A TBK1 variant causes autophagolysosomal and motoneuron pathology without neuroinflammation in mice.

Heterozygous mutations in the TBK1 gene can cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The majority of TBK1-ALS/FTD patients carry deleterious loss-of-expression mutations, and it is still unclear which TBK1 function leads to neurodegeneration. We investigated the impact of the pathogenic TBK1 missense variant p.E696K, which does not abolish protein expression, but leads to a selective loss of TBK1 binding to the autophagy adaptor protein and TBK1 substrate optineurin. Using organelle-specific proteomics, we found that in a knock-in mouse model and human iPSC-derived motor neurons, the p.E696K mutation causes presymptomatic onset of autophagolysosomal dysfunction in neurons precipitating the accumulation of damaged lysosomes. This is followed by a progressive, age-dependent motor neuron disease. Contrary to the phenotype of mice with full Tbk1 knock-out, RIPK/TNF-α-dependent hepatic, neuronal necroptosis, and overt autoinflammation were not detected. Our in vivo results indicate autophagolysosomal dysfunction as a trigger for neurodegeneration and a promising therapeutic target in TBK1-ALS/FTD.

An Innovative Approach to the Dismantlement of a Forensic Psychiatric Hospital in Italy: A Ten-year Impact Evaluation.

Aims: This study aimed to evaluate the impacts of a pilot project concerning the closure of a Forensic Psychiatric Hospital (FPH) inspired by Human Development Theory and the Capability Approach. Background: The dismantlement of the FPH of Barcellona Pozzo di Gotto (Sicily Region in Italy) began in 2010 with the pilot project Luce é Libertà and ended in 2017. With the closure of six FPHs, Italy officially became the first country worldwide to close such institutions. After the closure of FPHs, some critical issues emerged, and the debate shifted to developing small-scale facilities and residences for the execution of security measures (RESM). However, few studies have provided results on the cohort of patients discharged from FPHs. Objective: Following are the objectives of this study: a) Assessing the effectiveness of the pilot project in terms of better functioning accordingly to the Classification of Functioning of Disability and Health (ICF) framework, social and labour insertion, health conditions, level of dangerousness to other, rate of readmission in forensic services, b) cost analysis, and c) describing how the CA has been applied and translated into methodological and administrative devices and concrete intervention strategies. Methods: A pre-post evaluation design was performed with a comparison between the intervention and the control group for the healthcare cost analysis. Data were collected from 2010 to 2019 at three points: T0) as a baseline, T1 and T2) for the follow-up. The instruments are a structured questionnaire, the Scale HoNOS Secure, 4 sub-scales of ICF (Activity and participation dimensions: sociality, culture, and knowledge, daily life, income, and work) (Cronbach's Alpha from 0.76 to 0.94), and n.20 interviews with key stakeholders and beneficiaries. Results: Main results include a) the discharge of 55 patients through the use of a person-centered approach and the Personal Capability Budget (PCB), b) the expansion of substantial freedom of choice and the improvement of ICF score (t-test Sig. <, 02), c) the reduction of the risk for others and themselves (Mean Diff. -2,15 Sig. .000), d) at T2 42% of beneficiaries achieved a job placement and 36% were living in one's own home, e) at T2 the need of security measures has reduced from the initial 70% to 6.8%, and f) reduction of the healthcare costs from the fourth year onwards. Conclusion: Indications emerge to support processes of deinstitutionalisation and capabilities expansion through innovative models, a person-centered approach supported by PCBs, social finance, and social impact investments.

First molecular characterization of Escherichia coli O157:H7 isolates from clinical samples in Paraguay using whole-genome sequencing Molecular characterization of Escherichia coli O157 isolates from Paraguay / Primera caracterización molecular de aislamientos de Escherichia coli O157:H7 provenientes de muestras clínicas en Paraguay utilizando secuenciación de genoma completo

Abstract Escherichia coli O157:H7 is a foodborne pathogen implicated in numerous outbreaks worldwide that has the ability to cause extra-intestinal complications in humans. The Enteropathogens Division of the Central Public Health Laboratory (CPHL) in Paraguay is working to improve the genomic characterization of Shiga toxin-producing E. coli (STEC) to enhance laboratory-based surveillance and investigation of foodborne disease outbreaks. Whole genome sequencing (WGS) is proposed worldwide to be used in the routine laboratory as a high-resolution tool that allows to have all the results in a single workflow. This study aimed to carry out for the first time, the genomic characterization by WGS of nine STEC O157:H7 strains isolated from human samples in Paraguay. We were able to identify virulence and resistance mechanisms, MLST subtype, and even establish the phylogenetic relationships between isolates. Furthermore, we detected the presence of strains belonging to hypervirulent clade 8 in most of the isolates studied.

Resumen Escherichia coli O157:H7 es un patógeno transmitido por alimentos implicado en numerosos brotes en todo el mundo y es capaz de causar complicaciones extraintestinales en humanos. La sección de «Enteropatógenos¼ del Laboratorio Central de Salud Pública trabaja en mejorar la caracterización genómica de STEC, de modo de potenciar la vigilancia laboratorial y la investigación de brotes de enfermedades transmitidas por alimentos. La secuenciación de genoma completo (WGS, por sus siglas en inglés) se propone a nivel mundial como una herramienta de alta resolución para ser utilizada en el laboratorio de rutina, ya que permite obtener todos los resultados en un único proceso. El objetivo de este trabajo fue llevar a cabo, por primera vez, la caracterización genómica por WGS de nueve cepas STEC O157:H7 aisladas en Paraguay a partir de muestras de origen humano. Pudimos identificar los factores de virulencia, los mecanismos de resistencia, el subtipo MLST, e incluso pudimos establecer la relación filogenética entre los aislamientos. Además, detectamos que la mayoría de las cepas pertenecían al clado hipervirulento 8.

Non-canonical telomere protection role of FOXO3a of human skeletal muscle cells regulated by the TRF2-redox axis.

Telomeric repeat binding factor 2 (TRF2) binds to telomeres and protects chromosome ends against the DNA damage response and senescence. Although the expression of TRF2 is downregulated upon cellular senescence and in various aging tissues, including skeletal muscle tissues, very little is known about the contribution of this decline to aging. We previously showed that TRF2 loss in myofibers does not trigger telomere deprotection but mitochondrial dysfunction leading to an increased level of reactive oxygen species. We show here that this oxidative stress triggers the binding of FOXO3a to telomeres where it protects against ATM activation, revealing a previously unrecognized telomere protective function of FOXO3a, to the best of our knowledge. We further showed in transformed fibroblasts and myotubes that the telomere properties of FOXO3a are dependent on the C-terminal segment of its CR2 domain (CR2C) but independent of its Forkhead DNA binding domain and of its CR3 transactivation domain. We propose that these non-canonical properties of FOXO3a at telomeres play a role downstream of the mitochondrial signaling induced by TRF2 downregulation to regulate skeletal muscle homeostasis and aging.

Racial and gender-based disparities and trends in common psychiatric conditions in liver cirrhosis hospitalizations: A ten-year United States study.

BACKGROUND: Chronic liver disease is associated with various neuropsychiatric conditions. There are currently no large studies assessing and comparing the prevalence of psychiatric illnesses based on patient profiles and the etiology of cirrhosis. AIM: To examine the trends of hospitalizations among psychiatric conditions in cirrhosis. METHODS: We used the National Inpatient Sample database 2016-2019 for the primary diagnosis of liver cirrhosis. The outcomes included the prevalence, trends, and associations of psychiatric diagnoses in these hospitalizations. Chi-square for categorical variables and the Wilcoxon rank test for continuous variables were utilized. RESULTS: The prevalence of generalized anxiety disorder (GAD) in liver cirrhosis hospitalizations increased from 0.17% in 2009 to 0.92% in 2019 (P < 0.001). The prevalence of depression increased from 7% in 2009 to 12% in 2019 (P < 0.001). Attention deficit hyperactivity disorder (ADHD) prevalence increased from 0.06% to 0.24%. The prevalence of schizophrenia increased from 0.59% to 0.87% (P < 0.001). Schizoaffective disorder prevalence increased from 0.10% to 0.35% (P < 0.001). Post-traumatic stress disorder (PTSD) prevalence displayed increasing trends from 0.36% in 2009 to 0.93% in 2019 (P < 0.001). The prevalence of suicidal ideation increased from 0.23% to 0.56% in 2019. Cirrhosis related to alcoholic liver disease [adjusted odds ratios (aOR) 1.18, 95%CI 1.08-1.29, P < 0.001] and non-alcoholic fatty liver disease (NAFLD) (aOR 1.14, 95%CI 1.01-1.28, P = 0.025) was associated with depression more than other causes. Alcohol- and NAFLD-associated cirrhosis had a stronger link to psychiatric disorders. Females had a higher association with GAD (aOR 2.56, 95%CI 2.14-3.06, P < 0.001), depression (aOR 1.78, 95%CI 1.71-1.84, P < 0.001), bipolar disorder (aOR 1.64, 95%CI 1.52-1.77, P < 0.001] and chronic fatigue (aOR 2.31, 95%CI 1.31-4.07, P < 0.001) when compared to males. Blacks, Hispanics, and Asian/Native Americans had a significantly lower association with GAD, depression, bipolar disorder, PTSD, and ADHD when compared to the white race. CONCLUSION: The prevalence of psychiatric comorbidities in liver cirrhosis hospitalizations has increased over the last decade. Females had a higher association with psychiatric disorders compared to males. Blacks, Hispanics, and Asian/Native Americans had lower associations with psychiatric comorbidities compared to the white race.

First molecular characterization of Escherichia coli O157:H7 isolates from clinical samples in Paraguay using whole-genome sequencing.

Escherichia coli O157:H7 is a foodborne pathogen implicated in numerous outbreaks worldwide that has the ability to cause extra-intestinal complications in humans. The Enteropathogens Division of the Central Public Health Laboratory (CPHL) in Paraguay is working to improve the genomic characterization of Shiga toxin-producing E. coli (STEC) to enhance laboratory-based surveillance and investigation of foodborne disease outbreaks. Whole genome sequencing (WGS) is proposed worldwide to be used in the routine laboratory as a high-resolution tool that allows to have all the results in a single workflow. This study aimed to carry out for the first time, the genomic characterization by WGS of nine STEC O157:H7 strains isolated from human samples in Paraguay. We were able to identify virulence and resistance mechanisms, MLST subtype, and even establish the phylogenetic relationships between isolates. Furthermore, we detected the presence of strains belonging to hypervirulent clade 8 in most of the isolates studied.

Facilitadores de la Violencia de Pareja Percibidos por Víctimas y Victimarios: Estudio Exploratorio en el Contexto de la Teoría del Aprendizaje Social / Facilitators of Intimate Partner Violence as Perceived by Victims and Perpetrators: An Exploratory Study in the Context of Social Learning Theory

Resumen Pocos estudios han documentado la percepción de víctimas y victimarios con respecto a los factores facilitadores e instigadores de la violencia de pareja. El objetivo del presente estudio fue evaluar la percepción de víctimas y victimarios de violencia de pareja con respecto a factores facilitadores e instigadores de la violencia. Participaron 27 víctimas de violencia de pareja con edades entre 18 y 71 años (media = 34.25) y 27 victimarios jurídicamente confirmados, con edades entre 19 y 62 años (media = 40), quienes respondieron un cuestionario integrado por una lista sobre factores facilitadores e instigadores de la violencia de pareja y de datos sociodemográficos. Ambos grupos coincidieron en señalar al estrés y consumo de sustancias como propiciadoras de violencia, así como a la madre de su pareja como instigadoras. El diseño de intervenciones para tratar o prevenir violencia de pareja requieren identificar los factores que la facilitan, incluyendo a las familias circundantes ya que podrían no sólo tolerar o justificar la violencia, sino incluso inducirla. Finalmente, se discuten algunas diferencias notorias entre perpetradores y víctimas respecto de otras variables propiciadoras de violencia en el contexto de la teoría del aprendizaje social.

Abstract Few studies have documented the opinion of victims and perpetrators regarding the facilitating and instigating factors of intimate partner violence. The objective of this study was to evaluate the perception of victims and perpetrators of intimate partner violence regarding facilitating and instigating factors of violence. Participants were 27 victims of intimate partner violence aged between 18 and 71 years (mean = 34.25) and 27 legally confirmed offenders, aged between 19 and 62 years (mean = 40), who answered a questionnaire consisting of a list of facilitating factors and instigators of intimate partner violence and sociodemographic data. Both groups agreed in pointing to stress and substance use as propitiators of violence, as well as the mother of their partner as instigators. The design of interventions to treat or prevent intimate partner violence requires identifying the factors that facilitate it, including the surrounding families, since they may not only tolerate or justify the violence, but even induce it. Finally, some notorious differences between perpetrators and victims are discussed with respect to other variables that promote violence in the context of social learning theory.

Mortality and bleeding complications of COVID-19 critically ill patients with venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) disease in COVID-19 patients is a remarkable issue, especially its relationship with bleeding events and mortality. The objective of this study was to describe the outcomes of critically ill patients with COVID-19, hospitalized in the Intensive Care Unit (ICU), in relationship with VTE during their stay. METHODS: This is a prospective cohort study of critically ill COVID-19 patients in two hospitals that underwent a venous ultrasound at the beginning of follow-up of both lower limbs in April 2020. In case of clinical suspicion of new VTE during the 30-day follow-up, additional ultrasound or thoracic CT were performed. Global VTE frequency, major bleeding events and survival were collected, and their predictors were studied. RESULTS: We included 230 patients. After 30 days of follow-up, there were 95 VTE events in 86 patients (37.4%). Thirteen patients (5.7%) developed major bleeding complications and 42 patients (18.3%) died. None of the comorbidities or previous treatments were related with bleeding events. D-Dimer at admission was significantly related with VTE development and mortality. Independent predictors of mortality in the regression model were older age (>66 years), D-Dimer at admission (>1.500 ng/mL) and low lymphocyte count (<0.45×109/L) with an AUC in the ROC curve of 0.81 (95% CI: 0.73-0.89). Patients presenting these three conditions presented a mortality of 100% in the predictive model. CONCLUSIONS: VTE frequency in ICU COVID-19 patients is high and risk of major bleeding is low. Comorbidities and laboratory parameters of admission in these patients can be a useful tool to predict mortality.

Uptake of potentially toxic elements by edible plants in experimental mining Technosols: preliminary assessment.

A study was carried out to evaluate the absorption of potentially toxic elements from mining Technosols by three types of vegetable plants (broccoli (Brassica oleracea var. italica), lettuce (Lactuca sativa) and onion (Allium cepa)), the different parts of which are intended for human and farm animal consumption (leaves, roots, edible parts). The preliminary results obtained highlight the importance of the design of the mining Technosols used for agricultural purposes, obtained from soils and sediments of mining origin and amended with residues of high calcium carbonate concentrations (limestone filler and construction and demolition wastes). The experiment was carried out in a greenhouse, and the total metal(loid)s concentration (As, Pb, Cd, Cu, Fe, Mn and Zn) of the soil, rhizosphere, aqueous leachates and plant samples was monitored, the translocation and bioconcentration factors (TF and BCF, respectively) being calculated. The characterization of the soils included a mobilization study in media simulating different environmental conditions that can affect these soils and predicting the differences in behavior of each Technosol. The results obtained showed that the levels of potentially toxic elements present in the cultivated species are within the range of values mentioned in the literature when they were cultivated in soils with calcareous amendments. However, when the plants were grown in contaminated soils, the potentially toxic elements levels varied greatly according to the species, being higher in onions than in lettuce. Experiments with the use of lime filler or construction and demolition wastes for soil remediation result in crops that, in principle, do not present health risks and are similar in development to those grown on non-contaminated soil.

Assessment of risk from lead intake in mining areas: proposal of indicators.

This study discusses an estimate of the risk associated with the intake of soil contaminated by lead, based on the nature of the source, through a detailed study of the parameters that can influence the bioaccessibility of the element from soil intake. Statistical variables that are related to the solubility and bioavailability of lead are used for this purpose. This includes considering the values of pH, electrical conductivity, particle size, mineralogical composition and the bioaccessibility/bioasimilability of lead. Obtaining an algorithm, represented by different probability distributions of the parameters considered, needs a thorough knowledge of the source materials, which may allow estimating/evaluating the intake health risk provided by the concentration of the metal present. The selected materials are from sites affected by mining activities in the Region of Murcia (SE of Spain) and soils in nearby areas, using a total of 186 samples. Soil samples, once screened and homogenized, were parameterized by determining pH, electrical conductivity, granulometry, both total and water-extractable Pb content. Oral bioaccessibility tests were also performed, and a detailed mineralogical analysis by X-ray diffraction was carried out.

Acute Pharmacological Effects and Oral Fluid Concentrations of the Synthetic Cannabinoids JWH-122 and JWH-210 in Humans After Self-Administration: An Observational Study.

Synthetic cannabinoids (SCs) are a group of new psychoactive drugs used recreationally with potential health risks. They are monitored by the EU Early Warning System since 2010 due to severe adverse effects on consumers. JWH-122 and JWH-210 are naphthoylindole SCs and potent cannabinoid receptor CB1 and CB2 agonists. Information about the effects of SCs usually is available from intoxication cases and surveys, and few studies on humans after controlled administration or observational/naturalistic studies using standardized measures of cardiovascular and subjective effects are available. The aim of this study was to evaluate the acute pharmacological effects of JWH-122 and JWH-210 recreational consumption in a 4 h observational study and assess their disposition in oral fluid (OF). Sixteen volunteers self-administered 1 mg dose of JWH-122 (n = 8) or 2.25 mg mean dose of JWH-210 (range 2-3 mg, n = 8) by inhalation (smoking). Physiological parameters including blood pressure (systolic and diastolic), heart rate (HR), and cutaneous temperature were measured. A set of visual analog scales, the 49-item short-form version of the Addiction Research Center Inventory (ARCI), and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were used for the evaluation of subjective effects. OF was collected at baseline and at 10, 20, and 40 min and 1, 2, 3, and 4 h after self-administration. Statistically significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR were observed after JWH-122 self-administration but not after JWH-210 self-administration. JWH-210 self-administration produced significant changes in subjective drug effects, similar to those induced by THC (intensity, high, good effects, and hunger). The subjective effects following JWH-122 consumption were minimal. The maximal effects were mostly observed 20 min after intake. JWH-122 and JWH 210 OF concentration reached a peak 20 min after administration and could not be detected after 3 h. The results demonstrated a different pattern of effects of these two SCs. Due to the limitations of our observational study, further research with a larger sample and controlled studies are needed to better define the acute pharmacological effect and health risk profile of JWH-122 and JWH-210.

Determinantes sociales de salud y su relación con desnutrición infantil en dos comunidades étnicas colombianas / Social determinants and malnutrition of infants from two Colombian indigenous communities

RESUMEN Objetivo Identificar la relación entre los determinantes sociales de la salud y el estado nutricional de los niños pertenecientes a dos comunidades indígenas de la Costa Caribe colombiana, los wayús y los zenús. Métodos Estudio transversal que aborda el estado nutricional de los wayús y los zenús en edad preescolar y escolar. Incluyendo, además, estimación de determinantes sociales de la salud, referida por cuidadores de menores, que aborda algunos aspectos de ejes de desigualdad de tipo estructural (etnia, territorio, edad y sexo) e intermedios: vivienda, entorno y redes, mediante instrumentos de salud familiar. Se estandarizaron métricas de talla, peso e insumos de familiograma y ecomapa. Se estimaron medidas descriptivas de tipo frecuentistas y de medidas de tendencia central. Se estimó la odds ratio y su relación con variables independientes. Resultados La prevalencia de desnutrición global en la etnia Wayú fue del 59,1% IC (47,569,8) y en la etnia Zenú del 22,4% IC (15,9-30,4) para una p<0,001. Esta diferencia se relaciona con factores de riesgo intermediarios de saneamiento: inadecuadas excretas con OR=2.54; IC (1.42-4.53) p=0.002, la falta de empleo OR=1.94; IC (1.09-3.46) P=0.03 y falta de acceso a servicios de salud occidental OR=2.42; IC (1.34-4.40) p=0.005. Conclusiones La mejora en la nutrición requiere intervenir determinantes intermedios relacionados con saneamiento, modelo de salud, intersectorialidad de políticas en salud más enfoque étnico-cultural y territorial.

ABSTRACT Objetive To identify the relationship between the Health's Social Determinants and the nutritional status of children belonging to two indigenous communities on the Colombian Caribbean coast, the Wayú and the Zenú. Methods Cross-sectional study that addresses nutritional status in wayúes and zenúes at preschool and school age. Also including the estimation of health's social determinants, referred by minor's caregivers, which addresses some aspects of structural ¡nequality axes (ethnicity, territory, age, and sex) and intermediates: housing, environment, and networks, through health instruments family. Metrics for height, weight, and inputs for the familiogram and ecomap were standardized. Descriptive measures of frequencies and central tendency were estimated. Odds ratio and its relationship with ¡ndependent variables were estimated. Results The prevalence of global malnutrition in the Wayú ethnic group was 59.1% (47.5-69.8) and in the Zenú ethnic group 22.4% (15.9-30.4) for a p<0.001. This difference is related to intermedíate risk factors with sanitation: inadequate excreta with OR=2.54; CI (1.42-4.53) p=0.002, lack of employment OR=1.94; CI (1.09-3.46) P=0.03 and lack of access to western health services OR=2.42; IC (1.34-4.40) p=0.005. Conclusions Improvement in nutrition requires the intervention of intermediate determinants related to sanitation, health model, intersectoriality of health policies plus an ethnic-cultural and territorial focus.

Acute Pharmacological Effects and Oral Fluid Biomarkers of the Synthetic Cannabinoid UR-144 and THC in Recreational Users.

Synthetic cannabinoids (SCs) are one of the most frequent classes of new psychoactive substances monitored by the EU Early Warning System and World Health Organization. UR-144 is a SC with a relative low affinity for the CB1 receptor with respect to that for the CB2 receptor. As with other cannabinoid receptor agonists, it has been monitored by the EU Early Warning System since 2012 for severe adverse effects on consumers. Since data for UR-144 human pharmacology are very limited, an observational study was carried out to evaluate its acute pharmacological effects following its administration using a cannabis joint as term of comparison. Disposition of UR-144 and delta-9-tetrahydrocannibinol (THC) was investigated in oral fluid. Sixteen volunteers smoked a joint prepared with tobacco and 1 or 1.5 mg dose of UR-144 (n = 8) or cannabis flowering tops containing 10 or 20 mg THC (n = 8). Physiological variables including systolic and diastolic blood pressure, heart rate and cutaneous temperature were measured. A set of Visual Analog Scales (VAS), the Addiction Research Centre Inventory (ARCI)-49-item short form version and the Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) were administered to evaluate subjective effects. Oral fluid was collected at baseline, 10, 20, 40 min and 1, 2, 3 and 4 h after smoking, for UR-144 or THC concentration monitoring. Results showed significant statistical increases in both systolic and diastolic blood pressure and heart rate after both UR-144 and cannabis smoking. Both substances produced an increase in VAS related to stimulant-like and high effects, but scores were significantly higher after cannabis administration. No hallucinogenic effects were observed. Maximal oral fluid UR-144 and THC concentrations appeared at 20 and 10 min after smoking, respectively. The presence of UR-144 in oral fluid constitutes a non-invasive biomarker of SC consumption. The results of this observational study provide valuable preliminary data of the pharmacological effects of UR-144, showing a similar profile of cardiovascular effects in comparison with THC but lower intensity of subjective effects. Our results have to be confirmed by research in a larger sample to extensively clarify pharmacological effects and the health risk profile of UR-144.

Thoracic Aortic Mural Thrombus, Right Ventricular Clot and Pulmonary Embolism in a Patient With COVID-19 Pneumonia.

Since the outbreak of the COVID-19 pandemic, increasing evidence suggests that infected patients present a high incidence of thrombotic complications. We report a 67-year-old-woman admitted for severe acute respiratory syndrome coronavirus 2 infection. Chest CT images showed bilateral ground glass opacities, bilateral pulmonary embolism, right ventricular clot in transit and 2 thoracic aortic mural thrombus. Therapy was initiated with subcutaneous low-molecular-weight heparin, and the patient was discharged at 20 days asymptomatic. Complete resolution of the aortic thrombus was observed in a 1-month surveillance CT angiogram. Our case illustrates vascular complications in a COVID-19 patient and its effective treatment with anticoagulation.

Paraplegia Following Type B Acute Aortic Dissection Can Spare the Spinal Cord.

Ischemic lumbosacral plexopathy secondary to an acute aortic dissection is a rare condition that is usually unilateral and frequently accompanied by a simultaneous spinal cord infarction. The functional prognosis relies on the severity of the nervous system involvement being usually worse when the spinal cord is involved. We present a case of a 46-year-old man who suffered an acute type B aortic dissection presenting as acute paraplegia due to bilateral ischemic lumbosacral plexopathy treated with thoracic endovascular aortic repair. An up-to-date review of the literature on ischemic lumbosacral plexus injury is provided.

Tuberculosis extra-pulmonar en niños bajo 15 años de edad internados en el Centro Hospitalario Pereira Rossell, Uruguay / Extrapulmonary tuberculosis in children under the age of 15 hospitalized at the Pereira Rossell Hospital Center, Uruguay

Resumen Introducción: La tuberculosis es un problema de salud pública de alta prevalencia. Los niños constituyen una población de riesgo de enfermar y evolucionar a formas graves. Objetivo: Describir la frecuencia, características epidemiológicas, clínicas y evolutivas de los pacientes bajo 15 años de edad, internados por tuberculosis extra-pulmonar (TBCEP) en el Centro Hospitalario Pereira Rossell-Uruguay, durante 2009 a 2019. Pacientes y Métodos: Estudio descriptivo, retrospectivo, revisión de historias clínicas y registros de la Comisión Honoraria para la Lucha Antituberculosa. Variables: edad, sexo, nexo epidemiológico, clínica, confirmación diagnóstica, tratamiento y complicaciones. Resultados: Se registraron 77 casos de TBCEP, fueron hospitalizados en este centro 45 (58%). Media de edad 7 años, varones 25 (56%). Todos recibieron vacuna BCG. Se identificó nexo epidemiológico en 28 (62%). Las formas de TBCEP fueron: pleural 26 (58%), sistema nervioso central (SNC) 9 (20%), linfoganglionar 4 (9%), cutánea 2 (5%), ósea 1 (2%), peritoneal 1 (2%), pleural-peritoneal 1 (2%), ósea-SNC 1 (2%). Confirmación etiológica hubo en 23 (51%): mediante cultivo 16, GeneXpert 5, por ambos 2. Completaron tratamiento 36 (80%). Presentaron complicaciones 4 (9%): status convulsivo 2, hemorragia cerebral 1, fallo orgánico múltiple 1. Conclusiones: La TBCEP ocurrió en niños previamente sanos. El diagnóstico requiere alto índice de sospecha y la confirmación el empleo simultáneo de varias técnicas diagnósticas.

Abstract Background: Tuberculosis is a public health problem. Children constitute a population at risk of becoming ill and evolving into serious forms. Aim: To describe the frequency, epidemiological, clinical and evolutionary characteristics of children under 15 years of age hospitalized for extrapulmonary tuberculosis (EPTB) at the Pereira Rossell Hospital-Uruguay, during 2009-2019. Methods: Descriptive, retrospective study, review of medical records and records of the Honorary Commission for the Fight Against Tuberculosis. Variables: age, sex, epidemiological and clinical link, diagnostic confirmation, treatment and complications. Results: 77 cases of EPTB were registered, 45 (58%) were hospitalized in this center. Average age 7 years, males 25 (56%). All received the Bacillus Calmette-Guérin vaccine. An epidemiological link was identified in 28 (62%). The forms of EPTB were: pleural 26 (58%), central nervous system (CNS) 9 (20%), lymphoganglionic 4 (9%), cutaneous 2 (5%), bone 1 (2%), peritoneal 1 (2%), pleural- peritoneal 1 (2%), bone-CNS 1 (2%). Etiology was confirmed in 23 (51%): by culture 16, GeneXpert 5, by both 2. Thirty-six (80%) patients completed treatment. Four (9%) presented complications: convulsive state 2, cerebral hemorrhage 1, multiple organ failure 1. Conclusions: EPTB occurred in previously healthy children. The diagnosis requires a high index of suspicion and the confirmation of the simultaneous use of several diagnostic techniques.

Optimized NGS Approach for Detection of Aneuploidies and Mosaicism in PGT-A and Imbalances in PGT-SR.

The detection of chromosomal aneuploidies and mosaicism degree in preimplantation embryos may be essential for achieving pregnancy. The aim of this study was to determine the robustness of diagnosing homogenous and mosaic aneuploidies using a validated algorithm and the minimal resolution for de novo and inherited deletions and duplications (Del/Dup). Two workflows were developed and validated: (a,b) preimplantation genetic testing for uniform whole and segmental aneuploidies, plus mixtures of euploid/aneuploid genomic DNA to develop an algorithm for detecting mosaicism; and (c) preimplantation genetic testing for structural rearrangements for detecting Del/Dup ≥ 6 Mb. Next-generation sequencing (NGS) was performed with automatic library preparation and multiplexing up to 24-96 samples. Specificity and sensitivity for PGT-A were both 100% for whole chromosomes and segmentals. The thresholds stablished for mosaicism were: euploid embryos (<30% aneuploidy), low mosaic (from 30% to <50%), high mosaic (50-70%) or aneuploid (>70%). In the PGT-SR protocol, changes were made to increase the detection level to ≥6 Mb. This is the first study reporting an accurate assessment of semiautomated-NGS protocols using Reproseq on pools of cells. Both protocols allow for the analysis of homogeneous and segmental aneuploidies, different degrees of mosaicism, and small Del/Dup with high sensitivity and specificity.

Endovascular Infrarenal Aortic Aneurysm Repair Performed in a Hybrid Operating Room Versus Conventional Operating Room Using a C-Arm.

BACKGROUND: To compare contrast usage and radiation exposure during endovascular aneurysm repair (EVAR) using mobile C-arm imaging in a conventional operating room (OR) or fixed angiographic equipment in a hybrid OR (HR). METHODS: A retrospective unicenter study from May 2016 to August 2019. All consecutive patients undergoing standard EVAR were included. Patients were divided into 2 groups. Group OR included EVARs performed in a conventional OR with a mobile C-arm (May 2016 to April 2018) and group HR included EVARs performed with a fixed angiographic equipment in an HR (May 2018 to August 2019). Data collected included patient demographics, aneurysm diameter, neck length, radiation dose: median dose-area product (DAP), fluoroscopy time, total operative time, contrast use, and 30-day clinical outcomes. RESULTS: A total of 77 patients were included in the study (42 patients in group OR and 35 patients in group HR). There was no difference in age, body mass index (BMI), mean aneurysm, and neck length between groups. Patients in the group HR received less contrast volume (108.6 mL [±41.5] vs. 162.5 mL [±52.6]; P < 0.001), but higher radiation dose (154 Gy cm2 [±102.9] vs. 61.5 Gy cm2 [±42.4]; P < 0.001). There were no differences in fluoroscopy time (20.4 min [±8.5] vs. 23.2 min [±12.4]; P = 0.274) and total operative time (106.4 [±22.3] vs. 109.4 [±25.8]; P = 0.798). No difference was found in terms of 30-day complication rates or operative mortality between groups. DAP was positively correlated with BMI in the group OR (Spearman's rank correlation coefficient rs, 0.580; P < 0.001), but no correlation could be seen in the group HR (rs, 0.408; P = 0.028). CONCLUSIONS: Routine EVAR performed in a hybrid fixed-imaging suite may be associated with less contrast usage, but higher radiation exposure in our center. The significantly higher radiation exposure when the mobile C-arm is replaced by an HR should not be underestimated.

[Extrapulmonary tuberculosis in children under the age of 15 hospitalized at the Pereira Rossell Hospital Center, Uruguay]. / Tuberculosis extra-pulmonar en niños bajo 15 años de edad internados en el Centro Hospitalario Pereira Rossell, Uruguay.

BACKGROUND: Tuberculosis is a public health problem. Children constitute a population at risk of becoming ill and evolving into serious forms. AIM: To describe the frequency, epidemiological, clinical and evolutionary characteristics of children under 15 years of age hospitalized for extrapulmonary tuberculosis (EPTB) at the Pereira Rossell Hospital-Uruguay, during 2009-2019. METHODS: Descriptive, retrospective study, review of medical records and records of the Honorary Commission for the Fight Against Tuberculosis. VARIABLES: age, sex, epidemiological and clinical link, diagnostic confirmation, treatment and complications. RESULTS: 77 cases of EPTB were registered, 45 (58%) were hospitalized in this center. Average age 7 years, males 25 (56%). All received the Bacillus Calmette-Guérin vaccine. An epidemiological link was identified in 28 (62%). The forms of EPTB were: pleural 26 (58%), central nervous system (CNS) 9 (20%), lymphoganglionic 4 (9%), cutaneous 2 (5%), bone 1 (2%), peritoneal 1 (2%), pleural- peritoneal 1 (2%), bone-CNS 1 (2%). Etiology was confirmed in 23 (51%): by culture 16, GeneXpert 5, by both 2. Thirty-six (80%) patients completed treatment. Four (9%) presented complications: convulsive state 2, cerebral hemorrhage 1, multiple organ failure 1. CONCLUSIONS: EPTB occurred in previously healthy children. The diagnosis requires a high index of suspicion and the confirmation of the simultaneous use of several diagnostic techniques.

La vuelta al fútbol tras la reconstrucción del ligamento cruzado anterior / Return to football practice after anterior cruciate reconstruction / Retornar ao treino de futebol após a reconstrução do cruzado anterior

OBJETIVO: analizar las publicaciones recientes que se centran en la vuelta a la práctica futbolística tras la reconstrucción del ligamento cruzado anterior. MÉTODO: se revisaron artículos originales inglés, español y portugués publicados en los últimos cinco años en las bases de datos Pubmed, Medline, Scopus, Cinhal y Sport Discus. RESULTADOS: se encontraron 49 artículos y tras la aplicación de criterios de inclusión y exclusión se procedieron a analizar 14 artículos. De estos, 8 tenían una muestra de futbolistas masculinos, 5 con femeninas y uno con ambos sexos. CONCLUSIÓN: Los artículos seleccionados ponen de relieve que existen ciertos factores que pueden marcar el regreso a la práctica futbolística tras la reconstrucción del ligamento cruzado anterior como el nivel de profesionalización, el dolor, la falta de confianza, el sexo o el tipo de injerto

OBJECTIVE: The objective of this review will be to analyze recent publications that focus on the return to football practice after the reconstruction of the anterior cruciate ligament. METHOD: We reviewed original English, Spanish and Portuguese articles published in the last five years in the Pubmed, Medline, Scopus, Cinhal and Sport Discus databases. RESULTS: 49 articles were found and after applying the inclusion and exclusion criteria, 14 articles were analyzed. Of these, 8 had a sample of male soccer players, 5 with female players and one with both sexes. CONCLUSIONS: The selected articles highlight that there are certain factors that can mark the return to football practice after the reconstruction of the anterior cruciate ligament as the level of professionalization, pain, lack of confidence, sex or type of graft

OBJETIVO: analisar publicações recentes que enfocam o retorno à prática de futebol após a reconstrução do ligamento cruzado anterior. MÉTODO: artigos originais em inglês, espanhol e português publicados nos últimos cinco anos foram revisados nas bases de dados Medline, Pubmed, Scopus, Cinhal e Sport Discus. RESULTADOS: foram encontrados 49 artigos e, após a aplicação dos critérios de inclusão e exclusão, foram analisados 14 artigos. Destes, 8 tinham uma amostra de jogadores de futebol do sexo masculino, 5 com jogadores do sexo feminino e um com ambos os sexos. CONCLUSÃO: Os artigos selecionados destacam que existem alguns fatores que podem marcar o retorno à prática do futebol após a reconstrução do ligamento cruzado anterior. como o nível de profissionalização, dor, falta de confiança, sexo ou tipo de enxerto