Stability of perpendicular magnetohydrodynamic shocks in materials with ideal and nonideal equations of state.

Magnetized target fusion approach to inertial confinement fusion involves the formation of strong shocks that travel along a magnetized plasma. Shocks, which play a dominant role in thermalizing the upstream kinetic energy generated in the implosion stage, are seldom free from perturbations, and they wrinkle in response to upstream or downstream disturbances. In Z-pinch experiments, significant plasma instability mitigation was observed with pre-embedded axial magnetic fields. To isolate effects, in this work we theoretically study the impact of perpendicular magnetic fields on the planar shock dynamics for different equations of state. For fast magnetosonic shocks in ideal gases, it was found that the magnetic field amplifies the intensity of the perturbations when γ>2 or it weakens them when γ<2. Weak shocks have been found to be stable regardless of the magnetic plasma intensity and gas compressibility; however, for sufficiently strong shocks the magnetic fields can promote a neutral stability/SAE at the shock if the adiabatic index is higher than 1+sqrt[2]. Results have been validated with numerical simulations performed with the FLASH code.

Cholangioscopy under direct visualization: skill progress during a dedicated Image-Guided Surgery Course.

AIMS: Training programs are essential to introduce new methods for bile duct clearance. Visual examination via cholangioscopy is ideal to diagnose and treat biliary tract diseases such as cancer and choledocholithiasis. However, surgeons rarely use cholangioscopes. Specific training is required to master laparoscopic and percutaneous cholangioscopy. This study aims to assess skill acquisition and retention during cholangioscopy training in the Image-Guided Therapies Masterclass. METHODS: This prospective study enrolled 17 physicians undergoing training in interventional treatments of biliary diseases. A novel disposable cholangioscope and access kit were used with a biliary tract model including two simulated common bile duct (CBD) stones. The curriculum required visualization of all critical structures before removal of one stone with a Dormia basket. After informed consent, demographic data and time to exercise completion were recorded on each of two subsequent training days. Task-specific questions were measured at the completion of training using a Likert scale (strongly disagree to strongly agree, 1-5 points). RESULTS: All participants successfully completed the task (6F/11 M, age 36 ± 5 years; 13 surgeons, 4 interventional radiologists; median experience with percutaneous procedures 2 years, range 0-20). Significant improvement in mean task completion time was observed (day 1: 172 ± 59 s, day 2: 89 ± 45 s; P < 0.0001). All task-specific questions were answered with a median rating of 5/5: "The platform facilitates cholangioscopy" and "This training method accelerates gain in proficiency and is useful for residents/fellows" (IQR 5-5), "This platform is useful to measure the proficiency level" and "There is an application for simulation in percutaneous surgery training" (IQR 4.5-5), "The platform is user-friendly" and "The model quality recreates realistic scenarios" (IQR 4-5). CONCLUSION: Cholangioscopic bile duct exploration and stone retrieval were achieved by all participants using a dedicated training program and physical simulator. Significant skill progress was observed during 2 days of dedicated training.

Percutaneous transhepatic cholangioscopy for benign and malignant biliary disease using a novel short single-operator cholangioscope.

BACKGROUND: The length of conventional single-use cholangioscopes poses a challenge for percutaneous or laparoscopic approaches for direct visualization of the biliary tract. The aim of this retrospective observational clinical study was to assess the use of a dedicated percutaneous short single-operator cholangioscope (PSSOC) for diagnosis and treatment of benign or malignant biliary diseases. METHODS: Retrospective analysis of a prospectively maintained database including all consecutive patients undergoing percutaneous transhepatic cholangioscopy with the PSSOC between 06/2021 and 01/2023. RESULTS: Forty patients were included (22F/18 M, age 58.7 ± 16.7 years). The diagnostic and therapeutic management plan was based on procedural findings. Indications were bile duct obstruction associated with complex anatomy (n = 13), choledocholithiasis (n = 11), suspected malignant stenosis of the biliary tract (n = 11), biliary stent placement (n = 2) and removal (n = 1), and failed endoscopic retrograde cholangiopancreatography (n = 2). The cholangioscopies were diagnostic (n = 5), therapeutic (n = 20) or both simultaneously (n = 15). The most frequent procedures were electrohydraulic lithotripsy (n = 25) and biopsy sampling (n = 12). Complications occurred in 7 cases (17.5%), including cholangitis (n = 4, B2), pleural perforation (n = 1, B2), portal bleeding (n = 1, B3), and Tako-Tsubo syndrome (n = 1, B3), classified according to the Society of Interventional Radiology classification. Intraprocedural visual diagnosis was confirmed by the histopathologic result in 11/12 patients in which biopsies were performed (91.7%). PSSOC was relevant to avoid surgery in 2 patients (5%) with indeterminate strictures, allowing to rule out malignancy and treat the lithiasis. CONCLUSIONS: Direct visualization of the biliary tract enabled targeted biopsies for histopathological diagnosis. The visual and histopathological diagnoses were concordant in all but one case. Percutaneous cholangioscopy with a dedicated PSSOC allows to optimize identification and treatment of complex biliary disease including biliary lithiasis while assessing bile duct patency. The clinical use of the novel PSSOC system was safe and effective and could prevent surgical exploration in select patients.

Análisis del sistema XIDE en la gestión de la sobredemanda asistencial / Analysis of the XIDE system in the management of overdemand for care

Objetivo Valorar el impacto y la idoneidad del sistema de citación XIDE en la gestión de la sobredemanda asistencial del centro de salud de Monforte de Lemos (Lugo). Material y métodos Estudio descriptivo, transversal, observacional y analítico. La población de estudio estuvo formada por los pacientes añadidos a la agenda ordinaria como «forzado» o «forzado urgente». La muestra poblacional se obtuvo durante el periodo del 15 de julio al 15 de agosto de 2022. El análisis comparativo se realizó con periodos previos a la implantación del XIDE y la concordancia XIDE/observadores se estimó mediante el cálculo del índice κ de Cohen. Resultados Observamos un aumento de la presión asistencial, tanto en número de consultas/día como en la proporción de consultas forzadas, que han aumentado en un 30-34%. El grupo mayor de 85 años y las mujeres son los mayoritarios en la sobredemanda. El 83,04% de las consultas urgentes fueron citadas mediante el sistema XIDE. El motivo de consulta más frecuente fue el de sospecha de COVID (24,64%), con una concordancia del 51,4% en este grupo y del 65,5% de forma global. Apreciamos un elevado sobretriaje en los tiempos de atención asignados, incluso cuando coincide el motivo de consulta, con una pobre concordancia estadística con los observadores. Destaca la elevada proporción en la sobredemanda de pacientes pertenecientes a otros cupos del centro de salud, por lo que una adecuada gestión de los recursos humanos con una cobertura adecuada de las ausencias lograría reducirla en un 48,5%, mientras que el sistema XIDE (en el supuesto ideal de una concordancia absoluta) solo lograría reducirla en un 43%. Conclusiones La escasa fiabilidad del XIDE se debe fundamentalmente al triaje inadecuado, más que al fracaso en el objetivo de disminuir la sobredemanda, por lo que no puede sustituir a un sistema de triaje realizado por personal sanitario (AU)

Objective To assess the impact and suitability of the XIDE citation system in the management of over-demand for care at the Monforte de Lemos Health Center (Lugo, Spain). Material and methods Descriptive, cross-sectional, observational and analytical study. The study population was the patients with appointments to the elderly in the ordinary agenda as «forced» or «urgent forced». The population sample was obtained during the period from July 15 to August 15, 2022. The comparative analysis was performed with periods prior to the implementation of XIDE and the XIDE/observer concordance was estimated by calculating Cohen's kappa index. Results We observed an increase in care pressure, both in the number of consultations/day and in the proportion of forced consultations, which have increased by 30-34%. The group over 85 years of age and women are the majority in excess demand. The 83.04% of urgent consultations were cited through the XIDE system, the most frequent reason for consultation being «suspected COVID» (24.64%), with a concordance of 51.4% in this group and 65.5% globally. We appreciate a high overtriage in the assigned attention times, even when the reason for consultation coincides, with a poor statistical concordance with the observers. The high proportion in the overdemand of patients belonging to other places in the health center stands out, so that adequate management of human resources with adequate coverage of absences would reduce it by 48.5%, while the XIDE system (in the ideal assumption of absolute concordance) would only manage to reduce it by 43%. Conclusions The low reliability of the XIDE is mainly due to inadequate triage, rather than the failure to reduce overdemand, so it cannot replace a triage system performed by health personnel (AU)

Behaviour of mesopredatory coral reef fishes in response to threats from sharks and humans.

Both sharks and humans present a potentially lethal threat to mesopredatory fishes in coral reef systems, with implications for both population dynamics and the role of mesopredatory fishes in reef ecosystems. This study quantifies the antipredator behaviours mesopredatory fishes exhibit towards the presence of large coral reef carnivores and compares these behavioural responses to those elicited by the presence of snorkelers. Here, we used snorkelers and animated life-size models of the blacktip reef shark (Carcharhinus melanopterus) to simulate potential predatory threats to mesopredatory reef fishes (lethrinids, lutjanids, haemulids and serranids). The responses of these reef fishes to the models and the snorkelers were compared to those generated by three non-threatening controls (life-size models of a green turtle [Chelonia mydas], a PVC-pipe [an object control] and a Perspex shape [a second object control]). A Remote Underwater Stereo-Video System (Stereo-RUV) recorded the approach of the different treatments and controls and allowed accurate measurement of Flight Initiation Distance (FID) and categorization of the type of flight response by fishes. We found that mesopredatory reef fishes had greater FIDs in response to the approach of threatening models (1402 ± 402-1533 ± 171 mm; mean ± SE) compared to the controls (706 ± 151-896 ± 8963 mm). There was no significant difference in FID of mesopredatory fishes between the shark model and the snorkeler, suggesting that these treatments provoked similar levels of predator avoidance behaviour. This has implications for researchers monitoring behaviour in situ or using underwater census as a technique to estimate the abundance of reef fishes. Our study suggests that, irrespective of the degree to which sharks actually consume these mesopredatory reef fishes, they still elicit a predictable and consistent antipredator response that has the potential to create risk effects.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

[Analysis of the XIDE system in the management of overdemand for care]. / Análisis del sistema XIDE en la gestión de la sobredemanda asistencial.

OBJECTIVE: To assess the impact and suitability of the XIDE citation system in the management of over-demand for care at the Monforte de Lemos Health Center (Lugo, Spain). MATERIAL AND METHODS: Descriptive, cross-sectional, observational and analytical study. The study population was the patients with appointments to the elderly in the ordinary agenda as «forced¼ or «urgent forced¼. The population sample was obtained during the period from July 15 to August 15, 2022. The comparative analysis was performed with periods prior to the implementation of XIDE and the XIDE/observer concordance was estimated by calculating Cohen's kappa index. RESULTS: We observed an increase in care pressure, both in the number of consultations/day and in the proportion of forced consultations, which have increased by 30-34%. The group over 85 years of age and women are the majority in excess demand. The 83.04% of urgent consultations were cited through the XIDE system, the most frequent reason for consultation being «suspected COVID¼ (24.64%), with a concordance of 51.4% in this group and 65.5% globally. We appreciate a high overtriage in the assigned attention times, even when the reason for consultation coincides, with a poor statistical concordance with the observers. The high proportion in the overdemand of patients belonging to other places in the health center stands out, so that adequate management of human resources with adequate coverage of absences would reduce it by 48.5%, while the XIDE system (in the ideal assumption of absolute concordance) would only manage to reduce it by 43%. CONCLUSIONS: The low reliability of the XIDE is mainly due to inadequate triage, rather than the failure to reduce overdemand, so it cannot replace a triage system performed by health personnel.

XAIRE: An ensemble-based methodology for determining the relative importance of variables in regression tasks. Application to a hospital emergency department.

Nowadays it is increasingly important in many applications to understand how different factors influence a variable of interest in a predictive modeling process. This task becomes particularly important in the context of Explainable Artificial Intelligence. Knowing the relative impact of each variable on the output allows us to acquire more information about the problem and about the output provided by a model. This paper proposes a new methodology, XAIRE, that determines the relative importance of input variables in a prediction environment, considering multiple prediction models in order to increase generality and avoid bias inherent in a particular learning algorithm. Concretely, we present an ensemble-based methodology that promotes the aggregation of results from several prediction methods to obtain a relative importance ranking. Also, statistical tests are considered in the methodology in order to reveal significant differences between the relative importance of the predictor variables. As a case study, XAIRE is applied to the arrival of patients in a Hospital Emergency Department, which has resulted in one of the largest sets of different predictor variables in the literature. Results show the extracted knowledge related to the relative importance of the predictors involved in the case study.

Lactoferrin gene polymorphisms associated with clinical mastitis in Honduran Holstein inheritance cows.

BACKGROUND: Lactoferrin (LTF) is an iron-binding glycoprotein found in milk and other exocrine secretion with antibacterial activity proposed as an alternative to mastitis treatment or prevention. LTF has been proposed as a candidate gene for mastitis resistance selection. The aim of this paper was to assess LTF promotor to explore variations with potential association to mastitis resistance in dairy cows from Honduras. METHODS: A resequencing of promotor and Exon I of LTF gene in extreme mastitis susceptibility cows (126 Holstein and Holstein crossbred) was performed. RESULTS: Eight polymorphisms were found in promotor region, four of them were novel variations. Two were important by frequency among extreme groups, but a polymorphism in - 421 A/T position was significantly (P = 0.0188) associated to mastitis susceptibility. CONCLUSION: Results support the key role of regulatory region of LTF gene. Some candidate genes are proposed in association with mastitis traits and implications are discussed.

HIV Knowledge, Risk Behaviors, and Testing Among Chinese-, Korean-, and Vietnamese-American Women.

The relationship between HIV knowledge and testing behavior is poorly understood among young Chinese-, Korean-, and Vietnamese-American women. This study assesses: (1) levels of HIV/AIDS knowledge, (2) lifetime and annual prevalence of HIV testing, and (3) whether higher levels of HIV knowledge were associated with increased likelihood of testing after controlling for HIV risk behaviors. Fifty-one percent reported lifetime HIV testing (n=117); among those tested, 53% were tested within the past year. A significant and positive association between scores on the HIV Knowledge Questionnaire (HIV KQ-45) and HIV testing was identified. This association was no longer statistically significant after controlling for sexual risk behaviors. Participants were most knowledgeable about HIV symptoms (88.6%) and least knowledgeable about treatment options (56.8%). Future studies should further characterize cultural factors affecting these women's sexual practices, as well develop culturally adapted HIV educational interventions to increase HIV knowledge and testing rates.

SAFETY AND EFFICACY OF THYMIC PEPTIDES IN THE TREATMENT OF HOSPITALIZED COVID-19 PATIENTS IN HONDURAS.

Coronavirus disease 2019 (Covid-19) active cases continue to demand the development of safe and effective treatments. This is the first clinical trial to evaluate the safety and efficacy of oral thymic peptides. ; We conducted a nonrandomized phase 2 trial with a historic control group to evaluate the safety and efficacy of a daily 250-mg oral dose of thymic peptides in the treatment of hospitalized Covid-19 patients. Comparisons based on standard care from registry data were performed after propensity score matching. The primary outcomes were survival, time to recovery, and number of participants with treatment-related adverse events or side effects by day 20. ; A total of 44 patients were analyzed in this study: 22 in the thymic peptide group and 22 in the standard care group. There were no deaths in the intervention group compared to 24% mortality in standard care by day 20 (log-rank P=0.02). Kaplan-Meier analysis showed a significantly shorter time to recovery by day 20 in the thymic peptide group than in the standard care group (median, 6 days vs. 12 days; hazard ratio for recovery, 2.75 [95% confidence interval, 1.34 to 5.62]; log-rank P=0.002). No side effects or adverse events were reported. ; In patients hospitalized with Covid-19, the use of thymic peptides resulted in no side effects, adverse events, or deaths by day 20. Compared with the registry data, a significantly shorter time to recovery and mortality reduction were measured.

[Periodic plasmapheresis as maintenance treatment in relapsing-remitting multiple sclerosis, a new therapeutic line? A case report]. / Plasmaféresis periódica como tratamiento de mantenimiento en la esclerosis múltiple remitente-recurrente, ¿nueva línea terapéutica? A propósito de un caso.

INTRODUCTION: Relapsing-remitting multiple sclerosis (RRMS) treatment has significantly changed in recent years because of the discovery of new molecules that have shown efficacy as maintenance treatment. However, the classical treatment for acute attacks is based on corticosteroids administration, being the periodical plasmapheresis the alternative treatment in the case of refractory patients. We introduce a case of relapsing-remitting multiple sclerosis treated with a classical acute attacks therapy: plasmapheresis. CASE REPORT: The case of a 39-year-old patient who was diagnosed with relapsing-remitting multiple sclerosis, postpartum debut and aggresive course, who, after suboptimal response to disease modifying therapies (alemtuzumab and ocrelizumab), receives combination treatment with outpatient periodic plasmapheresis every 3 weeks as maintenance therapy. Good tolerance and response. Clinical stability with this treatment. She has not required new hospital admissions for acute attacks of multiple sclerosis from February 2020 to March 2021. CONCLUSION: Although more specific studies are needed, this case provides information on a potential new maintenance treatment for patients with relapsing-remitting multiple sclerosis refractory to disease-modifying drug therapies.

TITLE: Plasmaféresis periódica como tratamiento de mantenimiento en la esclerosis múltiple remitente-recurrente, ¿nueva línea terapéutica? A propósito de un caso.Introducción. El tratamiento de la esclerosis múltiple remitente-recurrente ha evolucionado significativamente en los últimos años con el descubrimiento de nuevas moléculas eficaces como tratamiento de mantenimiento. Por otro lado, el tratamiento de los brotes de esta enfermedad se basa clásicamente en corticoides, y en los casos refractarios a esta terapia se utiliza plasmaféresis. Presentamos un caso de esclerosis múltiple remitente-recurrente tratada periódicamente con una terapia que se ha utilizado clásicamente para los brotes: plasmaféresis. Caso clínico. Mujer de 39 años con esclerosis múltiple remitente-recurrente de inicio en el posparto, gran carga lesional y curso agresivo, en quien, ante una respuesta subóptima a terapias modificadoras de la enfermedad (alemtuzumab y ocrelizumab), se decide iniciar un tratamiento combinado junto con plasmaféresis periódicas ambulatorias cada tres semanas como tratamiento de mantenimiento. Se constata una buena tolerancia a esta terapia y evolución, y se produce estabilidad clínica. No ha requerido nuevos ingresos hospitalarios por brotes desde febrero de 2020 a marzo de 2021. Conclusión. Aunque es necesario que se realicen más estudios, este caso ofrece información sobre un potencial tratamiento de mantenimiento para pacientes con esclerosis múltiple remitente-recurrente refractaria a terapias con fármacos modificadores de la enfermedad.

Plasmaféresis periódica como tratamiento de mantenimiento en la esclerosis múltiple remitente-recurrente, ¿nueva línea terapéutica? A propósito de un caso / Periodic plasmapheresis as maintenance treatment in relapsing-remitting multiple sclerosis, a new therapeutic line? A case report

Introducción: El tratamiento de la esclerosis múltiple remitente-recurrente ha evolucionado significativamente en los últimos años con el descubrimiento de nuevas moléculas eficaces como tratamiento de mantenimiento. Por otro lado, el tratamiento de los brotes de esta enfermedad se basa clásicamente en corticoides, y en los casos refractarios a esta terapia se utiliza plasmaféresis. Presentamos un caso de esclerosis múltiple remitente-recurrente tratada periódicamente con una terapia que se ha utilizado clásicamente para los brotes: plasmaféresis. Caso clínico: Mujer de 39 años con esclerosis múltiple remitente-recurrente de inicio en el posparto, gran carga lesional y curso agresivo, en quien, ante una respuesta subóptima a terapias modificadoras de la enfermedad (alemtuzumab y ocrelizumab), se decide iniciar un tratamiento combinado junto con plasmaféresis periódicas ambulatorias cada tres semanas como tratamiento de mantenimiento. Se constata una buena tolerancia a esta terapia y evolución, y se produce estabilidad clínica. No ha requerido nuevos ingresos hospitalarios por brotes desde febrero de 2020 a marzo de 2021. Conclusión: Aunque es necesario que se realicen más estudios, este caso ofrece información sobre un potencial tratamiento de mantenimiento para pacientes con esclerosis múltiple remitente-recurrente refractaria a terapias con fármacos modificadores de la enfermedad.(AU)

Introduction: Relapsing-remitting multiple sclerosis (RRMS) treatment has significantly changed in recent years because of the discovery of new molecules that have shown efficacy as maintenance treatment. However, the classical treatment for acute attacks is based on corticosteroids administration, being the periodical plasmapheresis the alternative treatment in the case of refractory patients. We introduce a case of relapsing-remitting multiple sclerosis treated with a classical acute attacks therapy: plasmapheresis. Case report: The case of a 39-year-old patient who was diagnosed with relapsing-remitting multiple sclerosis, postpartum debut and aggresive course, who, after suboptimal response to disease modifying therapies (alemtuzumab and ocrelizumab), receives combination treatment with outpatient periodic plasmapheresis every 3 weeks as maintenance therapy. Good tolerance and response. Clinical stability with this treatment. She has not required new hospital admissions for acute attacks of multiple sclerosis from February 2020 to March 2021. Conclusion: Although more specific studies are needed, this case provides information on a potential new maintenance treatment for patients with relapsing-remitting multiple sclerosis refractory to disease-modifying drug therapies.(AU)

The Stickland Reaction Precursor trans-4-Hydroxy-l-Proline Differentially Impacts the Metabolism of Clostridioides difficile and Commensal Clostridia.

An intact gut microbiota confers colonization resistance against Clostridioides difficile through a variety of mechanisms, likely including competition for nutrients. Recently, proline was identified as an important environmental amino acid that C. difficile uses to support growth and cause significant disease. A posttranslationally modified form, trans-4-hydroxyproline, is highly abundant in collagen, which is degraded by host proteases in response to C. difficile toxin activity. The ability to dehydrate trans-4-hydroxyproline via the HypD glycyl radical enzyme is widespread among gut microbiota, including C. difficile and members of the commensal Clostridia, suggesting that this amino acid is an important nutrient in the host environment. Therefore, we constructed a C. difficile ΔhypD mutant and found that it was modestly impaired in fitness in a mouse model of infection, and was associated with an altered microbiota when compared to mice challenged with the wild-type strain. Changes in the microbiota between the two groups were largely driven by members of the Lachnospiraceae family and the Clostridium genus. We found that C. difficile and type strains of three commensal Clostridia had significant alterations to their metabolic gene expression in the presence of trans-4-hydroxyproline in vitro. The proline reductase (prd) genes were elevated in C. difficile, consistent with the hypothesis that trans-4-hydroxyproline is used by C. difficile to supply proline for energy metabolism. Similar transcripts were also elevated in some commensal Clostridia tested, although each strain responded differently. This suggests that the uptake and utilization of other nutrients by the commensal Clostridia may be affected by trans-4-hydroxyproline metabolism, highlighting how a common nutrient may be a signal to each organism to adapt to a unique niche. Further elucidation of the differences between them in the presence of hydroxyproline and other key nutrients will be important in determining their role in nutrient competition against C. difficile. IMPORTANCE Proline is an essential environmental amino acid that C. difficile uses to support growth and cause significant disease. A posttranslationally modified form, hydroxyproline, is highly abundant in collagen, which is degraded by host proteases in response to C. difficile toxin activity. The ability to dehydrate hydroxyproline via the HypD glycyl radical enzyme is widespread among gut microbiota, including C. difficile and members of the commensal Clostridia, suggesting that this amino acid is an important nutrient in the host environment. We found that C. difficile and three commensal Clostridia strains had significant, but different, alterations to their metabolic gene expression in the presence of hydroxyproline in vitro. This suggests that the uptake and utilization of other nutrients by the commensal Clostridia may be affected by hydroxyproline metabolism, highlighting how a common nutrient may be a signal to each organism to adapt to a unique niche. Further elucidation of the differences between them in the presence of hydroxyproline and other key nutrients will be important to determining their role in nutrient competition against C. difficile.

Cefalea asociada con el uso de equipo de protección personal durante la pandemia de la COVID-19: una forma práctica de mejorar esta condición. Réplica.

TITLE: Cefalea asociada con el uso de equipo de protección personal durante la pandemia de la COVID-19: una forma práctica de mejorar esta condición. Réplica.

Drug connectivity mapping and functional analysis reveal therapeutic small molecules that differentially modulate myelination.

Disruption or loss of oligodendrocytes (OLs) and myelin has devastating effects on CNS function and integrity, which occur in diverse neurological disorders, including Multiple Sclerosis (MS), Alzheimer's disease and neuropsychiatric disorders. Hence, there is a need to develop new therapies that promote oligodendrocyte regeneration and myelin repair. A promising approach is drug repurposing, but most agents have potentially contrasting biological actions depending on the cellular context and their dose-dependent effects on intracellular pathways. Here, we have used a combined systems biology and neurobiological approach to identify compounds that exert positive and negative effects on oligodendroglia, depending on concentration. Notably, next generation pharmacogenomic analysis identified the PI3K/Akt modulator LY294002 as the most highly ranked small molecule with both pro- and anti-oligodendroglial concentration-dependent effects. We validated these in silico findings using multidisciplinary approaches to reveal a profoundly bipartite effect of LY294002 on the generation of OPCs and their differentiation into myelinating oligodendrocytes in both postnatal and adult contexts. Finally, we employed transcriptional profiling and signalling pathway activity assays to determine cell-specific mechanisms of action of LY294002 on oligodendrocytes and resolve optimal in vivo conditions required to promote myelin repair. These results demonstrate the power of multidisciplinary strategies in determining the therapeutic potential of small molecules in neurodegenerative disorders.

Shotgun metagenome sequencing of a Sudanese toombak snuff tobacco: genetic attributes of a high tobacco-specific nitrosamine containing smokeless tobacco product.

The most alarming aspect of the Sudanese toombak smokeless tobacco is that it contains high levels of highly toxic tobacco-specific nitrosamines (TSNAs). Understanding the microbiology of toombak is of relevance because TSNAs are an indirect result of microbial-mediated nitrate reductions. We conducted shotgun metagenomic sequencing on a toombak product for which relevant features are presented here. The microbiota was composed of over 99% Bacteria. The most abundant taxa included Actinobacteria, specifically the genera Enteractinococcus and Corynebacterium, while Firmicutes were represented by the family Bacillaceae and the genus Staphylococcus. Selected gene targets were nitrate reduction and transport, antimicrobial resistance, and other genetic transference mechanisms. Canonical nitrate reduction and transport genes (i.e. nar) were found for Enteractinococcus and Corynebacterium while various species of Staphylococcus exhibited a notable number of antimicrobial resistance and genetic transference genes. The nitrate reduction activity of the microbiota in toombak is suspected to be a contributing factor to its high levels of TSNAs. Additionally, the presence of antimicrobial resistance and transference genes could contribute to deleterious effects on oral and gastrointestinal health of the end user. Overall, the high toxicity and increased incidences of cancer and oral disease of toombak users warrants further investigation into the microbiology of toombak.

Extremely long-range, high-temperature Josephson coupling across a half-metallic ferromagnet.

The Josephson effect results from the coupling of two superconductors across a spacer such as an insulator, a normal metal or a ferromagnet to yield a phase coherent quantum state. However, in junctions with ferromagnetic spacers, very long-range Josephson effects have remained elusive. Here we demonstrate extremely long-range (micrometric) high-temperature (tens of kelvins) Josephson coupling across the half-metallic manganite La0.7Sr0.3MnO3 combined with the superconducting cuprate YBa2Cu3O7. These planar junctions, in addition to large critical currents, display the hallmarks of Josephson physics, such as critical current oscillations driven by magnetic flux quantization and quantum phase locking effects under microwave excitation (Shapiro steps). The latter display an anomalous doubling of the Josephson frequency predicted by several theories. In addition to its fundamental interest, the marriage between high-temperature, dissipationless quantum coherent transport and full spin polarization brings opportunities for the practical realization of superconducting spintronics, and opens new perspectives for quantum computing.

[Headache associated with the use of personal protective equipment during the COVID-19 pandemic: an international survey]. / Cefalea asociada con el uso de equipo de protección personal durante la pandemia de COVID-19: una encuesta internacional.

INTRODUCTION: The COVID-19 pandemic and the use of personal protective equipment (PPE) in the healthcare setting provide a unique opportunity to study PPE-associated headaches (PPEAH). SUBJECTS AND METHODS: We conducted an online survey to assess the prevalence and clinical characteristics of PPEAH. The survey was voluntary, anonymous and addressed to medical and non-medical personnel. We used descriptive statistics and univariate and multivariate comparative analyses to identify factors associated with the development of PPEAH and its impact on work capacity. RESULTS: Out of 886 respondents, 88% (780) reported wearing PPE. Most of them were physicians (81%), 52.4% of whom were women. The prevalence of PPEAH was 65.5% (511/780) and 73.8% (377/511) were de novo headaches. PPEAH was acute, oppressive, bifrontal and of moderate intensity, and subsided with the removal of the PPE. Accompanying symptoms were common, and migraine and/or dysautonomic features were highly prevalent. Female sex, age > 40 years, use of PPE > 6 hours/day and the combination of an N95 mask and goggles were associated with the occurrence of PPEAH. There were factors associated with a negative impact on the ability to work because of the PPEAH. DISCUSSION: PPEAH may be a form of external compression headache (ECH); however, it has distinctive features that overlap with other primary and/or secondary headache disorders. CONCLUSIONS: PPEAH is prevalent and impacts on work-related activities. One subgroup presents characteristics not previously described in ECH.

TITLE: Cefalea asociada con el uso de equipo de protección personal durante la pandemia de COVID-19: una encuesta internacional.Introducción. La pandemia de COVID-19 y el uso de equipo de protección personal (EPP) en el entorno de la atención médica brindan una oportunidad única para estudiar la cefalea relacionada con el EPP (CREPP). Sujetos y métodos. Realizamos una encuesta en línea para evaluar la prevalencia y las características clínicas de la CREPP. La encuesta fue voluntaria, anónima y dirigida a personal médico y no médico. Utilizamos estadística descriptiva y análisis comparativos univariados y multivariados para identificar factores asociados con el desarrollo de CREPP y su impacto en la capacidad de trabajo. Resultados. De 886 encuestados, el 88% (780) notificó que usaba EPP. La mayoría eran médicos (81%), un 52,4% mujeres. La prevalencia de CREPP fue del 65,5% (511/780) y el 73,8% (377/511) fueron cefaleas de novo. La CREPP fue aguda, opresiva, bifrontal y de intensidad moderada, y remitía con el retiro del EPP. Los síntomas acompañantes fueron comunes, y las características migrañosas y/o disautonómicas fueron altamente prevalentes. El sexo femenino, la edad > 40 años, el uso de EPP > 6 horas/día y la combinación de mascarilla N95 y gafas se asociaron con la aparición de CREPP. Hubo factores asociados con un impacto negativo en la capacidad para trabajar debido a la CREPP. Discusión. La CREPP podría ser una forma de cefalea por compresión externa (CCE); no obstante, tiene características distintivas que se superponen con otros trastornos de cefaleas primarias y/o secundarias. Conclusiones. La CREPP es frecuente e impacta en las actividades relacionadas con el trabajo. Un subgrupo presenta características no descritas previamente en la CCE.