RESUMEN

Older adults with cognitive impairment often experience low mobility and functional decline in hospital, transfer to facility-based transitional care programs, and have poorer outcomes compared to those without cognitive impairment. This protocol paper describes a study which aims to determine the feasibility of, satisfaction with, and efficacy of a nurse-led mobility intervention (OASIS Walking Intervention) for older adults with cognitive impairment in facility-based transitional care programs in Ontario, Canada. A quasi-experimental one-group time series feasibility study will be conducted. A sample size of 26 participants will be recruited from two transitional care programs in Ontario, Canada. Participants will receive the OASIS Walking Intervention for up to 45 minutes per session, 5 sessions per week, for 6 weeks. The intervention consists of: 1) a patient-centered communication care plan; 2) sit to stand activity; and 3) a walking program. Feasibility will be determined by: a) recruitment rate; b) retention rate; and c) adherence. Efficacy of the intervention will be determined by the change over time in older adults' lower extremity muscle strength, mobility, and functional status and by their discharge destination (home vs. nursing home). Satisfaction will be measured using the Client Satisfaction Questionnaire. Efficacy outcomes will be measured before the start of the intervention, after 3 weeks of the intervention, and immediately after 6-week intervention. Descriptive statistics will be used for measures of feasibility, satisfaction, and discharge destination. Repeated measures analysis of variance (RM-ANOVA) will be used to analyze efficacy. Ethics approval has been received for this study. Findings from the study will be used to refine the intervention for use in a definitive pilot trial. Results will be disseminated via peer-reviewed publications, international conferences, through group presentations at the study sites, and through the study site networks. Trial registration: The trial has been registered on Clinicaltrials.gov (NCT06150339).

Asunto(s)

Disfunción Cognitiva , Estudios de Factibilidad , Cuidado de Transición , Caminata , Humanos , Anciano , Disfunción Cognitiva/terapia , Femenino , Masculino , Ontario , Anciano de 80 o más Años , Satisfacción del Paciente

RESUMEN

BACKGROUND: Asymptomatic carriage of infected red blood cells (iRBCs) can be prevalent in communities regardless of transmission patterns and can occur with infection of different Plasmodium species. Clinical immunity dampens the inflammatory responses leading to disease symptoms in malaria. The aim of this study was to define the immunological correlates of asymptomatic carriage of Plasmodium falciparum in a highly exposed population. METHODS: 142 asymptomatic Plasmodium-infected individuals greater than 2 years of age without fever (body temperature <37.5 ℃) were followed weekly for 10 weeks before being treated with artemisinin-based combination therapy (ACT). Plasma levels of 38 cytokines were measured at baseline by Luminex and the quantity and growth inhibitory activities of circulating parasite-reactive antibodies measured. The Plasmodium antigen tested included P. falciparum merozoite extract (ME) and schizont extract (SE), and the recombinant proteins erythrocyte binding antigen 175 (EBA-175) and merozoite surface protein 1 (MSP-119). RESULTS: Median levels of IgG against P. falciparum EBA-175 and MSP-119 at baseline were significantly higher in those older than 20 years of age compared with the younger age group and appeared to correlate with better parasite control. Amongst all participants there were no discernible changes in IgG levels over time. Parasite density was higher in the younger age group and associated with IL-10, TNF and MCP-1 levels. A balanced IL-10:TNF ratio was associated with asymptomatic malaria regardless of age, and balanced ratios of IL-10/TNF and IL-10/IFN-γ were the only significant correlate of maintenance of asymptomatic malaria over the course of the study in individuals 20 years of age and younger. CONCLUSION: The above findings indicate that asymptomatic carriage of P. falciparum in children living in a hyperendemic area occurs independently of IgG but is associated with a balanced inflammatory cytokine ratio.

Asunto(s)

Portador Sano , Citocinas , Inmunoglobulina G , Malaria Falciparum , Plasmodium falciparum , Humanos , Plasmodium falciparum/inmunología , Plasmodium falciparum/fisiología , Niño , Inmunoglobulina G/sangre , Preescolar , Malaria Falciparum/epidemiología , Malaria Falciparum/inmunología , Malaria Falciparum/parasitología , Citocinas/sangre , Adolescente , Masculino , Femenino , Portador Sano/epidemiología , Adulto Joven , Infecciones Asintomáticas/epidemiología , Anticuerpos Antiprotozoarios/sangre , Enfermedades Endémicas/estadística & datos numéricos

Asunto(s)

Unión Europea , Paraquat , Humanos , Paraquat/envenenamiento , Herbicidas/envenenamiento , Masculino

RESUMEN

BACKGROUND: Patient navigation interventions (PNIs) can provide personalized support and promote appropriate coordination or continuation of health and social care services. Online PNIs have demonstrated excellent potential for improving patient knowledge, transition readiness, self-efficacy, and use of services. However, the characteristics (ie, intervention type, mode of delivery, duration, frequency, outcomes and outcome measures, underlying theories or mechanisms of change of the intervention, and impact) of existing online PNIs to support the health and social needs of individuals with illness remain unclear. OBJECTIVE: This scoping review of the existing literature aims to identify the characteristics of existing online PNIs reported in the literature. METHODS: A scoping review based on the guidelines outlined in the Joanna Briggs Institute framework was conducted. A search for peer-reviewed literature published between 1989 and 2022 on online PNIs was conducted using MEDLINE, CINAHL, Embase, PsycInfo, and Cochrane Library databases. Two independent reviewers conducted 2 levels of screening. Data abstraction was conducted to outline key study characteristics (eg, study design, population, and intervention characteristics). The data were analyzed using descriptive statistics and qualitative content analysis. RESULTS: A total of 100 studies met the inclusion criteria. Our findings indicate that a variety of study designs are used to describe and evaluate online PNIs, with literature being published between 2003 and 2022 in Western countries. Of these studies, 39 (39%) studies were randomized controlled trials. In addition, we noticed an increase in reported online PNIs since 2019. The majority of studies involved White females with a diagnosis of cancer and a lack of participants aged 70 years or older was observed. Most online PNIs provide support through navigation, self-management and lifestyle changes, counseling, coaching, education, or a combination of support. Variation was noted in terms of mode of delivery, duration, and frequency. Only a small number of studies described theoretical frameworks or change mechanisms to guide intervention. CONCLUSIONS: To our knowledge, this is the first review to comprehensively synthesize the existing literature on online PNIs, by focusing on the characteristics of interventions and studies in this area. Inconsistency in reporting the country of publication, population characteristics, duration and frequency of interventions, and a lack of the use of underlying theories and working mechanisms to inform intervention development, provide guidance for the reporting of future online PNIs.

RESUMEN

Staphylococcus aureus is a major human pathogen. An effective anti-S. aureus vaccine remains elusive as the correlates of protection are ill-defined. Targeting specific T cell populations is an important strategy for improving anti-S. aureus vaccine efficacy. Potential bottlenecks that remain are S. aureus-induced immunosuppression and the impact this might have on vaccine-induced immunity. S. aureus induces IL-10, which impedes effector T cell responses, facilitating persistence during both colonization and infection. Thus, it was hypothesized that transient targeting of IL-10 might represent an innovative way to improve vaccine efficacy. In this study, IL-10 expression was elevated in the nares of persistent carriers of S. aureus, and this was associated with reduced systemic S. aureus-specific Th1 responses. This suggests that systemic responses are remodeled because of commensal exposure to S. aureus, which negatively implicates vaccine function. To provide proof of concept that targeting immunosuppressive responses during immunization may be a useful approach to improve vaccine efficacy, we immunized mice with T cell-activating vaccines in combination with IL-10-neutralizing antibodies. Blocking IL-10 during vaccination enhanced effector T cell responses and improved bacterial clearance during subsequent systemic and subcutaneous infection. Taken together, these results reveal a potentially novel strategy for improving anti-S. aureus vaccine efficacy.

Asunto(s)

Interleucina-10 , Infecciones Estafilocócicas , Vacunas Estafilocócicas , Staphylococcus aureus , Interleucina-10/metabolismo , Interleucina-10/inmunología , Animales , Infecciones Estafilocócicas/prevención & control , Infecciones Estafilocócicas/inmunología , Vacunas Estafilocócicas/inmunología , Ratones , Staphylococcus aureus/inmunología , Femenino , Ratones Endogámicos C57BL , Células TH1/inmunología , Inmunización/métodos , Humanos , Anticuerpos Neutralizantes/inmunología , Eficacia de las Vacunas , Vacunación/métodos

RESUMEN

Lower respiratory tract infections are common in malaria-endemic areas, and there is some evidence that co-infections between various bacteria/viruses and Plasmodium may affect disease prognosis. In this study, we report the novel finding that co-infection with influenza/A/X31 protects mice from death by Plasmodium berghei NK65-Edinburgh, a model of severe malarial pulmonary leak which underpins malaria-associated acute lung injury (MA-ALI) and malaria-associated acute respiratory distress (MA-ARDS). Co-infected mice exhibit equivalent parasitemia as mice with malaria only, suggesting that the survival phenotype is due to differences in immune kinetics. We demonstrated that the pulmonary leak typical of Pb E is attenuated in co-infected mice without alteration in CD8 T cell activation and recruitment to the lung. Upon further examination of the immune response to influenza/A/X31 we identified a population of arginase 1-expressing alveolar macrophages that traffic to the lungs early during infection. In vitro these macrophages inhibit CD8 T cell activation and proliferation better than non-arginase expressing cells. Removal of arginase-1 expressing alveolar macrophages in vivo via administration of the antimetabolite gemcitabine removed the protective effects of influenza/A/X31co-infection on MA-ALI. This study opens a route to better understanding of how to modulate the immunopathology observed in pulmonary leak associated with severe malaria, which must be achieved to rationally design therapeutic interventions for MA-ARDS / MA-ALI.

RESUMEN

Infertility affects ∼12 % of couples, with environmental chemical exposure as a potential contributor. Of the chemicals that are actively manufactured, very few are assessed for reproductive health effects. Rodents are commonly used to evaluate reproductive effects, which is both costly and time consuming. Thus, there is a pressing need for rapid methods to test a broader range of chemicals. Here, we developed a strategy to evaluate large numbers of chemicals for reproductive toxicity via a yeast, S. cerevisiae high-throughput assay to assess gametogenesis as a potential new approach method (NAM). By simultaneously assessing chemicals for growth effects, we can distinguish if a chemical affects gametogenesis only, proliferative growth only or both. We identified a well-known mammalian reproductive toxicant, bisphenol A (BPA) and ranked 19 BPA analogs for reproductive harm. By testing mixtures of BPA and its analogs, we found that BPE and 17 ß-estradiol each together with BPA showed synergistic effects that worsened reproductive outcome. We examined an additional 179 environmental chemicals including phthalates, pesticides, quaternary ammonium compounds and per- and polyfluoroalkyl substances and found 57 with reproductive effects. Many of the chemicals were found to be strong reproductive toxicants that have yet to be tested in mammals. Chemicals having affect before meiosis I division vs. meiosis II division were identified for 16 gametogenesis-specific chemicals. Finally, we demonstrate that in general yeast reproductive toxicity correlates well with published reproductive toxicity in mammals illustrating the promise of this NAM to quickly assess chemicals to prioritize the evaluation for human reproductive harm.

Asunto(s)

Compuestos de Bencidrilo , Contaminantes Ambientales , Gametogénesis , Fenoles , Saccharomyces cerevisiae , Saccharomyces cerevisiae/efectos de los fármacos , Compuestos de Bencidrilo/toxicidad , Gametogénesis/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Fenoles/toxicidad , Reproducción/efectos de los fármacos , Estradiol/toxicidad , Disruptores Endocrinos/toxicidad , Pruebas de Toxicidad/métodos , Animales , Ensayos Analíticos de Alto Rendimiento

RESUMEN

Polybrominated diphenyl ethers (PBDEs) exposure is associated with preterm birth. Laboratory studies suggest that PBDEs lead to elevated oxidative stress, a known contributor to preterm birth in epidemiologic studies. We hypothesized that elevated levels of PBDEs would be associated with increased oxidative stress during human pregnancy. Participants in this analysis were enrolled in the Chemicals in Our Bodies cohort and resided in the San Francisco Bay Area (N=201). Four PBDEs (BDE-47, -99, -100, -153) were measured in second trimester serum. Urinary oxidative stress biomarkers were measured at two timepoints (second and third trimester) and included 8-isoprostane-prostaglandin-F2α [8-iso-PGF2α], 2,3-dinor-5,6-dihydro-8-iso-PGF2α, 2,3-dinor-8-iso-PGF2α, and prostaglandin-F2α [PGF2α]. Associations between individual PBDEs and oxidative stress biomarkers (averaged and trimester specific) were examined using linear regression. Quantile g-computation and Bayesian kernel machine regression (BKMR) were used to assess cumulative effects of PBDEs. Quantile g-computation showed that higher concentrations of PBDEs were associated with increasing 8-iso-PGF2α, 2,3-dinor-8-iso-PGF2α, and PGF2α. Associations were greatest in magnitude for second trimester levels of 2,3-dinor-8-iso-PGF2α (mean change per quartile increase=0.25, 95% confidence interval=0.09, 0.41). Associations were similar using BKMR and linear regression. Our findings suggest that oxidative stress may be a plausible biological pathway by which PBDE exposure might lead to preterm birth.

RESUMEN

While high-throughput (HTP) assays have been proposed as platforms to rapidly assess reproductive toxicity, there is currently a lack of established assays that specifically address germline development/function and fertility. We assessed the applicability domains of yeast (S. cerevisiae) and nematode (C. elegans) HTP assays in toxicity screening of 124 environmental chemicals, determining their agreement in identifying toxicants and their concordance with reproductive toxicity in vivo. We integrated data generated in the two models and compared results using a streamlined, semi-automated benchmark dose (BMD) modeling approach. We then extracted and modeled relevant mammalian in vivo data available for the matching chemicals included in the Toxicological Reference Database (ToxRefDB). We ranked potencies of common compounds using the BMD and evaluated correlation between the datasets using Pearson and Spearman correlation coefficients. We found moderate to good correlation across the three data sets, with r = 0.48 (95% CI: 0.28-1.00, p<0.001) and rs = 0.40 (p=0.002) for the parametric and rank order correlations between the HTP BMDs; r = 0.95 (95% CI: 0.76-1.00, p=0.0005) and rs = 0.89 (p=0.006) between the yeast assay and ToxRefDB BMDs; and r = 0.81 (95% CI: 0.28-1.00, p=0.014) and rs = 0.75 (p=0.033) between the worm assay and ToxRefDB BMDs. Our findings underscore the potential of these HTP assays to identify environmental chemicals that exhibit reproductive toxicity. Integrating these HTP datasets into mammalian in vivo prediction models using machine learning methods could further enhance the predictive value of these assays in future rapid screening efforts.

RESUMEN

Reproduction is a functional outcome that relies on complex cellular, tissue, and organ interactions that span the developmental period to adulthood. Thus, the assessment of its disruption by environmental chemicals would benefit significantly from scalable and innovative approaches to testing using functionally comparable reproductive models such as the nematode C. elegans. We adapted a previously described low-throughput in vivo chromosome segregation assay using C. elegans predictive of reproductive toxicity and leveraged available public data sources (ToxCast, ICE) to screen and characterize 133 physiologically-relevant chemicals in a high-throughput manner. The screening outcome was further validated in a second, independent in vivo assay assessing embryonic viability. In total, 13 chemicals were classified as reproductive toxicants with the two most active chemicals belonging to the large family of Quaternary Ammonium Compounds (QACs) commonly used as disinfectants but with limited available reproductive toxicity data. We compared the results from the C. elegans assay with ToxCast in vitro data compiled from 700+ cell response assays and 300+ signaling pathways-based assays. We did not observe a difference in the bioactivity or in the average potency (AC50) between the top and bottom chemicals. However, the intended target categories were significantly different between the classified chemicals with, in particular, an over-representation of steroid hormone targets for the high Z-score chemicals. Taken together, these results point to the value of in vivo models that scale to high-throughput level for reproductive toxicity assessment and to the need to prioritize the assessment of QACs impacts on reproduction.

Asunto(s)

Caenorhabditis elegans , Contaminantes Ambientales , Reproducción , Caenorhabditis elegans/efectos de los fármacos , Animales , Reproducción/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Pruebas de Toxicidad/métodos , Ensayos Analíticos de Alto Rendimiento

RESUMEN

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

Asunto(s)

Fluorocarburos , Lípidos , Humanos , Femenino , Embarazo , Lípidos/sangre , Fluorocarburos/sangre , Salud Infantil , Estudios de Cohortes , Estudios Transversales , Adulto , Contaminantes Ambientales/sangre , Exposición a Riesgos Ambientales , Exposición Materna , Niño

RESUMEN

Atopic dermatitis (AD) is an inflammatory skin condition with a childhood prevalence of up to 25%. Microbial dysbiosis is characteristic of AD, with Staphylococcus aureus the most frequent pathogen associated with disease flares and increasingly implicated in disease pathogenesis. Therapeutics to mitigate the effects of S. aureus have had limited efficacy and S. aureus-associated temporal disease flares are synonymous with AD. An alternative approach is an anti-S. aureus vaccine, tailored to AD. Experimental vaccines have highlighted the importance of T cells in conferring protective anti-S. aureus responses; however, correlates of T cell immunity against S. aureus in AD have not been identified. We identify a systemic and cutaneous immunological signature associated with S. aureus skin infection (ADS.aureus) in a pediatric AD cohort, using a combined Bayesian multinomial analysis. ADS.aureus was most highly associated with elevated cutaneous chemokines IP10 and TARC, which preferentially direct Th1 and Th2 cells to skin. Systemic CD4+ and CD8+ T cells, except for Th2 cells, were suppressed in ADS.aureus, particularly circulating Th1, memory IL-10+ T cells, and skin-homing memory Th17 cells. Systemic γδ T cell expansion in ADS.aureus was also observed. This study suggests that augmentation of protective T cell subsets is a potential therapeutic strategy in the management of S. aureus in AD.

Asunto(s)

Dermatitis Atópica , Infecciones Cutáneas Estafilocócicas , Staphylococcus aureus , Dermatitis Atópica/inmunología , Dermatitis Atópica/microbiología , Humanos , Staphylococcus aureus/inmunología , Niño , Femenino , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/microbiología , Masculino , Preescolar , Piel/microbiología , Piel/inmunología , Piel/patología , Quimiocina CXCL10/inmunología , Quimiocina CXCL10/metabolismo , Células TH1/inmunología , Células Th2/inmunología , Células Th17/inmunología , Teorema de Bayes , Linfocitos T CD8-positivos/inmunología , Interleucina-10/metabolismo , Interleucina-10/inmunología , Linfocitos Intraepiteliales/inmunología , Antígenos de Diferenciación de Linfocitos T , Glicoproteínas de Membrana

RESUMEN

BACKGROUND: There is a lack of research on the relationship between water fluoridation and pregnancy outcomes. OBJECTIVES: We assessed whether hypothetical interventions to reduce fluoride levels would improve birth outcomes in California. METHODS: We linked California birth records from 2000 to 2018 to annual average fluoride levels by community water system. Fluoride levels were collected from consumer confidence reports using publicly available data and public record requests. We estimated the effects of a hypothetical intervention reducing water fluoride levels to 0.7 ppm (the current level recommended by the US Department of Health and Human Services) and 0.5 ppm (below the current recommendation) on birth weight, birth-weight-for-gestational age z-scores, gestational age, preterm birth, small-for-gestational age, large-for-gestational age, and macrosomia using linear regression with natural cubic splines and G-computation. Inference was calculated using a clustered bootstrap with Wald-type confidence intervals. We evaluated race/ethnicity, health insurance type, fetal sex, and arsenic levels as potential effect modifiers. RESULTS: Fluoride levels ranged from 0 to 2.5 ppm, with a median of 0.51 ppm. There was a small negative association on birth weight with the hypothetical intervention to reduce fluoride levels to 0.7 ppm [-2.2g; 95% confidence interval (CI): -4.4, 0.0] and to 0.5 ppm (-5.8g; 95% CI: -10.0, -1.6). There were small negative associations with birth-weight-for-gestational-age z-scores for both hypothetical interventions (0.7 ppm: -0.004; 95% CI: -0.007, 0.000 and 0.5 ppm: -0.006; 95% CI: -0.013, 0.000). We also observed small negative associations for risk of large-for-gestational age for both the hypothetical interventions to 0.7 ppm [risk difference (RD)=-0.001; 95% CI: -0.002, 0.000 and 0.5 ppm (-0.001; 95% CI: -0.003, 0.000)]. We did not observe any associations with preterm birth or with being small for gestational age for either hypothetical intervention. We did not observe any associations with risk of preterm birth or small-for-gestational age for either hypothetical intervention. CONCLUSION: We estimated that a reduction in water fluoride levels would modestly decrease birth weight and birth-weight-for-gestational-age z-scores in California. https://doi.org/10.1289/EHP13732.

Asunto(s)

Fluoruración , Fluoruros , Resultado del Embarazo , California/epidemiología , Humanos , Fluoruración/estadística & datos numéricos , Femenino , Embarazo , Resultado del Embarazo/epidemiología , Recién Nacido , Fluoruros/análisis , Peso al Nacer/efectos de los fármacos , Nacimiento Prematuro/epidemiología , Adulto , Edad Gestacional , Recién Nacido Pequeño para la Edad Gestacional

RESUMEN

BACKGROUND: Infra-popliteal interventions for chronic limb-threatening ischemia (CLTI) can be impacted by the morphology of the tibial vessels. The aim of this study was to examine the impact of a novel morphology-driven classification on the outcomes of isolated tibial intervention for CLTI. METHODS: A database of patients undergoing isolated tibial interventions for CLTI at a single center between 2010 and 2020 was retrospectively queried. Patients with isolated infra-popliteal disease were identified, and their anatomy was scored as present or absent for lesion calcification (1 point), target vessel diameter<3.0 mm (1 point), lesion length>300 mm (1 point), and poor pedal runoff score (1 point). Patients were then divided into 3 groups: low risk (0 or 1 points), moderate risk (2 points), and high risk (3 or 4 points). Intention to treat analysis by the patient was performed. Limb-based patency (the absence of reintervention, occlusion, critical stenosis [>70%], or hemodynamic compromise with ongoing symptoms of CLTI as it related to the patency of the preoperatively determined target artery pathway) was assessed. Patient-oriented outcomes of amputation-free survival (AFS; survival without major amputation) and freedom from major adverse limb events (MALE; above ankle amputation of the index limb or major reintervention: new bypass graft, jump/interposition graft revision) were evaluated. RESULTS: 1,607 patients (55% male, average age 60 years, 3,846 vessels) underwent tibial intervention for CLTI. The majority of the patients were diabetic and of Hispanic origin. Morphologically, 27%, 31%, and 42% of the vessels were categorized as low risk, moderate risk, and high risk, respectively. There was a significant worsening of the infra-popliteal Global Limb Anatomic Staging System (GLASS) grading as the morphological risk increased. The 30-day major adverse cardiac events (MACE) were equivalent across the groups and were under the stated objective performance goal (OPG) of ≤10%. In contrast, both the 30-day MALE and the 30-day major amputations were significantly different across the groups, with the low-risk group remaining under the OPG of ≤9% and ≤4%, respectively, while the moderate risk and high risk exceeded the goal threshold. For the OPG, freedom from MALE was 60 ± 5%, 46 ± 5%, and 22 ± 9% at 5 years for low-, moderate-, and high-risk groups, respectively (mean ± standard error of the mean; P = 0.008). Overall AFS was 55 ± 5%, 37 ± 6%, and 18 ± 7% at 5 years for low-, moderate-, and high-risk groups, respectively (mean ± standard error of the mean; P = 0.003). CONCLUSIONS: Tibial anatomic morphology impacts isolated tibial endovascular intervention with adverse morphology associated with poorer short- and long-term outcomes. Risk stratification based on anatomic predictors should be an additional consideration as one intervenes on infra-popliteal vessels for CLTI.

Asunto(s)

Amputación Quirúrgica , Isquemia Crónica que Amenaza las Extremidades , Bases de Datos Factuales , Recuperación del Miembro , Enfermedad Arterial Periférica , Arterias Tibiales , Grado de Desobstrucción Vascular , Humanos , Masculino , Estudios Retrospectivos , Femenino , Anciano , Factores de Riesgo , Enfermedad Arterial Periférica/fisiopatología , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/cirugía , Arterias Tibiales/fisiopatología , Arterias Tibiales/diagnóstico por imagen , Arterias Tibiales/cirugía , Factores de Tiempo , Persona de Mediana Edad , Medición de Riesgo , Isquemia Crónica que Amenaza las Extremidades/cirugía , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Supervivencia sin Progresión , Anciano de 80 o más Años , Resultado del Tratamiento , Isquemia/fisiopatología , Isquemia/cirugía , Isquemia/diagnóstico por imagen , Isquemia/terapia

RESUMEN

The field of fish microbiome research has rapidly been advancing, primarily focusing on farmed or laboratory fish species rather than natural or marine fish populations. This study sought to reveal the distinctive gut bacteriome composition and diversity within the anadromous fish species Tenualosa ilisha (hilsa), which holds the status of being the national fish of Bangladesh. We conducted an analysis on 15 gut samples obtained from 15 individual hilsa fishes collected from three primary habitats (e.g., freshwater = 5, brackish water = 5 and marine water = 5) in Bangladesh. The analysis utilized metagenomics based on 16S rRNA gene sequencing targeting the V3-V4 regions. Our comprehensive identification revealed a total of 258 operational taxonomic units (OTUs). The observed OTUs were represented by six phyla, nine classes, 19 orders, 26 families and 40 genera of bacteria. Our analysis unveiled considerable taxonomic differences among the habitats (freshwater, brackish water, and marine water) of hilsa fishes, as denoted by a higher level of shared microbiota (p = 0.007, Kruskal-Wallis test). Among the identified genera in the gut of hilsa fishes, including Vagococcus, Morganella, Enterobacter, Plesiomonas, Shigella, Clostridium, Klebsiella, Serratia, Aeromonas, Macrococcus, Staphylococcus, Proteus, and Hafnia, several are recognized as fish probiotics. Importantly, some bacterial genera such as Sinobaca, Synechococcus, Gemmata, Serinicoccus, Saccharopolyspora, and Paulinella identified in the gut of hilsa identified in this study have not been reported in any aquatic or marine fish species. Significantly, we observed that 67.50% (27/40) of bacterial genera were found to be common among hilsa fishes across all three habitats. Our findings offer compelling evidence for the presence of both exclusive and communal bacteriomes within the gut of hilsa fishes, exhibiting potential probiotic properties. These observations could be crucial for guiding future microbiome investigations in this economically significant fish species.

Asunto(s)

Peces , Microbioma Gastrointestinal , ARN Ribosómico 16S , Animales , Bangladesh , Microbioma Gastrointestinal/genética , Peces/microbiología , ARN Ribosómico 16S/genética , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Biodiversidad , Filogenia

RESUMEN

Reproduction is a functional outcome that relies on complex cellular, tissue, and organ interactions that span the developmental period to adulthood. Thus, the assessment of its disruption by environmental chemicals is remarkably painstaking in conventional toxicological animal models and does not scale up to the number of chemicals present in our environment and requiring testing. We adapted a previously described low-throughput in vivo chromosome segregation assay using C. elegans predictive of reproductive toxicity and leveraged available public data sources (ToxCast, ICE) to screen and characterize 133 physiologically-relevant chemicals in a high-throughput manner. The screening outcome was further validated in a second, independent in vivo assay assessing embryonic viability. In total, 13 chemicals were classified as reproductive toxicants with the two most active chemicals belonging to the large family of Quaternary Ammonium Compounds (QACs) commonly used as disinfectants but with limited available reproductive toxicity data. We compared the results from the C. elegans assay with ToxCast in vitro data compiled from 700+ cell response assays and 300+ signaling pathways-based assays. We did not observe a difference in the bioactivity or in average potency (AC50) between the top and bottom chemicals. However, the intended target categories were significantly different between the classified chemicals with, in particular, an over-representation of steroid hormone targets for the high Z-score chemicals. Taken together, these results point to the value of in vivo models that scale to high-throughput level for reproductive toxicity assessment and to the need to prioritize the assessment of QACs impacts on reproduction.

RESUMEN

Terrain parks (TP) are popular attractors to snowsport resorts for both skiers and snowboarders, however there is some concern about the risk of severe injury. TP risk management needs to balance the business case against the human cost of injury. To inform effective TP risk management strategies, it essential to understand risk factors, and injury frequency and severity. To this end, a retrospective inductive analysis of Canada West Ski Areas Association's Accident Analyzer database (2008-2009 to 2017-2018). Inclusion criteria., (i) at least 8 seasons of matching injury and participation data, (ii) minimum of 10 TP injuries p.a., (iii) activity either skiing or snowboarding, and (iv) injury location was coded as terrain park/rail. Data was excluded for ticket type N/A. Anonymised and deidentified secondary data was entered into SPSS for analysis. Between group differences were explored via χ2 analysis with Yates' Continuity Correction for 2 × 2 tables and an inductive data driven approach to explore other factors. From this data, 12,602 injuries were in TPs across 28 resorts. 11,940 (94.7%) met the inclusion criteria (14.2% female; 86.5% <25 years; 73.0% snowboarders. 50.8% were male snowboarders <25 years). Higher levels of helmet use were not correlated with a decline in reported head injuries. Day-ticket holders were more likely to be injured on their first two uses of a run than season pass holders. More snowboarders injured in TPs (59.7%) went to hospital than skiers (51.0%). Thus, participants injured in TP are typically younger, male, and snowboarders with either a Season Pass or day ticket, thus potentially a distinct target group for injury mitigation and prevention strategies and communications. The application of other frameworks such as the hierarchy of control and socioecological framework reflects the complex multifactorial systems in which snowsports occur and from which more targeted risk management strategies may emerge to mitigate injury risk while maintaining TP appeal.

Asunto(s)

Disruptores Endocrinos , Combustibles Fósiles , Humanos , Disruptores Endocrinos/efectos adversos

RESUMEN

Despite significant progress in medical research and public health efforts, gaps in knowledge of women's heart health remain across epidemiology, presentation, management, outcomes, education, research, and publications. Historically, heart disease was viewed primarily as a condition in men and male individuals, leading to limited understanding of the unique risks and symptoms that women experience. These knowledge gaps are particularly problematic because globally heart disease is the leading cause of death for women. Until recently, sex and gender have not been addressed in cardiovascular research, including in preclinical and clinical research. Recruitment was often limited to male participants and individuals identifying as men, and data analysis according to sex or gender was not conducted, leading to a lack of data on how treatments and interventions might affect female patients and individuals who identify as women differently. This lack of data has led to suboptimal treatment and limitations in our understanding of the underlying mechanisms of heart disease in women, and is directly related to limited awareness and knowledge gaps in professional training and public education. Women are often unaware of their risk factors for heart disease or symptoms they might experience, leading to delays in diagnosis and treatments. Additionally, health care providers might not receive adequate training to diagnose and treat heart disease in women, leading to misdiagnosis or undertreatment. Addressing these knowledge gaps requires a multipronged approach, including education and policy change, built on evidence-based research. In this chapter we review the current state of existing cardiovascular research in Canada with a specific focus on women.

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En dépit des avancées importantes de la recherche médicale et des efforts en santé publique, il reste des lacunes dans les connaissances sur la santé cardiaque des femmes sur les plans de l'épidémiologie, du tableau clinique, de la prise en charge, des résultats, de l'éducation, de la recherche et des publications. Du point de vue historique, la cardiopathie a d'abord été perçue comme une maladie qui touchait les hommes et les individus de sexe masculin. De ce fait, la compréhension des risques particuliers et des symptômes qu'éprouvent les femmes est limitée. Ces lacunes dans les connaissances posent particulièrement problème puisqu'à l'échelle mondiale la cardiopathie est la cause principale de décès chez les femmes. Jusqu'à récemment, la recherche en cardiologie, notamment la recherche préclinique et clinique, ne portait pas sur le sexe et le genre. Le recrutement souvent limité aux participants masculins et aux individus dont l'identité de genre correspond au sexe masculin et l'absence d'analyses de données en fonction du sexe ou du genre ont eu pour conséquence un manque de données sur la façon dont les traitements et les interventions nuisent aux patientes féminines et aux individus dont l'identité de genre correspond au sexe féminin, et ce, de façon différente. Cette absence de données a mené à un traitement sous-optimal et à des limites de notre compréhension des mécanismes sous-jacents de la cardiopathie chez les femmes, et est directement reliée à nos connaissances limitées, et à nos lacunes en formation professionnelle et en éducation du public. Le fait que les femmes ne connaissent souvent pas leurs facteurs de risque de maladies du cœur ou les symptômes qu'elles peuvent éprouver entraîne des retards de diagnostic et de traitements. De plus, le fait que les prestataires de soins de santé ne reçoivent pas la formation adéquate pour poser le diagnostic et traiter la cardiopathie chez les femmes les mène à poser un mauvais diagnostic ou à ne pas traiter suffisamment. Pour pallier ces lacunes de connaissances, il faut une approche à plusieurs volets, qui porte notamment sur l'éducation et les changements dans les politiques, et qui repose sur la recherche fondée sur des données probantes. Dans ce chapitre, nous passons en revue l'état actuel de la recherche existante sur les maladies cardiovasculaires au Canada, plus particulièrement chez les femmes.