∆4-3-oxo-5ß-reductase deficiency: favorable outcome in 16 patients treated with cholic acid.

BACKGROUND: Oral cholic acid therapy is an effective therapy in children with primary bile acid synthesis deficiencies. Most reported patients with this treatment have 3ß-hydroxy-Δ5-C27-steroid oxidoreductase deficiency. The aim of the study was the evaluation of cholic acid therapy in a cohort of patients with the rarer Δ4-3-oxosteroid 5ß-reductase (Δ4-3-oxo-R) deficiency. METHODS: Sixteen patients with Δ4-3-oxo-R deficiency confirmed by AKR1D1 gene sequencing who received oral cholic acid were retrospectively analyzed. RESULTS: First symptoms were reported early in life (median 2 months of age), with 14 and 3 patients having cholestatic jaundice and severe bleeding respectively. Fifteen patients received ursodeoxycholic acid before diagnosis, with partial improvement in 8 patients. Four patients had liver failure at the time of cholic acid initiation. All 16 patients received cholic acid from a median age of 8.1 months (range 3.1-159) and serum liver tests normalized in all within 6-12 months of treatment. After a median cholic acid therapy of 4.5 years (range 1.1-24), all patients were alive with their native liver. Median daily cholic acid dose at last follow-up was 8.3 mg/kg of body weight. All patients, but one, had normal physical examination and all had normal serum liver tests. Fibrosis, evaluated using liver biopsy (n = 4) or liver elastography (n = 9), had stabilized or improved. Cholic acid therapy enabled a 12-fold decrease of 3-oxo-∆4 derivatives in urine. Patients had normal growth and quality of life. The treatment was well tolerated without serious adverse events and signs of hepatotoxicity. CONCLUSIONS: Oral cholic acid therapy is a safe and effective treatment for patients with Δ4-3-oxo-R deficiency.

Clinical examination and imaging resources in children and adolescent back pain.

Back pain is a relatively common complaint in children and adolescents. The pediatric patient presenting with back pain can often be challenging, and there are many well-known organic diagnoses that should not be missed. In younger children, an organic cause of back pain can often be found. However, back pain in older children and adolescents is often "non-specific." The differential diagnosis of back pain in children includes neoplasms, developmental, and inflammatory conditions. Basic steps should include an in-depth anamnesis, a systematic physical examination, and standard spine radiographs (anteroposterior and lateral). Nevertheless, advanced diagnostic imaging and laboratory studies should be included when indicated to avoid missing or delaying a serious diagnosis. If other types of imaging tests are necessary (magnetic resonance imaging, computed tomography, bone scan, or single photon emission computed tomography), they should be guided by diagnostic suspicion.

Dataset of user interactions across four large pilots on the use of augmented reality in learning experiences.

Augmented Reality in education can support students in a wide range of cognitive tasks-fostering understanding, remembering, applying, analysing, evaluating, and creating learning-relevant information more easily. It can help keep up engagement, and it can render learning more fun. Within the framework of a multi-year investigation encompassing primary and secondary schools across Europe, the ARETE project developed several Augmented Reality applications, providing tools for user interaction and data collection in the education sector. The project developed innovative AR learning technology and methodology, validating these in four comprehensive pilot studies, in total involving more than 2,900 students and teachers. Each pilot made use of a different Augmented Reality application covering specific subjects (English literacy skills, Mathematics and Geography, Positive Behaviour, plus, additionally, an Augmented Reality authoring tool applied in a wide range of subjects). In this paper, we introduce the datasets collected during the pilots, describe how the data enabled the validation of the technology, and how the approach chosen could enhance existing augmented reality applications in data exploration and modelling.

[Influencia de la pandemia de la COVID-19 en la distribución de la bronquiolitis aguda en España.] / Influencia de la pandemia de la COVID-19 en la distribución de la bronquiolitis aguda en España.

OBJECTIVE: Bronchiolitis is the leading cause of hospitalization in children under one year of age, with annual epidemics. Since the onset of the SARS-CoV-2 coronavirus disease pandemic (COVID-19), there has been a change in the transmission of other respiratory viruses. Our aim in this paper was to describe how COVID-19 had affected the distribution of acute bronchiolitis in our country. METHODS: We conducted a retrospective descriptive study of the cases of bronchiolitis treated in a sample of Spanish hospitals belonging to four autonomous communities. A chi-square test and Student's t- test were used to compare epidemiological and demographic variables between patients attending the hospital with bronchiolitis during January 2021-June 2021 with patients attending the hospital in the previous three years (2018-2020). RESULTS: We analyzed 6,124 cases of bronchiolitis (58.8% males and 41.2% females). The mean age was 0.5 years (SD: 0.4). In 2020, we observed a decrease of bronchiolitis cases compared to 2019 of 67%. During 2020 and 2021, the epidemic season started in January-February and peaked in June. During the first half of 2021, the highest percentage of admissions for bronchiolitis associated with RSV infection was observed in hospitals in central Spain corresponding to the Autonomous Community of Madrid (78.5% of admissions). CONCLUSIONS: The COVID-19 pandemic significantly modifies the seasonality of bronchiolitis. In our country, the flow and distribution of the disease are not uniform. It starts in the center of Spain and ends on the coast.

OBJETIVO: La bronquiolitis es la primera causa de hospitalización en menores de un año, presentándose en forma de epidemias anuales. Desde el inicio de la pandemia por la enfermedad causada por el coronavirus SARS-CoV-2 (COVID-19) se ha producido un cambio en la transmisión de otros virus respiratorios. Nuestro objetivo en este trabajo fue describir cómo había afectado la pandemia de la COVID-19 a la distribución de la bronquiolitis aguda en nuestro país. METODOS: Realizamos un estudio descriptivo retrospectivo de los casos de bronquiolitis atendidos en una muestra de hospitales españoles que pertenecían a cuatro comunidades autónomas. Empleado el test chi-cuadrado y la prueba t de Student comparamos variables epidemiológicas y demográficas de los casos de bronquiolitis atendidos durante enero de 2021 y junio 2021, con los tres años anteriores (2018-2020). RESULTADOS: Analizamos 6.124 casos de bronquiolitis (58,8% varones y 41,2% mujeres). La media de edad fue de 0,5 años (DE: 0,4). En 2020 observamos un descenso de casos de bronquiolitis con respecto a 2019 del 67%. Durante 2020 y 2021 la temporada epidémica empezó en enero-febrero y alcanzó su pico máximo en junio. Durante el primer semestre de 2021, el porcentaje más elevado de ingresos por bronquiolitis asociados a infección VRS fue observado en hospitales del centro de España correspondientes a la Comunidad Autónoma de Madrid (78,5% de los ingresos). CONCLUSIONES: La pandemia por la COVID-19 modifica de manera significativa la estacionalidad de la bronquiolitis. En nuestro país, el flujo y distribución de la enfermedad no es uniforme, comenzado por el centro peninsular y, por último, la zona litoral.

Influencia de la pandemia dela COVID-19 en la distribución de la bronquiolitis aguda en España / Influence of the pandemic of COVID-19 in distribution of acute bronchiolitis in Spain

Fundamentos: La bronquiolitis es la primera causa de hospitalización en menores de un año, presentándose en forma de epidemias anuales. Desde el inicio de la pandemia por la enfermedad causada por el coronavirus SARS-CoV-2 (COVID-19) se ha producido un cambio en la transmisión de otros virus respiratorios. Nuestro objetivo en este trabajo fue describir cómo había afectado la pandemia de la COVID-19 a la distribución de la bronquiolitis aguda en nuestro país. Métodos: Realizamos un estudio descriptivo retrospectivo de los casos de bronquiolitis atendidos en una muestra de hospitales españoles que pertenecían a cuatro comunidades autónomas. Empleado el test chi-cuadrado y la pruebat de Student comparamos variables epidemiológicas y demográficas de los casos de bronquiolitis atendidos durante enero de 2021 y junio 2021, con los tres años anteriores (2018-2020). Resultados: Analizamos 6.124 casos de bronquiolitis (58,8% varones y 41,2% mujeres). La media de edad fue de 0,5 años (DE: 0,4). En 2020 observamos un descenso de casos de bronquiolitis con respecto a 2019 del 67%. Durante 2020 y 2021 la temporada epidémica empezó en enero-febrero y alcanzó su pico máximo en junio. Durante el primer semestre de 2021, el porcentaje más elevado de ingresos por bronquiolitis asociados a infección VRS fue observado en hospitales del centro de España correspondientes a la Comunidad Autónoma de Madrid (78,5% de los ingresos). Conclusiones: La pandemia por la COVID-19 modifica de manera significativa la estacionalidad de la bronquiolitis. En nuestro país, el flujo y distribución de la enfermedad no es uniforme, comenzado por el centro peninsular y, por último, la zona litoral.(AU)

Background: Bronchiolitis is the leading cause of hospitalization in children under one year of age, with annual epidemics. Sincethe onset of the SARS-CoV-2 coronavirus disease pandemic (COVID-19), there has been a change in the transmission of other respiratory viruses. Our aim in this paper was to describe how COVID-19 had affected the distribution of acute bronchiolitis in our country. Methods: We conducted a retrospective descriptive study of the cases of bronchiolitis treated in a sample of Spanish hospitals belonging to four autonomous communities. A chi-square test and Student’s t- test were used to compare epidemiological and demographicvariables between patients attending the hospital with bronchiolitis during January 2021-June 2021 with patients attending the hospital in the previous three years (2018-2020). Results: We analyzed 6,124 cases of bronchiolitis (58.8% males and 41.2% females). The mean age was 0.5 years (SD: 0.4). In 2020, weobserved a decrease of bronchiolitis cases compared to 2019 of 67%. During 2020 and 2021, the epidemic season started in January-February and peaked in June. During the first half of 2021, the highest percentage of admissions for bronchiolitis associated with RSVinfection was observed in hospitals in central Spain corresponding to the Autonomous Community of Madrid (78.5% of admissions).Conclusions: The COVID-19 pandemic significantly modifies the seasonality of bronchiolitis. In our country, the flow and distri-bution of the disease are not uniform. It starts in the center of Spain and ends on the coast.(AU)

Health-Related Quality of Life in Patients Living with Wilson Disease in Spain: A Cross-Sectional Observational Study.

Wilson disease (WD) is a rare copper metabolism disorder caused by mutations in the ATP7B gene. It usually affects young individuals and can produce hepatic and/or neurological involvement, potentially affecting health-related quality of life (HRQoL). We assessed HRQoL in a cohort of Spanish patients with WD and evaluated disease impact on several domains of patients' lives, treatment adherence, drug preference and satisfaction, and healthcare resource utilisation in a cross-sectional, retrospective, multicentric, observational study. A total of 102 patients were included: 81.4% presented isolated liver involvement (group H) and 18.6% presented neurological or mixed involvement (group EH). Up to 30% of patients reported a deteriorated emotional status with anxiety and depression, which was greater in the EH subgroup; the use of neuropsychiatric drugs was high. Over 70% of the patients were satisfied with their current treatment but complained about taking too many pills, stating they would consider switching to another more patient-friendly treatment if available. The Simplified Medication Adherence Questionnaire revealed only 22.5% of patients were fully adherent to therapy, suggesting that alternative therapies are needed. This real-world study, even though is highly enriched with hepatic patients and mild disease, shows that WD impacts patients' HRQoL, especially in the emotional domain.

Post-Pandemic Feeding Patterns and Mediterranean Diet Adherence in Spanish Toddlers.

During the last decade, feeding patterns, more specifically those of children, have worsened-affecting dietary habits and Mediterranean diet adherence. Here, we examine the post-pandemic feeding habits of Spanish toddlers. A total of 2465 parents of children aged between 12 and 36 months completed an online 25-item multiple-choice survey asking about dietary habits and Mediterranean diet adherence. Only 34 children (1.38%) had an adequate intake of all of the food groups included in the questionnaire. Adherence worsened as toddlers grew (p < 0.0001). Further, lower compliance was found in children with a higher intake of fast food (p < 0.001), those with siblings (p = 0.0045), and children who were the second or third child (p = 0.0005). The food group with the most commonly reported adequate intake was fish (88% of children), followed by pulses (80%), water (79%), and meat (78%). Cow's milk was the most commonly consumed dairy product among all age groups analyzed. Half of the children exhibited a low consumption of milk and dairy products. These results showed that a lack of adherence to a balanced diet is common among Spanish toddlers in the post-pandemic period and that greater parent education could improve the nutrition of toddlers.

cleAR: an interoperable architecture for multi-user AR-based school curricula.

Although there are some experiences that demonstrate the validity of the use of augmented reality in schools to help students understand and retain complex concepts, augmented reality has not been widely adopted in the education sector yet. This is in part because it is hard to use augmented reality applications in collaborative learning scenarios and to integrate them in the existing school curricula. In this work, we present an interoperable architecture that simplifies the creation of augmented reality applications, enables multi-user student collaboration and provides advanced mechanisms for data analysis and visualization. A review of the literature together with a survey answered by 47 primary and secondary school teachers allowed us to identify the design objectives of cleAR, an architecture for augmented reality-based collaborative educational applications. cleAR has been validated through the development of three proofs of concept. cleAR provides a more mature technological ecosystem that will foster the emergence of augmented reality applications for education and their inclusion in existing school programs.

Long-term evolution of shrub prescribed burning effects on topsoil organic matter and biological activity in the Central Pyrenees (NE-Spain).

Since the last half of the 20th Century, scrubs have been invading subclimatic grasslands in the montane and subalpine stages of Spain due to the decrease of the grazing activity. This shrub encroachment reduces biodiversity and the ecopastoral value of the region and leads to the accumulation of woody fuel, which represents a high fire risk. To control the encroachment, prescribed burnings are performed but their effects on soils over the years are still undetermined. This study aims to research about the long-term effects of a prescribed burn of Echinospartum horridum (Vahl) Roth. on topsoil organic matter and biological activity. Soil sampling was carried out in Tella-Sin (Central Pyrenees, Aragón, Spain) and four treatments were selected: unburned (UB), immediately burned (B0), burned 6 years before (B6, mid-term) and burned 10 years before (B10, long-term). Among the obtained results, an immediately after burning decrease on ß-D-glucosidase activity (GLU) was found, which did not recover over time. Other properties did not have an immediate reduction but did so over time: total soil organic carbon (SOC), labile carbon (DOC), total nitrogen (TN), basal soil respiration (bSR). And others were not affected at all: microbial biomass carbon (MBC), and the microbial metabolic quotient (qCO2). Moreover, the normalized soil respiration (nSR) increased with the time, which implies an acceleration of the potential mineralization of soil organic carbon. In short, although the elimination of the dense shrubs by fire has not entailed major immediate soil modifications, which would be typical of a low severity prescribed burn, several mid- and long-term effects in the C cycle have been observed. Future studies will have to discern what is the main cause of these modifications (soil microbial composition, edaphoclimatic changes, lack of soil cover and soil loss, soil fertility, etc.).

Kidney Transplant Outcomes in Elderly Population: A Systematic Review and Meta-analysis.

Context: Owing to population ageing, a growing number of kidney transplants (KTs) in elderly population are being performed. KT is the best treatment for patients with end-stage renal disease (ESRD). However, in older patients, the decision between dialysis and KT can be difficult due to potential inferior outcomes. Few studies have been published addressing this issue, and literature outcomes are controversial. Objective: To conduct a systematic review and meta-analysis to appraise the evidence about outcomes of KT in elderly patients (>70 yr). Evidence acquisition: A systematic review and meta-analysis (PROSPERO registration: CRD42022337038) was performed. Search was conducted on PubMed and LILACS databases. Comparative and noncomparative studies addressing outcomes (overall survival [OS], graft survival [GS], complications, delayed graft function [DGF], primary nonfunction, graft loss, estimated glomerular filtrate rate, or acute rejection) of KT in people older than 70 yr were included. Evidence synthesis: Of the 10 357 yielded articles, 19 met the inclusion criteria (18 observational studies, one prospective multicentre study, and no randomised controlled trials), enrolling a total of 293 501 KT patients. Comparative studies reporting enough quantitative data for target outcomes were combined. There were significant inferior 5-yr OS (relative risk [RR], 1.66; 95% confidence interval [CI], 1.18-2.35) and 5-yr GS in the elderly group (RR, 1.37; 95% CI, 1.14-1.65) to those in the <70-yr group. Short-term GS at 1 and 3 yr was similar between groups, and similar findings occurred with DGF, graft loss, and acute rejection rates. Few data about postoperative complications were reported. Conclusions: Elderly recipients have worse OS at all time points and long-term GS compared with younger recipients (<70 yr). Postoperative complications were under-reported and could not be assessed. The DGF, acute rejection, death with functioning graft, and graft loss were not inferior in elderly recipients. Geriatric assessment in this setting might be useful for selecting better elderly candidates for KT. Patient summary: Compared with younger population, kidney transplant in elderly patients has inferior patient and graft survival outcomes in the long term.

German brass for Benin Bronzes: Geochemical analysis insights into the early Atlantic trade.

Utilizing geochemical analysis, this study identifies the sources of European brass used in the casting of the renowned Benin Bronzes, produced by the Edo people of Nigeria. It is commonly believed that distinctive brass rings known as "manillas", used as currency in the European trade in West Africa, also served as a metal source for the making of the Bronzes. However, prior to the current study, no research had conclusively connected the Benin artworks and the European manillas. For this research, manillas from shipwrecks in African, American and European waters dating between the 16th and 19th Century were analysed using ICP-MS analysis. Comparing trace elements and lead isotope ratios of manillas and Benin Bronzes identifies Germany as the principal source of the manillas used in the West African trade between the 15th and 18th centuries before British industries took over the brass trade in the late 18th century.

SAXS imaging reveals optimized osseointegration properties of bioengineered oriented 3D-PLGA/aCaP scaffolds in a critical size bone defect model.

Healing large bone defects remains challenging in orthopedic surgery and is often associated with poor outcomes and complications. A major issue with bioengineered constructs is achieving a continuous interface between host bone and graft to enhance biological processes and mechanical stability. In this study, we have developed a new bioengineering strategy to produce oriented biocompatible 3D PLGA/aCaP nanocomposites with enhanced osseointegration. Decellularized scaffolds -containing only extracellular matrix- or scaffolds seeded with adipose-derived mesenchymal stromal cells were tested in a mouse model for critical size bone defects. In parallel to micro-CT analysis, SAXS tensor tomography and 2D scanning SAXS were employed to determine the 3D arrangement and nanostructure within the critical-sized bone. Both newly developed scaffold types, seeded with cells or decellularized, showed high osseointegration, higher bone quality, increased alignment of collagen fibers and optimal alignment and size of hydroxyapatite minerals.

Percepción de riesgo de la COVID-19 en gestantes ante la nueva normalidad

La pandemia derivada de la enfermedad por coronavirus 2019, está caracterizada por una elevada propagación en la población y la no percepción del riesgo es una amenaza que se enfrenta en la gestión de esta pandemia. Se realizó un estudio descriptivo transversal en 320 gestantes que acudieron a la consulta de ultrasonido en el Policlínico Carlos J. Finlay de Santiago de Cuba con el objetivo de realizar un diagnóstico de la percepción que tienen las gestantes sobre la COVID 19 ante la nueva normalidad. Se utilizaron variables cualitativas que evaluaron la percepción de riesgo sobre la COVID 19. Para la obtención de la información se les aplicó una encuesta. A pesar de que el 93,1 % de las encuestadas consideran la COVID 19 como una enfermedad grave, un porciento considerable saludaría a las personas con besos y abrazos, dudaría en ingresar si fuese contacto de un paciente sospechoso y confirmado, no consideraría necesario las acciones de control al viajero, realizarían fiestas familiares, no se preocuparían ante cualquier síntoma si no han tenido contacto con casos sospechosos y confirmados, consideran que la COVID no tiene consecuencias para todos, solo para los pacientes vulnerables y lo más alarmante que el 71,5 % no sienten temor a contagiarse porque las gestantes no son vulnerables. La percepción real del riesgo para la salud aún es mínima, y las gestantes no concientizan que constituyen un grupo vulnerable para esta enfermedad.

The pandemic derived from coronavirus disease 2019 is characterized by a high spread in the population and the non-perception of risk is a threat faced in the management of this pandemic. A cross-sectional descriptive study was carried out in 320 pregnant women who attended the ultrasound consultation at the Carlos J. Finlay Polyclinic in Santiago de Cuba with the aim of making a diagnosis of the perception that pregnant women have about COVID 19 in the face of the new normality. Qualitative variables were used to evaluate the perception of risk on COVID 19. To obtain the information, a survey was applied. Despite the fact that 93.1% of those surveyed consider COVID 19 to be a serious illness, a considerable percentage would greet people with kisses and hugs, would hesitate to enter if they were the contact of a suspected and confirmed patient, would not consider necessary the traveler control actions, they would hold family parties, they would not worry about any symptoms if they have not had contact with suspected and confirmed cases, they consider that COVID does not have consequences for everyone, only for vulnerable patients and the most alarming thing is that 71, 5% are not afraid of getting infected because pregnant women are not vulnerable. The real perception of health risk is still minimal, and pregnant women are not aware that they constitute a vulnerable group for this disease.

A pandemia derivada da doença do coronavírus 2019, caracteriza-se por uma elevada propagação na população e a não perceção de risco é uma ameaça enfrentada na gestão desta pandemia. Foi realizado um estudo transversal descritivo em 320 gestantes que compareceram à consulta de ultrassom na Policlínica Carlos J. Finlay, em Santiago de Cuba, com o objetivo de fazer um diagnóstico da percepção que as gestantes têm sobre a COVID 19 diante da nova normalidade. Variáveis qualitativas foram utilizadas para avaliar a percepção de risco sobre a COVID 19. Para a obtenção das informações, aplicou-se um levantamento. Apesar de 93,1% dos entrevistados considerarem a COVID 19 como uma doença grave, uma porcentagem considerável cumprimentaria as pessoas com beijos e abraços, hesitaria em entrar se fosse um contato de um paciente suspeito e confirmado, não consideraria necessário controlar o viajante, realizaria festas familiares, não se preocuparia com nenhum sintoma se não tivesse tido contato com casos suspeitos e confirmados, consideram que a COVID não tem consequências para todos, apenas para os doentes vulneráveis e o mais alarmante é que 71,5% não têm medo de se infectarem porque as grávidas não são vulneráveis. A percepção real do risco à saúde ainda é mínima, e as gestantes não percebem que constituem um grupo vulnerável para essa doença.

Reading Strategies for Children with Developmental Language Disorder.

Developmental language disorder (DLD) is considered a neurodevelopmental disorder that compromises language comprehension and/or expression and constitutes a risk factor for learning to read. The aim of the present study was to analyse the reading strategies used by students with DLD to read sentences. There is evidence in the literature that, when linguistic resources are insufficient, the keyword strategy (identifying some of the words in the sentence with their own semantic content, with barely no processing of the function words) is used to read sentences. A total of 31 primary and secondary school students diagnosed with DLD were evaluated using the PEALE battery. The results reveal that students with DLD present heterogeneous profiles that are below the established reading level for their age. In addition, children with DLD and better reading skills use the keyword strategy to read sentences. In conclusion, clinical and educational implications for reading intervention in individuals with DLD are discussed.

Estado actual del traumatismo craneoencefálico en niños en el estado de Querétaro.

No disponible.

Addressing the Relationship Between Testosterone Levels and Urethral Stricture: A Case-Control Study.

PURPOSE: Hypoandrogenism may have an association with urethral stricture. This study aimed to identify and quantify the association between testosterone levels and urethral stricture. MATERIALS AND METHODS: A case-control study was conducted from January 2019 to January 2021. The case group included patients diagnosed with anterior urethral stricture who visited our urethral office of the urology department, while the control group included patients who visited our practice due to clinical conditions unrelated to voiding. In both groups, a 10 cc blood sample collection was scheduled between 7:30 and 9:30 a.m. The outcome was case/control status. The exposure variables were total testosterone, free testosterone, bioavailable testosterone, and hypoandrogenism (total testosterone < 300 ng/dL). The adjusted ORs were calculated for each exposure. Age, body mass index, hypertension, diabetes, smoking, and thyroxine levels were considered possible confounding factors. RESULTS: A total of 149 cases (mean age 59.5) were compared to 67 controls (64.3). Urethral stricture cases showed significantly lower mean total testosterone than controls (394 ng/dL vs 488 ng/dL). Similarly, the hypoandrogenism rate was significantly higher in the urethral stricture group (26% vs 7.5%). Each 100 unit increase in total testosterone was related to a 34% decrease in the odds of urethral stricture (adjusted OR 0.66, 95% CI: 0.51-0.86). Similarly, each increase of 1 unit of free testosterone and 10 units of bioavailable testosterone was associated with a decrease of 18% and 10%, respectively. A strong direct relationship was observed between hypoandrogenism and urethral stricture (adjusted OR 4.01, 95% CI: 1.37-11.7). CONCLUSIONS: Our study demonstrates an independent association between hypoandrogenism and anterior urethral stricture.

Cuestionario de reacciones vasovagales a la donación de sangre en una institución de salud / Questionnaire of vasovagal reactions to blood donation in a health institution

Resumen: Objetivo: Identificar mediante un cuestionario de signos y síntomas vasovagales a donadores de sangre, con el fin de registrar los antecedentes que aumentan la probabilidad de presentar reacciones vasovagales. Materiales y Métodos: Se aplico un cuestionario a donadores de sangre, durante tres meses, en el banco de sangre en una institución de salud de tercer nivel. Resultados: El 100% de los donadores respondió negativamente a las preguntas del cuestionario, pero el 1.3% de ellos presentaron reacción vasovagal, siendo el mareo, palidez y náusea el signo y síntomas más frecuentemente mostrados. Al comparar dos grupos con y sin reacción vasovagal pareados por sexo, edad e índice de masa corporal, no hubo diferencias entre ellos. Conclusiones: Los donadores en nuestro país son fundamentalmente de reemplazo, por lo que se debe considerar esta circunstancia además de sus motivaciones, para el diseño de encuestas dirigidas a esta población.

Abstract: Objective: Identify, trough a vasovagal signs and symptoms questionnaire, blood donors in order to record the antecedents that increases the probability of presenting vasovagal reactions. Materials and Methods: A questionnaire was applied to blood donors, for three months, in the blood bank in a third-level health institution. Results: 100% of the donors answered negatively to the questions in the questionnaire, but 1.3% of them presented vasovagal reaction, with dizziness, pallor and nausea being the most frequently shown sing and symptoms. When comparing two groups with and without vasovagal reaction matched by sex, age and body mass index, there were no differences between them. Conclusions: Donors in our country are fundamentally replacement donors, so this circumstance plus their motivations should be considered for the design of surveys aimed at this population.

CRISPR-mediated TGFBR2 knockout renders human ovarian cancer tumor-infiltrating lymphocytes resistant to TGF-ß signaling.

BACKGROUND: The correlation between elevated T-cell infiltration and improved survival of ovarian cancer (OvCa) patients suggests that endogenous tumor-infiltrating lymphocytes (TIL) possess some degree of antitumor activity that can be harnessed for OvCa immunotherapy. We previously optimized a protocol for ex vivo OvCa TIL expansion for adoptive cell therapy, which is now being tested in a clinical trial at our institution (NCT03610490). Building on this success, we embarked on genetic modification of OvCa TIL to overcome key immunosuppressive factors present in the tumor microenvironment. Here, we present the preclinical optimization of CRISPR/Cas9-mediated knockout of the TGF-ß receptor 2 (TGFBR2) in patient-derived OvCa TIL. METHODS: OvCa TILs were generated from four patients' tumor samples obtained at surgical resection and subjected to CRISPR/Cas9-mediated knockout of TGFBR2 before undergoing a rapid expansion protocol. TGFBR2-directed gRNAs were comprehensively evaluated for their TGFBR2 knockout efficiency and off-target activity. Furthermore, the impact of TGFBR2 knockout on TIL expansion, function, and downstream signaling was assayed. RESULTS: TGFBR2 knockout efficiencies ranging from 59±6% to 100%±0% were achieved using 5 gRNAs tested in four independent OvCa TIL samples. TGFBR2 knockout TIL were resistant to immunosuppressive TGF-ß signaling as evidenced by a lack of SMAD phosphorylation, a lack of global transcriptional changes in response to TGF-ß stimulation, equally strong secretion of proinflammatory cytokines in the presence and absence of TGF-ß, and improved cytotoxicity in the presence of TGF-ß. CRISPR-modification itself did not alter the ex vivo expansion efficiency, immunophenotype, nor the TCR clonal diversity of OvCa TIL. Importantly for clinical translation, comprehensive analysis of CRISPR off-target effects revealed no evidence of off-target activity for our top two TGFBR2-targeting gRNAs. CONCLUSIONS: CRISPR/Cas9-mediated gene knockout is feasible and efficient in patient-derived OvCa TIL using clinically-scalable methods. We achieved efficient and specific TGFBR2 knockout, yielding an expanded OvCa TIL product that was resistant to the immunosuppressive effects of TGF-ß. This study lays the groundwork for clinical translation of CRISPR-modified TIL, providing opportunities for engineering more potent TIL therapies not only for OvCa treatment, but for the treatment of other solid cancers as well.

Phylogenetic Analysis of the Complete Mitochondrial Genomes in the Ten Rupicapra Subspecies and Implications for the Existence of Multiple Glacial Refugia in Europe.

The current distribution of populations in Europe is marked by the effects of glaciations that occurred during the Pleistocene. Temperate species were isolated in glacial refugia that were the sources of postglacial recolonization. The traditional glacial refuge areas were the Iberian, the Italian and the Balkan peninsulas. Here we revisit the evolutionary history of chamois (Rupicapra genus) to evaluate other sites in continental Europe and Anatolia that have been suggested as potential refuges. We have obtained the complete mitochondrial sequence of seven chamois, including the subspecies parva, carpatica, caucasica, and asiatica whose mitochondrial genome had not been yet reported. These, together with the other fourteen sequences already in the GenBank, represent the different geographical populations of the Rupicapra genus. The phylogenetic analysis showed the three old clades, dating from the early Pleistocene, already reported: mtW in the Iberian Peninsula, mtC in the Appenines and the Massif of Chartreuse, and mtE comprising all the population from the Alps to the east. The genomes within each of the clades mtW and mtE, showed divergence times larger than 300 thousand years. From here, it can be argued that the present-day lineages across Europe are very old and their split dates back to the middle Pleistocene.