Myostatin serum levels depends on age and diet in athletic and no athletic dogs.

Myostatin is a growth factor related to muscular mass atrophy via mTOR pathway inhibition. Mutations in this gene have been correlated with high muscular mass development in different species of mammals, including human and dogs. Different studies have shown that sport practice increases myostatin gene expression. Some of them were conducted in canine breeds selected for different sport practices, including mushing sports. In this study, body weight, muscular mass, and serum levels of myostatin were analysed in different canine breeds, selected, and not selected for sprint and middle-distance racing, and the effect on epidemiological factors was evaluated. Sex, reproductive status, and canine breed affects body weight and muscular mass, being higher in males, and in sled canine breed. Age has an effect in body weight and myostatin serum levels, being lower in elder dogs. Sport practice and type of diet had an effect in muscular mass development but not in myostatin serum levels. Results showed a high positive correlation between muscular mass and body weight but not with myostatin levels. These results suggest that independent-myostatin mechanisms of mTOR pathway regulation could be related to muscular mass development in dogs.

Transcriptome and microbiome-immune changes across preinvasive and invasive anal cancer lesions.

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy linked to high-risk Human papillomavirus (HPV) infection, which develops from precursor lesions like Low-Grade Squamous Intraepithelial Lesions (LGSIL) and High-Grade Squamous Intraepithelial Lesions (HGSIL). ASCC incidence varies across populations, posing increased risk for People Living with HIV (PLWH). Our investigation focused on transcriptomic and metatranscriptomic changes from Squamous Intraepithelial Lesions (SILs) to ASCC. Metatranscriptomic analysis highlighted specific bacterial species (e.g., Fusobacterium nucleatum, Bacteroides fragilis) more prevalent in ASCC than precancerous lesions. These species correlated with gene encoding enzymes (Acca, glyQ, eno, pgk, por) and oncoproteins (FadA, dnaK), presenting potential diagnostic or treatment markers. Unsupervised transcriptome analysis identified distinct sample clusters reflecting histological diagnosis, immune infiltrate, HIV/HPV status, and pathway activities, recapitulating anal cancer progression's natural history. Our study unveiled molecular mechanisms in anal cancer progression, aiding in stratifying HGSIL cases based on low- or high-risk progression to malignancy.

Implications of sedation during the use of noninvasive ventilation in children with acute respiratory failure (SEDANIV Study).

BACKGROUND: The objective of this study was to analyze the effects of sedation administration on clinical parameters, comfort status, intubation requirements, and the pediatric intensive care unit (PICU) length of stay (LOS) in children with acute respiratory failure (ARF) receiving noninvasive ventilation (NIV). METHODS: Thirteen PICUs in Spain participated in a prospective, multicenter, observational trial from January to December 2021. Children with ARF under the age of five who were receiving NIV were included. Clinical information and comfort levels were documented at the time of NIV initiation, as well as at 3, 6, 12, 24, and 48 h. The COMFORT-behavior (COMFORT-B) scale was used to assess the patients' level of comfort. NIV failure was considered to be a requirement for endotracheal intubation. RESULTS: A total of 457 patients were included, with a median age of 3.3 months (IQR 1.3-16.1). Two hundred and thirteen children (46.6%) received sedation (sedation group); these patients had a higher heart rate, higher COMFORT-B score, and lower SpO2/FiO2 ratio than did those who did not receive sedation (non-sedation group). A significantly greater improvement in the COMFORT-B score at 3, 6, 12, and 24 h, heart rate at 6 and 12 h, and SpO2/FiO2 ratio at 6 h was observed in the sedation group. Overall, the NIV success rate was 95.6%-intubation was required in 6.1% of the sedation group and in 2.9% of the other group (p = 0.092). Multivariate analysis revealed that the PRISM III score at NIV initiation (OR 1.408; 95% CI 1.230-1.611) and respiratory rate at 3 h (OR 1.043; 95% CI 1.009-1.079) were found to be independent predictors of NIV failure. The PICU LOS was correlated with weight, PRISM III score, respiratory rate at 12 h, SpO2 at 3 h, FiO2 at 12 h, NIV failure and NIV duration. Sedation use was not found to be independently related to NIV failure or to the PICU LOS. CONCLUSIONS: Sedation use may be useful in children with ARF treated with NIV, as it seems to improve clinical parameters and comfort status but may not increase the NIV failure rate or PICU LOS, even though sedated children were more severe at technique initiation in the present sample.

MINIstock: Model for INsect Inclusion in sustainable agriculture: USDA-ARS's research approach to advancing insect meal development and inclusion in animal diets.

Animal agriculture is under pressure to increase efficiency, sustainability, and innovation to meet the demands of a rising global population while decreasing adverse environmental effects. Feed cost and availability are 2 of the biggest hurdles to sustainable production. Current diets depend on sources of grain and animal byproduct protein for essential amino acids which have limited sustainability. Insects have arisen as an attractive, sustainable alternative protein source for animal diets due to their favorable nutrient composition, low space and water requirements, and natural role in animal diets. Additionally, insects are capable of bioremediating waste streams including agricultural and food waste, manure, and plastics helping to increase their sustainability. The insect rearing industry has grown rapidly in recent years and shows great economic potential. However, state-of-the-art research is urgently needed to overcome barriers to adoption in commercial animal diets such as regulatory restrictions, production scale issues, and food safety concerns. To address this need, the USDA Agricultural Research Service "MINIstoc: Model for INsect Inclusion" project was created to bring together diverse scientists from across the world to synergistically advance insect meal production and inclusion in animal diets. Here, we provide a short review of insects as feed while describing the MINIstock project which serves as the inspiration for the Journal of Economic Entomology Special Collection "Insects as feed: sustainable solutions for food waste and animal production practices."

Exploring Heavy Metal and Metalloid Exposure in Children: A Pilot Biomonitoring Study near a Sugarcane Mill.

Sugarcane production has been linked to the release of heavy metals and metalloids (HM/MTs) into the environment, raising concerns about potential health risks. This study aimed to assess the levels of 19 HM/MTs in children living near a sugarcane mill through a pilot biomonitoring investigation. We investigated sex-related differences in these element levels and their correlations. A cross-sectional study was conducted, analyzing data from 20 children in the latter part of 2023. Spearman correlation coefficients with 95% confidence intervals (CIs) were used to assess the relationships between urinary HM/MT levels. Detectable levels of 17 out of the 19 HM/MTs were found across the entire study sample, with arsenic and copper detectable in 95% of the children. Titanium exhibited higher levels in boys compared to girls (p = 0.017). We identified 56 statistically significant correlations, with 51 of them being positive, while the remaining coefficients indicated negative relationships. This study characterized HM/MT levels in school-aged children residing near a sugarcane mill through a pilot biomonitoring investigation. Further research employing larger sample sizes and longitudinal assessments would enhance our understanding of the dynamics and health impacts of HM/MT exposure in this vulnerable population.

Glomerular Hypertrophy and Splenic Red Pulp Degeneration Concurrent with Oxidative Stress in 3xTg-AD Mice Model for Alzheimer's Disease and Its Exacerbation with Sex and Social Isolation.

The continuously expanding field of Alzheimer's disease (AD) research is now beginning to defocus the brain to take a more systemic approach to the disease, as alterations in the peripheral organs could be related to disease progression. One emerging hypothesis is organ involvement in the process of Aß clearance. In the present work, we aimed to examine the status and involvement of the kidney as a key organ for waste elimination and the spleen, which is in charge of filtering the blood and producing lymphocytes, and their influence on AD. The results showed morphological and structural changes due to acute amyloidosis in the kidney (glomeruli area) and spleen (red pulp area and red/white pulp ratio) together with reduced antioxidant defense activity (GPx) in 16-month-old male and female 3xTg-AD mice when compared to their age- and sex-matched non-transgenic (NTg) counterparts. All these alterations correlated with the anxious-like behavioral phenotype of this mouse model. In addition, forced isolation, a cause of psychological stress, had a negative effect by intensifying genotype differences and causing differences to appear in NTg animals. This study further supports the relevance of a more integrative view of the complex interplay between systems in aging, especially at advanced stages of Alzheimer's disease.

Infodemia, salud mental, personas mayores: su caracterización en tiempos de pandemia covid-19 / Infodemia, mental health, older people: its characterization in times of the covid-19 pandemic / Infodemia, saúde mental, idosos: sua caracterização em tempos de pandemia da covid-19

Introducción: "Infodemia" define a aquella información que se divulga rápidamente y sin mayor evidencia, ocasionando desinformación y malos hábitos sanitarios. Objetivo: Caracterizar a las personas mayores con respecto a salud mental e infodemia. Materiales y métodos: estudio cuantitativo, descriptivo, transversal. Muestra no probabilística, conformada por 195 personas mayores, quienes respondieron cuestionario telefónico u online para: Infodemia, Escala de Estrés Percibido, Escala de Depresión Geriátrica Yesavage e Inventario de Ansiedad Generalizada. Previa aceptación de consentimiento informado. Estudio fue aprobado por Comité ético acreditado. Resultados: 58% fueron mujeres, 90% se encontraban jubilados y/o pensionados. El 65% percibía un sueldo igual o menor a US 300. El promedio de horas destinado a información por Covid-19 fue de 5±2,5. La mayoría se sintió afectado/a física y psicológicamente por las noticias. Casi el 30% de los encuestados refirió miedo y ansiedad frente al número de muertos e infectados. 65% se sintió estresado, 9% presentó depresión grave y 20% mostró ansiedad generalizada en este periodo. Discusión: la población mundial está envejeciendo y durante la pandemia fueron los más vulnerables a Covid-19. Este grupo se sintió afectado física y psicológicamente por la información recibida y por ello se requiere romper el ciclo de la desinformación, siendo los profesionales de enfermería los más idóneos para ello. Conclusiones: Las personas mayores se sintieron afectadas por la Infodemia. Se requiere del trabajo multidisciplinario para hacer frente a esta problemática, reforzando la alfabetización para la salud, como estrategia para que las personas mayores logren discriminar la exorbitante información de salud circulante.

Introduction: "Infodemic" defines information that is disseminated quickly and without further evidence, causing misinformation and bad health habits. Objective: Characterize older people with respect to mental health and infodemic. Materials and methods: quantitative, descriptive, cross-sectional study. Non-probabilistic sample, made up of 195 older people, who answered a telephone or online questionnaire for: Infodemic, Perceived Stress Scale, Yesavage Geriatric Depression Scale and Generalized Anxiety Inventory. Prior acceptance of informed consent. Study was approved by an accredited ethical committee. Results: 58% were women, 90% were retired and/or pensioners. 65% received a salary equal to or less than US 300. The average number of hours allocated to Covid-19 information was 5±2.5. The majority felt physically and psychologically affected by the news. Almost 30% of those surveyed reported fear and anxiety regarding the number of deaths and infections. 65% felt stressed, 9% presented severe depression and 20% showed generalized anxiety in this period. Discussion: The world's population is aging and during the pandemic they were the most vulnerable to Covid-19. This group felt physically and psychologically affected by the information received and therefore it is necessary to break the cycle of misinformation, with nursing professionals being the most suitable for this. Conclusions: Older people felt affected by the Infodemic. Multidisciplinary work is required to address this problem, reinforcing health literacy, as a strategy for older people to be able to discriminate the exorbitant circulating health information.

Introdução: "Infodemia" define informações que são divulgadas rapidamente e sem maiores evidências, causando desinformação e maus hábitos de saúde. Os idosos foram os mais vulneráveis aos efeitos da Covid-19, pouco se sabe sobre a sua saúde mental e a infodemia neste período. Objetivo: Caracterizar os idosos quanto à saúde mental e à infodemia. Materiais e métodos: estudo quantitativo, descritivo, transversal. Amostra não probabilística, composta por 195 idosos, que responderam a questionário telefônico ou online de: Infodemia, Escala de Estresse Percebido, Escala de Depressão Geriátrica de Yesavage e Inventário de Ansiedade Generalizada. Aceitação prévia do consentimento informado. O estudo foi aprovado por um comitê de ética credenciado. Resultados: 58% eram mulheres, 90% eram aposentadas e/ou pensionistas. 65% recebiam um salário igual ou inferior a US$ 300. O número médio de horas destinadas à informação sobre a Covid-19 foi de 5±2,5. A maioria sentiu-se física e psicologicamente afetada pela notícia. Quase 30% dos entrevistados relataram medo e ansiedade em relação ao número de mortes e infecções. 65% sentiram-se estressados, 9% apresentaram depressão grave e 20% apresentaram ansiedade generalizada neste período. Discussão: A população mundial está envelhecendo edurante a pandemia eles eram os mais vulneráveis à Covid-19. Este grupo sentiu-se afetado física e psicologicamente pelas informações recebidas e por isso é necessário quebrar o ciclo de desinformação, sendo os profissionais de enfermagem os mais indicados para isso. Conclusões: Os idosos sentiram-se afetados pela Infodemia. É necessário um trabalho multidisciplinar para resolver este problema, reforçando a literacia em saúde, como estratégia para que os idosos consigam discriminar a exorbitante informação de saúde que circula.

Potential molecular patterns for tuberculosis susceptibility in diabetic patients with poor glycaemic control: a pilot study.

Type 2 diabetes (DM2) is an increasingly prevalent disease that challenges tuberculosis (TB) control strategies worldwide. It is significant that DM2 patients with poor glycemic control (PDM2) are prone to developing tuberculosis. Furthermore, elucidating the molecular mechanisms that govern this susceptibility is imperative to address this problem. Therefore, a pilot transcriptomic study was performed. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), tuberculosis (TB), comorbidity TB-DM2, DM2 (HbA1c 6.5-8.9%), and PDM2 (HbA1c > 10%) groups (n = 4 each) were analyzed by differential expression using microarrays. We use a network strategy to identify potential molecular patterns linking the differentially expressed genes (DEGs) specific for TB-DM2 and PDM2 (p-value < 0.05, fold change > 2). We define OSM, PRKCD, and SOCS3 as key regulatory genes (KRGs) that modulate the immune system and related pathways. RT-qPCR assays confirmed upregulation of OSM, PRKCD, and SOCS3 genes (p < 0.05) in TB-DM2 patients (n = 18) compared to CTRL, DM2, PDM2, or TB groups (n = 17, 19, 15, and 9, respectively). Furthermore, OSM, PRKCD, and SOCS3 were associated with PDM2 susceptibility pathways toward TB-DM2 and formed a putative protein-protein interaction confirmed in STRING. Our results reveal potential molecular patterns where OSM, PRKCD, and SOCS3 are KRGs underlying the compromised immune response and susceptibility of patients with PDM2 to develop tuberculosis. Therefore, this work paved the way for fundamental research of new molecular targets in TB-DM2. Addressing their cellular implications, and the impact on the diagnosis, treatment, and clinical management of TB-DM2 could help improve the strategy to end tuberculosis for this vulnerable population.

Association between lipid profile and clinical outcomes in COVID-19 patients.

High-density lipoprotein cholesterol (HDL-c) removes cholesterol, an essential component in lipid rafts, and this cholesterol removal can regulate protein attachment to lipid rafts, modulating their functionality in the immune cell response. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can alter the lipid profile, there is little information on the role of HDL-c and other lipids in prognostic of the coronavirus disease 2019 (COVID-19) in Mexican population. This study aims to evaluate the predictive value of HDL-c and lipid profile on severity and survival of 102 patients infected with SARS-CoV-2 during the COVID-19 first wave. Our findings, derived from univariate and multivariate Cox proportional hazards regression models, highlighted age and hypertension as significant predictors of survival (HR = 1.04, p = 0.012; HR = 2.78, p = 0.027), while gender, diabetes, and obesity showed no significant impact. Triglycerides and HDL-c levels notably influenced mortality, with elevated triglycerides and lower HDL-c associated with higher mortality risk (p = 0.032). This study underscores the importance of lipid profiles alongside traditional risk factors in assessing COVID-19 risk and outcomes. It contributes to the understanding of COVID-19 patient management and emphasizes the need for further investigation into the role of dyslipidemia in influencing COVID-19 prognosis, potentially aiding in refined risk stratification and therapeutic strategies.

Unveiling the role of KSHV-infected human mesenchymal stem cells in Kaposi's sarcoma initiation.

Kaposi's sarcoma (KS) may derive from Kaposi's sarcoma herpesvirus (KSHV)-infected human mesenchymal stem cells (hMSCs) that migrate to sites characterized by inflammation and angiogenesis, promoting the initiation of KS. By analyzing the RNA sequences of KSHV-infected primary hMSCs, we have identified specific cell subpopulations, mechanisms, and conditions involved in the initial stages of KSHV-induced transformation and reprogramming of hMSCs into KS progenitor cells. Under proangiogenic environmental conditions, KSHV can reprogram hMSCs to exhibit gene expression profiles more similar to KS tumors, activating cell cycle progression, cytokine signaling pathways, endothelial differentiation, and upregulating KSHV oncogenes indicating the involvement of KSHV infection in inducing the mesenchymal-to-endothelial (MEndT) transition of hMSCs. This finding underscores the significance of this condition in facilitating KSHV-induced proliferation and reprogramming of hMSCs towards MEndT and closer to KS gene expression profiles, providing further evidence of these cell subpopulations as precursors of KS cells that thrive in a proangiogenic environment.

A concept for international societally relevant microbiology education and microbiology knowledge promulgation in society.

EXECUTIVE SUMMARY: Microbes are all pervasive in their distribution and influence on the functioning and well-being of humans, life in general and the planet. Microbially-based technologies contribute hugely to the supply of important goods and services we depend upon, such as the provision of food, medicines and clean water. They also offer mechanisms and strategies to mitigate and solve a wide range of problems and crises facing humanity at all levels, including those encapsulated in the sustainable development goals (SDGs) formulated by the United Nations. For example, microbial technologies can contribute in multiple ways to decarbonisation and hence confronting global warming, provide sanitation and clean water to the billions of people lacking them, improve soil fertility and hence food production and develop vaccines and other medicines to reduce and in some cases eliminate deadly infections. They are the foundation of biotechnology, an increasingly important and growing business sector and source of employment, and the centre of the bioeconomy, Green Deal, etc. But, because microbes are largely invisible, they are not familiar to most people, so opportunities they offer to effectively prevent and solve problems are often missed by decision-makers, with the negative consequences this entrains. To correct this lack of vital knowledge, the International Microbiology Literacy Initiative-the IMiLI-is recruiting from the global microbiology community and making freely available, teaching resources for a curriculum in societally relevant microbiology that can be used at all levels of learning. Its goal is the development of a society that is literate in relevant microbiology and, as a consequence, able to take full advantage of the potential of microbes and minimise the consequences of their negative activities. In addition to teaching about microbes, almost every lesson discusses the influence they have on sustainability and the SDGs and their ability to solve pressing problems of societal inequalities. The curriculum thus teaches about sustainability, societal needs and global citizenship. The lessons also reveal the impacts microbes and their activities have on our daily lives at the personal, family, community, national and global levels and their relevance for decisions at all levels. And, because effective, evidence-based decisions require not only relevant information but also critical and systems thinking, the resources also teach about these key generic aspects of deliberation. The IMiLI teaching resources are learner-centric, not academic microbiology-centric and deal with the microbiology of everyday issues. These span topics as diverse as owning and caring for a companion animal, the vast range of everyday foods that are produced via microbial processes, impressive geological formations created by microbes, childhood illnesses and how they are managed and how to reduce waste and pollution. They also leverage the exceptional excitement of exploration and discovery that typifies much progress in microbiology to capture the interest, inspire and motivate educators and learners alike. The IMiLI is establishing Regional Centres to translate the teaching resources into regional languages and adapt them to regional cultures, and to promote their use and assist educators employing them. Two of these are now operational. The Regional Centres constitute the interface between resource creators and educators-learners. As such, they will collect and analyse feedback from the end-users and transmit this to the resource creators so that teaching materials can be improved and refined, and new resources added in response to demand: educators and learners will thereby be directly involved in evolution of the teaching resources. The interactions between educators-learners and resource creators mediated by the Regional Centres will establish dynamic and synergistic relationships-a global societally relevant microbiology education ecosystem-in which creators also become learners, teaching resources are optimised and all players/stakeholders are empowered and their motivation increased. The IMiLI concept thus embraces the principle of teaching societally relevant microbiology embedded in the wider context of societal, biosphere and planetary needs, inequalities, the range of crises that confront us and the need for improved decisioning, which should ultimately lead to better citizenship and a humanity that is more sustainable and resilient. ABSTRACT: The biosphere of planet Earth is a microbial world: a vast reactor of countless microbially driven chemical transformations and energy transfers that push and pull many planetary geochemical processes, including the cycling of the elements of life, mitigate or amplify climate change (e.g., Nature Reviews Microbiology, 2019, 17, 569) and impact the well-being and activities of all organisms, including humans. Microbes are both our ancestors and creators of the planetary chemistry that allowed us to evolve (e.g., Life's engines: How microbes made earth habitable, 2023). To understand how the biosphere functions, how humans can influence its development and live more sustainably with the other organisms sharing it, we need to understand the microbes. In a recent editorial (Environmental Microbiology, 2019, 21, 1513), we advocated for improved microbiology literacy in society. Our concept of microbiology literacy is not based on knowledge of the academic subject of microbiology, with its multitude of component topics, plus the growing number of additional topics from other disciplines that become vitally important elements of current microbiology. Rather it is focused on microbial activities that impact us-individuals/communities/nations/the human world-and the biosphere and that are key to reaching informed decisions on a multitude of issues that regularly confront us, ranging from personal issues to crises of global importance. In other words, it is knowledge and understanding essential for adulthood and the transition to it, knowledge and understanding that must be acquired early in life in school. The 2019 Editorial marked the launch of the International Microbiology Literacy Initiative, the IMiLI. HERE, WE PRESENT: our concept of how microbiology literacy may be achieved and the rationale underpinning it; the type of teaching resources being created to realise the concept and the framing of microbial activities treated in these resources in the context of sustainability, societal needs and responsibilities and decision-making; and the key role of Regional Centres that will translate the teaching resources into local languages, adapt them according to local cultural needs, interface with regional educators and develop and serve as hubs of microbiology literacy education networks. The topics featuring in teaching resources are learner-centric and have been selected for their inherent relevance, interest and ability to excite and engage. Importantly, the resources coherently integrate and emphasise the overarching issues of sustainability, stewardship and critical thinking and the pervasive interdependencies of processes. More broadly, the concept emphasises how the multifarious applications of microbial activities can be leveraged to promote human/animal, plant, environmental and planetary health, improve social equity, alleviate humanitarian deficits and causes of conflicts among peoples and increase understanding between peoples (Microbial Biotechnology, 2023, 16(6), 1091-1111). Importantly, although the primary target of the freely available (CC BY-NC 4.0) IMiLI teaching resources is schoolchildren and their educators, they and the teaching philosophy are intended for all ages, abilities and cultural spectra of learners worldwide: in university education, lifelong learning, curiosity-driven, web-based knowledge acquisition and public outreach. The IMiLI teaching resources aim to promote development of a global microbiology education ecosystem that democratises microbiology knowledge.

Acute Kidney Injury in the Context of COVID-19: An Analysis in Hospitalized Mexican Patients.

During the COVID-19 pandemic, a considerable proportion of patients developed a severe condition that included respiratory failure, shock, or multiple organ dysfunction. Acute Kidney Injury (AKI) has been recognized as a possible cause of severe COVID-19 development. Given this, this study investigates the occurrence and consequences of AKI in Mexican patients to contribute to better knowledge and management of this problem. Methods: Using a retrospective observational cohort methodology, we investigated 313 cases from a cohort of 1019 patients diagnosed with COVID-19 at the IMSS Zacatecas General Hospital of Zone No. 1 in 2020. The prevalence of AKI was determined using the AKIN criteria based on serum creatinine levels and a detailed review of demographic characteristics, medical history, comorbidities, and clinical development. Results: The data showed a 25.30% prevalence of AKI among patients infected with severe COVID-19. Remarkably, these patients with AKI exhibited an advanced age (>65 years), arterial hypertension, a higher number of white blood cells during admission and the hospital stay, and elevated levels of C-reactive protein, serum creatinine, and blood urea nitrogen (BUN). Clinically, patients with AKI had signs of prostration, pneumonia, and the requirement for ventilatory assistance when compared to those without AKI. Finally, those diagnosed with AKI and COVID-19 had a 74% death rate. Relative risk analyses indicated that age (>65 years), arterial hypertension, high creatinine levels, endotracheal intubation, and pneumonia are associated with the development of AKI. On the other hand, among the protective factors against AKI, high hemoglobin levels and the consumption of statins during COVID-19 were found. Conclusions: The findings of this study underscore the significance of promptly identifying and effectively managing AKI to potentially alleviate the negative consequences of this complication within the Mexican population during COVID-19.

Headache and Other Factors Modifying Cerebrospinal Fluid Opening Pressure in Pediatric Patients.

Cerebrospinal fluid opening pressure values are associated with various neurologic diseases; however, numerous factors can modify this measurement. This study aims to describe factors related to modifications in opening pressure measurements in pediatric patients. Methods: A retrospective analysis of lumbar punctures in pediatric patients conducted by the neuropediatrics group with institutional standardization. Bivariate and linear regression analyses were performed to determine the association between opening pressure and variables included in the study. Results: 544 events, median age 107 months, median opening pressure 19.7 cm H2O. Bivariate analysis found no association with medication use; anesthetics that increased opening pressure were remifentanil (P = .02) and propofol (P = .05), along with a positive linear correlation between opening pressure and age (P < .0001). Multiple linear regression analysis revealed that age, BMI, male gender, and remifentanil use were associated with an increase in opening pressure, whereas corticosteroid withdrawal was associated with a reduction in opening pressure. There is an interaction between age and headache, with an association with increased opening pressure up to around 140 months. Conclusion: This study identifies factors associated with changes in opening pressure, crucial for estimating normal opening pressure values in children. Headaches, anesthetic use, and corticosteroid withdrawal are confirmed as significant factors.

Parotid hypersalivation after inferior salivatory nucleus glutamate/NMDA receptor excitation in the rat.

Although salivation is essential during eating behavior, little is known about the brainstem centers that directly control the salivary glands. With regard to the inferior salivatory nucleus (ISN), the site of origin of the parasympathetic preganglionic cell bodies that innervate the parotid glands, previous anatomical studies have located it within the rostrodorsal medullary reticular formation. However, to date there is no functional data that shows the secretory nature of the somas grouped in this region. To activate only the somas and rule out the activation of the efferent fibers from and the afferent fibers to the ISN, in exp. 1, NMDA neurotoxin was administered to the rostrodorsal medullary region and the secretion of saliva was recorded during the following hour. Results showed an increased secretion of parotid saliva but a total absence of submandibular-sublingual secretion. In exp. 2, results showed that the hypersecretion of parotid saliva after NMDA microinjection was completely blocked by the administration of atropine (a cholinergic blocker) but not after administration of dihydroergotamine plus propranolol (α and ß-adrenergic blockers, respectively). These findings suggest that the somata of the rostrodorsal medulla are secretory in nature, controlling parotid secretion via a cholinergic pathway. The data thus functionally supports the idea that these cells constitute the ISN.

Safety and effectiveness of isavuconazole in real-life non-neutropenic patients.

OBJECTIVES: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. METHODS: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. RESULTS: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. CONCLUSION: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.

Characterization of an extremophile bacterial acid phosphatase derived from metagenomics analysis.

Acid phosphatases are enzymes that play a crucial role in the hydrolysis of various organophosphorous molecules. A putative acid phosphatase called FS6 was identified using genetic profiles and sequences from different environments. FS6 showed high sequence similarity to type C acid phosphatases and retained more than 30% of consensus residues in its protein sequence. A histidine-tagged recombinant FS6 produced in Escherichia coli exhibited extremophile properties, functioning effectively in a broad pH range between 3.5 and 8.5. The enzyme demonstrated optimal activity at temperatures between 25 and 50°C, with a melting temperature of 51.6°C. Kinetic parameters were determined using various substrates, and the reaction catalysed by FS6 with physiological substrates was at least 100-fold more efficient than with p-nitrophenyl phosphate. Furthermore, FS6 was found to be a decamer in solution, unlike the dimeric forms of crystallized proteins in its family.

Biosynthesis of fragrance 2-phenylethanol from sugars by Pseudomonas putida.

BACKGROUND: Petrochemicals contribute to environmental issues, with concerns ranging from energy consumption and carbon emission to pollution. In contrast, microbial biorefineries offer eco-friendly alternatives. The solvent-tolerant Pseudomonas putida DOT-T1E serves as a suitable host for producing aromatic compounds, specifically L-phenylalanine and its derivative, 2-phenylethanol (2-PE), which find widespread applications in various industries. RESULTS: This study focuses on enhancing 2-PE production in two L-phenylalanine overproducing strains of DOT-T1E, namely CM12-5 and CM12-5Δgcd (xylABE), which grow with glucose and glucose-xylose, respectively. To synthesize 2-PE from L-phenylalanine, these strains were transformed with plasmid pPE-1, bearing the Ehrlich pathway genes, and it was found higher 2-PE production with glucose (about 50-60 ppm) than with xylose (< 3 ppm). To understand the limiting factors, we tested the addition of phenylalanine and intermediates from the Ehrlich and shikimate pathways. The results identified intracellular L-phenylalanine as a key limiting factor for 2-PE production. To overcame this limitation, a chorismate mutase/prephenate dehydratase variant-insentive to feedback inhibition by aromatic amino acids-was introduced in the producing strains. This led to increased L-phenylalanine production and subsequently produced more 2-PE (100 ppm). Random mutagenesis of the strains also produced strains with higher L-phenylalanine titers and increased 2-PE production (up to 120 ppm). The improvements resulted from preventing dead-end product accumulation from shikimate and limiting the catabolism of potential pathway intermediates in the Ehrlich pathway. The study explored agricultural waste substrates, such as corn stover, sugarcane straw and corn-syrup as potential C sources. The best results were obtained using 2G substrates at 3% (between 82 and 100 ppm 2-PE), with glucose being the preferred sugar for 2-PE production among the monomeric sugars in these substrates. CONCLUSIONS: The findings of this study offer strategies to enhance phenylalanine production, a key substrate for the synthesis of aromatic compounds. The ability of P. putida DOT-T1E to thrive with various C-sources and its tolerance to substrates, products, and potential toxicants in industrial wastes, are highlighted. The study identified and overcome possible bottlenecks for 2-PE production. Ultimately, the strains have potential to become efficient microbial platforms for synthesizing 2-PE from agro-industrial waste materials.

Protocol to evaluate the antiviral effect of FDA-approved drugs against dengue virus in Huh7 cells and AG129 mice.

Finding an effective therapy against diseases caused by flaviviruses remains a challenge. Here, we present a protocol to test Food and Drug Administration-approved drugs that inhibit host nuclear protein import, promoting a reduction of dengue infection. We describe steps for analyzing the drug effect on nuclear import inhibition of cellular and viral proteins by confocal microscopy or western blotting. We then describe procedures for measuring the antiviral drug effects on virus-infected cells by flow cytometry and testing drug efficacy in dengue-infected AG129 mice by survival assays. For complete details on the use and execution of this protocol, please refer to Palacios-Rápalo et al.1.

Comparative toxicological analysis of two pristine carbon nanomaterials (graphene oxide and aminated graphene oxide) and their corresponding degraded forms using human in vitro models.

Despite the wide application of graphene-based materials, the information of the toxicity associated to some specific derivatives such as aminated graphene oxide is scarce. Likewise, most of these studies analyse the pristine materials, while the available data regarding the harmful effects of degraded forms is very limited. In this work, the toxicity of graphene oxide (GO), aminated graphene oxide (GO-NH2), and their respective degraded forms (dGO and dGO-NH2) obtained after being submitted to high-intensity sonication was evaluated applying in vitro assays in different models of human exposure. Viability and ROS assays were performed on A549 and HT29 cells, while their skin irritation potential was tested on a reconstructed human epidermis model. The obtained results showed that GO-NH2 and dGO-NH2 substantially decrease cell viability in the lung and gastrointestinal models, being this reduction slightly higher in the cells exposed to the degraded forms. In contrast, this parameter was not affected by GO and dGO which, conversely, showed the ability to induce higher levels of ROS than the pristine and degraded aminated forms. Furthermore, none of the materials is skin irritant. Altogether, these results provide new insights about the potential harmful effects of the selected graphene-based nanomaterials in comparison with their degraded counterparts.

Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders.

The relationship between sleep, glial cells, and the endocannabinoid system represents a multifaceted regulatory network with profound implications for neuroinflammation and cognitive function. The molecular underpinnings of sleep modulation by the endocannabinoid system and its influence on glial cell activity are discussed, shedding light on the reciprocal relationships that govern these processes. Emphasis is placed on understanding the role of glial cells in mediating neuroinflammatory responses and their modulation by sleep patterns. Additionally, this review examines how the endocannabinoid system interfaces with glia-immune signaling to regulate inflammatory cascades within the central nervous system. Notably, the cognitive consequences of disrupted sleep, neuroinflammation, and glial dysfunction are addressed, encompassing implications for neurodegenerative disorders, mood disturbances, and cognitive decline. Insights into the bidirectional modulation of cognitive function by the endocannabinoid system in the context of sleep and glial activity are explored, providing a comprehensive perspective on the potential mechanisms underlying cognitive impairments associated with sleep disturbances. Furthermore, this review examines potential therapeutic avenues targeting the endocannabinoid system to mitigate neuroinflammation, restore glial homeostasis, and normalize sleep patterns. The identification of novel therapeutic targets within this intricate regulatory network holds promise for addressing conditions characterized by disrupted sleep, neuroinflammation, and cognitive dysfunction. This work aims to examine the complexities of neural regulation and identify potential avenues for therapeutic intervention.