AEDV expert recommendations on the management of suppurative sexually transmitted infections. / Recomendaciones de expertos de la AEDV sobre el manejo de infecciones venéreas supurativas.

The incidence of sexually transmitted infections (STIs) is increasing in Spain. Suppurative STIs are one of the most frequent reasons for consultation in specialized centers. The reason for suppurative STIs is multiple and their empirical treatment varies with the currently growing problem of antimicrobial resistance. Dermatologists are trained and prepared to treat these diseases, but their correct management requires active knowledge of national and international guidelines. The present document updates, reviews and summarizes the main expert recommendations on the management and treatment of these STIs.

The influence of early life socio-environmental factors on executive performance in a healthy adult sample.

OBJECTIVE: Attempts have been made (with research efforts encouraged) to deconstruct the "race" concept into language, cultural, and life experience variables that can help explain performance differences found between ethnic groups (Romero et al., 2009). The extant empirical literature reveals that early environmental factors and life experiences (e.g., socioeconomic status) are related to cognitive test performance in adulthood (Byrd et al., 2006). This study examined the explanatory value of early life childhood resources in the relationship between ethnicity and neuropsychological test performance in adulthood. PARTICIPANTS/ METHODS: Neurologically and psychologically healthy African American (n = 40), Caucasian (n = 14), and Hispanic (n = 107) college students ranging from 19-38 years of age. On average, participants had completed around 13 years of education, indicating that the majority were in the early stages of their undergraduate studies and mostly consisted of females (72%). Each participant completed a comprehensive neuropsychological battery that included tests of executive function and an extensive background questionnaire. RESULTS: A one-way analysis of variance (ANOVA) revealed that the CA group was significantly older (F (2, 160) = 18.38, p = .045) compared to the AA and H groups, but the groups did not differ in terms of number of years of educations or gender. Also, an ANOVA revealed significant group test performance differences on the Stroop-C [F (2, 160) = 1.53, p = .047], but not on the TMT-B and COWAT. Furthermore, a Tukey post hoc revealed that there were no significant differences in test performance on Stroop-C between the groups. Hierarchical multiple regression analyses revealed that group performance differences on executive function tests were medium or non-existent and only partially explained by years of education and early life financial resources. CONCLUSION: The results are discussed in light of the existing literature, study strengths and limitations, as well as directions for future research. This research can aid in pinpointing variables crucial for interpreting differences in neuropsychological assessments among diverse populations, holding potential implications for intervention research and policy settings. It is particularly relevant in the context of the continuously evolving social, political, and economic landscapes of societies.

Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.

PURPOSE: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population. METHODS: We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies. RESULTS: TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls. CONCLUSION: Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.

Decreased oxytocin plasma levels and oxytocin receptor expression associated with aggressive behavior in aggressive-impulsive disorders.

INTRODUCTION: This study aims to enhance the understanding of the association between the phenotypic and endophenotypic characteristics of impulsive-aggressive disorders, through the study of plasma oxytocin (OXT) and oxytocin receptor (OXTR) levels in patients with borderline personality disorder (BPD) and patients with eating disorders (ED), as well as to examine the relationship of OXT system with aggressive behavior in these disorders. METHODS: 68 patients with BPD, 67 patients with ED and 57 healthy control subjects were examined for plasma oxytocin levels and protein expression of OXTR in blood mononuclear cells. Aggressive behavior was assessed using the State-Trait Anger Expression Inventory (STAXI-2). Other self and hetero-aggressive behaviors were also evaluated through interviews. RESULTS: BPD and ED patients exhibited significantly lower plasma oxytocin levels than control subjects. Furthermore, BPD patients demonstrated significantly reduced expression of OXTR compared to controls. Plasma oxytocin levels negatively correlated with verbal aggression, while OXTR expression was inversely associated with the STAXI trait subscale. CONCLUSIONS: The findings validate the existence of oxytocin system dysfunction in impulsive-aggressive disorders. They also support the link between low OXT levels in plasma and OXTR expression and the impulsive-aggressive behavior that characterizes these patients in both state and trait situations.

Estabilidad fisicoquímica y microbiológica de un colirio de insulina 10 UI/mL / Physicochemical and microbiological stability of a 10 IU/mL insulin eye drop

Objetivo: Los pacientes con defectos epiteliales corneales persistentes son, a menudo, refractarios a los tratamientos convencionales. La insulina tópica surge como una posible alternativa, habiendo demostrado su efectividad y seguridad. Sin embargo, en la bibliografía actual disponible, hay una falta de estudios de estabilidad. El objetivo del presente trabajo fue evaluar la estabilidad fisicoquímica y microbiológica de un colirio de insulina 10 UI/ml durante 28 días. Método: Estudio de estabilidad fisicoquímica y microbiológica. Se elaboraron 2 lotes (A y B) de colirios de insulina 10 UI/ml, manteniendo el lote B cerrado hasta el día 15. Las variables fisicoquímicas analizadas fueron la concentración de insulina mediante inmunoanálisis quimioluminiscente, pH y osmolaridad. El estudio microbiológico se realizó mediante pruebas de esterilidad mientras que el estudio descriptivo se analizó mediante visualización directa. Resultados: No se observaron cambios significativos de concentración (±10%) en los colirios a excepción de 2 valores en una de las muestras del lote B. El pH y la osmolaridad se mantuvieron dentro de los rangos fisiológicos del ojo. No se observó crecimiento microbiano ni cambios en las características organolépticas. Conclusiones: Se puede considerar al colirio de insulina 10 UI/ml estable durante 28 días en refrigeración manteniendo el frasco abierto desde el día de su elaboración.(AU)

Objective: Patients with persistent corneal epithelial defects are often refractory to conventional treatments. Topical insulin emerges as a possible alternative of proven effectiveness and safety. However, in the current available literature, there is a lack of stability studies. The main objective of this study was to evaluate the physicochemical and microbiological stability of a 10 IU/ml insulin eye drop for 28 days. Methods: Physicochemical and microbiological stability study. Two batches (A and B) of 10 IU/ml insulin eye drops were prepared, keeping batch B closed until day 15. The physicochemical variables analysed were insulin concentration by chemiluminescent immunoassay, pH and osmolarity. The microbiological study was performed by sterility tests while the descriptive study was assessed by direct visualization. Results: No significant concentration changes (±10%) were observed in the eye drops except for 2 values in one of the samples from batch B. The pH and osmolarity remained within the physiological ranges of the eye. No microbiological growth or changes in organoleptic characteristics were observed. Conclusions: Insulin 10 UI/ml eye drops can be considered stable for 28 days under refrigeration if the bottle is kept open from the day of its preparation.(AU)

Evolution of physico-chemical parameters, microorganism diversity and volatile organic compound of apple pomace exposed to ambient conditions.

In apple processing, waste material known as apple pomace amounts to 45% of production volumes. When this residue is stored in open-air for its stabilization and potential uses, Volatile Organic Compounds (VOCs) are produced, resulting in environmental and odor pollution, and must be managed to avoid their impact. This work aims to study the emission of VOCs utilizing TD-GC/MS and its relationship with changes in physico-chemical (moisture, pH, proteins, among others) and biological (bacteria and fungi using Illumina MiSeq) parameters under three environmental conditions: open-air (outdoors), under-roof (indoors) and oxygen-free. The 8-month study results showed a gradual increase in odorous VOCs and microbial diversity, a product of chemical and biological transformation processes in the samples. A 30% increase in odorant compounds responsible for the unpleasant smell was observed, especially esters, aldehydes and hydrocarbons in samples stored in oxygen-free and Open-air conditions. Increases in VOCs over time were associated with changes in physico-chemical and biological parameters, as well as fluctuations in environmental variables (temperature, relative humidity, and precipitation). The results of this research allow establishing a relationship between storage conditions and the production of VOCs. In addition, recommendations for waste storage time are provided for the most common uses of apple pomace based on the physico-chemical parameters observed, in order to avoid the generation of odorous compounds. Of all storage methods analyzed, under-roof is the most adequate in practice. This study's findings are pertinent for managing agribusiness waste and its potential environmental pollution.

Extraction methods of algae oils for the production of third generation biofuels - A review.

Microalgae are the main source of third-generation biofuels because they have a lipid content of 20-70%, can be abundantly produced and do not compete in the food market besides other benefits. Biofuel production from microalgae is a promising option to contribute for the resolution of the eminent crisis of fossil energy and environmental pollution specially in the transporting sector. The choice of lipid extraction method is of relevance and associated to the algae morphology (i.e., rigid cells). Therefore, it is essential to develop suitable extraction technologies for economically viable and environment-friendly lipid recovery processes with the aim of achieving a commercial production of biofuels from this biomass. This review presents an exhaustive analysis and discussion of different methods and processes of lipid extraction from microalgae for the subsequent conversion to biodiesel. Physical methods based on the use of supercritical fluids, ultrasound and microwaves were reviewed. Chemical methods using solvents with different polarities, aside from mechanical techniques such as mechanical pressure and enzymatic methods, were also analyzed. The advantages, drawbacks, challenges and future prospects of lipid extraction methods from microalgae have been summarized to provide a wide panorama of this relevant topic for the production of economic and sustainable energy worldwide.

Primary bedaquiline resistance in Karakalpakstan, Uzbekistan.

BACKGROUND: Bedaquiline (BDQ) is widely used in the treatment of rifampicin-resistant TB (RR-TB). However, resistance to BDQ is now emerging. There are no standardised regimens for BDQ-resistant TB. This study aims to share experience in managing primary BDQ-resistant TB.METHODS: We performed a retrospective study of patients treated for RR-TB in Karakalpakstan, Uzbekistan, from January 2017 to March 2022. We identified patients with resistance to BDQ with no history of BDQ exposure. We describe baseline characteristics, treatment and follow-up of these patients.RESULTS: Twelve of the 1,930 patients (0.6%) had baseline samples resistant to BDQ with no history of BDQ exposure, 75% (9/12) of whom had been previously treated for TB. Ten (83.3%) were resistant to fluoroquinolones; respectively 66% and 50% had culture conversion by Month 3 and Month 6. The interim treatment outcomes were as follows: unfavourable treatment outcomes (3/12, 25%), favourable outcomes (2/12, 17%); the remaining seven (58%) were continuing treatment.CONCLUSIONS: A large proportion of the cases had previously been treated for TB and had TB resistant to quinolone. Both patients who had not experienced culture conversion by Month 3 had an unfavourable treatment outcome. Therefore, we recommend monthly monitoring of culture status for patients on treatment regimens for BDQ resistance.

Bacteria associated with apical periodontitis promotes in vitro the differentiation of macrophages to osteoclasts.

OBJECTIVE: To analyze the possible in vitro effect of the cytokine RANKL and bacteria involved in apical periodontitis on the differentiation of macrophages into osteoclasts. MATERIAL AND METHODS: Bacteria were isolated (mainly E. faecium and E. faecalis) from the root canal of fifty patients with apical periodontitis, the possible effect of these bacteria on the phagocytic activity of the monocyte cell line THP-1 was analyzed by flow cytometry. Furthermore, the effect of these bacteria (alone or in combination with the cytokine RANKL) on the differentiation of THP-1 macrophages into osteoclasts was analyzed through the expression of the receptor RANK and the tartrate-resistant acid phosphatase TRAP. Finally, the release of different cytokines (IL-1ß, TNF-α, IL-6, IL-8, IL-10, and IL-12p70) by THP-1 cells induced to differentiate into osteoclasts was also analyzed. RESULTS: We observed a significant proportion of THP-1 cells were able to internalize E. faecium and E. faecalis. Furthermore, these bacteria were able to induce (alone or in combination with RANKL) a significant expression of RANK by THP-1 macrophages; accordingly, E. faecium and E. faecalis induced very significant levels of TRAP in these cells. Finally, during the differentiation of THP-1 macrophages induced by RANKL or bacteria, a significant release of the pro-inflammatory cytokines IL-6 and TNF-α was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest that the causative agents of apical periodontitis can induce the differentiation of osteoclasts as well as the release of pro-inflammatory cytokines, phenomena that may have an important role in the bone damage observed in this condition.

Controlled evolution of three-dimensional magnetic states in strongly coupled cylindrical nanowire pairs.

Cylindrical magnetic nanowires are promising systems for the development of three-dimensional spintronic devices. Here, we simulate the evolution of magnetic states during fabrication of strongly-coupled cylindrical nanowires with varying degrees of overlap. By varying the separation between wires, the relative strength of exchange and magnetostatic coupling can be tuned. Hence, we observe the formation of six fundamental states as a function of both inter-wire separation and wire height. In particular, two complex three-dimensional magnetic states, a 3D Landau Pattern and a Helical domain wall, are observed to emerge for intermediate overlap. These two emergent states show complex spin configurations, including a modulated domain wall with both Néel and Bloch character. The competition of magnetic interactions and the parallel growth scheme we follow (growing both wires at the same time) favours the formation of these anti-parallel metastable states. This works shows how the engineering of strongly coupled 3D nanostructures with competing interactions can be used to create complex spin textures.

Pediatric perianal Crohn's disease behavior in the era of biologic therapy. / Comportamiento de la afectación perianal en pacientes pediátricos con enfermedad de Crohn en la era de la terapia biológica.

AIM OF THE STUDY: To describe perianal Crohn's disease behavior and the role of biological therapy in a sample of pediatric patients. METHODS: A retrospective study of pediatric patients with Crohn's disease (CD) treated in our institution from 2017 to 2021, with a minimum follow up period of 6 months, was conducted. Patients were divided whether they had perianal disease (PD) or not. Baseline characteristics, extension of disease, growth failure rate, aggressive pattern rate, use of biological therapy and need for surgery, among other variables, were compared between both groups. Clinical and/or radiological improvement in the last 6 months of follow up was considered good control of PD. RESULTS: Seventy eight pediatric patients with CD were included. Median age at diagnosis was 10.5 years, and median follow up time was 3.8 years. 64.1% patients were male. Of all, 15 (19.2%) had perianal disease, of which 10 had fistulizing findings and 5 had non fistulizing findings. PD was presented at diagnosis in 8 patients, and the rest developed it in a median time of 1 year from diagnosis. PD was associated with growth failure (p = 0.003), use of biological therapies (p = 0.005), and need for second line of biologics (p = 0.005). Most patients (12/15, 80%) had good control of PD with the treatment received. CONCLUSIONS: CD patients with PD seem to need a more aggressive treatment, with biological therapies playing a key role for its handling nowadays. These patients require close nutritional evaluation that ensures proper development and growth.

OBJETIVO DEL ESTUDIO: Describir el comportamiento de la enfermedad de Crohn perianal y el papel de la terapia biológica en una muestra de pacientes pediátricos. METODOS: Estudio retrospectivo de pacientes pediátricos con enfermedad de Crohn (EC) tratados en nuestro centro entre 2017 y 2021, con un seguimiento mínimo de seis meses. Los pacientes se dividieron en función de si tenían enfermedad perianal (EP) o no. Se compararon entre ambos grupos las características iniciales, la extensión de la enfermedad, el índice de retraso en el crecimiento, el índice de patrón agresivo, el empleo de terapia biológica y la necesidad de cirugía, entre otras variables. Se consideró un buen control de la EP una mejoría clínica o radiológica en los 6 últimos meses de seguimiento. RESULTADOS: Se incluyeron 78 pacientes pediátricos con EC. La edad mediana en el momento del diagnóstico fue de 10,5 años, y el tiempo mediano de seguimiento fue de 3,8 años. El 64,1% de los pacientes eran varones. Del total, 15 (19,2%) tenían enfermedad perianal, de los cuales 10 presentaban hallazgos fistulizantes y 5 no fistulizantes. La EP estaba presente en el momento del diagnóstico en 8 pacientes, y el resto la desarrolló en una mediana de 1 año desde el diagnóstico. La EP se asoció con retraso en el crecimiento (p = 0,003), empleo de terapias biológicas (p = 0,005) y necesidad de una segunda línea de terapia biológica (p = 0,005). La mayoría de los pacientes (12/15, 80%) tuvieron un buen control de la EP con el tratamiento recibido. CONCLUSIONES: Los pacientes de EC con EP parecen necesitar un tratamiento más agresivo, en el que las terapias biológicas desempeñan hoy en día un papel fundamental. Estos pacientes precisan de una estrecha evaluación nutricional que garantice su correcto crecimiento y desarrollo.

Comportamiento de la afectación perianal en pacientes pediátricos con enfermedad de Crohn en la era de la terapia biológica / Pediatric perianal Crohn’s disease behavior in the era of biologic therapy

Objetivo del estudio: Describir el comportamiento de la enfermedad de Crohn perianal y el papel de la terapia biológica en una muestra de pacientes pediátricos. Métodos: Estudio retrospectivo de pacientes pediátricos con enfermedad de Crohn (EC) tratados en nuestro centro entre 2017 y 2021, con un seguimiento mínimo de seis meses. Los pacientes se dividieron en función de si tenían enfermedad perianal (EP) o no. Se compararon entre ambos grupos las características iniciales, la extensión de la enfermedad, el índice de retraso en el crecimiento, el índice de patrón agresivo, el empleo de terapia biológica y la necesidad de cirugía, entre otras variables. Se consideró un buen control de la EP una mejoría clínica o radiológica en los 6 últimos meses de seguimiento. Resultados: Se incluyeron 78 pacientes pediátricos con EC. La edad mediana en el momento del diagnóstico fue de 10,5 años, y el tiempo mediano de seguimiento fue de 3,8 años. El 64,1% de los pacientes eran varones. Del total, 15 (19,2%) tenían enfermedad perianal, de los cuales 10 presentaban hallazgos fistulizantes y 5 no fistulizantes. La EP estaba presente en el momento del diagnóstico en 8 pacientes, y el resto la desarrolló en una mediana de 1 año desde el diagnóstico. La EP se asoció con retraso en el crecimiento (p = 0,003), empleo de terapias biológicas (p = 0,005) y necesidad de una segunda línea de terapia biológica (p = 0,005). La mayoría de los pacientes (12/15, 80%) tuvieron un buen control de la EP con el tratamiento recibido. Conclusiones: Los pacientes de EC con EP parecen necesitar un tratamiento más agresivo, en el que las terapias biológicas desempeñan hoy en día un papel fundamental. Estos pacientes precisan de una estrecha evaluación nutricional que garantice su correcto crecimiento y desarrollo.(AU)

Aim of the study: To describe perianal Crohn’s disease behavior and the role of biological therapy in a sample of pediatric patients. Methods: A retrospective study of pediatric patients with Crohn’s disease (CD) treated in our institution from 2017 to 2021, with a minimum follow up period of 6 months, was conducted. Patients were divided whether they had perianal disease (PD) or not. Baseline characteristics, extension of disease, growth failure rate, aggressive pattern rate, use of biological therapy and need for surgery, among other variables, were compared between both groups. Clinical and/or radiological improvement in the last 6 months of follow up was considered good control of PD. Results: Seventy eight pediatric patients with CD were included. Median age at diagnosis was 10.5 years, and median follow up time was 3.8 years. 64.1% patients were male. Of all, 15 (19.2%) had perianal disease, of which 10 had fistulizing findings and 5 had non fistulizing findings. PD was presented at diagnosis in 8 patients, and the rest developed it in a median time of 1 year from diagnosis. PD was associated with growth failure (p = 0.003), use of biological therapies (p = 0.005), and need for second line of biologics (p = 0.005). Most patients (12/15, 80%) had good control of PD with the treatment received. Conclusions: CD patients with PD seem to need a more aggressive treatment, with biological therapies playing a key role for its handling nowadays. These patients require close nutritional evaluation that ensures proper development and growth.(AU)

Social and Structural Influences on Multiracial Identification and Health: a Public Health Mandate to Precisely Measure, Theorize, and Better Understand Multiracial Populations.

There is a growing group of adolescents and young adults in the USA who identify as multiracial. However, very little research, especially health research, focuses on understanding multiracial identification and health and behavioral outcomes for multiracial populations in comparison to their single-race counterparts. Understanding the intersectional influences on this identification process is critical to updating the literature on racial and ethnic identity and health with more accurate identifications and categories. It is especially critical that there is an explicit focus on understanding the impact of structural racism and discrimination when studying the process of racial identification and the impact on health. This review takes an interdisciplinary approach relying on a review of multiple research literatures: the historical literature on race, racism and categorization, psychological and adolescent medicine literatures on adolescent development, the sociological literature on racial and ethnic identification, and the limited public health research beginning to disentangle multiracial health outcomes. An empirically testable conceptual framework is offered to frame the organization of this review-demonstrating the multiple spheres of influence on racial and ethnic identification and the implication for health outcomes.

Implementation of a major trauma team. Analysis of activation and care times in patients admitted to the ICU.

OBJECTIVE: To analyze the factors associated with the activation of the severe trauma care team (STAT) in patients admitted to the ICU, to measure its impact on care times, and to analyze the groups of patients according to activation and level of anatomical involvement. DESIGN: Prospective cohort study of severe trauma admitted to the ICU. From June 2017 to May 2019. Risk factors for the activation of the STAT analysed with logistic regression and CART type classification tree. SETTING: Second level hospital ICU. PATIENTS: Patients admitted consecutively. INTERVENTIONS: No. MAIN VARIABLES OF INTEREST: STAT activation. Demographic variables. Injury severity (ISS), intentionality, mechanism, assistance times, evolutionary complications, and mortality. RESULTS: A total of 188 patients were admitted (46.8% of STAT activation), median age of 52 (37-64) years (activated 47 (27-62) vs not activated 55 (42-67) P = 0.023), males 84.0%. No difference in mortality according to activation. The logistic model finds as factors: care (16.6 (2.1-13.2)) and prehospital intubation (4.2 (1.8-9.8)) and severe lower extremity injury (4.4 (1.6-12.3)). Accidental fall (0.2 (0.1-0.6)) makes activation less likely. The CART model selects the type of trauma mechanism and can separate high and low energy trauma. CONCLUSIONS: Factors associated with STAT activation were prehospital care, requiring prior intubation, high-energy mechanisms, and severe lower extremity injuries. Shorter care times if activated without influencing mortality. We must improve activation in older patients with low-energy trauma and without prehospital care.

Síndrome hemofagocítico en pacientes con leucemia linfocítica crónica tratados con ibrutinib. A propósito de dos casos / Haemophagocytic syndrome in patient with chronic lymphocytic leukaemia treated with ibrutinib. Two cases report

Se presentan dos casos de sospecha de síndrome hemofagocítico secundario en pacientes con leucemia linfocítica crónica, tratados con ibrutinib, síndrome que puede ser letal y que tiene lugar por una activación inmune excesiva. En el presente artículo se describe el desarrollo del síndrome, su diagnóstico, el tratamiento y su desenlace, acorde a las guías y protocolos de diagnóstico, actuación y tratamiento. Es destacable por el hecho de ser una reacción adversa rara de la que no se conoce muy bien la causa, multifactorial, de diferente inicio y evolución, como ocurre en los dos casos que se presentan, no recogida en ficha técnica. Se sitúan los casos junto a un pequeño número de casos también publicados. (AU)

We presented two cases of suspected secondary haemophagocytic syndrome in patients with chronic lymphocytic leukaemia treated with ibrutinib, syndrome that could be letal and that occurs due to excessive immune activation. This article describes the evolution, diagnosis, treatment, and denouement, according to protocols and guidelines for diagnosis and therapeutic decision-making. It is noteworthy, because is a rare adverse event, not present in product monograph, whose cause is not weel known, multifactorial, with different onset and evolution, as in the two cases presented. The cases are placed next to a small number of publicated cases. (AU)

Exonic variants of the P2RX7 gene in familial multiple sclerosis.

INTRODUCTION: Several studies have analysed the presence of P2RX7 variants in patients with MS, reporting diverging results. METHODS: Our study analyses P2RX7 variants detected through whole-exome sequencing (WES). RESULTS: We analysed P2RX7, P2RX4, and CAMKK2 gene variants detected by whole-exome sequencing in all living members (n = 127) of 21 families including at least 2 individuals with multiple sclerosis. P2RX7 gene polymorphisms previously associated with autoimmune disease. Although no differences were observed between individuals with and without multiple sclerosis, we found greater polymorphism of gain-of-function variants of P2RX7 in families with individuals with multiple sclerosis than in the general population. Copresence of gain-of-function and loss-of-function variants was not observed to reduce the risk of presenting the disease. Three families displayed heterozygous gain-of-function SNPs in patients with multiple sclerosis but not in healthy individuals. We were unable to determine the impact of copresence of P2RX4 and CAMKK2 variants with P2RX7 variants, or the potential effect of the different haplotypes described in the gene. No clinical correlations with other autoimmune diseases were observed in our cohort. CONCLUSIONS: Our results support the hypothesis that the disease is polygenic and point to a previously unknown mechanism of genetic predisposition to familial forms of multiple sclerosis. P2RX7 gene activity can be modified, which suggests the possibility of preventive pharmacological treatments for families including patients with familial multiple sclerosis.

Variant rs4149584 (R92Q) of the TNFRSF1A gene in patients with familial multiple sclerosis.

INTRODUCTION: Genomic studies have identified numerous genetic variants associated with susceptibility to multiple sclerosis (MS); however, each one explains only a small percentage of the risk of developing the disease. These variants are located in genes involved in specific pathways, which supports the hypothesis that the risk of developing MS may be linked to alterations in these pathways, rather than in specific genes. We analyzed the role of the TNFRSF1A gene, which encodes one of the TNF-α receptors involved in a signaling pathway previously linked to autoimmune disease. METHODS: We included 138 individuals from 23 families including at least 2 members with MS, and analyzed the presence of exonic variants of TNFRSF1A through whole-exome sequencing. We also conducted a functional study to analyze the pathogenic mechanism of variant rs4149584 (-g.6442643C > G, NM_001065.4:c.362 G > A, R92Q) by plasmid transfection into human oligodendroglioma (HOG) cells, which behave like oligodendrocyte lineage cells; protein labeling was used to locate the protein within cells. We also analyzed the ability of transfected HOG cells to proliferate and differentiate into oligodendrocytes. RESULTS: Variant rs4149584 was found in 2 patients with MS (3.85%), one patient with another autoimmune disease (7.6%), and in 5 unaffected individuals (7.46%). The 2 patients with MS and variant rs4149584 were homozygous carriers and belonged to the same family, whereas the remaining individuals presented the variant in heterozygosis. The study of HOG cells transfected with the mutation showed that the protein does not reach the cell membrane, but rather accumulates in the cytoplasm, particularly in the endoplasmic reticulum and near the nucleus; this suggests that, in the cells presenting the mutation, TNFRSF1 does not act as a transmembrane protein, which may alter its signaling pathway. The study of cell proliferation and differentiation found that transfected cells continue to be able to differentiate into oligodendrocytes and are probably still capable of producing myelin, although they present a lower rate of proliferation than wild-type cells. CONCLUSIONS: Variant rs4149584 is associated with risk of developing MS. We analyzed its functional role in oligodendrocyte lineage cells and found an association with MS in homozygous carriers. However, the associated molecular alterations do not influence the differentiation into oligodendrocytes; we were therefore unable to confirm whether this variant alone is pathogenic in MS, at least in heterozygosis.

Horizontally and vertically sensitive schlieren and shadowgraph system.

Visualizing and quantifying certain variables are essential in fluid flow studies. If we add that these tasks should be achieved in great detail, it would be beneficial to implement optical techniques that would reveal these characteristics. Based on this premise, we present a z-schlieren setup that allows simultaneous recording of horizontal and vertical sensitivity schlieren images and shadowgraph images. These two visualization techniques complement each other since each method has its own strengths and weaknesses. The optical system employs two ultra-thin filters, an RGB light-emitting diode (LED), and a color digital camera. As a result, the data obtained are significantly improved over the existing standard schlieren methods. Furthermore, the fluid flow is better analyzed by combining the schlieren and shadowgraph techniques since a straightforward optical system gathers helpful information. The performance of the optical system is demonstrated by visualizing the convective fluid flow of a candle flame and measuring the temperature fields of the flow of a heated rectangular plate.

El polimorfismo de un solo nucleótido rs1800795 en el gen IL6 no está asociado con el glaucoma primario de ángulo abierto en la población mexicana / The rs1800795 single nucleotide polymorphism in the IL6 gene is not associated with primary open angle glaucoma in Mexican population

Objetivo La interleucina 6 (IL-6) es una citoquina proinflamatoria con efectos pleiotrópicos que se ha relacionado con el glaucoma primario de ángulo abierto (GPAA) debido a su efecto particular de protección de las células ganglionares de la retina (CGR) contra la apoptosis. Se han asociado diferentes polimorfismos de un solo nucleótido (PSN) con el GPAA. El objetivo de este estudio fue determinar si existe una asociación entre el PSN de IL-6 rs1800795 (−174 G>C) y un mayor riesgo de padecer GPAA en la población mexicana occidental. Métodos Se incluyeron 165 pacientes mestizos mexicanos no emparentados con GPAA y 108 sujetos de control. Se extrajo el ADN genómico de los leucocitos y se purificó, seguido de la genotipificación y la amplificación por reacción en cadena de la polimerasa (PCR) con sondas TaqMan® Biosystem®. Se evaluó la diversidad alélica y genotípica entre los casos y los sujetos de control. Resultados No hubo asociación estadísticamente significativa entre las frecuencias alélicas y genotípicas, ni con modelos de asociación genética dominante ni recesiva (p>0,05). Conclusiones Aunque existe un papel de la IL6 en la fisiopatología del GPAA, nuestros resultados descartan la asociación entre la IL-6 y el PSN rs1800795 mostrando no ser un índice de mayor riesgo de GPAA en la población mexicana (AU)

Purpose Interleukin-6 (IL-6) is a proinflammatory cytokine with pleiotropic effects which has been related to primary open angle glaucoma (POAG) due to its particular effect of protecting the retinal ganglion cells (RGc) from the apoptosis. Different single nucleotide polymorphisms (SNP) have been associated with POAG. The aim of this study was to determine whether an association between IL-6 rs1800795 (−174 G>C) SNP and a higher risk for POAG is present in western Mexican population. Methods One hundred and sixty-five unrelated Mexican mestizo patients with POAG and 108 control subjects were included. Genomic DNA was extracted from leukocytes and purified, followed by genotyping and amplification by polymerase chain reaction (PCR) with Taqman Biosystem probes. Allelic and genotypic diversity was evaluated between cases and control subjects. Results There was no statistically significant association between allele and genotype frequencies, neither with dominant nor recessive genetic association models (P>.05). Conclusion Even though there is a role of IL6 in the pathophysiology of POAG, our results ruled out the association between IL-6 and the rs1800795 SNP showing not to be an index of higher risk for POAG in Mexican population (AU)