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The ependyma lining the third ventricle (3V) in the mediobasal hypothalamus plays a crucial role in energy balance and glucose homeostasis. It is characterized by a high functional heterogeneity and plasticity, but the underlying molecular mechanisms governing its features are not fully understood. Here, 5481 hypothalamic ependymocytes were cataloged using FACS-assisted scRNAseq from fed, 12h-fasted, and 24h-fasted adult male mice. With standard clustering analysis, typical ependymal cells and ß2-tanycytes appear sharply defined, but other subpopulations, ß1- and α-tanycytes, display fuzzy boundaries with few or no specific markers. Pseudospatial approaches, based on the 3V neuroanatomical distribution, enable the identification of specific versus shared tanycyte markers and subgroup-specific versus general tanycyte functions. We show that fasting dynamically shifts gene expression patterns along the 3V, leading to a spatial redistribution of cell type-specific responses. Altogether, we show that changes in energy status induce metabolic and functional switches in tanycyte subpopulations, providing insights into molecular and functional diversity and plasticity within the tanycyte population.
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Células Ependimogliais , Jejum , Metabolismo dos Lipídeos , Neurônios , Animais , Células Ependimogliais/metabolismo , Masculino , Jejum/metabolismo , Camundongos , Neurônios/metabolismo , Epêndima/metabolismo , Epêndima/citologia , Hipotálamo/metabolismo , Hipotálamo/citologia , Camundongos Endogâmicos C57BL , Metabolismo Energético , Terceiro Ventrículo/metabolismo , Glucose/metabolismoRESUMO
Molecular cages are three-dimensional supramolecular structures that completely wrap guest molecules by encapsulation. We describe a rare comparative study between a metallo-organic cage and a fully organic analogous system, obtained by hydrazone bond formation self-assembly. Both cages are able to encapsulate the anticancer drug doxorubicin, with the organic cage forming a 1 : 1 inclusion complex with µM affinity, whereas the metallo-organic host experiences disassembly by interaction with the drug. Stability experiments reveal that the ligands of the metallo-organic cage are displaced in buffer at neutral, acidic, and basic pH, while the organic cage only disassembles under acidic conditions. Notably, the organic cage also shows minimal cell toxicity, even at high doses, whilst the doxorubicin-cage complex shows in vitro anti-cancer activity. Collectively, these results show that the attributes of the pure organic molecular cage are suitable for the future challenges of in vivo drug delivery using molecular cages.
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This work proposes for the first time protecting-reflecting on both sides of plated mirrors and a solution to polycarbonate surface vulnerability to weathering and scratching using tungsten disulfide (WS2) by mechanical polishing. The ability of the dynamic chemical plating (DCP) technique to deposit Ag films at the nanometer scale on a polycarbonate (PC) substrate and its characteristics to be metallized is also shown. These deposits hold significant promise for concentrated solar power (CSP) applications. Complementarily, the application of WS2 as a reflective film for CSP by mechanical polishing on smooth polycarbonate surfaces is both novel and practical. This technique is innovative and scalable without needing reactants or electrical potential, making it highly applicable in real-world scenarios, including, potentially, on-site maintenance. The effects of surface morphology and adhesion, and the reflectivity parameters of the silver metallic surfaces were investigated. Wettability was investigated because it is important for polymeric surfaces in the activation and metal deposition immediately after redox reactions. The flame technique improved wettability by modifying the surface with carbonyl and carboxyl functional groups, with PC among the few industrial polymers that resisted such a part of the process. The change in the chemical composition, roughness, and wettability of the surfaces effectively improved the adhesion between the Ag film and the PC substrate. However, it did not significantly affect the adhesion between PC and WS2 and showed its possible implementation as a first surface mirror. Overall, this work provides a scalable, innovative method for improving the durability and reflectivity of polycarbonate-based mirrors, with significant implications for CSP applications.
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The creation of complex hollow nanostructures with precise control over size and shape represents a great challenge in supramolecular soft materials. Here, we have further developed a bioinspired methodology for the formation of aqueous nanotubes of well-defined dimensions and pore coating through the self-assembly of amphiphiles that are chemically programmed with complementary nucleobases. These nanotubes are endowed with a hydrophobic lumen, whose diameter can be expanded as a function of the monomer length, in which apolar dyes can be efficiently encapsulated.
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BACKGROUND: Parents are the primary decision makers for their children's vaccination, yet, we have limited knowledge on what influences their decision making related to COVID-19 vaccination. The study aimed to understand these different considerations that shape the decisions of parents of children aged 5-11 years old. METHODS: We conducted a qualitative study that included online focus group discussions (FGDs) with parents of children aged 5-11 years old. Data was collected between July 26th, 2022, and February 15th, 2023. A total of eight FGDs were conducted, audio-recorded and transcribed verbatim. Thematic analysis was conducted, and peer debriefing was used to ensure methodological rigor. RESULTS: Findings revealed that parents of vaccinated and unvaccinated children employed language of risk-benefit analysis to inform their decision-making. Parents of vaccinated children highlighted concerns about spreading COVID-19, family member's health, and long COVID-19. For parents of unvaccinated children, they perceived potential vaccine side effects as more harmful than the risks associated with COVID-19. Participants contended that there was a lack of transparency from the government and public health agencies, highlighting inconsistent messaging which had fractured their trust in COVID-19-related recommendations and mandates. CONCLUSIONS: Our results indicate that improved transparency on how evidence is developed and why recommendations and mandates shift during the pandemic would foster trust in the government and public health agencies. Open communication with health providers on the potential risks and benefits would also improve caregivers confidence in the vaccine.
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Cuticular hydrocarbon (CHCs) variation has been detected in various insect taxa, but the potential contribution of cuticular compounds for analyzing intraspecific diversity at the population level has been little explored. Here we assess for the first time intraspecific variation in the CHC profile of stingless bees, using the species Melipona beecheii and Nannotrigona perilampoides. The objective is determining whether intraspecific variation can be useful for population identification. We found species-specific chemical patterns and extensive variation within each species. Notably, chemotypes were significantly associated to geographic origin in N. perilampoides but less so in M. beecheii and we discuss possible explanations for these patterns. Our results support the use of CHCs in conjunction with other methods in emerging problems such as undetected colony mobilization across regions. As CHCs are involved in several aspects of stingless bee recognition and interactions, it would be essential to unravel how these chemical signatures evolve across populations.
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Hidrocarbonetos , Animais , Abelhas/metabolismo , Hidrocarbonetos/análise , Hidrocarbonetos/metabolismo , Especificidade da EspécieRESUMO
BACKGROUND: Infection is a leading cause of total joint arthroplasty failure. In previous studies, we found correlations between the level of contamination, concentrations of airborne particles, and the number of staff present. In this study, we focused on the apparel of nonscrubbed operating room (OR) staff to elucidate their contribution to the airborne microbial load. METHODS: We compared hospital-laundered scrubs to disposable coveralls using 2 methods. (1) Participants entered an isolation chamber with a controlled environment and completed tasks for 1 hour wearing both the approved and alternative OR attire. Settle plates collected viable contaminants that were shed by the participants during testing. (2) Lab members conducted standardized maneuvers in a functional OR that simulated typical movements of the nurse, anesthesiologist, implant representative, and entering/exiting staff. An airborne particle counter and settle plates were positioned throughout the OR. After 1 hour, the staff changed apparel and repeated the test. Each session of both phases consisted of 2 tests by the same individuals on the same day. RESULTS: There was approximately a 10-fold difference in the settlement rate of viable particles between groups when employing the isolation chamber. The settle rate for scrubs was 5,519 ± 1,381 colony forming units (CFUs)/m2/h, while the settle rate for coveralls was 505 ± 55 CFUs/m2/h (P = .008). During testing in the OR, 218.7 ± 35 CFUs/m2/h were captured for scrubs, compared with 50.5 ± 13 CFUs/m2/h for the coverall (P < .01). The concentration of airborne particles collected for scrubs was 4,952.1 ± 495 particles/m3 and 1,065 ± 53 particles/m3 for the coveralls (P < .01). This was a 77% and 79% reduction for both measures, respectively. CONCLUSIONS: The open nature of standard scrubs allows contaminated particles to escape into the OR environment, whereas the one-piece design of the coveralls restricts pathways of escape. The results of this study may be helpful when developing hospital infection prevention policies.
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Lightning strikes, a prominent meteorological event, pose a significant risk of triggering technological disruptions within the process industry. To better understand this phenomenon, an analysis focused on past lightning-triggered events was carried out, examining open-source industrial-accident databases to compile a new NaTech-driven dataset of 689 records. First, an overall quantitative analysis revealed that over 80 % of these events involved incidents or loss of containment. Notably, 83.3 % of them occurred during the spring and summer, indicating a seasonal pattern. Based on the frequency of functional attributes, the chemical and petrochemical macro-sector was the most vulnerable, followed by storage and warehousing. About 40 % of all classifiable events happened on storage equipment, while 21 % happened on electric and electronic devices. Given the lack of valuable information for the principal source of data (NRC), the technological scenarios triggered were characterized using a refined subset of 127 observations, obtained considering the "other sources" of data. Fire scenarios predominated at 56 %; coincidentally, roughly 70 % of all scenarios involved hazardous substances classified as physical hazards. Estimated losses for the available information underscored the adverse consequences of lightning-triggered NaTech events, highlighting their major impact on both safety and the environment. An analysis of the event tree showed the logical path from the lightning strike to the final ignition scenarios (considering a subset of 107 records). This path accounted for 36 % of the classifiable records that directly affected the structure, while more than 50 % of them did not. Bayesian network structures made it possible to get conditional probabilities from the event tree and improved the model by adding attributes for vulnerable equipment and macro-sectors. In order to deal with the uncertain data, algorithms were used to generalize the models that were obtained from smaller subsets of data with more accurate information to the whole dataset. It provides an important additional view of unclassifiable data that otherwise remained in the dark. This novel insight contributes to increase the vulnerability awareness of industrial assets against lightning strikes.
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The gut microbiome plays a fundamental role in metabolism, as well as the immune and nervous systems. Microbial imbalance (dysbiosis) can contribute to subsequent physical and mental pathologies. As such, interest has been growing in the microbiota-gut-brain brain axis and the bioelectrical communication that could exist between bacterial and nervous cells. The aim of this study was to investigate the bioelectrical profile (electrome) of two bacterial species characteristic of the gut microbiome: a Proteobacteria Gram-negative bacillus Escherichia coli (E. coli), and a Firmicutes Gram-positive coccus Enterococcus faecalis (E. faecalis). We analyzed both bacterial strains to (i) validate the fluorescent probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, DiBAC4(3), as a reliable reporter of the changes in membrane potential (Vmem) for both bacteria; (ii) assess the evolution of the bioelectric profile throughout the growth of both strains; (iii) investigate the effects of two neural-type stimuli on Vmem changes: the excitatory neurotransmitter glutamate (Glu) and the inhibitory neurotransmitter γ-aminobutyric acid (GABA); (iv) examine the impact of the bioelectrical changes induced by neurotransmitters on bacterial growth, viability, and cultivability using absorbance, live/dead fluorescent probes, and viable counts, respectively. Our findings reveal distinct bioelectrical profiles characteristic of each bacterial species and growth phase. Importantly, neural-type stimuli induce Vmem changes without affecting bacterial growth, viability, or cultivability, suggesting a specific bioelectrical response in bacterial cells to neurotransmitter cues. These results contribute to understanding the bacterial response to external stimuli, with potential implications for modulating bacterial bioelectricity as a novel therapeutic target.
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Eixo Encéfalo-Intestino , Microbioma Gastrointestinal , Eixo Encéfalo-Intestino/fisiologia , Enterococcus faecalis/fisiologia , Escherichia coli , Ácido Glutâmico/metabolismo , Ácido gama-Aminobutírico/metabolismo , Potenciais da Membrana , HumanosRESUMO
The study aimed to analyze the tactical sprint actions performed by Spanish professional soccer players, considering their playing positions and the match status at the time of each action. Thirty-two Spanish male professional soccer players from a LaLiga Spanish Second Division (LaLiga SmarthBank) team participated in this study. Actions above 85% of the players' maximum velocity during 42 official matches were collected by an optical tracking system ChyronHego® and were synchronized using Mediacoach software (LaLiga, Madrid, Spain). Then, actios were analyzed trough an observation instrument designed to assess the type of tactical action performed by players. Central defenders (CD) and wide defenders (WD) were mainly involved in recovery runs. Central midfielders (CM) also frequently performed recovery runs and pressing actions. Wide midfielders (WM) were often engaged in runs in behind/penetrate actions, while forwards (F) had a diverse range of sprint actions, including pressing, runs in behind/penetrate, and breaking into the box. It was observed that F performed fewer chase actions than expected. On the other hand, CD, WD, and CM engaged in a greater number of recovery run actions than expected. CD also performed more close down/interception actions than expected, while CM, WM, and F performed fewer close down/interception actions than expected. When their team was losing, WM performed more recovery run actions than expected. CM made more runs with the ball when their team was winning CD showed a higher frequency of breaks into the box when their team was winning. These findings provide valuable information regarding the tactical aspects of sprinting in soccer, facilitating the design of specific training tasks that not only address the physical demands associated with each playing position but also considering the tactical context in which sprints occur.
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Desempenho Atlético , Corrida , Futebol , Futebol/fisiologia , Humanos , Masculino , Desempenho Atlético/fisiologia , Corrida/fisiologia , Adulto , Adulto Jovem , Espanha , AtletasRESUMO
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent type of liver disease worldwide. The exact pathophysiology behind MASLD remains unclear; however, it is thought that a combination of factors or "hits" act as precipitants for disease onset and progression. Abundant evidence supports the roles of diet, genes, metabolic dysregulation, and the intestinal microbiome in influencing the accumulation of lipids in hepatocytes and subsequent progression to inflammation and fibrosis. Currently, there is no cure for MASLD, but lifestyle changes have been the prevailing cornerstones of management. Research is now focusing on the intestinal microbiome as a potential therapeutic target for MASLD, with the spotlight shifting to probiotics, antibiotics, and fecal microbiota transplantation. In this review, we provide an overview of how intestinal microbiota interact with the immune system to contribute to the pathogenesis of MASLD and metabolic dysfunction-associated steatohepatitis (MASH). We also summarize key microbial taxa implicated in the disease and discuss evidence supporting microbial-targeted therapies in its management.
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Progressão da Doença , Microbioma Gastrointestinal , Humanos , Transplante de Microbiota Fecal , Sistema Imunitário/metabolismo , Probióticos/uso terapêutico , Fígado Gorduroso/microbiologia , Fígado Gorduroso/imunologia , Animais , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Antibacterianos/uso terapêutico , Fígado/metabolismoRESUMO
INTRODUCTION: Although COVID-19 vaccine safety in 5-11-year-old children has been documented, half of Ontarian children this age remain unvaccinated. This study aimed to assess caregivers' vaccine acceptance for 5-11-year-old children and identify factors associated with vaccine non-acceptance. METHODS: A multi-language self-administered survey was sent to caregivers of 5-11-year-old children through schools and community health centers within the Greater Toronto Area from April-July 2022. Sociodemographic characteristics and immunization behaviours were collected for caregivers, their 5-11-year-old children, and any older siblings. The primary outcome, COVID-19 vaccine acceptance, was previous uptake of COVID-19 vaccine or caregiver intent to vaccinate for their 5-11-year-old child. Data were analyzed using descriptive statistics and multivariable logistic regression. RESULTS: In total, 807 caregivers were included in analysis. Although 93â¯% of caregivers had received two doses of COVID-19 vaccine, 77â¯% had a 5-11-year-old child who received at least one dose of vaccine. Caregivers age was associated with vaccine acceptance (vs.â¯<â¯40â¯years; adjusted odds ratio [aOR] 2.1, 95â¯% confidence interval [CI] 1.4-3.1 for ages 40-49; aOR 2.8, 95â¯% CI 1.1-7.1 for ages ≥50â¯years). Immunization factors associated with vaccine acceptance included caregiver COVID-19 vaccination (aOR 38.1 vs. unvaccinated caregivers; 95â¯% CI 15.8-92.3), older siblings COVID-19 vaccination (aOR 49.2 vs. unvaccinated siblings; 95â¯% CI 18.3-132.3), and recent influenza vaccination for the child (aOR 6.9 vs. no influenza vaccine; 95â¯% CI 4.6-10.5). Among 189 caregivers with unvaccinated 5-11-year-old children, the most common reasons for non-acceptance were concerns about long-term side effects (59â¯%), lack of experience vaccinating children (41â¯%), and concerns that vaccines were developed too quickly (39â¯%). CONCLUSION: Acceptance of COVID-19 vaccination for 5-11-year-old children were associated with caregiver vaccine behaviors and sociodemographic factors. These findings highlight groups of caregivers that can be targeted for educational interventions and concerns that may be addressed to increase vaccine confidence.
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Vacinas contra COVID-19 , COVID-19 , Cuidadores , Vacinação , Humanos , Vacinas contra COVID-19/administração & dosagem , Masculino , Feminino , Cuidadores/estatística & dados numéricos , Cuidadores/psicologia , Estudos Transversais , Criança , COVID-19/prevenção & controle , Pré-Escolar , Adulto , Ontário , Vacinação/estatística & dados numéricos , Vacinação/psicologia , Inquéritos e Questionários , Pessoa de Meia-Idade , SARS-CoV-2 , Hesitação Vacinal/estatística & dados numéricos , Hesitação Vacinal/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricosRESUMO
There is scarce evidence on sociodemographic and lifestyle characteristics that may explain adherence to different dietary patterns (DPs) during pregnancy. Our aims were to identify dietary patterns in a sample of pregnant Mexican women and to describe their association with selected sociodemographic and lifestyle characteristics. This is a secondary cross-sectional analysis of 252 mothers of children that participated as controls in a hospital-based case-control study of childhood leukemia. We obtained parents' information about selected sociodemographic characteristics, as well as alcohol and tobacco consumption. We also obtained dietary information during pregnancy. We identified DPs using cluster and factor analyses and we estimated their association with characteristics of interest. We identified two DPs using cluster analysis, which we called "Prudent" and "Non healthy", as well as three DPs through factor analysis, namely "Prudent", "Processed foods and fish", and "Chicken and vegetables". Characteristics associated with greater adherence to "Prudent" patterns were maternal education, older paternal age, not smoking, and being a government employee and/or uncovered population. Likewise, the "Processed foods and fish" pattern was associated with greater maternal and paternal education, as well as those with less household overcrowding. We did not identify sociodemographic variables related to the "Chicken and Vegetables" pattern. Our results may be useful to identify target populations that may benefit from interventions aimed to improve individual dietary decisions during pregnancy.
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Dieta , Estilo de Vida , Humanos , Feminino , México , Gravidez , Adulto , Estudos Transversais , Dieta/estatística & dados numéricos , Fatores Socioeconômicos , Comportamento Alimentar , Fatores Sociodemográficos , Estudos de Casos e Controles , Adulto Jovem , Fenômenos Fisiológicos da Nutrição Materna , Padrões DietéticosRESUMO
Nutrient-induced blooms of the globally abundant freshwater toxic cyanobacterium Microcystis cause worldwide public and ecosystem health concerns. The response of Microcystis growth and toxin production to new and recycled nitrogen (N) inputs and the impact of heterotrophic bacteria in the Microcystis phycosphere on these processes are not well understood. Here, using microbiome transplant experiments, cyanotoxin analysis, and nanometer-scale stable isotope probing to measure N incorporation and exchange at single cell resolution, we monitored the growth, cyanotoxin production, and microbiome community structure of several Microcystis strains grown on amino acids or proteins as the sole N source. We demonstrate that the type of organic N available shaped the microbial community associated with Microcystis, and external organic N input led to decreased bacterial colonization of Microcystis colonies. Our data also suggest that certain Microcystis strains could directly uptake amino acids, but with lower rates than heterotrophic bacteria. Toxin analysis showed that biomass-specific microcystin production was not impacted by N source (i.e. nitrate, amino acids, or protein) but rather by total N availability. Single-cell isotope incorporation revealed that some bacterial communities competed with Microcystis for organic N, but other communities promoted increased N uptake by Microcystis, likely through ammonification or organic N modification. Our laboratory culture data suggest that organic N input could support Microcystis blooms and toxin production in nature, and Microcystis-associated microbial communities likely play critical roles in this process by influencing cyanobacterial succession through either decreasing (via competition) or increasing (via biotransformation) N availability, especially under inorganic N scarcity.
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Microbiota , Microcistinas , Microcystis , Nitrogênio , Microcystis/metabolismo , Microcystis/crescimento & desenvolvimento , Microcistinas/metabolismo , Nitrogênio/metabolismo , Aminoácidos/metabolismoRESUMO
Background: Chronic obstructive pulmonary disease (COPD) is a common preventable illness that carries a large global economic and social burden. The global initiative for chronic obstructive lung disease (GOLD) guidelines has been utilized as a global strategy for the continued COPD diagnosis, assessment, and treatment. We aimed to determine if the adherence to the 2021 GOLD guideline directed management influenced outcomes. Materials and Methods: Retrospective medical records review of adult patients with COPD, who received care in our office during the entire year of 2021. Patients managed as per the 2021 GOLD guidelines were compared with those who received usual care. Results: Among 242 patients, 171 (70.7%) were GOLD management adherent (GA) and 71 (29.3%) were GOLD non-adherent (GNA). Certain comorbidities were associated with higher frequencies in the GA group, such as allergic rhinitis (63.2 vs. 18.3%; P < 0.001), coronary artery disease (55.9 vs. 38.0%; P = 0.011), GERD (63.2 vs. 32.4%; P < 0.001), anemia (38.6 vs. 19.7%; P = 0.004), malignancy (34.5 vs. 19.7%; P = 0.023), and immunodeficiency (12.3 vs. 1.4%; P = 0.007). There was no significant difference in the mortality between the GA and GNA groups (5.3 vs. 9.9%; P = 0.254). Although the frequency of number of exacerbations was greater in the GA group, the difference in the mean number of exacerbations was not statistically significant (0.39 ± 1.08 vs. 0.39 ± 1.14; P = 0.984). Conclusion: We found no significant difference in the patient outcomes, such as number of exacerbations of COPD and mortality, when comparing the 2021 GOLD guideline adherent versus GOLD guideline non-adherent management of COPD.
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Understanding the mechanisms involved in colonic epithelial differentiation is key to unraveling the alterations causing inflammatory conditions and cancer. Organoid cultures provide an unique tool to address these questions but studies are scarce. We report a differentiation system toward enterocytes and goblet cells, the two major colonic epithelial cell lineages, using colon organoids generated from healthy tissue of colorectal cancer patients. Culture of these organoids in medium lacking stemness agents resulted in a modest ultrastructural differentiation phenotype with low-level expression of enterocyte (KLF4, KRT20, CA1, FABP2) and goblet cell (TFF2, TFF3, AGR2) lineage markers. BMP pathway activation through depletion of Noggin and addition of BMP4 resulted in enterocyte-biased differentiation. Contrarily, blockade of the Notch pathway using the γ-secretase inhibitor dibenzazepine (DBZ) favored goblet cell differentiation. Combination treatment with BMP4 and DBZ caused a balanced strong induction of both lineages. In contrast, colon tumor organoids responded poorly to BMP4 showing only weak signals of cell differentiation, and were unresponsive to DBZ. We also investigated the effects of 1α,25-dihydroxyvitamin D3 (calcitriol) on differentiation. Calcitriol attenuated the effects of BMP4 and DBZ on colon normal organoids, with reduced expression of differentiation genes and phenotype. Consistently, in normal organoids, calcitriol inhibited early signaling by BMP4 as assessed by reduction of the level of phospho-SMAD1/5/8. Our results show that BMP and Notch signaling play key roles in human colon stem cell differentiation to the enterocytic and goblet cell lineages and that calcitriol modulates these processes favoring stemness features.
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Proteína Morfogenética Óssea 4 , Calcitriol , Proteínas de Transporte , Diferenciação Celular , Colo , Dibenzazepinas , Células Caliciformes , Fator 4 Semelhante a Kruppel , Organoides , Receptores Notch , Transdução de Sinais , Humanos , Organoides/efeitos dos fármacos , Organoides/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proteína Morfogenética Óssea 4/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/citologia , Colo/patologia , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Calcitriol/farmacologia , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/metabolismo , Dibenzazepinas/farmacologia , Linhagem da Célula/efeitos dos fármacos , Enterócitos/metabolismo , Enterócitos/efeitos dos fármacos , Enterócitos/citologia , Vitamina D/farmacologiaRESUMO
INTRODUCTION: Suicide is a complex, global public health problem. The Colombian clinical practice guideline provides relevant input for its prevention, diagnosis and treatment. The objective was to evaluate the methodological quality, credibility and applicability of the Colombian clinical practice guideline for suicidal behaviour. METHODS: An academic group of 12 evaluators was established to assess the guide and its recommendations in a standardised way, using the AGREE-II and AGREE-REX instruments. The evaluations were given in the range of 0.0-1.0 with 0.7 as a cut-off point for appropriate quality. RESULTS: The global assessment of the AGREE-II was greater than 0.7 in the dimensions: "scope and objective" (0.86), "clarity of presentation" (0.89), "applicability" (0.73) and "editorial independence" (0.89). The lowest scores were for "participation of those involved" (0.67) and "rigour in preparation" (0.69). With the AGREE-REX, the results in all dimensions were below 0.70, which indicates lower quality and suitability for use. CONCLUSIONS: The adoption process of the Colombian guideline for suicidal behaviour was a rigorous methodological process, while the practice recommendations were valued as of low applicability due to low support in local evidence. It is necessary to strengthen the generation and synthesis of evidence at the national level to give greater support and applicability to the practice recommendations.
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Guias de Prática Clínica como Assunto , Ideação Suicida , Humanos , Colômbia , Prevenção do SuicídioRESUMO
The purpose of this investigation was to evaluate the microbial quality and safety of rabbit meat. A total of 49 rabbit meat samples were taken at the retail level. The mesophiles, staphylococci, Enterobacterales, and Pseudomonas spp. counts were 4.94 ± 1.08, 2.59 ± 0.70, 2.82 ± 0.67, and 3.23 ± 0.76 log CFU/g, respectively. Campylobacter spp. were not detected in any sample. Listeria monocytogenes was isolated from one sample (2.04%) at levels below 1.00 log CFU/g. Multi-resistant S aureus was found in seven samples (14.9%). Methicillin-resistant S. aureus, S. epidermidis, S. haemolyticus, M. caseolyticus, and M. sciuri were found in a sample each (10.20%), and all of them were multi-resistant. Multi-resistant ESBL-producing E. coli were detected in two samples from the same retailer (4.08%). The high resistance found in methicillin-resistant staphylococci and ESBL-producing E. coli is of particular concern, and suggests that special measures should be taken in rabbit meat.
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Large transcellular pores elicited by bacterial mono-ADP-ribosyltransferase (mART) exotoxins inhibiting the small RhoA GTPase compromise the endothelial barrier. Recent advances in biophysical modeling point toward membrane tension and bending rigidity as the minimal set of mechanical parameters determining the nucleation and maximal size of transendothelial cell macroaperture (TEM) tunnels induced by bacterial RhoA-targeting mART exotoxins. We report that cellular depletion of caveolin-1, the membrane-embedded building block of caveolae, and depletion of cavin-1, the master regulator of caveolae invaginations, increase the number of TEMs per cell. The enhanced occurrence of TEM nucleation events correlates with a reduction in cell height due to the increase in cell spreading and decrease in cell volume, which, together with the disruption of RhoA-driven F-actin meshwork, favor membrane apposition for TEM nucleation. Strikingly, caveolin-1 specifically controls the opening speed of TEMs, leading to their dramatic 5.4-fold larger widening. Consistent with the increase in TEM density and width in siCAV1 cells, we record a higher lethality in CAV1 KO mice subjected to a catalytically active mART exotoxin targeting RhoA during staphylococcal bloodstream infection. Combined theoretical modeling with independent biophysical measurements of plasma membrane bending rigidity points toward a specific contribution of caveolin-1 to membrane stiffening in addition to the role of cavin-1/caveolin-1-dependent caveolae in the control of membrane tension homeostasis.