including ventilator-associated pneumonia and bacteraemia has been described during the COVID-19 pandemic. However, information regarding the impact of COVID-19 on the incidence of catheter-related bloodstream infections (CR-BSIs) is very limited. AIM: To evaluate the impact of the COVID-19 pandemic in the evolution of CR-BSIs in a large hospital. METHODS: This was a retrospective study comparing the incidence, aetiology and outcome of CR-BSIs during the months of March to May 2019 (pre-pandemic) and 2020 (during the pandemic). FINDINGS: The number of patients with one or more CR-BSIs in 2019 and 2020 were 23 and 58, respectively (1.89 vs 5.53/1000 admissions); P<0.001. Median time from catheter implantation to demonstration of CR-BSI was 27.5 days (range 11.75-126.00 days) in the 2019 cases and 16.0 days (range 11.00-23.50 days) in the 2020 population (P=0.032). CONCLUSIONS: A dramatic increase of CR-BSIs was found during the COVID-19 pandemic. Reinforcement of classic and new preventive measures is necessary.

Conocimientos, prácticas y estilos de vida durante COVID-19 entre estudiantes universitarios en México: encuesta en línea / Knowledge, practices and lifestyle during COVID-19 among university students in Mexico: online survey

Introducción: la pandemia del síndrome respiratorio agudo grave Sars-CoV-2 causado por un coronavirus que se denominó COVID-19, revolucionado de forma importante los estilos de vida de la población universitaria, la población requiere de conocimientos y tener buenas prácticas para evitar el contagio por medio del autocuidado, los retos y adaptaciones del aprendizaje en un entorno virtual conlleva a formas de vida modificadas relacionadas con un incremento de sedentarismo, estrés y temor al contagio, entre otros. Objetivo: determinar los estilos de vida saludables, conocimientos y prácticas de cuidado por causa de la pandemia de COVID-19 en estudiantes de enfermería de la Universidad de Morelos. Material y métodos: estudio descriptivo, transversal, con participación de 265 estudiantes. Se aplicaron los cuestionarios en línea HPLP-II, valora estilos de vida y cuestionario ex profeso para conocimientos, práctica del cuidado durante la pandemia, durante septiembre a octubre 2020. Resultados: conocimientos: los estudiantes sólo reconocen la sintomatología respiratoria, mencionan que practican sólo algunas de las medidas de seguridad, se obtuvo asociaciones entre conocimientos, práctica y estilos de vida p=<.05. Discusión: estudios en Perú, Colombia, España y México, revelan resultados semejantes y significativos, relacionan calidad de vida y estilos de vida, conocimientos, actitudes y prácticas adecuadas, así como actitudes positivas de estudiantes universitarios ante la COVID-19. Conclusión: la población universitaria es vulnerable al contagio, aún no han dimensionado la magnitud del problema que se vive, cuentan con escasos recursos, los estilos de vida se fragilizan al afectar las dimensiones alimentación, actividad y ejercicio, control del estrés, relaciones interpersonales, entre otras.

Introduction: the severe acute respiratory syndrome Sars-CoV-2 pandemic, caused by a coronavirus called COVID-19, has significantly revolutionized the lifestyles of the university population, it requires knowledge and good practices to avoid contagion through self-care; the challenges and adaptations of learning in a virtual environment lead to modified lifestyles, related to an increase in sedentary lifestyle, stress and fear of contagion, among others. Objective: determine healthy lifestyles, knowledge and care practices due to the Covid-19 pandemic in nursing students at the University of Morelos. Material and methods: descriptive, cross-sectional study, with participation of 265 students. The HPLP-II online questionnaires were applied, asses lifestyles and an exprofessional questionnaire for knowledge, and practice of care during the pandemic, were applied during September to October 2020. Results: knowledge: students only recognize respiratory symptoms; they mention that they practice only some of safety measures, associations were obtained between knowledge, practice and lifestyles, p = <. 05. Discussion: studies in Peru, Colombia, Spain and Mexico reveal similar and significant results; these relate quality of life and lifestyles, knowledge, attitudes and appropriate practices, as well as positive attitudes of university students towards COVID-19. Conclusion: the university population is vulnerable to contagion, it has not yet dimensioned the magnitude of the problem that it is experiencing, it has few resources, and lifestyles are weakened by affecting the dimensions of nutrition, activity and exercise, stress control, interpersonal relationships, among others.

The effects of dietary calcium and phosphorus level, and feed form during rearing on growth performance, bone traits and egg production in brown egg-type pullets from 0 to 32 weeks of age.

In a 3 × 2 factorial arrangement, effects of feed form (crumbles (CWS), mash (MWS), both with inclusion of 3% finely ground wheat straw, or crumbles with inclusion of 3% oat hulls (COH)), and dietary Ca and P (high and low Ca-P) from 0 to 16 wk of age were studied on growth performance, bone characteristics, and gizzard development of egg-type pullets. The cross-over effect of feeding strategy during rearing on laying performance and egg shell quality was studied from 19 to 32 wk of age. From 0 to 16 wk, ADG, ADFI, and feed conversion ratio (FCR) were improved with CWS and COH compared to MWS, but ADG and FCR were improved with MWS compared to CWS and COH from 11 to 16 wk. Uniformity of BW till 11 wk, and tibia breaking strength at 6 and 16 wk were higher with CWS and COH compared to MWS. Tibia ash content at 11 wk and relative empty proventriculus + gizzard weight (EPG) were lower with CWS and COH compared to MWS, also relative EPG at 11 and 16 wk was higher with COH compared to CWS. At 25 wk BW was lower with MWS compared to CWS and COH, but BW was equal for all treatments at 32 wk. The FCR for egg production was improved with COH compared to MWS. Egg shell parameters were not affected by feed form during rearing. Low Ca-P decreased BW uniformity at 6 wk, relative keel bone weight and ash content at 11 wk, tibia ash content at 11 and 16 wk, increased relative EPG at 6 wk, and improved egg shell quality at 32 wk of age. It was concluded that feeding CWS and COH compared to MWS increased growth performance, but had no clear cross-over effect on egg production. Low dietary Ca-P led to a lower bone mineralization during rearing, nevertheless improved egg shell quality at 32 wk.

Liver Stiffness at the Time of Sustained Virological Response Predicts the Clinical Outcome in People Living With Human Immunodeficiency Virus and Hepatitis C Virus With Advanced Fibrosis Treated With Direct-acting Antivirals.

BACKGROUND: Some people living with hepatitis C virus (HCV) with sustained virological response (SVR) develop hepatic complications. Liver stiffness (LS) predicts clinical outcome in people living with human immunodeficiency virus (HIV) with active HCV coinfection, but information after SVR is lacking. We aimed to analyze the predictive ability of LS at SVR for liver complications in people living with HIV/HCV with advanced fibrosis treated with direct-acting antivirals (DAA). METHODS: In sum, 640 people living with HIV/HCV fulfilling the following criteria were included: (i) Achieved SVR with DAA-including regimen; (ii) LS ≥ 9.5 kPa before therapy; and (iii) LS measurement available at SVR. The primary endpoint was the occurrence of a liver complication-hepatic decompensation or hepatocellular carcinoma (HCC)-or requiring liver transplant after SVR. RESULTS: During a median (Q1-Q3) follow-up of 31.6 (22.7-36.6) months, 19 (3%) patients reached the primary endpoint. In the multivariate analysis, variables (subhazard ratio [SHR] [95% confidence interval]) associated with developing clinical outcomes were: prior hepatic decompensations (3.42 [1.28-9.12]), pretreatment CPT class B or C (62.5 [3.08-1246.42]) and MELD scores (1.37 [1.03-1.82]), CPT class B or C at SVR (10.71 [1.32-87.01]), CD4 cell counts <200/µL at SVR time-point (4.42 [1.49-13.15]), FIB-4 index at SVR (1.39 [1.13-1.70]), and LS at SVR (1.05 [1.02-1.08] for 1 kPa increase). None of the 374 patients with LS <14kPa at SVR time-point developed a liver complication or required hepatic transplant. CONCLUSIONS: LS at the time of SVR after DAA therapy predicts the clinical outcome of people living with HIV/HCV with advanced fibrosis. These results suggest that LS measurement may be helpful to select candidates to be withdrawn from surveillance programs.

Structural Glycoprotein E2 of Classical Swine Fever Virus Interacts with Host Protein Dynactin Subunit 6 (DCTN6) during the Virus Infectious Cycle.

The E2 protein in classical swine fever (CSF) virus (CSFV) is the major virus structural glycoprotein and is an essential component of the viral particle. E2 has been shown to be involved in several functions, including virus adsorption, induction of protective immunity, and virulence in swine. Using the yeast two-hybrid system, we previously identified a swine host protein, dynactin subunit 6 (DCTN6) (a component of the cell dynactin complex), as a specific binding partner for E2. We confirmed the interaction between DCTN6 and E2 proteins in CSFV-infected swine cells by using two additional independent methodologies, i.e., coimmunoprecipitation and proximity ligation assays. E2 residues critical for mediating the protein-protein interaction with DCTN6 were mapped by a reverse yeast two-hybrid approach using a randomly mutated E2 library. A recombinant CSFV mutant, E2ΔDCTN6v, harboring specific substitutions in those critical residues was developed to assess the importance of the E2-DCTN6 protein-protein interaction for virus replication and virulence in swine. CSFV E2ΔDCTN6v showed reduced replication, compared with the parental virus, in an established swine cell line (SK6) and in primary swine macrophage cultures. Remarkably, animals infected with CSFV E2ΔDCTN6v remained clinically normal during the 21-day observation period, which suggests that the ability of CSFV E2 to bind host DCTN6 protein efficiently during infection may play a role in viral virulence.IMPORTANCE Structural glycoprotein E2 is an important component of CSFV due to its involvement in many virus activities, particularly virus-host interactions. Here, we present the description and characterization of the protein-protein interaction between E2 and the swine host protein DCTN6 during virus infection. The E2 amino acid residues mediating the interaction with DCTN6 were also identified. A recombinant CSFV harboring mutations disrupting the E2-DCTN6 interaction was created. The effect of disrupting the E2-DCTN6 protein-protein interaction was studied using reverse genetics. It was shown that the same amino acid substitutions that abrogated the E2-DCTN6 interaction in vitro constituted a critical factor in viral virulence in the natural host, domestic swine. This highlights the potential importance of the E2-DCTN6 protein-protein interaction in CSFV virulence and provides possible mechanisms of virus attenuation for the development of improved CSF vaccines.

Estimation of missed bloodstream infections without the third blood culture set: a retrospective observational single-centre study.

OBJECTIVES: The question of whether to obtain two or three sets of blood cultures to assess the aetiology of bloodstream infections (BSIs) remains open to debate. Few studies have assessed the proportion of BSIs missed without the third blood culture set (BCS). The aim of our study was to determine the proportion of BSIs that would be missed without the third BCS in a hospital where obtaining three BCSs is the standard of care. METHODS: We performed a descriptive retrospective study in Hospital Gregorio Marañón (Madrid) from 2010 to 2013. We included all episodes of BSI in which three BCSs were systematically obtained. RESULTS: We included 4000 episodes of BSI between 2010 and 2013. Without the third BCS, we would have missed 298 (7.5%) episodes of BSI: 141 (47.3%) by gram-positive microorganisms, 147 (49.3%) by gram-negative microorganisms, and 10 (3.4%) by yeasts. In 132/298 (44.3%) of the episodes another clinical sample was obtained within a week of the BCS extraction; in 101/298 (33.9%), the same microorganism was present in a significant clinical sample other than blood. CONCLUSIONS: Our data suggest that performing a third BCS is useful, as not doing this could result in an unacceptable number of BSIs going undetected.

Molecular Characterization of the Viroporin Function of Foot-and-Mouth Disease Virus Nonstructural Protein 2B.

Nonstructural protein 2B of foot-and-mouth disease (FMD) virus (FMDV) is comprised of a small, hydrophobic, 154-amino-acid protein. Structure-function analyses demonstrated that FMDV 2B is an ion channel-forming protein. Infrared spectroscopy measurements using partially overlapping peptides that spanned regions between amino acids 28 and 147 demonstrated the adoption of helical conformations in two putative transmembrane regions between residues 60 and 78 and between residues 119 and 147 and a third transmembrane region between residues 79 and 106, adopting a mainly extended structure. Using synthetic peptides, ion channel activity measurements in planar lipid bilayers and imaging of single giant unilamellar vesicles (GUVs) revealed the existence of two sequences endowed with membrane-porating activity: one spanning FMDV 2B residues 55 to 82 and the other spanning the C-terminal region of 2B from residues 99 to 147. Mapping the latter sequence identified residues 119 to 147 as being responsible for the activity. Experiments to assess the degree of insertion of the synthetic peptides in bilayers and the inclination angle adopted by each peptide regarding the membrane plane normal confirm that residues 55 to 82 and 119 to 147 of 2B actively insert as transmembrane helices. Using reverse genetics, a panel of 13 FMD recombinant mutant viruses was designed, which harbored nonconservative as well as alanine substitutions in critical amino acid residues in the area between amino acid residues 28 and 147. Alterations to any of these structures interfered with pore channel activity and the capacity of the protein to permeabilize the endoplasmic reticulum (ER) to calcium and were lethal for virus replication. Thus, FMDV 2B emerges as the first member of the viroporin family containing two distinct pore domains.IMPORTANCE FMDV nonstructural protein 2B is able to insert itself into cellular membranes to form a pore. This pore allows the passage of ions and small molecules through the membrane. In this study, we were able to show that both current and small molecules are able to pass though the pore made by 2B. We also discovered for the first time a virus with a pore-forming protein that contains two independent functional pores. By making mutations in our infectious clone of FMDV, we determined that mutations in either pore resulted in nonviable virus. This suggests that both pore-forming functions are independently required during FMDV infection.

Isavuconazole is highly active in vitro against Candida species isolates but shows trailing effect.

OBJECTIVES: Isavuconazole is a triazole previously shown to have potent in vitro activity against Aspergillus spp., Mucorales and Candida spp. Unlike other azoles, it is unclear whether isavuconazole induces a trailing effect. We studied isavuconazole MICs for a large collection of Candida isolates from blood samples and determined the extent of the trailing effect when using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) E.Def 7.3.1 method. METHODS: A total of 762 molecularly identified Candida isolates from blood samples of 743 patients admitted to hospital (January 2007 to September 2017) were evaluated and further tested for in vitro susceptibility to isavuconazole following the EUCAST E.Def 7.3.1 test method. RESULTS: C. albicans showed the highest susceptibility, followed by C. parapsilosis and C. tropicalis (geometric mean MIC 0.0029 vs. 0.0049/0.0052, respectively; p <0.001). In contrast, C. glabrata and C. krusei had significantly higher MIC values (geometric mean MIC 0.171 vs. 0.117, respectively). Isavuconazole MIC distributions were not truncated at the lowest concentration tested except for C. albicans. Overall, the mean percentage of trailing was 13.6%, but differences among species were observed: C. glabrata, C. albicans and C. tropicalis exhibited higher trailing compared to C. parapsilosis and non-Candida yeasts (p <0.001). The percentage of non-wild-type C. albicans (considering the heavy trailer isolates as wild type), C. parapsilosis and C. glabrata isolates were 1.1% (4/357), 1.5% (3/201) and 1.1% (1/86), respectively. CONCLUSIONS: Isavuconazole showed high in vitro activity against Candida spp., particularly against C. albicans. A trailing effect is commonly observed with isavuconazole, particularly with C. glabrata.

La epigenética en el tratamiento del dolor / Epigenetics in the treatment of pain

Introducción: La epigenética se refiere a los cambios en el ADN e histonas que no implican alteraciones en la secuencia de nucleótidos y modifican la estructura y condensación de la cromatina, afectando de esta manera la expresión génica y el fenotipo. Las modificaciones epigenéticas son metilación del ADN y modificaciones de histonas. Objetivo: Realizar una revisión de la literatura sobre la importancia de la epigenética en la fisiopatología y el tratamiento del dolor. Materiales y métodos: se hizo una revisión de la bibliografía sobre el concepto de epigenética, sus bases biológicas, impacto sobre el dolor y su relación con posibles tratamientos. Resultados: Los mecanismos epigenéticos han cobrado cada vez más importancia debido a la creciente asociación con enfermedades complejas y comunes, así como por su influencia en el dolor y sus posibles tratamientos. Conclusiones: La epigenética tiene una clara relación en el dolor, en sus bases fisiopatológicas y posibles tratamientos

Introduction: Epigenetics refers to changes in DNA and histones that do not involve alterations in the nucleotide sequence and modify the structure and condensation of the chromatin, thus affecting gene expression and phenotype. Epigenetic modifications are DNA methylation and histone modifications. Objective: To carry out a review of the literature on the importance of Epigenetics in the pathophysiology and treatment of pain. Materials and methods: A review of the literature on the concept of epigenetics, its biological bases, the impact on pain and its relation to possible treatments. Results: Epigenetic mechanisms have become increasingly important due to the growing association with complex and common diseases, as well as their influence on pain and its possible treatments. Conclusions: Epigenetics has a clear relationship in pain, its pathophysiological bases and possible treatments

Identification of cisapride as new inhibitor of putrescine uptake in Trypanosoma cruzi by combined ligand- and structure-based virtual screening.

Nowadays, the pharmacological therapy for the treatment of Chagas disease is based on two old drugs, benznidazole and nifurtimox, which have restricted efficacy against the chronic phase of the illness. To overcome the lack of efficacy of the traditional drugs (and their considerable toxicity), new molecular targets have been studied as starting points to the discovery of new antichagasic compounds. Among them, polyamine transporter TcPAT12 (also known as TcPOT1.1) represents an interesting macromolecule, since polyamines are essential for Trypanosoma cruzi, the parasite that causes the illness, but it cannot synthesize them de novo. In this investigation we report the results of a combined ligand- and structure-based virtual screening for the discovery of new inhibitors of TcPAT12. Initially we filtered out ZINC and Drugbank databases with similarity and QSAR models and then we submitted the candidates to a validated docking based screening. Four structures were selected and tested in T. cruzi epimastigotes proliferation and two of them, Cisapride and [2-(cyclopentyloxy)phenyl]methanamine showed inhibitory effects. Additionally, we performed transport assays which demonstrated that Cisapride interferes with putrescine uptake in a specific mode.