Cationic Glucan Dendrimer Gel-Mediated Local Delivery of Anti-OC-STAMP-siRNA for Treatment of Pathogenic Bone Resorption.

Osteoclast stimulatory transmembrane protein (OC-STAMP) plays a pivotal role in the promotion of cell fusion during osteoclast differentiation (osteoclastogenesis) in the context of pathogenic bone resorption. Thus, it is plausible that the suppression of OC-STAMP through a bioengineering approach could lead to the development of an effective treatment for inflammatory bone resorptive diseases with minimum side effects. Here, we synthesized two types of spermine-bearing (Spe) cationic glucan dendrimer (GD) gels (with or without C12) as carriers of short interfering RNA (siRNA) to silence OC-STAMP. The results showed that amphiphilic C12-GD-Spe gel was more efficient in silencing OC-STAMP than GD-Spe gel and that the mixture of anti-OC-STAMP siRNA/C12-GD-Spe significantly downregulated RANKL-induced osteoclastogenesis. Also, local injection of anti-OC-STAMP-siRNA/C12-GD-Spe could attenuate bone resorption induced in a mouse model of periodontitis. These results suggest that OC-STAMP is a promising target for the development of a novel bone regenerative therapy and that C12-GD-Spe gel provides a new nanocarrier platform of gene therapies for osteolytic disease.

The Need and Opportunity to Update the Inventory of Plant Pathogenic Fungi and Oomycetes in Mexico.

Mexico generates specific phytosanitary regulations for each product and origin to prevent the entry of quarantine pests and/or delay their spread within the national territory, including fungi and oomycetes. Phytosanitary regulations are established based on available information on the presence or absence of these pathogens in the country; however, the compilation and precise analysis of reports is a challenging task due to many publications lacking scientific rigor in determining the presence of a taxon of phytosanitary interest in the country. This review evaluated various studies reporting the presence of plant pathogenic fungi and oomycetes in Mexico and concluded that some lists of diseases and phytopathogenic organisms lack technical-scientific basis. Thus, it highlights the need and presents an excellent opportunity to establish a National Collection of Fungal Cultures and a National Herbarium for obligate parasites, as well as to generate a National Database of Phytopathogenic Fungi and Oomycetes present in Mexico, supported by the combination of morphological, molecular, epidemiological, pathogenicity, symptom, and micrograph data. If realized, this would have a direct impact on many future applications related to various topics, including quarantines, risk analysis, biodiversity studies, and monitoring of fungicide resistance, among others.

Efficacy of the combination of water aerobics and metacognitive training on psychological and physical health variables and their relationship with SP1 and SP4 biomarkers in people with psychosis: a study protocol.

Background: Metacognitive Training (MCT) is widely used and effective in reducing positive symptoms in psychosis. Physical exercise, such as Water Aerobics (WA), improves general health, quality of life and symptoms as a low impact activity that allows social interactions. Preliminary results suggest a relationship between dopamine and psychotic symptoms, through SP transcription factors, SP1 and SP4 biomarkers. The aims of the project are to evaluate the efficacy of a combined intervention (WA and MCT) for psychosis to improve psychotic symptoms, physical health, and transcription levels of SP biomarkers. Materials and methods: This is a unicentric randomized controlled trial of three parallel intervention groups: MCT, WA and combined intervention. The estimated sample will be 48 patients with a psychotic spectrum disorder diagnosis. The assessment will be performed at baseline and at 2-months' follow-up. Instruments used in the assessment will include clinical, cognitive, metacognitive, social cognitive and psychosocial variables. Discussion: This will be the first study investigating the impact of the combination of MCT and WA in psychosis. Moreover, it will be the first study analyzing changes in the transcriptional biomarkers SP1 and SP4 after interventions. The results of this study may have clinical implications contributing to the improvement of treatment selection. Clinical trial registration: https://clinicaltrials.gov/, identifier: NCT05455593.

Thrombosis and infections associated with PICC in onco-hematological patients, what is their relevance?

PURPOSE: Peripherally inserted central venous catheters (PICC) in the onco-hematological patients may be associated with thrombosis or infections that may have short- to medium-term repercussions. MATERIAL AND METHODS: Single-centre retrospective analysis of a prospectively collected cohort. Primary objective was to establish the PICC-thrombosis and infections incidence. Secondary objectives were to analyze profile of patients suffering from these complications and variables associated with an increased likelihood of developing these events. RESULTS: 549 patients were recruited. 58.5% (n = 321) were oncology patients and 41.5% (n = 228) hematology patients. The incidence of PICC-associated thrombosis was 3.5% (n = 19). Thrombosis was associated with progression of the underlying malignant pathology in 10.6% (n = 2) of cases. No association was found between clinical variables analysed and development of thrombosis. Incidence of PICC-associated infections was 7.65% (n = 42). In the 30 days prior to PICC infection, 57.1% (n = 24) had a febrile syndrome of another focus, 73.8% (n = 11) had been hospitalized, 49.5% (n = 25) had a neutrophil count of 0-500 cells/mm3 and 47.6% (n = 20) had an episode of neutropenic fever. Variables significantly associated with the development of infection were hematological patients, high-flow PICC, 3-lm PICC or PICC insertion because of administration of vesicant therapy. CONCLUSIONS: Incidence of PICC-associated thrombosis is low and apparently less prognostically aggressive than other forms of thrombosis associated with cancer, without identify predictive factors. Infection was more prevalent and the identification of risk factors in our series could facilitate its prevention.

Prevalence and Antimicrobial Resistance of Listeria monocytogenes in Different Raw Food from Reynosa, Tamaulipas, Mexico.

Listeria (L.) monocytogenes is an opportunistic foodborne pathogen that causes listeriosis in humans and animals, reaching up to 30% case mortality. There are only a few reports in Mexico about the L. monocytogenes strains found in various foods. The aim of this study was to determine the prevalence of L. monocytogenes, serogroups, virulence genes, and antimicrobial resistance in different foods from Reynosa, Tamaulipas, Mexico. L. monocytogenes strains were characterized by microbiological and molecular methods. Susceptibility to 12 antibiotics was determined according to CLSI and EUCAST. A total of 300 samples of seafood, pasteurized and raw milk, cheese, beef, and chicken were collected from supermarkets and retail markets. The presence of L. monocytogenes was detected in 5.6% of the samples. Most strains belonged to serogroups 4b, 4d, and 4e (68.4%). All strains presented a minimum of four virulence genes; the most common were actA, hly, and plcB (92.1%). A high percentage of antimicrobial susceptibility was observed, with resistance only to STX-TMP (78.9%), STR (26.3%), MEM (21.0%), and E (2.6%). These results show that the foods in Reynosa, Tamaulipas, are a reservoir of L. monocytogenes and represent a potential health risk.

Sinus fungal balls caused by Syncephalastrum spp.: 2 clinical cases and literature review.

INTRODUCTION: Syncephalastrum spp. is a mucoral that rarely produces pathology. Fungal balls caused by this genus are infrequent. It requires early diagnosis and treatment to avoid associated morbidity and mortality. METHODS: We describe two clinical cases of sinus fungus balls caused by Syncephalastrum spp. and review the literature. RESULTS: Two patients were treated for sinus fungus balls. When their samples were analysed, the aetiology was determined to be Syncephalastrum spp. A case of pulmonary fungus ball due to Syncephalastrum spp. is described in the literature. All cases, including these described in the present study, had a good evolution after treatment. CONCLUSIONS: Syncephalastrum spp. is a filamentous fungus that should be considered as an aetiology of sinus fungus ball.

Attitudes and barriers to pulmonary arterial hypertension screening in systemic sclerosis patients: A survey of UK-based rheumatologists.

Objectives: The objectives were to explore rheumatologists' current clinical screening practices of pulmonary arterial hypertension in patients with systemic sclerosis in the United Kingdom and to identify barriers to screening and consider potential solutions. Methods: A survey of 31 questions was developed and included six sections: clinician demographics, the importance of screening, screening practices, barriers to screening, treatment and patient education. The survey was disseminated among rheumatologists working in the United Kingdom. Results: Forty-four rheumatologists working in the United Kingdom participated in the study, and the majority completed all the questions. Around one-third (37.0%) worked in specialised systemic sclerosis units (university or general hospitals (54.5% and 45.4%, respectively)). The majority recognised that systemic sclerosis-pulmonary arterial hypertension is a major cause of morbidity and mortality. Over half (60.0%) reported using the DETECT algorithm to screen for systemic sclerosis-pulmonary arterial hypertension, although other algorithms were also sometimes used. All of the respondents utilised transthoracic echocardiogram, and almost all (95.0%) performed pulmonary function tests for screening purposes. Various challenges and barriers were identified relating to systemic sclerosis-pulmonary arterial hypertension screening, with the difficulty in interpreting results from other hospitals and extended wait times for diagnostic tests being the most reported (76.0% and 74.0%, respectively). Most respondents agreed that access to key investigations (87.0%), ongoing clinician education (82.0%), multidisciplinary meetings (79.5%) and a better understanding of proposed screening algorithms (79.5%) could be potential solutions. Conclusion: Screening patients with systemic sclerosis for pulmonary arterial hypertension is crucial to improve survival, but variable practices exist among UK rheumatologists. Solutions include educating healthcare professionals on guidelines, sharing information between centres and integrating care services.

Systematic Review and Meta-Analysis of Automated Methods for Quantifying Enlarged Perivascular Spaces in the Brain.

Research into magnetic resonance imaging (MRI)- visible perivascular spaces (PVS) has recently increased, as results from studies in different diseases and populations are cementing their association with sleep, disease phenotypes, and overall health indicators. With the establishment of worldwide consortia and the availability of large databases, computational methods that allow to automatically process all this wealth of information are becoming increasingly relevant. Several computational approaches have been proposed to assess PVS from MRI, and efforts have been made to summarise and appraise the most widely applied ones. We systematically reviewed and meta-analysed all publications available up to September 2023 describing the development, improvement, or application of computational PVS quantification methods from MRI. We analysed 67 approaches and 60 applications of their implementation, from 112 publications. The two most widely applied were the use of a morphological filter to enhance PVS-like structures, with Frangi being the choice preferred by most, and the use of a U-Net configuration with or without residual connections. Older adults or population studies comprising adults from 18 years old onwards were, overall, more frequent than studies using clinical samples. PVS were mainly assessed from T2-weighted MRI acquired in 1.5T and/or 3T scanners, although combinations using it with T1-weighted and FLAIR images were also abundant. Common associations researched included age, sex, hypertension, diabetes, white matter hyperintensities, sleep and cognition, with occupation-related, ethnicity, and genetic/hereditable traits being also explored. Despite promising improvements to overcome barriers such as noise and differentiation from other confounds, a need for joined efforts for a wider testing and increasing availability of the most promising methods is now paramount.

Salivary biomarkers as pioneering indicators for diagnosis and severity stratification of pediatric long COVID.

Introduction: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), manifests as persistent and often debilitating symptoms enduring well beyond the initial COVID-19 infection. This disease is especially worrying in children since it can seriously alter their development. Presently, a specific diagnostic test or definitive biomarker set for confirming long COVID is lacking, relying instead on the protracted presence of symptoms post-acute infection. Methods: We measured the levels of 13 biomarkers in 105 saliva samples (49 from children with long COVID and 56 controls), and the Pearson correlation coefficient was used to analyse the correlations between the levels of the different salivary biomarkers. Multivariate logistic regression analyses were performed to determine which of the 13 analysed salivary biomarkers were useful to discriminate between children with long COVID and controls, as well as between children with mild and severe long COVID symptoms. Results: Pediatric long COVID exhibited increased oxidant biomarkers and decreased antioxidant, immune response, and stress-related biomarkers. Correlation analyses unveiled distinct patterns between biomarkers in long COVID and controls. Notably, a multivariate logistic regression pinpointed TOS, ADA2, total proteins, and AOPP as pivotal variables, culminating in a remarkably accurate predictive model distinguishing long COVID from controls. Furthermore, total proteins and ADA1 were instrumental in discerning between mild and severe long COVID symptoms. Discussion: This research sheds light on the potential clinical utility of salivary biomarkers in diagnosing and categorizing the severity of pediatric long COVID. It also lays the groundwork for future investigations aimed at unravelling the prognostic value of these biomarkers in predicting the trajectory of long COVID in affected individuals.

Insights into the function and regulation of the calcium-activated chloride channel TMEM16A.

The TMEM16A channel, a member of the TMEM16 protein family comprising chloride (Cl-) channels and lipid scramblases, is activated by the free intracellular Ca2+ increments produced by inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release after GqPCRs or Ca2+ entry through cationic channels. It is a ubiquitous transmembrane protein that participates in multiple physiological functions essential to mammals' lives. TMEM16A structure contains two identical 10-segment monomers joined at their transmembrane segment 10. Each monomer harbours one independent hourglass-shaped pore gated by Ca2+ ligation to an orthosteric site adjacent to the pore and controlled by two gates. The orthosteric site is created by assembling negatively charged glutamate side chains near the pore´s cytosolic end. When empty, this site generates an electrostatic barrier that controls channel rectification. In addition, an isoleucine-triad forms a hydrophobic gate at the boundary of the cytosolic vestibule and the inner side of the neck. When the cytosolic Ca2+ rises, one or two Ca2+ ions bind to the orthosteric site in a voltage (V)-dependent manner, thus neutralising the electrostatic barrier and triggering an allosteric gating mechanism propagating via transmembrane segment 6 to the hydrophobic gate. These coordinated events lead to pore opening, allowing the Cl- flux to ensure the physiological response. The Ca2+-dependent function of TMEM16A is highly regulated. Anions with higher permeability than Cl- facilitate V dependence by increasing the Ca2+ sensitivity, intracellular protons can replace Ca2+ and induce channel opening, and phosphatidylinositol 4,5-bisphosphate bound to four cytosolic sites likely maintains Ca2+ sensitivity. Additional regulation is afforded by cytosolic proteins, most likely by phosphorylation and protein-protein interaction mechanisms.

Life-course neighbourhood deprivation and brain structure in older adults: the Lothian Birth Cohort 1936.

Neighbourhood disadvantage may be associated with brain health but the importance of exposure at different stages of the life course is poorly understood. Utilising the Lothian Birth Cohort 1936, we explored the relationship between residential neighbourhood deprivation from birth to late adulthood, and global and local neuroimaging measures at age 73. A total of 689 participants had at least one valid brain measures (53% male); to maximise the sample size structural equation models with full information maximum likelihood were conducted. Residing in disadvantaged neighbourhoods in mid- to late adulthood was associated with smaller total brain (ß = -0.06; SE = 0.02; sample size[N] = 658; number of pairwise complete observations[n]=390), grey matter (ß = -0.11; SE = 0.03; N = 658; n = 390), and normal-appearing white matter volumes (ß = -0.07; SE = 0.03; N = 658; n = 390), thinner cortex (ß = -0.14; SE = 0.06; N = 636; n = 379), and lower general white matter fractional anisotropy (ß = -0.19; SE = 0.06; N = 665; n = 388). We also found some evidence on the accumulating impact of neighbourhood deprivation from birth to late adulthood on age 73 total brain (ß = -0.06; SE = 0.02; N = 658; n = 276) and grey matter volumes (ß = -0.10; SE = 0.04; N = 658; n = 276). Local analysis identified affected focal cortical areas and specific white matter tracts. Among individuals belonging to lower social classes, the brain-neighbourhood associations were particularly strong, with the impact of neighbourhood deprivation on total brain and grey matter volumes, and general white matter fractional anisotropy accumulating across the life course. Our findings suggest that living in deprived neighbourhoods across the life course, but especially in mid- to late adulthood, is associated with adverse brain morphologies, with lower social class amplifying the vulnerability.

Effects of a health promotion intervention in a Mexican population with celiac disease / Efectos de una intervención de promoción de salud en población mexicana con enfermedad celíaca / Efeitos de uma intervenção de promoção da saúde numa população mexicana com doença celíaca

Objective: To evaluate the effect of a health promotion care model in adolescents and young adults with Celiac Disease. Method: This is a quasi-experimental study with 152 pretest and 136 posttest participants aged between 15 and 35 years. The data were collected virtually between August and September 2023 through three questionnaires: sociodemographic, the Celiac Symptom Index and the Health Promoter Lifestyle Profile II - Spanish version. The variables were evaluated using the Wilcoxon test, with significance p < 0.05. Results: Regarding the celiac symptom index, statistically significant differences were found with a large effect size, where the pretest scores were higher than the posttest scores (p<0.001). Regarding lifestyle, it was found that health-promoting behaviors presented statistically significant differences with a large effect size; pretest scores were lower than posttest scores (p<.001). Conclusion: Carrying out educational interventions to promote health in people with celiac disease improves their lifestyle and reduces the symptoms of the disease, so the present study confirmed this hypothesis.

Objetivo: Evaluar el efecto de un modelo de cuidado de promoción de salud en adolescentes y adultos jóvenes con Enfermedad Celíaca. Método: Se trata de un estudio cuasiexperimental con 152 participantes pretest y 136 postest con edades comprendidas entre 15 y 35 años. Los datos fueron recolectados de manera virtual entre agosto y septiembre de 2023 a través de tres cuestionarios: sociodemográfico, del Índice de Síntomas Celíacos y del Perfil de estilo de vida Promotor de Salud II - versión en español. Las variables fueron evaluadas mediante la prueba de Wilcoxon, con significancia p < 0,05. Resultados: Con relación al índice de síntomas celíacos, se encontraron diferencias estadísticamente significativas con un tamaño del efecto grande, donde las puntuaciones pretest fueron mayores que las puntuaciones postest (p<0,001). En cuanto al estilo de vida, se encontraron que las conductas promotoras de la salud presentaron diferencias estadísticamente significativas con un tamaño del efecto grande, las puntuaciones pretest fueron inferiores a las puntuaciones postest (p<.001). Conclusión: Realizar intervenciones educativas para promover la salud en personas celíacas mejora su estilo de vida y reduce los síntomas de la enfermedad, por lo que el presente estudio confirmó esta hipótesis.

Objetivo: Avaliar o efeito de um modelo de atenção de promoção da saúde em adolescentes e adultos jovens com Doença Celíaca. Método: Trata-se de um estudo quase-experimental com 152 participantes pré-teste e 136 pós-teste com idades entre 15 e 35 anos. Os dados foram coletados virtualmente entre agosto e setembro de 2023 por meio de três questionários: sociodemográfico, Celiac Symptom Index e Health Promoter Lifestyle Profile II - versão em espanhol. As variáveis ​​foram avaliadas pelo teste de Wilcoxon, com significância p < 0,05. Resultados: Em relação ao índice de sintomas celíacos, foram encontradas diferenças estatisticamente significativas com grande tamanho de efeito, onde os escores do pré-teste foram superiores aos escores do pós-teste (p<0,001). Em relação ao estilo de vida, constatou-se que os comportamentos de promoção da saúde apresentaram diferenças estatisticamente significativas, com um grande tamanho de efeito inferior aos resultados do pós-teste (p<0,001). Conclusão: A realização de intervenções educativas para promoção da saúde em pessoas com doença celíaca melhora o seu estilo de vida e reduz os sintomas da doença, pelo que o presente estudo confirmou esta hipótese.

Impact of long-term white matter hyperintensity changes on mobility and dexterity.

White matter hyperintensities (WMH), a common feature of cerebral small vessel disease, are related to worse clinical outcomes after stroke. We assessed the impact of white matter hyperintensity changes over 1 year after minor stroke on change in mobility and dexterity, including differences between the dominant and non-dominant hands and objective in-person assessment versus patient-reported experience. We recruited participants with lacunar or minor cortical ischaemic stroke, performed medical and cognitive assessments and brain MRI at presentation and at 1 year. At both time points, we used the timed-up and go test and the 9-hole peg test to assess mobility and dexterity. At 1 year, participants completed the Stroke Impact Scale. We ran two linear mixed models to assess change in timed-up and go and 9-hole peg test, adjusted for age, sex, stroke severity (National Institutes of Health Stroke Scale), dependency (modified Rankin Score), vascular risk factor score, white matter hyperintensity volume (as % intracranial volume) and additionally for 9-hole peg test: Montreal cognitive assessment, hand (dominant/non-dominant), National Adult Reading Test (premorbid IQ), index lesion side. We performed ordinal logistic regression, corrected for age and sex, to assess relations between timed-up and go and Stroke Impact Scale mobility, and 9-hole peg test and Stroke Impact Scale hand function. We included 229 participants, mean age 65.9 (standard deviation = 11.13); 66% male. 215/229 attended 1-year follow-up. Over 1 year, timed-up and go time increased with aging (standardized ß [standardized 95% Confidence Interval]: 0.124[0.011, 0.238]), increasing National Institutes of Health Stroke Scale (0.106[0.032, 0.180]), increasing modified Rankin Score (0.152[0.073, 0.231]) and increasing white matter hyperintensity volume (0.176[0.061, 0.291]). Men were faster than women (-0.306[0.011, 0.238]). Over 1 year, slower 9-hole peg test was related to use of non-dominant hand (0.290[0.155, 0.424]), aging (0.102[0.012, 0.192]), male sex (0.182[0.008, 0.356]), increasing National Institutes of Health Stroke Scale (0.160 [0.094, 0.226]), increasing modified Rankin Score (0.100[0.032, 0.169]), decreasing Montreal cognitive assessment score (-0.090[-0.167, -0.014]) and increasing white matter hyperintensity volume (0.104[0.015, 0.193]). One year post-stroke, Stroke Impact Scale mobility worsened per second increase on timed-up and go, odds ratio 0.67 [95% confidence interval 0.60, 0.75]. Stroke Impact Scale hand function worsened per second increase on the 9-hole peg test for the dominant hand (odds ratio 0.79 [0.71, 0.86]) and for the non-dominant hand (odds ratio 0.88 [0.83, 0.93]). Decline in mobility and dexterity is associated with white matter hyperintensity volume increase, independently of stroke severity. Mobility and dexterity declined more gradually for stable and regressing white matter hyperintensity volume. Dominant and non-dominant hands might be affected differently. In-person measures of dexterity and mobility are associated with self-reported experience 1-year post-stroke.

Scientific Output by Latin American Women in Pediatric Surgical Sciences Over the Past 11 Years: A Bibliometric and Visual Analysis.

INTRODUCTION: This academic article discusses the historical underrepresentation of female in science, with a focus on Latin America. It highlights the importance of both technical and non-technical skills in the medical-surgical field, particularly the role of research skills. The study aims to quantify and characterize the scientific output of Latin American female researchers over the past decade, providing insights into the challenges and opportunities in low and middle-income countries. MATERIAL AND METHODS: A retrospective cross-sectional bibliometric study was conducted in 2023, focusing on pediatric surgical science journals in Scopus and PubMed. It assessed Latin American female participation, journal details, and interaction networks, using SPSS and Gephi software. The period analyzed was from January 2012 to December 2022. RESULTS: Between 2012 and 2022, 727 articles with Latin authorship in pediatric surgery were analyzed across 304 journals. Of these, 63.69% had female co-authors. The majority were original articles (53.13%), with contributions from Brazil, Mexico, and Chile. Notable journals included the Journal of Pediatric Surgery and Child's Nervous System. Keywords like Laparoscopy and Cardiac surgery were common. A growth trend in female Latin American publications was observed, despite temporary declines. CONCLUSIONS: This study highlights a growing trend in Latin American females' scientific contributions to pediatric surgery from 2012 to 2022, although a gender gap persists. The research mainly consists of primary data studies, with a focus on Brazil and Mexico from public institutions. The Journal of Pediatric Surgery featured prominently, and common topics included Laparoscopy, Cardiac surgery, Liver transplant, Congenital heart defects, and COVID-19. LEVEL OF EVIDENCE: IV.

Differential risk factor profile and neuroimaging markers of small vessel disease between lacunar ischemic stroke and deep intracerebral hemorrhage.

Background: Lacunar ischemic stroke (LIS) and deep intracerebral hemorrhage (dICH) are two stroke phenotypes of deep perforator arteriopathy. It is unclear what factors predispose individuals with deep perforator arteriopathy to either ischemic or hemorrhagic events. Objectives: We aimed to investigate risk factors and neuroimaging features of small vessel disease (SVD) associated with LIS versus dICH in a cross-sectional study. Methods: We included patients with clinically presenting, magnetic resonance imaging-confirmed LIS or dICH from two tertiary hospitals between 2010 and 2021. We recorded vascular risk factors and SVD markers, including lacunes, white matter hyperintensities (WMH), perivascular spaces (PVS), and cerebral microbleeds (CMB). Logistic regression modeling was used to determine the association between vascular risk factors, SVD markers, and stroke phenotype. We further created WMH probability maps to compare WMH distribution between LIS and dICH. Results: A total of 834 patients with LIS (mean age 61.7 ± 12.1 years) and 405 with dICH (57.7 ± 13.2 years) were included. Hypertension was equally frequent between LIS and dICH (72.3% versus 74.8%, p = 0.349). Diabetes mellitus, hyperlipidemia, smoking, and prior ischemic stroke were more associated with LIS [odds ratio (OR) (95% confidence interval (CI)), 0.35 (0.25-0.48), 0.32 (0.22-0.44), 0.31 (0.22-0.44), and 0.38 (0.18-0.75)]. Alcohol intake and prior ICH were more associated with dICH [OR (95% CI), 2.34 (1.68-3.28), 2.53 (1.31-4.92)]. Lacunes were more prevalent in LIS [OR (95% CI) 0.23 (0.11-0.43)], while moderate-to-severe basal-ganglia PVS and CMB were more prevalent in dICH [OR (95% CI) 2.63 (1.35-5.27), 4.95 (2.71-9.42)]. WMH burden and spatial distribution did not differ between groups. Conclusion: The microangiopathy underlying LIS and dICH reflects distinct risk profiles and SVD features, hence possibly SVD subtype susceptibility. Prospective studies with careful phenotyping and genetics are needed to clarify the mechanisms underlying this difference.

Testosterone Enhances KV Currents and Airway Smooth Muscle Relaxation Induced by ATP and UTP through P2Y4 Receptors and Adenylyl Cyclase Pathway.

Numerous studies suggest the involvement of adenosine-5'-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5'-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y2 and P2Y4 receptors and K+ channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K+ (KV) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K+ channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K+ currents, and this effect was abolished with flutamide (an androgen receptor antagonist). KV channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y2), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K+ currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y4 receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of KV1.2 and KV1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y4 signaling and KV channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males.

Chamaecyparis lawsoniana and Its Active Compound Quercetin as Ca2+ Inhibitors in the Contraction of Airway Smooth Muscle.

The Cupressaceae family includes species considered to be medicinal. Their essential oil is used for headaches, colds, cough, and bronchitis. Cedar trees like Chamaecyparis lawsoniana (C. lawsoniana) are commonly found in urban areas. We investigated whether C. lawsoniana exerts some of its effects by modifying airway smooth muscle (ASM) contractility. The leaves of C. lawsoniana (363 g) were pulverized mechanically, and extracts were obtained by successive maceration 1:10 (w:w) with methanol/CHCl3. Guinea pig tracheal rings were contracted with KCl, tetraethylammonium (TEA), histamine (HIS), or carbachol (Cch) in organ baths. In the Cch experiments, tissues were pre-incubated with D-600, an antagonist of L-type voltage-dependent Ca2+ channels (L-VDCC) before the addition of C. lawsoniana. Interestingly, at different concentrations, C. lawsoniana diminished the tracheal contractions induced by KCl, TEA, HIS, and Cch. In ASM cells, C. lawsoniana significantly diminished L-type Ca2+ currents. ASM cells stimulated with Cch produced a transient Ca2+ peak followed by a sustained plateau maintained by L-VDCC and store-operated Ca2+ channels (SOCC). C. lawsoniana almost abolished this last response. These results show that C. lawsoniana, and its active metabolite quercetin, relax the ASM by inhibiting the L-VDCC and SOCC; further studies must be performed to obtain the complete set of metabolites of the extract and study at length their pharmacological properties.

Non-hiatal diaphragmatic hernias: results of transabdominal and transthoracic surgical approaches at a fourth-level hospital.

OBJECTIVE: The objective of this study is to elucidate the clinical and demographic profiles, as well as perioperative outcomes, of patients undergoing surgery for non-hiatal diaphragmatic hernias. Additionally, it aims to analyse these outcomes based on the surgical approach employed (transthoracic versus transabdominal). METHODS: This retrospective, observational study was conducted at a single center and involved patients diagnosed with non-hiatal diaphragmatic hernia who underwent either emergency or elective surgery between July 2007 and March 2023. Clinical characteristics and perioperative outcomes of these patients were compared using appropriate statistical tests.The research protocol for this observational, retrospective, and comparative study followed the Declaration of Helsinki's ethical requirements. The need for Clinical Research Ethics Committee approval was waived according to our institutional law because the study was a retrospective cohort study based on anonymous data of patients. Informed consent was waived because this study involved the secondary analysis of patient medical records. Additionally, this study followed the STROBE guidelines for reporting observational studies. RESULTS: The analysis included 22 patients being 59.1% men, with median age of 61 years. The predominant clinical presentation was restrictive lung disease (40.9%). The majority of cases (68%) had traumatic aetiology with a median defect size of 4 cm (range of 3-8 cm). Elective surgery was performed in 15 cases (68.1%) and transthoracic approach was employed in 13 patients (54.5%). Postoperative major morbidity reached 27.2% and mortality within 30 days was 9.1%. Emergency surgeries accounted for 44.4% of transabdominal interventions, compared to 23% in the transthoracic subgroup (p = 0.376). There were no statistically significant differences between the transabdominal and trasnthoracic approaches in terms of global postoperative complications (88.8% vs. 84.6%, p = 1), major complications (44.4% vs 15.4%, p = 0.734), mortality (11.1% v 7.6%, p = 1) and recurrence (11.1% vs 7.6%, p = 1). Postoperative stay was significantly shorter in the transthoracic subgroup (6 days vs. 14 days, p = 0.011). CONCLUSIONS: Non-hiatal diaphragmatic hernias are characterized by significant postoperative major morbidity and mortality rates, standing at 27.2% and 9.1%, respectively, accompanied by a recurrence rate of 9.1%. Both transthoracic and transabdominal approaches demonstrate comparable short- and long-term outcomes.

Effect of UV-C disinfection and copper plating on healthcare-associated infections in a NICU with high ESBL infections.

INTRODUCTION: Healthcare-associated infections (HCAIs) in neonates are frequent and highly lethal, in particular those caused by extended spectrum beta-lactamase (ESBL) producing bacteria. We evaluated the beneficial effects of ultraviolet C (UV-C) disinfection and copper adhesive plating on HCAIs in the Neonatal Intensive Care Unit (NICU) of a third level paediatric hospital in Mexico City, both in combination of hand-hygiene (HH) and prevention bundles. METHODS: All NICU patients were included. There were 4 periods (P): P1: HH monitoring and prevention bundles; P2: P1+UV-C disinfection; P3: P2+Copper adhesive plating on frequent-contact surfaces and P4: Monitoring of P3 actions. RESULTS: 552 neonates were monitored during 15,467 patient days (PD). HCAI rates decreased from 11.03/1000 PD in P1 to 5.35/1000 PD in P4 (p=0.006). HCAIs with bacterial isolates dropped from 5.39/1000 PD in PI to 1.79/1000 PD in P4 (p=0.011). UV-C and copper were associated with significant HCAI prevention (RR 0.49, CI95% 0.30-0.81, p=0.005) and with lesser HCAIs with bacterial isolates (RR 0.33, CI95% 0.14-0.77, p=0.011). CONCLUSIONS: Copper adhesive plating combined with UV-C disinfection were associated with a drop in HCAI rates and with the elimination of ESBL-caused HCAIs. Hence, we propose that these strategies be considered in MDRO proliferation preventions.