Comparing cefazolin/ metronidazole, piperacillin-tazobactam, or c efoxitin as surgical antibiotic prophylaxis in patients undergoing pancreaticoduodenectomy: A retrospective cohort study.

BACKGROUND: Preoperative antibiotic options for pancreaticoduodenectomy (PD) include cefoxitin (CX), piperacillin-tazobactam (PT), or combined cefazolin and metronidazole (CM). Recent studies suggest the superiority of PT over CX, but evidence for CM is unclear. OBJECTIVE: To explore the impact of preoperative antibiotic selection (CM vs. PT and CX vs. PT) on the development of surgical site infections (SSI). METHODS: Consecutive adult patients at one institution who underwent PD from November 2017 to December 2021 and received either CM, PT, or CX preoperatively, were included. The primary outcome was SSI. Secondary outcomes included postoperative infections and clinically significant postoperative pancreatic fistula (POPF). Logistic regression models were used. RESULTS: Among 127 patients included in the study, PT, CM, and CX were administered in 46 (36.2%), 44 (34.6%), and 37 (29.4%) patients, respectively. There were 32 (27.1%) SSI, 20 (36.1%) infections, and 21 (22.9%) POPF events. PT use was associated with reduced risk of SSI compared to CX (OR: 0.32, 95% CI: 0.11-0.89, p = 0.03), but there was no difference as compared to CM (OR: 0.75, 95% CI: 0.27-2.13, p = 0.59). There were no differences in secondary outcomes. CONCLUSION: PT reduced SSI rates compared to CX but was no different to CM among patients undergoing PD at our center.

Quality of life following perioperative optimization with nutritional supplements in patients undergoing gastrointestinal surgery for cancer: A randomized, placebo-controlled feasibility clinical trial.

BACKGROUND: Up to two thirds of patients presenting for abdominal cancer surgery are malnourished pre-operatively. Perioperative nutritional supplementation has been proposed to improve surgical outcomes, though its effect on quality of life (QoL) is not yet understood. METHODS: A randomized controlled feasibility trial for perioperative nutrition among patients undergoing major abdominal cancer surgery was conducted. Participants in the intervention group received supplements for 30 days before surgery. Participants completed two QoL questionnaires (EORTC-QLQ-C-30 and FACT-G) at baseline, then 4 and 12 weeks postoperatively. Participants were compared between and within groups at baseline, Weeks 4, and 12 using t tests. Minimal clinically important differences (MCIDs) were considered as a 10-point worsening from baseline. RESULTS: Sixty-six participants were available for analysis in this study, including 33 in the intervention and 30 in the control arms. Baseline demographics were balanced between groups except for different rates of pancreas cancer (36% intervention vs. 9% control) and colorectal cancer (19% intervention vs. 34% control). At baseline, participants in the intervention group had lower overall QoL (59% vs. 77%, p = 0.01), role functioning (72% vs 88%, p = 0.045), and cognitive functioning (79% vs 90%, p = 0.047). Following surgery, role and physical functioning worsened in the control group, without significant differences between groups. Role functioning was persistently worsened at 12 weeks in the control group. The rates of MCIDs were similar between both intervention and control groups. DISCUSSION: Perioperative nutrition was associated with preservation of QoL in the postoperative period following major abdominal cancer surgery compared to placebo. SUMMARY: Among patients undergoing surgery for cancer, the majority present at high risk for malnutrition. In this placebo-controlled randomized trial among patients undergoing major abdominal surgery for cancer, preoperative nutrition supplementation was associated with the preservation of QoL in the postoperative period.

Usual interstitial pneumopathy in a patient with hypersensitivity pneumonitis and microscopic polyangiitis. Case report.

One of the most frequent diffuse interstitial lung diseases is hypersensitivity pneumonitis. It is related to exposure to diverse antigens, causing fibrosis in advanced stages, making the differential diagnosis with interstitial pulmonary fibrosis difficult as it overlaps with the usual interstitial pneumonia pattern. On the other hand, there are interstitial lung diseases associated with ANCA, such as microscopic polyangiitis, which is also related to the usual interstitial pneumonia pattern. We present the case of a 74-year-old male patient with chronic dyspnea, history of smoking and exposure to organic particles, in addition to a pattern suggestive of moderately severe restriction. The diagnosis was confirmed by histology of hypersensitivity pneumonitis by presenting granules, however, anti MPO and p-ANCA positivity was found, integrating the simultaneous diagnosis of microscopic polyangiitis. This is a case of difficult diagnosis since these pathologies have not been previously reported to coexist.

Venom of the neotropical rattlesnake, Crotalus culminatus: Intraspecific variation, neutralization by antivenoms, and immunogenicity in rabbits.

Crotalus culminatus is a medically significant species of rattlesnake in Mexico [1]. While the proteomic composition of its venom has been previously reported for both juvenile and adult specimens, there has been limited research into its functional properties, with only a few studies, including one focusing on coagulotoxicity mechanisms. In this study, we aimed to compare the biochemical and biological activities of the venom of juvenile and adult snakes. Additionally, we assessed antibody production using the venoms of juveniles and adults as immunogens in rabbits. Our findings reveal lethality and proteolytic activity differences between the venoms of juveniles and adults. Notably, juvenile venoms exhibited high proportions of crotamine, while adult venoms displayed a reduction of this component. A commercially available antivenom demonstrated effective neutralization of lethality of both juvenile and adult venoms in mice. However, it failed to neutralize the paralytic activity induced by crotamine, which, in contrast, was successfully inhibited by antibodies obtained from hyperimmunized rabbits. These results suggest the potential inclusion of C. culminatus venom from juveniles in commercial antivenom immunization schemes to generate antibodies targeting this small myotoxin.

Unveiling Sticholysin II and plasmid DNA interaction: Implications for developing non-viral vectors.

Non-viral gene delivery systems offer significant potential for gene therapy due to their versatility, safety, and cost advantages over viral vectors. However, their effectiveness can be hindered by the challenge of efficiently releasing the genetic cargo from endosomes to prevent degradation in lysosomes. To overcome this obstacle, functional components can be incorporated into these systems. Sticholysin II (StII) is one of the pore-forming proteins derived from the sea anemone Stichodactyla helianthus, known for its high ability to permeabilize cellular and model membranes. In this study, we aimed to investigate the interaction between StII, and a model plasmid (pDNA) as an initial step towards designing an improved vector with enhanced endosomal escape capability. The electrophoretic mobility shift assay (EMSA) confirmed the formation of complexes between StII and pDNA. Computational predictions identified specific residues involved in the StII-DNA interaction interface, highlighting the importance of electrostatic interactions and hydrogen bonds in mediating the binding. Atomic force microscopy (AFM) of StII-pDNA complexes revealed the presence of nodular fiber and toroid shapes. These complexes were found to have a predominantly micrometer size, as confirmed by dynamic light scattering (DLS) measurements. Despite increase in the overall charge, the complexes formed at the evaluated nitrogen-to-phosphorus (N/P) ratios still maintained a negative charge. Moreover, StII retained its pore-forming capacity regardless of its binding to the complexes. These findings suggest that the potential ability of StII to permeabilize endosomal membranes could be largely maintained when combined with nucleic acid delivery systems. Additionally, the still remaining negative charge of the complexes would enable the association of another positively charged component to compact pDNA. However, to minimize non-specific cytotoxic effects, it is advisable to explore methods to regulate the protein's activity in response to the microenvironment.

Impacto del uso de plataformas de video llamadas en las preocupaciones con la apariencia física en pacientes con Trastornos Alimentarios y de la población general durante la Pandemia por COVID 19 / Video call platforms impact on physical appearance concerns in patients with Eating Disorders and general population during the COVID 19 Pandemic

Resumen: Objetivo: Explorar el impacto del uso cotidiano de plataformas de videollamadas en las cogniciones, emociones y comportamientos relacionados con la autoimagen en pacientes con Trastornos del Comportamiento Alimentario (TCA) y personas de la población general, durante la pandemia por COVID-19. Métodos: Sesenta y ocho pacientes con TCA en tratamiento y 106 personas de la población general respondieron a un cuestionario diseñado para el estudio a través de Lime Survey; (98.5 y 79.2% respectivamente eran mujeres), con edad promedio de 17.6 (DE:3.47) y 33.5 (DE:9.35) respectivamente. Las pacientes discutieron y explicaron sus respuestas en cinco sesiones de terapia grupal presenciales dirigidas por un psiquiatra. Posteriormente, se realizó un análisis temático reflexivo con un enfoque inductivo para determinar las categorías. Resultados: Los pacientes reportaron una mayor incomodidad frente a la cámara, preocupación con la apariencia física, miedo a la crítica, vergüenza y sentimientos de vulnerabilidad, comparados con las personas de la población general. Predominaron los pensamientos negativos sobre la forma y el tamaño del rostro y otras partes del cuerpo y las conductas de chequeo y/o evitación de la imagen corporal, que interfirieron con la concentración y el rendimiento. Conclusión: además del impacto negativo de la pandemia de COVID-19 en la salud mental, la nueva virtualidad desafía a los clínicos a enfrentar dificultades adicionales con la imagen corporal en pacientes con TCA y alerta a la detección de nuevas preocupaciones dismórficas también en la población general.

Abstract: Objective: To explore the impact of video call platforms on physical appearance concerns (cognitions, emotions and behaviors) in Eating Disorders (ED) patients and in general population, during COVID 19 pandemic. Methods: Sixty-eight patients attending a treatment program for ED, and 106 people from the general population responded to a questionnaire designed for the study through Lime Survey; (98.5 and 79.2% respectively were women), with a mean age of 17.6 (SD:3.47) and 33.5 (SD:9.35) respectively. Patients discussed and explained their answers in five in vivo group therapy sessions directed by a psychiatrist. Then, a reflective thematic analysis with an inductive approach to determine the categories was performed. Results: Patients reported a higher discomfort in front of the camera, preoccupation with physical appearance, fear of criticism, embarrassment, and feelings of vulnerability, compared with general population. Negative thoughts about the shape and size of the face and other body parts predominated, as well as body image checking/avoidance behaviors that interfered with concentration and performance. Conclusion: In addition to the negative impact of the COVID-19 pandemic on mental health, the new virtuality challenges clinicians to face additional body image difficulties in ED patients and alerts on the detection of dysmorphic concerns in the general population as well.

Membrana de fibrina rica en plaquetas asociada al colgajo de reposición coronal tres años después

Fundamento la asociación de la membrana de fibrina rica en plaquetas con el colgajo de reposición coronal constituye una modalidad de la ingeniería de tejidos que aporta elementos regenerativos al proceso de reparación tisular. Objetivo evaluar la efectividad de la membrana de fibrina rica en plaquetas asociada al colgajo de reposición coronal en el tratamiento de la recesión periodontal tres años después. Métodos se realizó un cuasiexperimento en la facultad de Estomatología de Villa Clara, en el periodo marzo de 2017-julio de 2020, y con una población de estudio conformada por 46 pacientes portadores de recesión periodontal, quienes requerían recubrimiento radicular mediante el colgajo de reposición coronal. Se utilizó un muestreo no probabilístico intencional por criterios, y la muestra quedó conformada por 26 pacientes. Se establecieron sitios de estudio y sitios de control. Las variables estudiadas fueron: edad, sexo, largo de la recesión, clasificación de Miller, cobertura radicular, ancho y ganancia de la encía insertada, categorías de evaluación y efectividad del tratamiento. Resultados en el 88,68 % de los dientes ubicados en los sitios de estudio predominó la categoría de evaluación favorable. El porcentaje de efectividad a los tres años de la terapéutica fue superior en los sitios de estudio (54,71 %). Conclusiones se consideró más efectivo el tratamiento de la recesión periodontal con membrana de fibrina rica en plaquetas asociada al colgajo de reposición coronal a los tres años del proceder.

Foundation the association of the platelet-rich fibrin membrane with the coronal replacement flap constitutes a modality of tissue engineering that provides regenerative elements to the tissue repair process. Objective to evaluate the effectiveness of the platelet-rich fibrin membrane associated with the coronal repositioning flap in the treatment of periodontal recession three years later. Methods a quasi-experiment was carried out at the Villa Clara Dentistry Faculty, from March 2017 to July 2020, a study population of 46 patients with periodontal recession, who required root coverage using the replacement flap coronal. Intentional non-probabilistic sampling by criteria was used, and the sample of 26 patients. Study sites and control sites were established. The studied variables were: age, sex, recession length, Miller classification, root coverage, width and gain of the attached gingiva, evaluation categories and treatment effectiveness. Results in 88.68% of the teeth located in the study sites, the favorable evaluation category predominated. The effectiveness percentage three years after treatment was higher in the study sites (54.71%). Conclusions the treatment of periodontal recession with platelet-rich fibrin membrane associated with the coronal replacement flap was considered more effective three years after the procedure.

Competencies Development Strategy Using Augmented Reality for Self-Management of Learning in Manufacturing Laboratories (AR-ManufacturingLab).

Technological tools in education open new learning possibilities. This proposal describes integrating augmented reality and different educational elements to develop engineering competencies, specifically using specialized machinery in the manufacturing laboratory. It is necessary to encourage self-management of learning, where users interact with the devices employing an application that contains significant information about procedures to perform and essential elements to consider when manipulating the machinery. The machines involved include industrial robots, CNC (Computer Numerical Control) lathes and milling machines, and PLCs (Programmable Logic Controls). In a traditional training model, an instructor guides the users in learning how to manipulate the equipment. This proposal intends that the participants use their mobile devices to receive each machine's instruction and the necessary documentation. The participants' learning pace varies. So, the research aimed to reduce the deficit in the disciplinary competencies since, in the traditional methodology, there is no heterogeneity in understanding the contents. We designed a competency development strategy with six laboratory practices, integrating multimedia elements to address the significant learning content of each manufacturing cell device. Each lesson contained information about each device and a practice activity and self-evaluation to ensure learning the content.

Analysis of perceptions and emotional repercussions in Twitter users in Colombia during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has negatively impacted mental health. Up to a quarter of the population has reported mental health disorders. This has been studied mainly from a nosological perspective, according to diagnostic criteria. Nevertheless, we did not find studies that have explored the daily expressions of the population. Our objective was to evaluate the perceptions of the COVID-19 pandemic and its repercussions on the emotional well-being of the Colombian population. METHODS: We performed a Twitter metrics and trend analysis. Initially, in the trend analysis, we calculated the average duration in hours of the 20 most popular trending topics of the day in Colombia and we grouped them into trends related to COVID-19 and unrelated trends. Subsequently, we identified dates of events associated with the pandemic relevant to the country, and they were related to the behaviour of the trends studied. Additionally, we did an exploratory analysis of these, selected the tweets with the greatest reach and categorised them in an inductive way to analyse them qualitatively. RESULTS: Issues not related to COVID-19 were more far-reaching than those related to coronavirus. However, a rise in these issues was seen on some dates consistent with important events in Colombia. We found expressions of approval and disapproval, solidarity and accusation. Inductively, we identified categories of informative tweets, humour, fear, stigma and discrimination, politics and entities, citizen complaints, and self-care and optimism. CONCLUSIONS: The impact of the COVID-19 pandemic generates different reactions in the population, which increasingly have more tools to express themselves and know the opinions of others. Social networks play a fundamental role in the communication of the population, so this content could serve as a public health surveillance tool and a useful and accessible means of communication in the management of health crises.

Pilot Monitoring of Lead in Umbilical Cord Blood of Newborns Associated With the Use of Glazed Ceramics from Guanajuato, Mexico.

The use of lead-glazed pottery for cooking and storing food, a widespread practice in Mexico, represents a risk of exposure to lead from the human intrauterine stage. Therefore, a pilot study was carried out by means of the measurement of lead in umbilical cord blood by inductively coupled plasma mass spectrometry (ICP-MS) including 69 newborns from the Mexican state capital of Guanajuato, Guanajuato City, where the use of glazed clay is still widespread. Lifestyle and sociodemographic data were collected by interviewing the participating mothers. Hematological parameters and the anthropometry of the newborns and their mothers were analyzed; likewise, the G177C polymorphism in the ALAD gene was genotyped by PCR-RFLP as a marker of genetic vulnerability to lead. The geometric mean of lead in umbilical cord blood was 0.7 µg/dL (< limit of detection = 0.01-28.22). Boys presented higher values than girls (p = 0.03). Only 5.8% of these were above the safety value of the US Centers for Disease Control and Prevention (CDC) of 3.5 µg/dL. Correlations among lead concentrations, maternal age, weeks of gestation, newborn anthropometry, and hematological parameters were not found; however, the participating mothers who reported using glazed ceramics for cooking or storing food had the highest cord-blood lead concentrations (p = 0.04). Regarding genotyping, 97% had ALAD 1, while 3% had ALAD 1, 2; unfortunately, the sample size did not allow analysis of genetic vulnerability to lead. The preparation and conservation of food in handcrafted clay pottery increased the risk of having cord-blood lead values higher than those recommended by the CDC of 3.5 µg/dL (OR = 5; 95% CI:1.3-23; p = 0.01). Our preliminary results suggest that there continues to be intrauterine exposure to lead in Guanajuato.

Tracing last millennium cycles of Río de la Plata Plume Water input into the Southwestern Atlantic Ocean.

Recent studies established a strong connection between instrumental hydroclimatic changes in the Río de la Plata (RdlP) watershed and the influx of continental terrigenous material and productivity changes. This correspondence was further validated for the last millennium. Here, we identified centennial, multi-decadal, and interannual changes in diatom composition, as a proxy for La Plata Plume Water (PPW) discharge into the inner shelf. Core GeoB13813-4 diatom data were revisited, and grouped into freshwater, marine, and brackish categories for multivariate, timeseries, and correlation analyses. Such record exhibits a noteworthy resemblance to paleoclimatic and paleoceanographic variations throughout the past millennium. A Detrended Correspondence Analysis (DCA) on the dominant taxa, and Axis-1 revealed a salinity gradient over the past millennium. DCA1-scores exhibited significant correlation with reconstructions of El Niño Southern Oscillation (ENSO), the Pacific Decadal Oscillation (PDO), and the Atlantic Multidecadal Oscillation (AMO) over the same period. By plotting DCA1-scores, we inferred time intervals with varying levels of PPW influence. During ∼936-1500 CE, the PPW influence was weak, as the record was dominated by marine taxa, indicating lateral transport from the Brazilian upwelled water and a stronger influence of the Subtropical Shelf Water. After 1500 CE, a well-developed plume was inferred, with the highest influence occurring after 1800 CE, as evidenced by an increased presence of freshwater/brackish taxa. This increased PPW influence after 1500 CE can be attributed to the onset of more humid conditions and associated increased river discharge, particularly under El Niño conditions, with further ENSO intensification after 1800 CE. We identified significant centennial (250 years) and multidecadal cycles (25-50 years) in diatom community composition. These cycles are related to solar forcing, PDO, and AMO. During the 20th Century, cycles of 2 to 7 years were associated with interannual ENSO variability, while 40-year cycles were linked to AMO and PDO variability.

Análisis de percepciones y repercusiones emocionales en usuarios de Twitter en Colombia durante la pandemia de COVID-19

Introducción: La pandemia de COVID-19 ha impactado negativamente en la salud mental. Hasta un cuarto de la población ha reportado alteraciones de salud mental. Esto se ha estudiado principalmente desde una perspectiva nosológica según criterios diagnósticos; sin embargo, no encontramos estudios que hayan explorado las expresiones cotidianas de la población. Nuestro objetivo es evaluar las percepciones y repercusiones en el bienestar emocional de la población colombiana por la pandemia de COVID-19. Métodos: Se realizó un análisis de métricas y tendencias en Twitter. Inicialmente, en el análisis de tendencias se calculó el promedio de duración en horas de los 20 temas tendencia del día más populares en Colombia y las agrupamos en relacionadas con la COVID-19 y no relacionadas. Después se identificaron fechas de acontecimientos asociados con la pandemia relevantes para el país, y se relacionaron con el comportamiento de las tendencias estudiadas. Además, se hizo un análisis exploratorio de estas, se seleccionaron los tweets con mayor alcance y se categorizaron de forma inductiva para analizarlos cualitativamente. Resultados: Los temas no relacionados con COVID-19 tuvieron mayor alcance que los relacionados con coronavirus. No obstante, se vio un alza de estos temas en algunas fechas concordantes con hechos importantes en Colombia. Se hallaron manifestaciones de aprobación y desaprobación, de solidaridad y de acusación. De manera inductiva, se identificaron categorías de tweets informativos, humor, miedo, estigma y discriminación, política y entidades, denuncia ciudadana, y autocuidado y optimismo. Conclusiones: El impacto de la pandemia de COVID-19 genera diferentes reacciones en la población, que cada vez tienen más herramientas para expresarse y conocer las opiniones de los demás. Las redes sociales tienen un papel primordial en la comunicación de la población, por lo que este contenido podría servir como herramienta de vigilancia en salud pública y medio de comunicación útil y accesible en el manejo de crisis sanitarias.

Introduction: The COVID-19 pandemic has negatively impacted mental health. Up to a quarter of the population has reported mental health disorders. This has been studied mainly from a nosological perspective, according to diagnostic criteria. Nevertheless, we did not find studies that have explored the daily expressions of the population. Our objective was to evaluate the perceptions of the COVID-19 pandemic and its repercussions on the emotional well-being of the Colombian population. Methods: We performed a Twitter metrics and trend analysis. Initially, in the trend analysis, we calculated the average duration in hours of the 20 most popular trending topics of the day in Colombia and we grouped them into trends related to COVID-19 and unrelated trends. Subsequently, we identified dates of events associated with the pandemic relevant to the country, and they were related to the behaviour of the trends studied. Additionally, we did an exploratory analysis of these, selected the tweets with the greatest reach and categorized them in an inductive way to analyse them qualitatively. Results: Issues not related to COVID-19 were more far-reaching than those related to coronavirus. However, a rise in these issues was seen on some dates consistent with important events in Colombia. We found expressions of approval and disapproval, solidarity and accusation. Inductively, we identified categories of informative tweets, humour, fear, stigma and discrimination, politics and entities, citizen complaints, and self-care and optimism. Conclusions: The impact of the COVID-19 pandemic generates different reactions in the population, which increasingly have more tools to express themselves and know the opinions of others. Social networks play a fundamental role in the communication of the population, so this content could serve as a public health surveillance tool and a useful and accessible means of communication in the management of health crises.

Genome-wide CRISPR screen identifies genes synthetically lethal with GRA17, a nutrient channel encoding gene in Toxoplasma.

Toxoplasma gondii is a parasite that replicates within a specialized compartment called the parasitophorous vacuole (PV), which is surrounded by the PV membrane (PVM). To obtain essential nutrients, Toxoplasma must transport molecules across the PVM, a process mediated by the secreted parasite proteins GRA17 and GRA23. These proteins form pores in the PVM through which small molecules can diffuse in and out of the PV. GRA17 and GRA23 are synthetically lethal, suggesting that at least one pore type is essential for parasite survival. In the 'nutrient sensitized' Δgra17 strain it is likely that other Toxoplasma genes become essential, because they mediate nutrient acquisition from the host or are involved in the trafficking of GRA23 to the PVM. To identify these genes, a genome-wide loss-of-function screen was performed in wild-type and Δgra17 parasites, which identified multiple genes that were synthetically sick/lethal with GRA17. Several of these genes were involved in the correct localization of GRAs, including GRA17/GRA23, to the PVM. One of the top hits, GRA72, was predicted to form a pore on the PVM, and its deletion led to the formation of enlarged "bubble vacuoles" with reduced PVM small molecule permeability, similar to what was previously observed for Δgra17 parasites. Furthermore, Δgra72 parasites had reduced in vitro growth and virulence in mice. These findings suggest that in the absence of GRA17, other genes become essential, likely because they play a role in the proper localization of GRA23 (and other GRAs) or because they determine host-derived nutrient acquisition at the PVM.

Variation in CD8 T cell IFNγ differentiation to strains of Toxoplasma gondii is characterized by small effect QTLs with contribution from ROP16.

Introduction: Toxoplasma gondii induces a strong CD8 T cell response characterized by the secretion of IFNγ that promotes host survival during infection. The initiation of CD8 T cell IFNγ responses in vitro differs widely between clonal lineage strains of T. gondii, in which type I strains are low inducers, while types II and III strains are high inducers. We hypothesized this phenotype is due to a polymorphic "Regulator Of CD8 T cell Response" (ROCTR). Methods: Therefore, we screened F1 progeny from genetic crosses between the clonal lineage strains to identify ROCTR. Naïve antigen-specific CD8 T cells (T57) isolated from transnuclear mice, which are specific for the endogenous and vacuolar TGD057 antigen, were measured for their ability to become activated, transcribe Ifng and produce IFNγ in response to T. gondii infected macrophages. Results: Genetic mapping returned four non-interacting quantitative trait loci (QTL) with small effect on T. gondii chromosomes (chr) VIIb-VIII, X and XII. These loci encompass multiple gene candidates highlighted by ROP16 (chrVIIb-VIII), GRA35 (chrX), TgNSM (chrX), and a pair of uncharacterized NTPases (chrXII), whose locus we report to be significantly truncated in the type I RH background. Although none of the chromosome X and XII candidates bore evidence for regulating CD8 T cell IFNγ responses, type I variants of ROP16 lowered Ifng transcription early after T cell activation. During our search for ROCTR, we also noted the parasitophorous vacuole membrane (PVM) targeting factor for dense granules (GRAs), GRA43, repressed the response suggesting PVM-associated GRAs are important for CD8 T cell activation. Furthermore, RIPK3 expression in macrophages was an absolute requirement for CD8 T cell IFNγ differentiation implicating the necroptosis pathway in T cell immunity to T. gondii. Discussion: Collectively, our data suggest that while CD8 T cell IFNγ production to T. gondii strains vary dramatically, it is not controlled by a single polymorphism with strong effect. However, early in the differentiation process, polymorphisms in ROP16 can regulate commitment of responding CD8 T cells to IFNγ production which may have bearing on immunity to T. gondii.

La muestra en ensayos clínicos aleatorizados con análisis interino / Samples in randomized clinical trials with interim analysis

RESUMEN En este artículo se introducen los ensayos clínicos aleatorizados y conceptos básicos de la inferencia estadística. Se presenta como calcular el tamaño de muestra por tipo de desenlace e hipótesis a probar, junto con el código en el lenguaje de programación R para realizar su aplicación. Se presentan cuatro métodos para realizar el ajuste del tamaño de muestra original, cuando se planean análisis interinos. De una manera sencilla y concreta se busca realizar una introducción a estos temas, considerando las expresiones matemáticas que soportan los resultados y su implementación en programas estadísticos disponibles. Con el fin de acercar a los estudiantes de áreas de la salud a la estadística y al uso de programas estadísticos, aspectos poco considerados en su formación.

ABSTRACT This article introduces randomized clinical trials and basic concepts of statistical inference. We present methods for calculating the sample size by outcome type and the hypothesis to be tested, together with the code in the R programming language. We describe four methods for adjusting the original sample size for interim analyses. We sought to introduce these topics in a simple and concrete way, considering the mathematical expressions that support the results and their implementation in available statistical programs; therefore, bringing health students closer to statistics and the use of statistical programs, which are aspects that are rarely considered during their training.

Clinical insights from an unusual Turner syndrome manifestation: Congenital cutis verticis gyrata.

Cutis verticis gyrata (CVG) is classified as primary or secondary according to the absence or presence of underlying soft tissue abnormalities. We report an infant with Turner syndrome (TS) who in addition presented with CVG on the scalp. The skin biopsy revealed a hamartoma-like lesion. We reviewed the clinical and histopathological findings of the 13 reported cases of congenital CVG in patients with TS, including ours. In 11 of them, CVG was localized on the skin of the scalp, mainly on the parietal region, and in two, on the forehead. Clinically, CVG had a flesh-colored aspect, with absent or sparse hair, and was not progressive. CVG was classified as primary in four patients who had skin biopsy and it was attributed to the intrauterine lymphedema of TS. However, histopathology in two of these patients identified dermal hamartoma as a secondary cause of CVG, and in three others, including ours, there were hamartomatous changes. Although further studies are required, previous findings support the proposal that some CVG may instead be dermal hamartomas. This report alerts clinicians to recognize CVG as a low-frequency manifestation of TS, but also to consider the possible co-occurrence of TS in all female infants with CVG.

Evaluación de síntomas neuropsiquiátricos para la detección temprana de trastorno neurocognoscitivo / Evaluation of neuropsychiatry symptoms for the early detection of neurocognitive disorder

RESUMEN INTRODUCCIÓN: El diagnóstico oportuno del trastorno neurocognitivo es de los principales retos en la atención de los trastornos neurocognitivos. Por esto, se han generado estrategias para la detección preclínica de la enfermedad, entre ellas las destinadas a evaluar síntomas neuropsiquiátricos (NPS) como la escala Mild Behavior Impairment - Checklist (MBI-C). MÉTODOS: Inicialmente se realizó una búsqueda en BVSalud, Medline y PsycNet, luego se realizó una búsqueda en bola de nieve. Se incluyeron términos referentes a deterioro comportamental leve (abarcando los NPS en etapas tempranas), deterioro cognitivo leve y términos específicos del MBI-C. RESULTADOS: La presencia de NPS se asocia con un aumento en la incidencia anual de demencia. Al evaluarlos con MBI-C, su puntuación se correlaciona con biomarcadores como una mayor atrofia cortical, la presencia de la proteína β-amiloide, así como disminución en funciones ejecutivas como la capacidad de enfocar la atención y la memoria de trabajo. DISCUSIÓN: Los hallazgos en la literatura sugieren la utilidad de MBI-C como marcador de neurodegeneración en estadios previos a la demencia, esto mediante la evaluación de su capacidad predictiva de forma independiente y al compararla con otros biomarcadores. CONCLUSIONES: MBI-C supone ser un instrumento de fácil aplicabilidad e interpretación, sostenible e incluyente. Sin embargo, quedan vacíos sobre la pertinencia de esta escala, por lo que surge la necesidad de investigar este tema.

ABSTRACT INTRODUCTION: Early diagnosis of neurocognitive disorder is the main challenge of dementia health attention. Therefore, strategies for preclinical detection of the disease have been created, like those intended to evaluate neuropsychiatric symptoms (NPS), like the Mild Behavior Impairment - Checklist (MBI-C). METHODS: Research was performed in BVSalud, Medline, and Psynet. Then a snowball sampling was done. The terms included were mild behavioral impairment (included NPS in initial stages), mild cognitive impairment, and specific terms of MBI-C. RESULTS: The presence of NPS increase the incidence of dementia, with an annual conversion rate of 9%. About MBI-C, the score has been related to biomarkers like worse brain atrophy in patients with Parkinson's Disease and a positive relationship with the presence of B-amyloid protein. Also, Creese and cols. show that mild behavioral impairment (measured by MBI-C) is associated with a faster decrease in attention and working memory. DISCUSSION: MBI-C utility as a neurodegenerative marker has been demonstrated to detect cognitive, neuropsychiatry, and functional symptoms that may precede dementia by evaluating its predictive capacity alone and comparing it to other biomarkers. CONCLUSION: MBI-C is easy to apply and interpret, is sustainable and inclusive. However, there are still gaps in the relevance of the scale, so there is the need to continue investigating this topic.

The impacts of social determinants of health and cardiometabolic factors on cognitive and functional aging in Colombian underserved populations.

Global initiatives call for further understanding of the impact of inequity on aging across underserved populations. Previous research in low- and middle-income countries (LMICs) presents limitations in assessing combined sources of inequity and outcomes (i.e., cognition and functionality). In this study, we assessed how social determinants of health (SDH), cardiometabolic factors (CMFs), and other medical/social factors predict cognition and functionality in an aging Colombian population. We ran a cross-sectional study that combined theory- (structural equation models) and data-driven (machine learning) approaches in a population-based study (N = 23,694; M = 69.8 years) to assess the best predictors of cognition and functionality. We found that a combination of SDH and CMF accurately predicted cognition and functionality, although SDH was the stronger predictor. Cognition was predicted with the highest accuracy by SDH, followed by demographics, CMF, and other factors. A combination of SDH, age, CMF, and additional physical/psychological factors were the best predictors of functional status. Results highlight the role of inequity in predicting brain health and advancing solutions to reduce the cognitive and functional decline in LMICs.

Rise of toxic cyanobacterial blooms is promoted by agricultural intensification in the basin of a large subtropical river of South America.

Toxic cyanobacterial blooms are globally increasing with negative effects on aquatic ecosystems, water use and human health. Blooms' main driving forces are eutrophication, dam construction, urban waste, replacement of natural vegetation with croplands and climate change and variability. The relative effects of each driver have not still been properly addressed, particularly in large river basins. Here, we performed a historical analysis of cyanobacterial abundance in a large and important ecosystem of South America (Uruguay river, ca 1900 km long, 365,000 km2 basin). We evaluated the interannual relationships between cyanobacterial abundance and land use change, river flow, urban sewage, temperature and precipitation from 1963 to the present. Our results indicated an exponential increase in cyanobacterial abundance during the last two decades, congruent with an increase in phosphorus concentration. A sharp shift in the cyanobacterial abundance rate of increase after the year 2000 was identified, resulting in abundance levels above public health alert since 2010. Path analyses showed a strong positive correlation between cyanobacteria and cropland area at the entire catchment level, while precipitation, temperature and water flow effects were negligible. Present results help to identify high nutrient input agricultural practices and nutrient enrichment as the main factors driving toxic bloom formation. These practices are already exerting severe effects on both aquatic ecosystems and human health and projections suggest these trends will be intensified in the future. To avoid further water degradation and health risk for future generations, a large-scale (transboundary) change in agricultural management towards agroecological practices will be required.

Las floraciones de cianobacterias tóxicas vienen aumentando drásticamente a nivel mundial con efectos negativos en los ecosistemas acuáticos, los usos del agua y la salud humana. Los principales mecanismos promotores de las floraciones son la eutrofización, la construcción de represas, la contaminación con residuos urbanos, la pérdida de vegetación natural y el cambio y la variabilidad climáticos. Los efectos relativos de cada determinante aún no se han abordado adecuadamente, particularmente en las grandes cuencas fluviales de América del Sur. En este trabajo, realizamos un análisis histórico de la abundancia de cianobacterias en un gran e importante ecosistema de América del Sur (el Río Uruguay, c.a. 1.900 km de largo, cuenca de 365.000 km2). Evaluamos las relaciones entre la abundancia de cianobacterias y el cambio en los usos del suelo, el caudal de los ríos, la contaminación urbana, la temperatura y la precipitación desde 1963 hasta el presente. Nuestros resultados evidencian un aumento exponencial en la abundancia de cianobacterias durante las últimas dos décadas, de forma congruente con el aumento en la concentración de fósforo en agua. Fue identificado además, un cambio brusco en la tasa de aumento de la abundancia de cianobacterias después del año 2000, lo que resultó en niveles de alerta por encima de riesgo para la salud pública desde 2010. Los análisis estadísticos indicaron una fuerte y positiva correlación entre las cianobacterias y el área de cultivo en la cuenca, mientras que la precipitación, la temperatura y el flujo de agua fueron insignificantes. Estos resultados contribuyen a identificar que las prácticas agrícolas con alto aporte de nutrientes y el enriquecimiento de nutrientes son los principales impulsores de la formación de floraciones tóxicas. Estas prácticas ya están teniendo graves efectos en los ecosistemas acuáticos y la salud humana y las proyecciones sugieren que se intensificarán en el futuro. Para evitar una mayor degradación de la calidad del agua y el incremento de los riesgos para la salud de las generaciones futuras, se requerirá un cambio a gran escala (transfronterizo) en la gestión agrícola hacia prácticas agroecológicas.