TRPC5 controls the adrenaline-mediated counter regulation of hypoglycemia.

Hypoglycemia triggers autonomic and endocrine counter-regulatory responses to restore glucose homeostasis, a response that is impaired in patients with diabetes and its long-term complication hypoglycemia-associated autonomic failure (HAAF). We show that insulin-evoked hypoglycemia is severely aggravated in mice lacking the cation channel proteins TRPC1, TRPC4, TRPC5, and TRPC6, which cannot be explained by alterations in glucagon or glucocorticoid action. By using various TRPC compound knockout mouse lines, we pinpointed the failure in sympathetic counter-regulation to the lack of the TRPC5 channel subtype in adrenal chromaffin cells, which prevents proper adrenaline rise in blood plasma. Using electrophysiological analyses, we delineate a previously unknown signaling pathway in which stimulation of PAC1 or muscarinic receptors activates TRPC5 channels in a phospholipase-C-dependent manner to induce sustained adrenaline secretion as a crucial step in the sympathetic counter response to insulin-induced hypoglycemia. By comparing metabolites in the plasma, we identified reduced taurine levels after hypoglycemia induction as a commonality in TRPC5-deficient mice and HAAF patients.

Taxonomic diversity of terrestrial vertebrates in west-central Mexico: Conservation from a multi-taxa perspective.

Multi-taxa approaches are increasingly used because they describe complementary aspects of ecosystem dynamics from a community ecology perspective. In west-central Mexico, the complex biogeography and topography have created an environment where temperate and tropical forests converge, resulting in great biological diversity. Within this region, the Sierra de Quila Natural Protected Area (SQPA) offers an important example for understanding ecological community dynamics. We analyze the taxonomic diversity of terrestrial vertebrates in the SQPA by incorporating taxonomic levels associated with species. We evaluated the taxonomic diversity with i) an average taxonomic distinctiveness analysis (alpha diversity) and ii) an analysis of taxonomic dissimilarity and partitioning of turnover and differences in richness components (beta diversity). Tropical forests boast the highest taxonomic diversity of amphibians, reptiles, and birds, while temperate gallery forests exhibit lower values. Our results showed that terrestrial vertebrate alpha and beta diversity patterns respond mainly to contrasting vegetation types (tropical vs. temperate). Regarding beta diversity, the multi-vegetation type analysis showed the highest values for reptiles, followed by amphibians, birds, and mammals. Turnover had the highest contribution to beta diversity, while differences in richness were relevant for amphibians and reptiles, which could be related to their low mobility and sensitivity to environmental conditions. Despite the local scale, the SQPA presented high beta diversity, reflecting historical ecological processes in taxonomic composition derived from contrasting environments and constraints imposed on species. Evaluating taxonomic structure from a multi-taxa perspective is essential for conservation efforts because it allows the spatial recognition of biological assemblages as a first step for local interventions.

Contilisant+Tubastatin A Hybrids: Polyfunctionalized Indole Derivatives as New HDAC Inhibitor-Based Multitarget Small Molecules with In Vitro and In Vivo Activity in Neurodegenerative Diseases.

Herein, we describe the design, synthesis, and biological evaluation of 15 Contilisant+Tubastatin A hybrids. These ligands are polyfunctionalized indole derivatives developed by juxtaposing selected pharmacophoric moieties of Contilisant and Tubastatin A to act as multifunctional ligands. Compounds 3 and 4 were identified as potent HDAC6 inhibitors (IC50 = 0.012 µM and 0.035 µM, respectively), so they were further evaluated in Drosophila and human cell models of Parkinson's disease (PD). Both compounds attenuated PD-like phenotypes, such as motor defects, oxidative stress, and mitochondrial dysfunction in PD model flies. Ligands 3 and 4 were also studied in the transgenic Caenorhabditis elegans CL2006 model of Alzheimer's disease (AD). Both compounds were nontoxic, did not induce undesirable animal functional changes, inhibited age-related paralysis, and improved cognition in the thrashing assay. These results highlight 3 and 4 as novel multifunctional ligands that improve the features of PD and AD hallmarks in the respective animal models.

Anaplastic Plasma Cell Myeloma With Peritoneal Involvement.

Multiple myeloma (MM) is a B-cell neoplasm that rounds 15% of all hematological malignancies. The typical clinical presentation of MM includes hypercalcemia, renal failure, anemia and bone lesion (CRAB). Effusions due to MM may occur due to secondary involvement of other organs and rarely are present at the initial diagnosis. Anaplastic myeloma (AMM) is rare morphological variant of multiple myeloma with predisposition of extramedullary affection. Herein, we describe a case of malignant plasmacytic ascites at disease onset of anaplastic multiple myeloma.

Prevalence and population genetic analyses of parasites in invasive Vespa velutina and native Hymenoptera.

Invasive species pose a threat to the ecological balance of the ecosystems they invade by altering local host-pathogen dynamics. To investigate these relationships and their potential consequences, we examined the prevalence and genetic diversity patterns of Trypanosomatidae, Lipotrophidae, and Nosematidae in a collection of sympatric isolates of the invasive hornet Vespa velutina and local Hymenoptera from two recently colonized areas: Europe and South Korea. Data were gathered through PCR amplification and massive parallel sequencing, and analyses were conducted using population genetics tools. Parasite prevalences showed substantial variation depending on (i) the parasite family (Trypanosomatidae and Nosematidae were the most and less prevalent, respectively), (ii) location (e.g. Galicia displayed the highest pooled values), (iii) the season (highest in spring for Trypanosomatidae and Lipotrophidae), and (iv) the host. V. velutina exhibited significantly lower parasite occurrence than native Hymenoptera across all parasite families (consistent with the enemy release hypothesis), although this difference was less pronounced during the periods of heightened predatory activity, suggestive of trophic transmission. Parasite species displayed significant genetic differentiation between European and South Korean isolates, yet no differentiation was observed across hosts, suggesting that all Hymenoptera are exposed to a common local pathogen population. There was no indication that V. velutina acted as a carrier of foreign parasites to the invaded territories.

Sex-specific dietary patterns and their association with metabolic syndrome: Insights from a cross-sectional analysis.

AIMS: This study aims to identify a posteriori dietary patterns with a sex approach and to evaluate their association with metabolic syndrome criteria. METHODS: Cross-sectional study conducted in 6821 men and women between 55 and 75 years of age. Forty-two food groups were analyzed from dietary information collected with food frequency questionnaires, using principal component analysis and cluster analysis and then information from both statistical methods was compared. Prevalences were calculated foreach cluster group, based on the number and types of metabolic syndrome criteria they met. RESULTS: Following principal component analysis, two dietary patterns labeled "healthy" and "unhealthy" were identified in both men and women, due to the presence of foods that are considered more or less healthy. These same dietary patterns were found in cluster analysis plus an "intermediate" cluster consisting of both healthy and unhealthy foods. The presence of metabolic syndrome is related to the "healthy" dietary pattern in women and to the "unhealthy" dietary pattern in men. Comparison of the two statistical approaches showed a high level of correlation between them (weighted Kappa = 0.703 in women and weighted Kappa = 0.691 in men). CONCLUSIONS: Adherence to both healthy and unhealthy dietary pattern appears to be related to the development of MS. The differences found by sex make it necessary to develop interventions with a sex-specific approach.

Mental health predictors of Internet Gaming Disorder: a longitudinal study.

OBJECTIVE: We aim to evaluate whether a wide range of baseline mental disorders predict Internet Gaming Disorder (IGD) one to three years later, among university students. METHODS: Prospective cohort study with a follow-up period of one to three years (September 2018-June 2022) in 6 Mexican universities. Participants were first-year university students (N=2,144) free of symptoms indicative of IGD at entry (baseline). Ten mental disorders (bipolar, major depressive disorder, generalized anxiety disorder, panic disorder, alcohol use disorder, drug use disorder, binging and/or purging, intermittent explosive disorder, psychotic experiences, attention deficit hyperactivity disorder) at baseline were the main risk factors for IGD at the end of the follow-up. We used Cox regression to model the IGD incidence rate. RESULTS: Any mental disorder at baseline was associated with an increase in 2.33 times (1.26-4.31) the rate of IGD 1 to 3 years later. Several individual disorders were associated with rates of IGD in multiple models, with comorbid conditions diminishing most of these associations. CONCLUSIONS: Only major depressive disorder and bipolar disorder remained associated with a new case of IGD. Discrepant results from available longitudinal studies on the role of specific mental disorders in the development of IGD needs to be further investigated.

Abscisic acid, an evolutionary conserved hormone: Biosynthesis, therapeutic and diagnostic applications in mammals.

Abscisic acid (ABA), a phytohormone traditionally recognized for its role in plant stress responses, has recently emerged as a significant player in mammalian defense mechanisms. Like plants, various mammalian cell types synthesize ABA in response to specific health challenges, although the precise pathways remain not fully elucidated. ABA is associated with the regulation of inflammation and insulin signaling, prompting extensive research into its potential as a therapeutic agent for various diseases. ABA exerts its effects through its receptors, particularly PPAR-γ and LANCL-2, which serve as signaling hubs regulating numerous pathways. Through these interactions, ABA profoundly impacts mammalian health, and new ABA targets continue to be identified. Numerous studies in animal models demonstrate ABA's benefit in managing conditions such as neurological and psychiatric disorders, cancer, and malaria infections, all of which involve significant inflammatory dysregulation. In this manuscript we review the studies covering ABA synthesis and release in cell cultures, the signaling pathways regulated by ABA, and how these impact health in preclinical models. Furthermore, we highlight recent research suggesting that measuring ABA levels in human body fluids could serve as a useful biomarker for pathological conditions, providing insights into disease progression and treatment efficacy. This comprehensive review outlines the current understanding of ABA in mammalian pathophysiology, identifying gaps in knowledge, particularly concerning ABA biosynthesis and metabolism in mammals. In addition, this study emphasizes the need for clinical trials to validate the effectiveness of ABA-based therapies and its reliability as a biomarker for various diseases.

Hyperangulated versus Macintosh blades for intubation with videolaryngoscopy in ICU: the randomised multicentre INVIBLADE-ICU trial study protocol.

INTRODUCTION: Compared with the operating room, tracheal intubations in the intensive care unit (ICU) are associated with worsened glottic view, decreased first-time success rate and increase in the technical difficulty of intubation and incidence of complications. Videolaryngoscopes (VLs) have been proposed to improve airway management, and while recent studies have confirmed that VLs improve intubation conditions in this patient population, there remains a lack of clarity regarding the selection between a standard Macintosh blade or a hyperangulated one, to determine which yields the best outcomes. The purpose of this study was to compare successful intubation on the first attempt with the Macintosh VL versus the hyperangulated VL during tracheal intubation in ICU patients. We hypothesise that tracheal intubation using the hyperangulated VL will improve the frequency of successful intubation on the first attempt. METHODS AND ANALYSIS: The INtubation VIdeolaryngoscopy BLADE-ICU trial is a prospective, multicentre, open-label, interventional, randomised, controlled superiority study conducted in 29 ICUs in Spain. Patients will be randomly assigned in a 1:1 ratio to undergo intubation using a Macintosh VL (control group) or a hyperangulated VL (experimental group) for the first intubation attempt. The primary outcome is successful intubation on the first attempt. The secondary outcomes include the time to intubation, attempts for successful intubation, laryngoscopic vision assessed with the modified Cormack-Lehane scale, the need for adjuvant airway devices for intubation, difficulty assessed by the anaesthesiologist and complications during tracheal intubation. Enrolment began on 1 May 2024 and is expected to be completed in 2025. ETHICS AND DISSEMINATION: The study protocol was approved on 29 February 2024, by the Ethics Committee of Galicia (CEImG, code No. 2024-031).The results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT06322719.

Taxonomic diversity of amphibians (Amphibia, Anura) and reptiles (Reptilia, Testudines, Squamata) in a heterogeneous landscape in west-central Mexico: a checklist and notes on geographical distributions.

In Mexico, land use changes have significantly impacted the diversity of amphibians and reptiles in a negative way. In light of this, we evaluate the alpha and beta components of the taxonomic diversity of amphibians and reptiles in a heterogeneous landscape in west-central Mexico. Additionally, we provide a checklist of amphibian and reptile species recorded over nine years of observations within the studied landscape and surrounding areas. The land cover/use types with the highest species richness and alpha taxonomic diversity differed between amphibians and reptiles. Overall beta taxonomic diversity was high for both groups, but slightly higher in reptiles. This taxonomic differentiation mainly corresponded to a difference in the turnover component and was greater in pristine habitats compared to disturbed ones. The checklist records 20 species of amphibians (ten of which are endemic) and 48 of reptiles (30 endemics). Additionally, the study expands the known geographical distribution range of one species of frog and three species of snakes. Our findings suggest that heterogeneous landscapes with diverse land cover/use types can provide essential habitats for the conservation of amphibian and reptile species.

Lymphocytic esophagitis - A little-known cause of dysphagia.

Lymphocytic esophagitis is a little-known entity whose cause is not fully established, and which basically presents with dysphagia. It is characterized by the presence of an infiltrate mainly formed by lymphocytes and other signs of epithelial damage in the absence of other granulocytes. The lack of knowledge about this pathology as well as standardized diagnostic criteria complicates its diagnosis. We present the case of an 84-year-old male with dysphagia and pathological findings compatible with lymphocytic esophagitis, requiring several lines of treatment and even endoscopic dilation with subsequent clinical improvement.

Unlocking the puzzle: non-defining mutations in SARS-CoV-2 proteome may affect vaccine effectiveness.

Introduction: SARS-CoV-2 variants are defined by specific genome-wide mutations compared to the Wuhan genome. However, non-clade-defining mutations may also impact protein structure and function, potentially leading to reduced vaccine effectiveness. Our objective is to identify mutations across the entire viral genome rather than focus on individual mutations that may be associated with vaccine failure and to examine the physicochemical properties of the resulting amino acid changes. Materials and methods: Whole-genome consensus sequences of SARS-CoV-2 from COVID-19 patients were retrieved from the GISAID database. Analysis focused on Dataset_1 (7,154 genomes from Italy) and Dataset_2 (8,819 sequences from Spain). Bioinformatic tools identified amino acid changes resulting from codon mutations with frequencies of 10% or higher, and sequences were organized into sets based on identical amino acid combinations. Results: Non-defining mutations in SARS-CoV-2 genomes belonging to clades 21 L (Omicron), 22B/22E (Omicron), 22F/23A (Omicron) and 21J (Delta) were associated with vaccine failure. Four sets of sequences from Dataset_1 were significantly linked to low vaccine coverage: one from clade 21L with mutations L3201F (ORF1a), A27- (S) and G30- (N); two sets shared by clades 22B and 22E with changes A27- (S), I68- (S), R346T (S) and G30- (N); and one set shared by clades 22F and 23A containing changes A27- (S), F486P (S) and G30- (N). Booster doses showed a slight improvement in protection against Omicron clades. Regarding 21J (Delta) two sets of sequences from Dataset_2 exhibited the combination of non-clade mutations P2046L (ORF1a), P2287S (ORF1a), L829I (ORF1b), T95I (S), Y145H (S), R158- (S) and Q9L (N), that was associated with vaccine failure. Discussion: Vaccine coverage associations appear to be influenced by the mutations harbored by marketed vaccines. An analysis of the physicochemical properties of amino acid revealed that primarily hydrophobic and polar amino acid substitutions occurred. Our results suggest that non-defining mutations across the proteome of SARS-CoV-2 variants could affect the extent of protection of the COVID-19 vaccine. In addition, alteration of the physicochemical characteristics of viral amino acids could potentially disrupt protein structure or function or both.

Surgical Resolution of Patients With Hypertrophy of Papillary Muscles in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy encompasses a broad spectrum of muscular diseases that involve not only the interventricular septum and the left ventricular outflow tract but also the papillary muscles and the mitral valve apparatus. This article presents the successful surgical treatment of two patients with generalized hypertrophic cardiomyopathy with hypertrophy of the papillary muscles without severe septal hypertrophy: one with a history of unsuccessful chemical ablation and coronary disease following an interventional event, and another young patient without a history of chronic degenerative diseases who developed hypertrophic cardiomyopathy during her third pregnancy. Both patients with left ventricular outflow tract gradients greater than 55 mmHg and those who underwent surgical treatment had a gradient of less than 10 mmHg.

Development of New Lignin-Based Coatings with Ultraviolet Resistance for Biobased Composite Materials.

Nowadays, there is a challenge in searching for more sustainable alternatives to decrease the environmental impact of composite materials. In this work, we fabricate new composites based on a biobased-content epoxy system, lignin, and flax fiber; considering these materials could be promising due to their high renewable content of around 40%. In addition, another key requirement for composites, besides being sustainable, is that they present improved properties such as UV resistance. Therefore, throughout this work, priority was given to improving UV resistance in addition to taking into account sustainability. In order to carry out a complete characterization of the materials developed, the mechanical properties, brightness, and thermal, rheological, and fire behavior of these kinds of materials were analyzed by using vacuum-assisted resin infusion processes. By way of conclusion, it should be noted that the manufactured composite with the optimized formulation showed improved UV resistance using lignin and that it could be applied on internal and external walls according to the railway fire regulations.

Management of cytomegalovirus in adult solid organ transplant patients: GESITRA-IC-SEIMC, CIBERINFEC, and SET recommendations update.

Cytomegalovirus (CMV) infection remains a significant challenge in solid organ transplantation (SOT). The last international consensus guidelines on the management of CMV in SOT were published in 2018, highlighting the need for revision to incorporate recent advances, notably in cell-mediated immunity monitoring, which could alter the current standard of care. A working group including members from the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Transplantation (SET), developed consensus-based recommendations for managing CMV infection in SOT recipients. Recommendations were classified based on evidence strength and quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The final recommendations were endorsed through a consensus meeting and approved by the expert panel.

E-Health Interventions to Improve Health Outcomes in Patients with Systemic Lupus Erythematosus: A Systematic Review.

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that involves damage to one or more organs and systems. E-Health technologies have been used to improve the quality of care and to minimize the cost of rehabilitation services. This study aimed to provide the most recent and convincing evidence on the rehabilitation effects of e-Health interventions compared to conventional treatments. METHODS: A systematic review was conducted. Inclusion criteria were defined following PICO recommendations (i.e., populations, intervention, comparison and outcome measures). Methodological quality and risk-of-bias were assessed for each study. RESULTS: Six studies met the inclusion criteria, providing data on 743 individuals with SLE. Results indicated that e-Health interventions improved health outcomes, such as disease management or emotional status. Methodological quality was moderate and low risk-of-bias was found in the majority of the studies included. CONCLUSIONS: For patients with SLE, e-Health interventions are a safe rehabilitation intervention to improve health outcomes. However, more high-quality studies with large samples are needed, with a focus on the long-term outcomes of e-Health interventions for patients with SLE.

Serological and molecular survey of rat hepatitis E virus (Rocahepevirus ratti) in drug users.

ABSTRACTRat hepatitis E virus (ratHEV) is an emerging cause of acute hepatitis of zoonotic origin. Since seroprevalence studies are scarce, at-risk groups are almost unknown. Because blood-borne infections frequently occur in people with drug use, who are particularly vulnerable to infection due to lack of housing and homelessness, this population constitutes a priority in which ratHEV infection should be evaluated. Therefore, the aim of this study was to evaluate the ratHEV seroprevalence and RNA detection rate in drug users as a potential at-risk population. We designed a retrospective study involving individuals that attended drug rehabilitation centres. Exposure to ratHEV was assessed by specific antibody detection using ELISA and dot blot (DB) assay and the presence of active infection by ratHEV RNA detection using RT-qPCR. Three-hundred and forty-one individuals were included, the most of them being men (67.7%) with an average age of 45 years. A total of 17 individuals showed specific IgG antibodies against ratHEV (4.6%; 95% CI; 3.1%-7.9%). One case of active ratHEV infection was identified (0.3%; 95% CI: 0.1%-1.8%). This was a 57-year-old homeless woman with limited financial resources, who had active cocaine and heroin use via parenteral route. In conclusion, we identified a potential exposure to ratHEV among drug users. Targeted studies in drug users with proper control groups are necessary to evaluate high-risk populations and transmission routes more accurately.

Objectively Measured Sleep Duration and Health-Related Quality of Life in Older Adults with Metabolic Syndrome: A One-Year Longitudinal Analysis of the PREDIMED-Plus Cohort.

The aim of our cross-sectional and longitudinal study is to assess the relationship between daytime and night-time sleep duration and health-related quality of life (HRQoL) in adults with metabolic syndrome after a 1-year healthy lifestyle intervention. Analysis of the data from 2119 Spanish adults aged 55-75 years from the PREDIMED-Plus study was performed. Sleep duration was assessed using a wrist-worn accelerometer. HRQoL was measured using the SF-36 questionnaire. Linear regression models adjusted for socioeconomic and lifestyle factors and morbidity were developed. In cross-sectional analyses, participants with extreme night-time sleep duration categories showed lower physical component summary scores in Models 1 and 2 [ß-coefficient (95% confidence interval) <6 h vs. 7-9 h: -2, 3 (-3.8 to -0.8); p = 0.002. >9 h vs. 7-9 h: -1.1 (-2.0 to -0.3); p = 0.01]. Participants who sleep less than 7 h a night and take a nap are associated with higher mental component summary scores [ß-coefficient (95% confidence interval) 6.3 (1.3 to 11.3); p = 0.01]. No differences between night-time sleep categories and 12-month changes in HRQoL were observed. In conclusion, in cross-sectional analyses, extremes in nocturnal sleep duration are related to lower physical component summary scores and napping is associated with higher mental component summary scores in older adults who sleep less than 7 h a night.

Spatiotemporal dynamics of Ixodes ricinus abundance in northern Spain.

Ixodes ricinus is the most medically relevant tick species in Europe because it transmits the pathogens that cause Lyme borreliosis and tick-borne encephalitis. Northern Spain represents the southernmost margin of its main European range and has the highest rate of Lyme borreliosis hospitalisations in the country. Currently, the environmental determinants of the spatiotemporal patterns of I. ricinus abundance remain unknown in this region and these may differ from drivers in highly favourable areas for the species in Europe. Therefore, our study aimed to understand the main factors modulating questing I. ricinus population dynamics to map abundance patterns in northern Spain. From 2012 to 2014, monthly/fortnightly samplings were conducted at 13 sites in two regions of northern Spain to estimate spatiotemporal variation in I. ricinus questing abundance. Local abundance of I. ricinus was modelled in relation to variation in local biotic and abiotic environmental conditions by constructing generalised linear mixed models with a zero-inflated negative binomial distribution for overdispersed data. The different developmental stages of I. ricinus were most active at different times of the year. Adults and nymphs showed a peak of abundance in spring, while questing larvae were more frequent in summer. The main determinants affecting the spatiotemporal abundance of the different stages were related to humidity and temperature. For adults and larvae, summer seemed to be the most influential period for their abundance, while for nymphs, winter conditions and those of the preceding months seemed to be determining factors. The highest abundances of nymphs and adults were predicted for the regions of northern Spain with the highest rate of Lyme borreliosis hospitalisations. Our models could be the basis on which to build more accurate predictive models to identify the spatiotemporal windows of greatest potential interaction between animals/humans and I. ricinus that may lead to the transmission of I. ricinus-borne pathogens.