Development of a dispersive solid phase microextraction method based on the application of MgAl, NiAl, and CoAl-layered double hydroxides for the efficient removal of α- and ß-naphthol isomers from water samples by capillary electrophoresis.

The present work describes a quick, simple, and efficient method based on the use of layered double hydroxides (LDH) coupled to dispersive solid phase micro-extraction (DSPME) to remove α-naphthol (α-NAP) and ß-naphthol (ß-NAP) isomers from water samples. Three different LDHs (MgAl-LDH, NiAl-LDH, and CoAl-LDH) were used to study how the interlayer anion and molar ratio affected the removal performance. The critical factors in the DSPME procedure (pH, LDH amount, contact time) were optimized by the univariate method under the optimal conditions: pH, 4-8; LDH amount, 5 mg; and contact time, 2.5 min. The method can be successfully applied in real sample waters, removing NAP isomers even in ultra-trace concentrations. The large volume sample stacking (LVSS-CE) technique provides limits of detections (LODs) of 5.52 µg/L and 6.36 µg/L for α-naphthol and ß-naphthol, respectively. The methodology's precision was evaluated on intra- and inter-day repeatability, with %RSD less than 10% in all cases. The MgAl/Cl--LDH selectivity was tested in the presence of phenol and bisphenol A, with a removal rate of >92.80%. The elution tests suggest that the LDH MgAl/Cl--LDH could be suitable for pre-concentration of α-naphthol and ß-naphthol in future works.

First-line PARP inhibitor maintenance treatment in ovarian carcinoma for older adult women: a review of the current literature.

Ovarian cancer (OC) is the leading cause of death in women with gynecological cancers. Its diagnosis is more likely in advanced ages, with the older population being the most seen in consultations. Poly(ADP-ribose) inhibitors (PARPi) have changed OC clinical practice and evolution, showing great benefit. However, there is a lack of evidence of PARPi in elderly population that can impact the therapeutic decision and the safety/efficacy. It is necessary to avoid age as limiting factor in PARPis prescription. We conducted a review of the most relevant randomized phase III trials of maintenance PARPi after first-line treatment of advanced OC. We observed the lack of a single criterion for considering older patients, varying among trials. There is a benefit of PARPis in different populations. However, PARPi effect on quality of life is not reported, something of great relevance considering their vulnerability. Measures are needed to benefit older patients to better adapt PARPi treatment.

Comparison of Ten Surrogate Insulin Resistance and Obesity Markers to Identify Metabolic Syndrome in Mexican Adults.

Metabolic syndrome (MetS) is a group of clinical traits directly linked to type 2 diabetes mellitus and cardiovascular diseases, whose prevalence has been rising nationally and internationally. We aimed to evaluate ten known and novel surrogate markers of insulin resistance and obesity to identify MetS in Mexican adults. The present cross-sectional study analyzed 10575 participants from ENSANUT-2018. The diagnosis of MetS was based on the Adult Treatment Panel III (ATP III) criteria and International Diabetes Federation (IDF) criteria, stratified by sex and age group. According to ATP III, the best biomarker was the metabolic score for insulin resistance (METS-IR) in men aged 20-39 and 40-59 years and lipid accumulation product (LAP) in those aged ≥60 years. The best biomarker was LAP in women aged 20-39 and triglyceride-glucose index (TyG) in those aged 40-59 and ≥60 years. Using the IDF criteria, the best biomarker was LAP in men of all ages. TyG gave the best results in women of all ages. The best biomarker for diagnosis of MetS in Mexican adults depends on the criteria, including sex and age group. LAP and TyG are easy to obtain, inexpensive, and especially useful at the primary care level.

May Measurement Month 2021: an analysis of blood pressure screening results from Venezuela.

Cardiovascular diseases continue to be the main cause of death in Venezuela, and hypertension is the principal risk factor. The May Measurement Month (MMM) campaign is a global initiative aimed to raising awareness of hypertension, which has been conducted in Venezuela since 2017. May Measurement Month 2021 included 46 732 participants with a mean age of 56.4 years (SD 14.4), 57.9% of whom were female. The percentage with hypertension was 60.3% (57.9% of females and 63.7% of males), 82.3% (84.8% of females and 79.2% of males) were aware, and 80.2% were taking antihypertensive medication. Of those on antihypertensive medication, 44.2% (41.2% of females and 48.2% of males) were not controlled [blood pressure (BP) ≥ 140/≥90 mmHg], with 61.3% receiving one drug, 30.0% two drugs, and 8.7% three or more drugs. 87.5% of those on treatment reported taking it regularly. Conditions associated with higher BP levels include fewer years of education, having a previous diagnosis of hypertension, and women who were hypertensive during a previous pregnancy. Physical activity and pregnancy were conditions associated with lower BP levels. A previous positive COVID-19 test was reported in 11.1%, and one or more COVID-19 vaccinations reported in 22.7% of participants. Of those on antihypertensive medication, 78.8% reported their treatment was not affected by COVID-19. Results are consistent with previous MMM campaigns and indicate that the screening campaign is feasible and useful to identify hypertension even in exceptional conditions such as the COVID-19 pandemic.

Adipose Tissue Dysfunction and the Role of Adipocyte-Derived Extracellular Vesicles in Obesity and Metabolic Syndrome.

Obesity is a major public health issue that is associated with metabolic diseases including diabetes mellitus type 2 and metabolic syndrome. This pathology leads to detrimental cardiovascular health and secondary effects, such as lipotoxicity, inflammation, and oxidative stress. Recently, extracellular vesicles (EVs) have been highlighted as novel players participating in human physiology and pathophysiology. In obesity, adipose tissue is related to the active shedding of adipocyte-derived extracellular vesicles (AdEVs). The current review explores and highlights the role of AdEVs and their cargo in obesity and metabolic syndrome. AdEVs are proposed to play an important role in obesity and its comorbidities. AdEVs are biological nanoparticles mainly shed by visceral and subcutaneous adipose tissue, acting in physiological and pathophysiological conditions, and also carrying different cargo biomolecules, such as RNA, microRNA (miRNA), proteins, and lipids, among others. RNA and miRNA have local and systemic effects affecting gene expression in target cell types via paracrine and endocrine actions. State of the art analyses identified some miRNAs, such as miR-222, miR-23b, miR-4429, miR-148b, and miR-4269, that could potentially affect cell pathways involved in obesity-related comorbidities, such as chronic inflammation and fibrosis. Similarly, AdEVs-proteins (RBP4, perilipin-A, FABP, mimecan, TGFBI) and AdEVs-lipids (sphingolipids) have been linked to the obesity pathophysiology. The current knowledge about AdEVs along with further research would support and reveal novel pathways, potential biomarkers, and therapeutic options in obesity.

Clinical Characteristics of Ocular Mucous Membrane Pemphigoid: A Systematic Review and Meta-Analysis.

PURPOSE: To synthesize the evidence and generate a combined weighted measure on the frequency of ocular manifestations of mucous membrane pemphigoid (OMMP). METHODS: Systematic literature review and meta-analysis, searching PubMed, Embase, VHL, and Google Scholar. Articles reporting patients with mucous membrane pemphigoid and ocular involvement were included. At least, two reviewers independently and in parallel participated in all the following phases; preliminary screening, full-text review, risk of bias assessment by validated tools, and data extraction. Qualitative analysis and meta-analysis were conducted. This study was previously registered in PROSPERO (CRD42023451844). RESULTS: Thirty-five studies met the inclusion criteria, comprising 1,439 patients and 1,040 eyes summarized in qualitative analysis. Twenty-eight studies were included in the meta-analysis. Ages included ranged from 60.4 to 75 years. Women were reported with more frequency. The mean time for diagnosis was 55.1 months, usually with bilateral ocular disease in 90% (95% CI 78%; 96%). Trichiasis and entropion were the most frequent manifestations in up to 92%, followed by symblepharon and punctate keratitis. Ankyloblepharon, persistent epithelial defects, and visual impairment were less frequent complications. Direct immunofluorescence positivity in conjunctival biopsies was 54% (95% CI 43%; 64%). Extraocular involvement was highly frequent, being oral and skin involvement the most frequently reported. CONCLUSIONS: Our systematic review and meta-analysis evidenced that patients around 60 years of age are the most affected population with a female preponderance, usually with bilateral ocular involvement. Trichiasis and entropion were the most frequent findings; although visual impairment and persistent epithelial defects were less reported, they should not be overlooked in suspected OMMP.

Metal(loid) bioaccessibility and risk assessment of ashfall deposit from Popocatépetl volcano, Mexico.

Ash emission from volcanic eruptions affects the environment, society, and human health. This study shows the total concentration and lung bioaccessible fraction of eight potential toxic metal(loid)s in five Popocatépetl ashfall samples. Mineralogical phases and particle size distribution of the ashfall were analyzed by X-ray diffraction (XRD) and Scanning Electron Microscope (SEM) techniques, respectively. The bioaccessibility test of Gamble solution (GS) and Artificial Lysosomal Fluid (ALF) were conducted to simulate extracellular (pH 7) and intracellular (pH 4.5) conditions, respectively. The studied metal(loid)s showed the following total concentration (mg kg-1): 1.98 (As), 0.17 (Cd), 134.09 (Cr), 8.66 (Cu), 697.33 (Mn), 55.35 (Ni), 8.77 (Pb), and 104.10 (Zn). Geochemical indices suggested that some metal(loid)s are slightly enriched compared to the local soil background concentrations. Several mineralogical phases were identified in the collected ashfall deposits, such as plagioclase, pyroxene, and Fe-Ti oxide, among others. According to the risk assessment results, the non-carcinogenic risk related to ashfall exposure returns an HQ > 1 for children. In contrast, the estimation of carcinogenic risk was found to be within the tolerable limit. Metal(loid)s showed low bioaccessibility (< 30%) in GS and ALF, with the highest values found in ALF solution for As (12.18%) and Cu (7.57%). Despite their metal-bioaccessibility, our findings also showed that dominant ash particle size ranged between fine (< 2.5 µm) and extremely fine (< 1 µm), considered highly inhalable fractions. The results obtained in this work indicate that volcanic ashes are bioinsoluble and biodurable, and exhibit low bioaccessibility when in contact with lung human fluids.

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.

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.

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.

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.

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.

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.

Diagnostic support in pediatric craniopharyngioma using deep learning.

PURPOSE: We studied a pediatric group of patients with sellar-suprasellar tumors, aiming to develop a convolutional deep learning algorithm for radiological assistance to classify them into their respective cohort. METHODS: T1w and T2w preoperative magnetic resonance images of 226 Chilean patients were collected at the Institute of Neurosurgery Dr. Alfonso Asenjo (INCA), which were divided into three classes: healthy control (68 subjects), craniopharyngioma (58 subjects) and differential sellar/suprasellar tumors (100 subjects). RESULTS: The PPV among classes was 0.828±0.039, and the NPV was 0.919±0.063. Also explainable artificial intelligence (XAI) was used, finding that structures that are relevant during diagnosis and radiological evaluation highly influence the decision-making process of the machine. CONCLUSION: This is the first experience of this kind of study in our institution, and it led to promising results on the task of radiological diagnostic support based on explainable artificial intelligence (AI) and deep learning models.

Evaluation of Increasing Dietary Concentrations of a Multi-Enzyme Complex in Feedlot Lambs' Rations.

The objective of this study was to evaluate the effects of increasing levels of the M-E complex (xylanase, glucanase, cellulase, and invertase) Optimax E® on the performance of growing lambs, their digestibility, and their rumen microbiota, and to estimate NEm, NEg, and ruminal methane levels. Forty lambs (Katahdin x Dorset; 22.91 ± 4.16 kg) were randomly assigned to dietary concentrations of ME (0, 0.2, 0.4, and 0.8% DM) and fed individually for 77 days. Increasing M-E improved feed conversion (p < 0.05) as well as NEm and NEg (p < 0.05), which were associated with increased in vivo DM and NDF digestion (linear and quadratic p < 0.01). Few microbial families showed abundancy changes (Erysipelotrichaceae, Christensenellaceae, Lentisphaerae, and Clostridial Family XIII); however, the dominant phylum Bacteroidetes was linearly reduced, while Firmicutes increased (p < 0.01), resulting in a greater Firmicutes-to-Bacteroidetes ratio. Total Entodinium showed a quadratic response (p < 0.10), increasing its abundancy as the enzyme dose was augmented. The daily emission intensity of methane (per kg of DMI or AGD) was reduced linearly (p < 0.01). In conclusion, adding the M-E complex Optimax E® to growing lambs' diets improves their productive performance by acting synergistically with the rumen microbiota, modifying the Firmicutes-to-Bacteroidetes ratio toward more efficient fermentation, and shows the potential to reduce the intensity of greenhouse gas emissions from lambs.

Changes in EEG Activity and Cognition Related to Physical Activity in Older Adults: A Systematic Review.

Aging is generally associated with a decline in important cognitive functions that can be observed in EEG. Physical activity in older adults should be considered one of the main strategies to promote health and prevent disease in the elderly. The present study aimed to systematically review studies of EEG activity and cognitive function changes associated with physical activity in older adults. Records from PubMed, Scopus, and EBSCO databases were searched and, following the PRISMA guidelines, nine studies were included in the present systematic review. A risk of bias assessment was performed using the National Institute of Health Quality Assessment Tool for Case-control Studies instrument. The studies analyzed used two main strategies to determine the effects of physical activity on cognition and EEG: (1) multiscale entropy and power frequencies; and (2) event-related potentials. In terms of EEG activity, it can be concluded that exercise-induced neuroplasticity underlies improvements in cognitive function in healthy older adults.

Asociación entre metaplasia, displasia y cáncer de vesícula biliar en una EPS de Bogotá, Colombia / Association between metaplasia, dysplasia and gallbladder cancer in an EPS in Bogotá, Colombia

Introducción. El cáncer de vesícula biliar es el más común en el tracto biliopancreático y una importante causa de mortalidad. La metaplasia y la displasia han sido mencionados como probables precursores relacionados con la secuencia metaplasia-displasia-cáncer. El objetivo de este estudio fue establecer las posibles asociaciones entre estas alteraciones histopatológicas y su relación con la edad y el sexo de los pacientes. Métodos. Estudio observacional retrospectivo descriptivo, con un componente analítico de corte transversal. Se incluyeron los informes de patología de pacientes llevados a colecistectomía laparoscópica electiva y ambulatoria, entre enero de 2015 y diciembre de 2020, con colecistitis crónica, colelitiasis o pólipos vesiculares, mayores de 18 años. Se describieron las características demográficas por sexo y edad utilizando medias, desviaciones estándar y porcentajes. Se emplearon la prueba de chi cuadrado y la prueba exacta de Fisher para evaluar la asociación entre las variables cualitativas. Resultados. Se incluyeron 4871 informes de patología. En esta cohorte se encontró asociación estadísticamente significativa entre metaplasia, displasia y cáncer de vesícula (p<0,05), al igual que con el sexo y la edad de los pacientes. Conclusiones. Los resultados sugieren una asociación entre metaplasia, displasia y cáncer de vesícula biliar en la población estudiada. Se recomienda la realización de investigaciones complementarias para definir la posible causalidad entre metaplasia, displasia y cáncer de vesícula biliar en una población más heterogénea.

Introduction. Gallbladder cancer is the most common cancer in the biliopancreatic tract and an important cause of mortality. Metaplasia and dysplasia have been mentioned as probable precursors related to the metaplasia-dysplasia-cancer sequence. The objective of this study was to establish the possible associations between these histopathological alterations and their relationship with the age and sex of the patients. Methods. Descriptive retrospective observational study, with a cross-sectional analytical component. Pathology reports of patients undergoing elective and outpatient laparoscopic cholecystectomy were included between January 2015 and December 2020, with chronic cholecystitis, cholelithiasis, or gallbladder polyps, over 18 years of age. Demographic characteristics by sex and age was performed using means, standard deviations, and percentages. The chi2 test and Fisher's exact test were used to evaluate the association between the qualitative variables. Results. 4871 pathology reports were included. In this cohort, a statistically significant association was found between metaplasia, dysplasia, and gallbladder cancer (p<0.05), as well as with the sex and age of the patients. Conclusions. The results suggest an association between metaplasia, dysplasia and gallbladder cancer in the study population. Additional research is recommended to define the possible causality between metaplasia, dysplasia, and gallbladder cancer in a more heterogeneous population.

Genetic diversity of P1/pathogenic Leptospira species hosted by bats worldwide.

INTRODUCTION: Bats are a diverse group of mammals that have unique features allowing them to act as reservoir hosts for several zoonotic pathogens such as Leptospira. Leptospires have been classified into pathogenic, intermediate, and saprophytic groups and more recently into clades P1, P2, S1, and S2, being all the most important pathogenic species related to leptospirosis included within the P1/pathogenic clade. Leptospira has been detected from bats in several regions worldwide; however, the diversity of leptospires harboured by bats is still unknown. AIM: The aim of the present study was to determine the genetic diversity of Leptospira spp. harboured by bats worldwide. METHODS: A systematic review was conducted on four databases to retrieve studies in which Leptospira was detected from bats. All studies were screened to retrieve all available Leptospira spp. 16S rRNA sequences from the GenBank database and data regarding their origin. Sequences obtained were compared with each other and reference sequences of Leptospira species and analysed through phylogenetic analysis. RESULTS: A total of 418 Leptospira spp. 16S rRNA sequences isolated from 55 bat species from 14 countries were retrieved from 15 selected manuscripts. From these, 417 sequences clustered within the P1/pathogenic group, and only one sequence clustered within the P2/intermediate group. Six major clades of P1/pathogenic Leptospira spp. were identified, three of them composed exclusively of sequences obtained from bats. CONCLUSION: We identified that bats harbour a great genetic diversity of Leptospira spp. that form part of the P1/pathogenic clade, some of which are closely related to leptospirosis-associated species. This finding contributes to the knowledge of the diversity of leptospires hosted by bats worldwide and reinforces the role of bats as reservoirs of P1/pathogenic Leptospira spp.

TRPV4 Activation during Guinea Pig Airway Smooth Muscle Contraction Promotes Ca2+ and Na+ Influx.

Airway smooth muscle (ASM) contraction is determined by the increase in intracellular Ca2+ concentration ([Ca2+]i) caused by its release from the sarcoplasmic reticulum (SR) or by extracellular Ca2+ influx. Major channels involved in Ca2+ influx in ASM cells are L-type voltage-dependent Ca2+ channels (L-VDCCs) and nonselective cation channels (NSCCs). Transient receptor potential vanilloid 4 (TRPV4) is an NSCC recently studied in ASM. Mechanical stimuli, such as contraction, can activate TRPV4. We investigated the possible activation of TRPV4 by histamine (His)- or carbachol (CCh)-induced contraction in guinea pig ASM. In single myocytes, the TRPV4 agonist (GSK101) evoked an increase in [Ca2+]i, characterized by a slow onset and a plateau phase. The TRPV4 antagonist (GSK219) decreased channel activity by 94%, whereas the Ca2+-free medium abolished the Ca2+ response induced by GSK101. Moreover, GSK101 caused Na+ influx in tracheal myocytes. GSK219 reduced the Ca2+ peak and the Ca2+ plateau triggered by His or CCh. TRPV4 blockade shifted the concentration-response curve relating to His and CCh to the right in tracheal rings and reduced the maximal contraction. Finally, the activation of TRPV4 in single myocytes increased the Ca2+ refilling of the SR. We conclude that contraction of ASM cells after stimulation with His or CCh promotes TRPV4 activation, the subsequent influx of Ca2+ and Na+, and the opening of L-VDCCs. The entry of Ca2+ into ASM cells via TRPV4 and L-VDCCs contributes to optimal smooth muscle contraction.