Ecology of the free-living stages of cattle nematodes in the dry season in the Lerma Valley, Salta province, Argentina.

The objective of this work was to describe the dynamics of development and survival of the free-living stages of cattle gastrointestinal nematodes (GIN) in fecal matter (FM) and pasture during the dry season in the Lerma Valley, Salta province, northwestern Argentina (NWA) to contribute to GIN management. The climate in the region is characterized by a rainy summer followed by a dry season from middle autumn to early spring. Fecal matter from calves naturally infected with GIN was deposited on three experimental field plots in April, July and October 2019, corresponding to the beginning, middle and end of the dry season, respectively. Each experimental unit consisted of 7 stools of about 800 g and had four repetitions. To determine the development from egg to infective larvae (L3), the first sampling (5 g fecal matter) was performed from the 10th day post-contamination and continued every 3 days until L3 were found. Subsequently, a monthly sampling was made until two consecutive negative results were obtained. Sampling of pasture began three days after the L3 recovery from FM, and continued monthly until two negative results were obtained. The following parameters were evaluated: development time and development rate from egg to L3; permanence time of L3 in feces; time of appearance on pasture; migration rate; and permanence time of L3 on pasture. The main genera of parasites present were Cooperia and Haemonchus. Significant differences were observed in the development time among contamination months (p < 0.001); development time was highest in the July contamination (28 days), with October and April contamination averaging 9 and 10 days, respectively. Development time also showed significant differences (p < 0.01) among contamination months, being highest in October (31.48%). The highest permanence time in fecal matter values were recorded in the July contamination (183 days) and migration rate was highest in the October contamination (42.49%). The highest time of appearance on pasture value was recorded in the July contamination (117 days). Finally, the highest permanence time of L3 in feces values were detected in the October contamination (148 days). The results of this work show that fecal contamination in the NWA region in the dry season would play an epidemiological role in the GIN cycle as a source of infection for the next productive cycle in the rainy season.

Oncolytic adenovirus coding for shedding-resistant MICA enhances immune responses against tumors.

Cancer immunotherapies strive to overcome tumor-induced immune suppression and activate antitumor immune responses. Although cytotoxic T lymphocytes (CTLs) play a pivotal role in this process, natural killer (NK) cells have also demonstrated remarkable tumor-killing abilities, given their ability to discriminate tumor cells from normal cells and mediate specific antitumoral cytotoxicity. NK cells activation depends on a balance between activation and inhibition signals from several ligands/receptors. Among them, MICA/NKG2D axis is a master regulator of NK activation. MHC class I chain-related polypeptide A (MICA) expression is upregulated by many tumor cell lines and primary tumors and serves as a ligand for the activating NK group 2D (NKG2D) receptor on NK cells and subpopulations of T cells. However, cancer cells can cleave MICA, making it soluble and de-targeting tumor cells from NK cells, leading to tumor immune escape.In this study, we present ICOVIR15KK-MICAMut, an oncolytic adenovirus (OAdv) armed with a transgene encoding a non-cleavable MICA to promote NK-mediated cell-killing capacity and activate the immune response against cancer cells. We first demonstrated the correct MICA overexpression from infected cells. Moreover, our MICA-expressing OAdv promotes higher NK activation and killing capacity than the non-armed virus in vitro. In addition, the armed virus also demonstrated significant antitumor activity in immunodeficient mice in the presence of human PBMCs, indicating the activation of human NK cells. Finally, OAdv-MICA overexpression in immunocompetent tumor-bearing mice elicits tumor-specific immune response resulting in a greater tumor growth control.In summary, this study highlights the significance of NK cells in cancer immunotherapy and presents an innovative approach using a modified oncolytic virus to enhance NK cell activation and antitumor immune response. These findings suggest promising potential for future research and clinical applications.

Política industrial farmacéutica, un requisito clave para la autonomía sanitaria de Colombia

Colombia depende de la importación de medicamentos, así como de gran parte de los materiales (principios activos y excipientes) requeridos para su elaboración; problemática que genera consecuencias sanitarias y macroeconómicas, las cuales se agudizan en el contexto de desindustrialización nacional y de disrupción tecnológica. De esta manera, se acepta que la disponibilidad y acceso a medicamentos y otras tecnologías sanitarias esenciales son un requisito fundamental para alcanzar la autonomía sanitaria de un país. Por lo tanto, resulta imprescindible coordinar esfuerzos entre diversos sectores sociales para desarrollar una agenda pública enfocada a la creación de condiciones que fortalezcan las capacidades científicas y tecnológicas de la industria farmacéutica local, y con ello, mejorar el suministro farmacéutico del país. En el presente documento se presentan conceptos teóricos y prácticos que deberían ser considerados en la definición y materialización de una política pública encaminada a fortalecer la industria farmacéutica y favorecer la autonomía sanitaria de Colombia.

Colombia has a notorious dependency on the importation of medicines, as well as a large part of the materials (active ingredients and excipients) required for their manufacture. This problem generates health and macroeconomic consequences, which are exacerbated in the context of national deindustrialization and technological disruption. In this way, it is accepted that the availability and access to medicines and other essential health technologies are a fundamental requirement to achieve the health autonomy of a country. Therefore, it is crucial to coordinate efforts between several social sectors to develop a public agenda focused on creating conditions that allow strengthening the scientific and technological capabilities of the local pharmaceutical industry, thereby, improving the country's pharmaceutical supply. This document presents conceptual and practical topics that should be considered to defining and materializing a public policy aimed at strengthening the local pharmaceutical industry and favoring Colombia's sanitary autonomy.

Tuning domain wall oscillation frequency in bent nanowires through a mechanical analogy.

In this work, we present a theoretical model for domain wall (DW) oscillations in a curved magnetic nanowire with a constant curvature under the action of a uniaxial magnetic field. Our results show that the DW dynamics can be described as that of the mechanical pendulum, and both the NW curvature and the external magnetic field influence its oscillatory frequency. A comparison between our theoretical approach and experimental data in the literature shows an excellent agreement. The results presented here can be used to design devices demanding the proper control of the DW oscillatory motion in NWs.

Studies on Argentinean species of the Bahitini leafhopper genus Menosoma Ball, 1931 (Hemiptera: Cicadellidae); checklist, key to known species, and redescription of Menosoma taeniatum Linnavuori with a new country record.

The species of the genus Menosoma to occur in Argentina are revised. Menosoma taeniatum Linnavuori is redescribed using recent samples taken from Northeast Argentina. Overall habitus images of external and internal morphology are provided. In addition, a new country record is reported for Bolivia. An updated checklist and key to all Menosoma species known to occur in Argentina are also given.

Introduction of Asymmetry in the Fused 4-Oxalocrotonate Tautomerases.

Members of the 4-oxalocrotonate tautomerase (4-OT) subgroup in the tautomerase superfamily (TSF) are constructed from a single ß-α-ß unit and form homo- or heterohexamers, whereas those of the other four subgroups are composed of two consecutively joined ß-α-ß units and form trimers. A subset of sequences, double the length of the short 4-OTs, is found in the 4-OT subgroup. These "fused" 4-OTs form a separate subgroup that connects to the short 4-OTs in a sequence similarity network (SSN). The fused gene can be a template for the other four subgroups, resulting in the diversification of activity. Analysis of the SSN shows that multiple nodes in the fused 4-OTs connect to five linker nodes, which in turn connect to the short 4-OTs. Some fused 4-OTs are symmetric trimers and others are asymmetric trimers. The origin of this asymmetry was investigated by subjecting the sequences in three linker nodes and a closely associated fourth node to kinetic, mutagenic, and structural analyses. The results show that each sequence corresponds to the α- or ß-subunit of a heterohexamer that functions as a 4-OT. Mutagenesis indicates that the key residues in both are αPro1 and ßArg-11, like that of a typical 4-OT. Crystallographic analysis shows that both heterohexamers are asymmetric, where one heterodimer is flipped 180° relative to the other two heterodimers. The fusion of two subunits (α and ß) of one asymmetric heterohexamer generates an asymmetric trimer with 4-OT activity. Hence, asymmetry can be introduced at the heterohexamer level and then retained in the fused trimers.

Management of acute stroke. Specific nursing care and treatments in the stroke unit.

OBJECTIVE: This study provides a series of updated, evidence-based recommendations for the management of acute stroke. We aim to lay a foundation for the development of individual centres' internal protocols, serving as a reference for nursing care. METHODS: We review the available evidence on acute stroke care. The most recent national and international guidelines were consulted. Levels of evidence and degrees of recommendation are based on the Oxford Centre for Evidence-Based Medicine classification. RESULTS: The study describes prehospital acute stroke care, the operation of the code stroke protocol, care provided by the stroke team upon the patient's arrival at hospital, reperfusion treatments and their limitations, admission to the stroke unit, nursing care in the stroke unit, and discharge from hospital. CONCLUSIONS: These guidelines provide general, evidence-based recommendations to guide professionals who care for patients with acute stroke. However, limited data are available on some aspects, showing the need for continued research on acute stroke management.

Ba+2 ion trapping using organic submonolayer for ultra-low background neutrinoless double beta detector.

If neutrinos are their own antiparticles the otherwise-forbidden nuclear reaction known as neutrinoless double beta decay can occur. The very long lifetime expected for these exceptional events makes its detection a daunting task. In order to conduct an almost background-free experiment, the NEXT collaboration is investigating novel synthetic molecular sensors that may capture the Ba dication produced in the decay of certain Xe isotopes in a high-pressure gas experiment. The use of such molecular detectors immobilized on surfaces must be explored in the ultra-dry environment of a xenon gas chamber. Here, using a combination of highly sensitive surface science techniques in ultra-high vacuum, we demonstrate the possibility of employing the so-called Fluorescent Bicolor Indicator as the molecular component of the sensor. We unravel the ion capture process for these molecular indicators immobilized on a surface and explain the origin of the emission fluorescence shift associated to the ion trapping.

Alteraciones de la expresión génica en la infección por SARS-CoV-2 en distintos modelos de estudio / Alterations of gene expression in SARS-CoV-2 infection in different study models

Objetivo: La pandemia por SARS-CoV-2 ha supuesto un auténtico reto para el mundo científico debido a la rápida transmisión y elevada mortalidad que produce este nuevo coronavirus. La enfermedad asociada se ha denominado COVID-19 y abarca desde casos asintomáticos hasta graves que evolucionan rápidamente a síndrome de distrés respiratorio agudo, alteraciones multisistémicas y la muerte. La comunidad científica ha aunado esfuerzos para tratar de conocer mejor el proceso fisiopatológico de la infección con la intención de combatir de forma más eficaz la enfermedad. En este trabajo presentamos un estudio para conocer las alteraciones de la expresión génica provocadas por la infección. Metodología: Se han usado tres modelos de estudio distintos: cultivos de células epiteliales bronquiales, organoides de las vías respiratorias y muestras obtenidas de autopsias en pacientes, con y sin infección por SARS-CoV-2. Se han analizado los perfiles de expresión alterados por la infección en cada modelo, así como las categorías funcionales enriquecidas. Resultados: Solo 4 genes son comunes en los tres tipos de modelos de estudio, siendo el modelo de autopsias el más dispar. Dentro de los genes comunes en los modelos de cultivo celular y organoide de pulmón encontramos funciones relacionadas con procesos inflamatorios. Conclusiones: Los estudios in vitro son un buen modelo para tener una foto fija de las alteraciones en los patrones de infección, mientras que las autopsias no son un buen modelo debido al sesgo provocado por la necrosis. (AU)

Short summary: Three different study models have been used to study the gene expression profiles produced by SARS-CoV-2: bronchial epithelial cell cultures, airway organoids, and autopsy samples from patients with and without SARS-infection. CoV-2. Basis: The SARS-CoV-2 pandemic has been a real challenge for the scientific world due to the rapid transmission and high mortality caused by this new coronavirus. The associated disease has been named COVID-19 and ranges from asymptomatic to severe cases that rapidly progress to acute respiratory distress syndrome, multisystem disorders, and death. The scientific community has joined efforts to try to better understand the pathophysiological process of the infection with the intention of combating the disease more effectively. In this work we present a study to determine the alterations in gene expression caused by the infection. Methods: Three different study models have been used: bronchial epithelial cell cultures, airway organoids, and samples obtained from autopsies in patients with and without SARS-CoV-2 infection. The expression profiles altered by the infection in each model have been analyzed, as well as the functional categories enriched. Results: Only 4 genes are common in the three types of study models, the autopsy model being the most disparate. Within the common genes in cell and organoid culture models of the lung, we find functions related to inflammatory processes. Conclusions: In vitro studies are a good model to have a snapshot of alterations in infection patterns, while autopsies are not a good model due to bias caused by necrosis. (AU)

The Relation of CFTR-Genotype and Associated Comorbidities to Development of Pulmonary Atelectasis in Cystic Fibrosis Patients

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First Leptophobic Dark Matter Search from the Coherent-CAPTAIN-Mills Liquid Argon Detector.

We report the first results of a search for leptophobic dark matter (DM) from the Coherent-CAPTAIN-Mills (CCM) liquid argon (LAr) detector. An engineering run with 120 photomultiplier tubes (PMTs) and 17.9×10^{20} protons on target (POT) was performed in fall 2019 to study the characteristics of the CCM detector. The operation of this 10-ton detector was strictly light based with a threshold of 50 keV and used coherent elastic scattering off argon nuclei to detect DM. Despite only 1.5 months of accumulated luminosity, contaminated LAr, and nonoptimized shielding, CCM's first engineering run has already achieved sensitivity to previously unexplored parameter space of light dark matter models with a baryonic vector portal. With an expected background of 115 005 events, we observe 115 005+16.5 events which is compatible with background expectations. For a benchmark mediator-to-DM mass ratio of m_{V_{B}}/m_{χ}=2.1, DM masses within the range 9 MeV≲m_{χ}≲50 MeV are excluded at 90% C. L. in the leptophobic model after applying the Feldman-Cousins test statistic. CCM's upgraded run with 200 PMTs, filtered LAr, improved shielding, and 10 times more POT will be able to exclude the remaining thermal relic density parameter space of this model, as well as probe new parameter space of other leptophobic DM models.

Empiema subdural y su relación con hematomas subdurales: experiencia local y revisión de la literatura / Subdural empyema and its relationship to subdural hematomas: local experience and literature review

RESUMEN: Los empiemas subdurales, tanto los de aparición espontánea o como complicación en la evolución de un hematoma subdural (HSD), son infrecuentes y de los cuales existen pocas publicaciones en la literatura(1). En este trabajo se revisa una serie de 15 casos operados en el Hospital de Urgencia Asistencia Pública (HUAP) en un período de 15 años. Se observó que en general tienen buena evolución con el tratamiento instaurado en forma oportuna y que son larvados en su presentación, pudiendo llegar a ser diagnosticados incluso en el intraoperatorio. No se observó diferencia en su evolución cuando se operaron a través de una craniectomía o de una craneotomía (plaqueta)(2). No se encontró tampoco diferencia cuando se trataron con o sin drenaje. Como consenso general, deben ser tratados con antibioticoterapia prolongada de al menos 3-4 semanas para controlar el foco infeccioso(2). Ninguno de los casos revisados requirió de reintervención.

ABSTRACT Subdural empyemas, both spontaneous or as a complication in the evolution of subdural hematomas, are an uncommon fact of which there are few publications in literature. In this review we analyze a retrospective serie of 15 cases operated in HUAP in a period of 15 years. In general we don't observed differences in the outcome using different surgical techniques, both in those treated by craniectomy as those treated by craniotomy. Also we don't observed differences in those treated with or without drainage. In the same way is clear that the optimal period of antibiotic treatment must be 3-4 weeks to fully cover them. None of the cases treated, needed reintervention.

Nuevos biomarcadores de cáncer de pulmón basados en miRNA / [New biomarkers of lung cancer based on miRNA]

Objetivo: Determinar si existen diferencias de expresión entre los miRNA de tejido sano y tumoral de adenocarcinoma de pulmón y carcinoma epidermoide de pulmón, con lo que podrían ser usados como biomarcadores. Material y métodos: Se ha extraído y secuenciado el miRNA de tejido tumoral y sano adyacente de muestras de adenocarcinoma y carcinoma epidermoide de dieciséis pacientes intervenidos en el Hospital Regional de Málaga. Esas secuencias se han analizado con un flujo de trabajo bioinformático específico que conlleva varios pasos: 1o) preprocesar las lecturas, 2o) mapearlas sobre el genoma humano de referencia, 3o) determinar la expresión de los miRNA en cada una de las muestras, 4o) calcular su expresión diferencial entre el tejido sano y el tumoral de cada paciente, 5o) realizar un análisis funcional de los miRNA encontrados. Resultados: Hemos analizado los miRNA con expresión diferencial en cada uno de los tipos histológicos estudiados. El análisis del adenocarcinoma y carcinoma epidermoide de pulmón ha dado como resultado un total de 82 y 360 miRNA diferencialmente expresados (miDE), respectivamente. Hemos encontrado 50 miRNA comunes a los dos tipos histológicos, y su análisis funcional indica que están implicados en el crecimiento, desarrollo y movimiento celular, que se produce tanto en la célula normal como en el cáncer. Conclusiones: Los miDE encontrados son una fuente de biomarcadores, al tener una reprogramación específica en cáncer, y ser obtenibles de forma no invasiva. (AU)

Objective: Determine if there are differences in expression between the miRNAs of healthy and tumor tissue of lung adenocarcinoma and squamous cell carcinoma of the lung, with which they could be used as biomarkers. Material and methods: miRNA has been extracted and sequenced from tumor and adjacent healthy tissue from samples of adenocarcinoma and squamous cell carcinoma from sixteen patients operated at the Regional Hospital of Malaga. These sequences have been analyzed with a specific bioinformatic workflow that involves several steps: 1st) preprocessing the reads, 2nd) mapping them onto the reference human genome, 3rd) determining the expression of the miRNAs in each of the samples, 4th) calculate its differential expression between the healthy and tumor tissue of each patient, 5th) perform a functional analysis of the miRNAs found. Results: We have analyzed the miRNAs with differential expression in each of the histological types studied. Analysis of adenocarcinoma and squamous cell carcinoma of the lung has resulted in a total of 82 and 360 differentially expressed miRNAs (miDE), respectively. We have found 50 miRNAs common to the two histological types, and their functional analysis indicates that they are involved in cell growth, development and movement, which occurs both in normal cells and in cancer. Conclusions: The miDEs found are a source of biomarkers, as they have a specific reprogramming in cancer, and are obtainable non-invasively. (AU)

AGING-ASSOCIATED COGNITIVE DECLINE IS REVERSED BY D-SERINE SUPPLEMENTATION.

Brain aging is a natural process that involves structural and functional changes that lead to cognitive decline, even in healthy subjects. This detriment has been associated with N-methyl-D-aspartate receptor (NMDAR) hypofunction due to a reduction in the brain levels of D-serine, the endogenous NMDAR co-agonist. However, it is not clear if D-serine supplementation could be used as an intervention to reduce or reverse age-related brain alterations. In the present work, we aimed to analyze the D-serine effect on aging-associated alterations in cellular and large-scale brain systems that could support cognitive flexibility in rats. We found that D-serine supplementation reverts the age-related decline in cognitive flexibility, frontal dendritic spine density, and partially restored large-scale functional connectivity without inducing nephrotoxicity; instead, D-serine restored the thickness of the renal epithelial cells that were affected by age. Our results suggest that D-serine could be used as a therapeutic target to reverse age-related brain alterations.SIGNIFICANT STATEMENTAge-related behavioral changes in cognitive performance occur as a physiological process of aging. Then, it is important to explore possible therapeutics to decrease, retard or reverse aging effects on the brain. NMDA receptor hypofunction contributes to the aging-associated cognitive decline. In the aged brain, there is a reduction in the brain levels of the NMDAR co-agonist, D-Serine. However, it is unclear if chronic D-serine supplementation could revert the age-detriment in brain functions. Our results show that D-serine supplementation reverts the age-associated decrease in cognitive flexibility, functional brain connectivity, and neuronal morphology. Our findings raise the possibility that restoring the brain levels of D-serine could be used as a therapeutic target to recover brain alterations associated with aging.

The Issue of Monocyte Activation in ASD: Troubles with Translation.

Autism spectrum disorder (ASD) prevalence has increased year on year for the past two decades and currently affects 1 in 44 individuals in the US. An increasing number of studies have pointed to increased immune activation as both an etiological agent and also involved in the ongoing pathological process of ASD. Both adaptive and innate immune responses have been implicated. Evidence of innate dysregulation has so far included increased production of innate inflammatory cytokines, increased cell numbers, and altered activation in monocytes in the blood and microglia in the brain. Suggesting an orchestrated innate immune response may be involved in ASD. Hughes et al. (2022) recently assessed transcriptome differences that could underlie altered activation of monocytes using next-generation bulk-RNA sequencing on isolated CD14+ monocytes at baseline and after activation with different Toll-like receptor agonists. Circulating CD14+ monocyte from children with autistic disorder (AD) and children diagnosed with perverse developmental disorder not otherwise specified (PDD-NOS) were found to differ in a number of activation pathways after gene enrichment analysis compared to typically developing children. There was an overall upregulation in translational machinery in both neurodevelopmental disorder groups, whereas typically developing children were downregulated, indicating an issue with monocyte activation. Several identified differentially expressed genes in monocytes were also identified as ASD at-risk genes, according to the Simons Foundation Autism Research Initiative (SFARI), and genes involved in inflammatory bowel diseases. This work implicates altered monocyte activation with a lack of regulation as a potential mechanistic issue in ASD. Future work is warranted to evaluate how monocyte regulatory mechanisms differ in ASD individuals.

Time Series Transcriptomic Analysis of Bronchoalveolar Lavage Cells from Piglets Infected with Virulent or Low-Virulent Porcine Reproductive and Respiratory Syndrome Virus 1.

Porcine reproductive and respiratory syndrome virus (PRRSV) has evolved to escape the immune surveillance for a survival advantage leading to a strong modulation of host's immune responses and favoring secondary bacterial infections. However, limited data are available on how the immunological and transcriptional responses elicited by virulent and low-virulent PRRSV-1 strains are comparable and how they are conserved during the infection. To explore the kinetic transcriptional signature associated with the modulation of host immune response at lung level, a time-series transcriptomic analysis was performed in bronchoalveolar lavage cells upon experimental in vivo infection with two PRRSV-1 strains of different virulence, virulent subtype 3 Lena strain or the low-virulent subtype 1 3249 strain. The time-series analysis revealed overlapping patterns of dysregulated genes enriched in T-cell signaling pathways among both virulent and low-virulent strains, highlighting an upregulation of co-stimulatory and co-inhibitory immune checkpoints that were disclosed as Hub genes. On the other hand, virulent Lena infection induced an early and more marked "negative regulation of immune system process" with an overexpression of co-inhibitory receptors genes related to T-cell and NK cell functions, in association with more severe lung lesion, lung viral load, and BAL cell kinetics. These results underline a complex network of molecular mechanisms governing PRRSV-1 immunopathogenesis at lung level, revealing a pivotal role of co-inhibitory and co-stimulatory immune checkpoints in the pulmonary disease, which may have an impact on T-cell activation and related pathways. These immune checkpoints, together with the regulation of cytokine-signaling pathways, modulated in a virulence-dependent fashion, orchestrate an interplay among pro- and anti-inflammatory responses. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the major threats to swine health and global production, causing substantial economic losses. We explore the mechanisms involved in the modulation of host immune response at lung level performing a time-series transcriptomic analysis upon experimental infection with two PRRSV-1 strains of different virulence. A complex network of molecular mechanisms was revealed to control the immunopathogenesis of PRRSV-1 infection, highlighting an interplay among pro- and anti-inflammatory responses as a potential mechanism to restrict inflammation-induced lung injury. Moreover, a pivotal role of co-inhibitory and co-stimulatory immune checkpoints was evidenced, which may lead to progressive dysfunction of T cells, impairing viral clearance and leading to persistent infection, favoring as well secondary bacterial infections or viral rebound. However, further studies should be conducted to evaluate the functional role of immune checkpoints in advanced stages of PRRSV infection and explore a possible T-cell exhaustion state.