RSV and rhinovirus increase pneumococcal carriage acquisition and density, whereas nasal inflammation is associated with bacterial shedding.

Epidemiological studies report the impact of co-infection with pneumococcus and respiratory viruses upon disease rates and outcomes, but their effect on pneumococcal carriage acquisition and bacterial load is scarcely described. Here, we assess this by combining natural viral infection with controlled human pneumococcal infection in 581 healthy adults screened for upper respiratory tract viral infection before intranasal pneumococcal challenge. Across all adults, respiratory syncytial virus (RSV) and rhinovirus asymptomatic infection confer a substantial increase in secondary infection with pneumococcus. RSV also has a major impact on pneumococcal density up to 9 days post challenge. We also study rates and kinetics of bacterial shedding through the nose and oral route in a subset. High levels of pneumococcal colonization density and nasal inflammation are strongly correlated with increased odds of nasal shedding as opposed to cough shedding. Protection against respiratory viral infections and control of pneumococcal density may contribute to preventing pneumococcal disease and reducing bacterial spread.

Long-term sustainability of the water-agriculture-energy nexus in Brazil's MATOPIBA region: A case study using system dynamics.

The global demand for agricultural commodities has driven extensive land conversion to agriculture in Brazil, especially in the MATOPIBA region. This area encompasses the Rio Grande Basin, a major tributary of the São Francisco Basin that is known for expanding intensive irrigated agriculture and hydropower generation. However, recent data reveal declining precipitation and aquifer recharge, potentially exacerbating ongoing water and land conflicts. This study investigates the long-term sustainability of agricultural expansion amid the worsening water scarcity using a system dynamics model. Findings suggest that rising costs and decreasing profits due to irrigation water shortages may hinder the expansion of irrigated land. By 2040, the irrigation demand may remain partly unmet, while downstream flow and baseflow could decrease. Additionally, agricultural expansion will significantly raise energy demand, posing a developmental challenge. We suggest that ensuring the sustainability of the Rio Grande Basin depends on improved water management and exploring alternative energy sources to address existing constraints.

Optimal Minimum-Velocity Threshold to Predict One-repetition Maximum for the Back Squat.

The prediction of one-repetition maximum (1RM) is highly relevant for strength and conditioning. The optimal minimum-velocity threshold (MVT) was recently proposed to increase the accuracy of 1RM predictions. Individual load-velocity profiles (LVP) were obtained in 18 athletes enrolled in recreational soccer. Reliability analyses were computed for all LVP-derived variables. Estimations of 1RM were made based on general (0.3 m.s- 1), pre-individual (mean velocity at 1RM obtained in a preliminary session) and optimal MVT (velocity that eliminates the difference between actual and predicted 1RM, determined in a preliminary session). The accuracy of 1RM predictions was examined using absolute-percent error and Bland-Altman plots. Between-day reliability of the LVP and 1RM was good (intraclass-correlation coefficients - ICCs>0.9 and coefficients of variation - CVs<5%). The individual and optimal MVT reached moderate-to-good reliability (ICCs>0.9 and CVs<10%, respectively). The predictions based on the optimal MVT displayed greater accuracy than those obtained with the individual and general MVT (absolute percent error: 2.8 vs. 5.5 vs. 4.9%, respectively). However, wide limits of agreement (LoA) were found between actual and estimated 1RM using this approach (~15 kg). Data indicate that the optimal MVT provides better estimations of 1RM for the free-weight back squat than the general and the individual MVT.

Inflammation of the nasal mucosa is associated with susceptibility to experimental pneumococcal challenge in older adults.

Streptococcus pneumoniae colonization in the upper respiratory tract is linked to pneumococcal disease development, predominantly affecting young children and older adults. As the global population ages and comorbidities increase, there is a heightened concern about this infection. We investigated the immunological responses of older adults to pneumococcal-controlled human infection by analyzing the cellular composition and gene expression in the nasal mucosa. Our comparative analysis with data from a concurrent study in younger adults revealed distinct gene expression patterns in older individuals susceptible to colonization, highlighted by neutrophil activation and elevated levels of CXCL9 and CXCL10. Unlike younger adults challenged with pneumococcus, older adults did not show recruitment of monocytes into the nasal mucosa following nasal colonization. However, older adults who were protected from colonization showed increased degranulation of cluster of differentiation 8+ T cells, both before and after pneumococcal challenge. These findings suggest age-associated cellular changes, in particular enhanced mucosal inflammation, that may predispose older adults to pneumococcal colonization.

Infective Endocarditis After Endoscopic Stricture Dilation in Crohn's Disease.

Stricture formation is common in Crohn's disease, and endoscopic intervention plays an increasingly important role in managing these strictures. A 61-year-old man with biological aortic prosthesis and a 30-year history of ileocolonic stricturing Crohn's disease, managed with azathioprine and infliximab, presented with marked occlusive symptoms. Colonoscopy revealed a descending colon stricture, prompting endoscopic balloon dilation. At the time of the procedure, no prophylactic antibiotic was given. Subsequently, he developed Streptococcus gallolyticus endocarditis, necessitating aortic valve replacement. The authors present a case of late Streptococcus gallolyticus endocarditis associated with endoscopic balloon dilation of a Crohn-related colonic stricture.

Psychometric Properties of the Personality Inventory for DSM-5 faceted Brief Form in a Brazilian Community Sample.

OBJECTIVE: The aim of the present study was to verify the psychometric qualities of the PID-5-FBF in a community sample of Brazilian adults. The internal consistency of the facets and the internal structure of the dimensions were checked. In addition, we verified the correlations between the PID-5-FBF facets and domains with a five-factor model measure. METHODS: The sample of this study consists of the 774 Brazilian adults aged 18 to 73 years (mean 28.9±11.58) who answered the PID-5-FBF and BFI-2S. RESULTS: The alpha values were adequate. The internal structure was similar to the PID-5 original form. All the factors and dimensions of the PID-5-FBF have a negative association with agreeableness, while, on the other hand, all correlations with neuroticism were positive. Neuroticism was the factor with the highest correlation with the PID-5-FBF, and openness was the one with the lowest number of correlations. CONCLUSIONS: This research contributes to adding evidence of validity to the PID-5-FBF in the Brazilian community sample. Our results are important because it is the first study with the PID-FBF in a Brazilian sample.

Necrophilic behaviour in wild stump-tailed macaques (Macaca arctoides).

Necrophilic behavior (attempted copulation with corpses) has been scarcely reported in non-human primates, especially in the wild. Here is the first case of necrophilic behavior observed in wild stump-tailed macaques in Thailand. Six groups of total N > 460 individuals have been identified and habituated. The corpse of an adult female was found and directly observed for 2 days and by camera trap for 3 days. The cause of death could not be identified, but no prominent physical injury was detected. Within 3 days of the observation, three different males attempted copulation with the corpse. Noteworthy for this observation was that not only males in the group of the dead female but also males from different groups interacted with the corpse. Taken together, these observations suggest that some cues emanating from the corpse coupled with a nonresistant/passive orientation may have triggered these responses in the males. Given that necrophiliac responses have been scarcely reported in non-human primates, our findings provide new insight into these behaviors and to comparative thanatology in general.

An elderly patient's pancreatobiliary puzzle: unraveling diagnosis and treatment challenges.

Pancreatobiliary fistulas associated withntraductal Papillary Mucinous Neoplasm (IPMN) are rare and present therapeutic challenges. The authors describe the clinical course of an 81-year-old woman presenting with acute cholangitis, ultimately diagnosed with IPMN involving secondary ducts with focal high-grade dysplasia. Initial manifestations included elevated inflammatory markers, cholestasis, and imaging findings of a pancreatic lesion. Endoscopic retrograde cholangiopancreatography revealed dilation of both intrahepatic and extrahepatic bile ducts, along a cystic cluster originating from the pancreas, fistulizing into the common bile duct. Despite initial endoscopic interventions, recurrent cholestasis persisted. Subsequent multidisciplinary evaluation led to a cephalic duodenopancreatectomy. This case underscores the rarity of pancreatobiliary fistulas associated with IPMNs and the subsequent therapeutic challenges. The absence of standardized treatment algorithms for such intricate cases emphasizes the importance of individualized approaches. The fluoroscopy image displaying a cystic cluster originating from the pancreas and showing fistulization into the common bile duct is a rare image presented in our report, unique to this case.

COVID-19 and Adrenal Insufficiency: Unmasking the Link.

We describe a case of a 28-year-old male who presented with general malaise, fatigue, anorexia, occasional epigastric pain, and vomiting a few days after a mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Clinical evolution led to weight loss (6 kg in six months) and craving for salty foods. Physical examination revealed dehydration, hypotension, and hyperpigmentation of the skin and mucosal surfaces. Laboratory tests demonstrated normocytic normochromic anemia, acute kidney injury, hyperkalemia, hyponatremia, and compensated metabolic acidosis. Adrenal workup allowed us to establish a diagnosis of adrenal insufficiency (AI) due to autoimmune adrenalitis, considering findings of a low cortisol and positive 21-hydroxylase antibodies (21OH-Abs), as well as high serum renin and adrenocorticotropic hormone (ACTH). Atypical presentations and comorbidities may appear regarding coronavirus disease 2019 (COVID-19), such as the association between COVID-19 and the hypothalamic-pituitary-adrenal (HPA) axis, which may be affected in any patient with SARS-CoV-2 infection, thus making adrenal insufficiency a diagnosis to consider.

Characteristics and anatomic location of PD-1+TCF1+ stem-like CD8 T cells in chronic viral infection and cancer.

CD8 T cells play an essential role in antitumor immunity and chronic viral infections. Recent findings have delineated the differentiation pathway of CD8 T cells in accordance with the progenitor-progeny relationship of TCF1+ stem-like and Tim-3+TCF1- more differentiated T cells. Here, we investigated the characteristics of stem-like and differentiated CD8 T cells isolated from several murine tumor models and human lung cancer samples in terms of phenotypic and transcriptional features as well as their location compared to virus-specific CD8 T cells in the chronically lymphocytic choriomeningitis virus (LCMV)-infected mice. We found that CD8 tumor-infiltrating lymphocytes (TILs) in both murine and human tumors exhibited overall similar phenotypic and transcriptional characteristics compared to corresponding subsets in the spleen of chronically infected mice. Moreover, stem-like CD8 TILs exclusively responded and produced effector-like progeny CD8 T cells in vivo after antigenic restimulation, confirming their lineage relationship and the proliferative potential of stem-like CD8 TILs. Most importantly, similar to the preferential localization of PD-1+ stem-like CD8 T cells in T cell zones of the spleen during chronic LCMV infection, we found that the PD-1+ stem-like CD8 TILs in lung cancer samples are preferentially located not in the tumor parenchyma but in tertiary lymphoid structures (TLSs). The stem-like CD8 T cells are present in TLSs located within and at the periphery of the tumor, as well as in TLSs closely adjacent to the tumor parenchyma. These findings suggest that TLSs provide a protective niche to support the quiescence and maintenance of stem-like CD8 T cells in the tumor.

Prognostic Factors and Markers in Non-Small Cell Lung Cancer: Recent Progress and Future Challenges.

Lung cancer is a highly aggressive neoplasm and, despite the development of recent therapies, tumor progression and recurrence following the initial response remains unsolved. Several questions remain unanswered about non-small cell lung cancer (NSCLC): (1) Which patients will actually benefit from therapy? (2) What are the predictive factors of response to MAbs and TKIs? (3) What are the best combination strategies with conventional treatments or new antineoplastic drugs? To answer these questions, an integrative literature review was carried out, searching articles in PUBMED, NCBI-PMC, Google Academic, and others. Here, we will examine the molecular genetics of lung cancer, emphasizing NSCLC, and delineate the primary categories of inhibitors based on their molecular targets, alongside the main treatment alternatives depending on the type of acquired resistance. We highlighted new therapies based on epigenetic information and a single-cell approach as a potential source of new biomarkers. The current and future of NSCLC management hinges upon genotyping correct prognostic markers, as well as on the evolution of precision medicine, which guarantees a tailored drug combination with precise targeting.

Comparison of methods for controlling acquiescence bias in balanced and unbalanced scales / Comparação de métodos para o controle do viés da aquiescência em escalas balanceadas e desbalanceadas / Comparación de métodos para controlar el sesgo de aquiescencia en escalas balanceadas y no balanceadas

Controlling acquiescence bias typically involves the application of positive and negative keyed items. However, little is known about the effect of balancing positive and negative items on bias control. The aim of this study was to compare three Confirmatory Factor Analysis models (without control, MIMIC, and Random Intercept) to recover the factor structure of unbalanced and balanced instruments, using simulated and real data (from an instrument that assesses Personality). By controlling for acquiescence, the results indicated that the performance of balanced scales was better than that of unbalanced scales, as well as in the absence of control for response bias, when considering balanced and unbalanced scales. Thus, this research suggests the possibility of controlling acquiescence through balanced instruments associated with the use of statistical methods in modeling.(AU)

O controle do viés de aquiescência normalmente envolve a aplicação de itens positivos e negativos. Contudo, pouco se sabe sobre o efeito do balanceamento entre itens positivos e negativos sobre o controle do viés. O objetivo deste estudo foi comparar três modelos de Análise Fatorial Confirmatória (sem controle, MIMIC e Intercepto Randômico) para recuperar a estrutura fatorial de instrumentos desbalanceados e balanceados, a partir de dados simulados e reais (procedentes de um instrumento que avalia Personalidade). Mediante o controle da aquiescência, os resultados indicaram que a performance de escalas balanceadas foi melhor do que de escalas desbalanceadas, bem como na ausência de controle desse viés de resposta, ao considerar as escalas balanceadas e desbalanceadas. Dessa maneira, esta pesquisa aponta para a possibilidade de controle de aquiescência por meio de instrumentos balanceados associada ao uso dos métodos estatísticos na modelagem.(AU)

El control del sesgo de aquiescencia involucra la aplicación de ítems positivos y negativos. Sin embargo, el efecto del equilibrio entre ítems positivos y negativos en el control del sesgo sigue siendo una pregunta abierta. En este sentido, el objetivo de este estudio fue comparar tres modelos de Análisis Factorial Confirmatorio (sin control, MIMIC e Intercepto Aleatorio) para recuperar la estructura factorial de instrumentos balanceados y desbalanceados, a partir de datos simulados y reales (a partir de un instrumento que evalúa personalidad). El control de este sesgo de respuesta indicó que el desempeño de escalas balanceadas fue mejor que el de escalas desbalanceadas, así como en la ausencia del control de la aquiescencia, al considerar escalas balanceadas y desbalanceadas. Por lo tanto, esta investigación sugiere la posibilidad de controlar este sesgo de respuesta por medio de instrumentos balanceados asociados con el uso de métodos estadísticos modelado.(AU)

Transcriptome analysis of six tissues obtained post-mortem from sepsis patients.

Septic shock is a life-threatening clinical condition characterized by a robust immune inflammatory response to disseminated infection. Little is known about its impact on the transcriptome of distinct human tissues. To address this, we performed RNA sequencing of samples from the prefrontal cortex, hippocampus, heart, lung, kidney and colon of seven individuals who succumbed to sepsis and seven uninfected controls. We identified that the lungs and colon were the most affected organs. While gene activation dominated, strong inhibitory signals were also detected, particularly in the lungs. We found that septic shock is an extremely heterogeneous disease, not only when different individuals are investigated, but also when comparing different tissues of the same patient. However, several pathways, such as respiratory electron transport and other metabolic functions, revealed distinctive alterations, providing evidence that tissue specificity is a hallmark of sepsis. Strikingly, we found evident signals of accelerated ageing in our sepsis population.

An electronic health record cohort of Veterans with amyotrophic lateral sclerosis.

Objective: To assemble and characterize an electronic health record (EHR) dataset for a large cohort of US military Veterans diagnosed with ALS (Amyotrophic Lateral Sclerosis). Methods: An EHR dataset for 19,662 Veterans diagnosed with ALS between January 1, 2000 to December 31, 2020 was compiled from the Veterans Health Administration (VHA) EHR database by a query for ICD9 diagnosis (335.20) or ICD10 diagnosis (G12.21) for Amyotrophic Lateral Sclerosis. Results: The cohort is predominantly male (98.94%) and white (72.37%) with a median age at disease onset of 68 years and median survival from the date of diagnosis of 590 days. With the designation of ALS as a compensable illness in 2009, there was a subsequent increase in the number of Veterans diagnosed per year in the VHA, but no change in median survival. The cohort included a greater-than-expected proportion of individuals whose branch of service at the time of separation was the Army. Conclusions: The composition of the cohort reflects the VHA population who are at greatest risk for ALS. The greater than expected proportion of individuals whose branch of service at the time of separation was the Army suggests the possibility of a branch-specific risk factor for ALS.

Cutting Edge: Polycomb Repressive Complex 1 Subunit Cbx4 Positively Regulates Effector Responses in CD8 T Cells.

CTL differentiation is controlled by the crosstalk of various transcription factors and epigenetic modulators. Uncovering this process is fundamental to improving immunotherapy and designing novel therapeutic approaches. In this study, we show that polycomb repressive complex 1 subunit chromobox (Cbx)4 favors effector CTL differentiation in a murine model. Cbx4 deficiency in CTLs induced a transcriptional signature of memory cells and increased the memory CTL population during acute viral infection. It has previously been shown that besides binding to H3K27me3 through its chromodomain, Cbx4 functions as a small ubiquitin-like modifier (SUMO) E3 ligase in a SUMO-interacting motifs (SIM)-dependent way. Overexpression of Cbx4 mutants in distinct domains showed that this protein regulates CTL differentiation primarily in an SIM-dependent way and partially through its chromodomain. Our data suggest a novel role of a polycomb group protein Cbx4 controlling CTL differentiation and indicated SUMOylation as a key molecular mechanism connected to chromatin modification in this process.

An Ultrasound-Guided Latero-Ventral Approach to Perform the Quadratus Lumborum Block in Dog Cadavers.

The QL block is a high-level locoregional anesthesia technique, which aims to provide analgesia to the abdomen. Several approaches of the QL block have been studied to find out which one allows a greater distribution of the injectate. The aim of this study is to compare the traditional interfascial QL block (IQL) with a new latero-ventral approach (LVQL). We hypothesize that this new approach could be safer and easier to perform, since the injectate is administered more superficially and further away from vital structures. Our second objective is to assess whether a higher volume of injectate (0.6 mL/kg) could reach the ventral branches of the last thoracic nerves, leading to a blockade of the cranial abdomen. Six thawed canine cadavers (12 hemiabdomens) were used for this purpose. Both approaches were performed in all cadavers. A combination of methylene blue/iopromide was administered to each hemiabdomen, randomly assigned to the LVQL or IQL. No differences were found regarding the ease of perform the LVQL with respect to IQL. The results show that both techniques reached the ventral branches from L1 to L3, although only the IQL consistently stained the sympathetic trunk (5/6 IQL vs. 1/6 LVQL). The use of a higher volume did not enhance a more cranial distribution of the injectate.