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1.
Elife ; 122024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38687678

RESUMEN

Internalization from the cell membrane and endosomal trafficking of receptor tyrosine kinases (RTKs) are important regulators of signaling in normal cells that can frequently be disrupted in cancer. The adrenal tumor pheochromocytoma (PCC) can be caused by activating mutations of the rearranged during transfection (RET) receptor tyrosine kinase, or inactivation of TMEM127, a transmembrane tumor suppressor implicated in trafficking of endosomal cargos. However, the role of aberrant receptor trafficking in PCC is not well understood. Here, we show that loss of TMEM127 causes wildtype RET protein accumulation on the cell surface, where increased receptor density facilitates constitutive ligand-independent activity and downstream signaling, driving cell proliferation. Loss of TMEM127 altered normal cell membrane organization and recruitment and stabilization of membrane protein complexes, impaired assembly, and maturation of clathrin-coated pits, and reduced internalization and degradation of cell surface RET. In addition to RTKs, TMEM127 depletion also promoted surface accumulation of several other transmembrane proteins, suggesting it may cause global defects in surface protein activity and function. Together, our data identify TMEM127 as an important determinant of membrane organization including membrane protein diffusability and protein complex assembly and provide a novel paradigm for oncogenesis in PCC where altered membrane dynamics promotes cell surface accumulation and constitutive activity of growth factor receptors to drive aberrant signaling and promote transformation.


Asunto(s)
Membrana Celular , Proteínas de la Membrana , Proteínas Proto-Oncogénicas c-ret , Proteínas Proto-Oncogénicas c-ret/metabolismo , Proteínas Proto-Oncogénicas c-ret/genética , Humanos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Membrana Celular/metabolismo , Transducción de Señal , Transporte de Proteínas , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Proliferación Celular , Neoplasias de las Glándulas Suprarrenales/genética , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/patología
2.
JAC Antimicrob Resist ; 6(2): dlae037, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38500518

RESUMEN

Background: Pyrazinamide is one of four first-line antibiotics used to treat tuberculosis; however, antibiotic susceptibility testing for pyrazinamide is challenging. Resistance to pyrazinamide is primarily driven by genetic variation in pncA, encoding an enzyme that converts pyrazinamide into its active form. Methods: We curated a dataset of 664 non-redundant, missense amino acid mutations in PncA with associated high-confidence phenotypes from published studies and then trained three different machine-learning models to predict pyrazinamide resistance. All models had access to a range of protein structural-, chemical- and sequence-based features. Results: The best model, a gradient-boosted decision tree, achieved a sensitivity of 80.2% and a specificity of 76.9% on the hold-out test dataset. The clinical performance of the models was then estimated by predicting the binary pyrazinamide resistance phenotype of 4027 samples harbouring 367 unique missense mutations in pncA derived from 24 231 clinical isolates. Conclusions: This work demonstrates how machine learning can enhance the sensitivity/specificity of pyrazinamide resistance prediction in genetics-based clinical microbiology workflows, highlights novel mutations for future biochemical investigation, and is a proof of concept for using this approach in other drugs.

3.
J Clin Tuberc Other Mycobact Dis ; 35: 100431, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38523706

RESUMEN

Objective: We conducted a descriptive analysis of multi-drug resistant tuberculosis (MDR-TB) in Vietnam's two largest cities, Hanoi and Ho Chi Minh city. Methods: All patients with rifampicin resistant tuberculosis were recruited from Hanoi and surrounding provinces between 2020 and 2022. Additional patients were recruited from Ho Chi Minh city over the same time period. Demographic data were recorded from all patients, and samples collected, cultured, whole genome sequenced and analysed for drug resistance mutations. Genomic susceptibility predictions were made on the basis of the World Health Organization's catalogue of mutations in Mycobacterium tuberculosis associated with drug resistance, version 2. Comparisons were made against phenotypic drug susceptibility test results where these were available. Multivariable logistic regression was used to assess risk factors for previous episodes of tuberculosis. Results: 233/265 sequenced isolates were of sufficient quality for analysis, 146 (63 %) from Ho Chi Minh City and 87 (37 %) from Hanoi. 198 (85 %) were lineage 2, 20 (9 %) were lineage 4, and 15 (6 %) were lineage 1. 17/211 (8 %) for whom HIV status was known were infected, and 109/214 (51 %) patients had had a previous episode of tuberculosis. The main risk factor for a previous episode was HIV infection (odds ratio 5.1 (95 % confidence interval 1.3-20.0); p = 0.021). Sensitivity for predicting first-line drug resistance from whole genome sequencing data was over 90 %, with the exception of pyrazinamide (85 %). For moxifloxacin and amikacin it was 50 % or less. Among rifampicin-resistant isolates, prevalence of resistance to each non-first-line drug was < 20 %. Conclusions: Drug resistance among most MDR-TB strains in Vietnam's two largest cities is confined largely to first-line drugs. Living with HIV is the main risk factor among patients with MDR-TB for having had a previous episode of tuberculosis.

4.
Nutrients ; 16(6)2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38542711

RESUMEN

Higher rates of obesity in rural compared to urban districts suggest environmental differences that affect student health. This study examined urban-rural differences in districts' local wellness policies (LWPs) and LWP implementation environments. Cross-sectional data from two assessments in Texas were analyzed. In assessment one, each district's LWP was reviewed to see if 16 goals were included. In assessment two, an audit was conducted to identify the presence of a wellness plan (a document with recommendations for implementing LWPs), triennial LWP assessment, and school health advisory councils (SHACs) on the district website. Rural districts' LWPs had a smaller number of total goals (B = -2.281, p = 0.014), nutrition education goals (B = -0.654, p = 0.005), and other school-based activity goals (B = -0.675, p = 0.001) in their LWPs, compared to urban districts. Rural districts also had lower odds of having a wellness plan (OR = 0.520, 95% CI = 0.288-0.939), p = 0.030) and a SHAC (OR = 0.201, 95% CI = 0.113-0.357, p < 0.001) to support LWP implementation, compared to urban districts. More resources may be needed to create effective SHACs that can help develop and implement LWPs in rural areas. Important urban-rural differences exist in Texas LWPs and LWP implementation environments.


Asunto(s)
Política de Salud , Promoción de la Salud , Humanos , Estudios Transversales , Educación en Salud , Instituciones Académicas , Servicios de Salud Escolar , Política Nutricional
5.
Sci Rep ; 14(1): 7343, 2024 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-38538629

RESUMEN

Contact between humans and wildlife presents a risk for both zoonotic and anthropozoonotic disease transmission. In this study we report the detection of human strains of Mycobacterium tuberculosis in sun bears and an Asiatic black bear in a wildlife rescue centre in Cambodia, confirming for the first time the susceptibility of these bear species to tuberculosis when in close contact with humans. After genotyping revealed two different strains of M. tuberculosis from cases occurring between 2009 and 2019, 100 isolates from 30 sun bear cases, a single Asiatic black bear case, and a human case were subjected to whole genome sequencing. We combined single nucleotide polymorphism analysis and exploration of mixed base calls with epidemiological data to indicate the evolution of each outbreak. Our results confirmed two concurrent yet separate tuberculosis outbreaks and established a likely transmission route in one outbreak where the human case acted as an intermediatory between bear cases. In both outbreaks, we observed high rates of transmission and progression to active disease, suggesting that sun bears are highly susceptible to tuberculosis if exposed under these conditions. Overall, our findings highlight the risk of bi-directional transmission of tuberculosis between humans and captive bears in high human tuberculosis burden regions, with implied considerations for veterinary and public health. We also demonstrate the use of standard genomic approaches to better understand disease outbreaks in captive wildlife settings and to inform control and prevention measures.


Asunto(s)
Tuberculosis , Ursidae , Animales , Humanos , Ursidae/genética , Cambodia/epidemiología , Brotes de Enfermedades , Tuberculosis/epidemiología , Tuberculosis/veterinaria , Genómica
6.
J Clin Microbiol ; 62(4): e0128723, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38466092

RESUMEN

Mortality from tuberculous meningitis (TBM) remains around 30%, with most deaths occurring within 2 months of starting treatment. Mortality from drug-resistant strains is higher still, making early detection of drug resistance (DR) essential. Targeted next-generation sequencing (tNGS) produces high read depths, allowing the detection of DR-associated alleles with low frequencies. We applied Deeplex Myc-TB-a tNGS assay-to cerebrospinal fluid (CSF) samples from 72 adults with microbiologically confirmed TBM and compared its genomic drug susceptibility predictions to a composite reference standard of phenotypic susceptibility testing (pDST) and whole genome sequencing, as well as to clinical outcomes. Deeplex detected Mycobacterium tuberculosis complex DNA in 24/72 (33.3%) CSF samples and generated full DR reports for 22/24 (91.7%). The read depth generated by Deeplex correlated with semi-quantitative results from MTB/RIF Xpert. Alleles with <20% frequency were seen at canonical loci associated with first-line DR. Disregarding these low-frequency alleles, Deeplex had 100% concordance with the composite reference standard for all drugs except pyrazinamide and streptomycin. Three patients had positive CSF cultures after 30 days of treatment; reference tests and Deeplex identified isoniazid resistance in two, and Deeplex alone identified low-frequency rifampin resistance alleles in one. Five patients died, of whom one had pDST-identified pyrazinamide resistance. tNGS on CSF can rapidly and accurately detect drug-resistant TBM, but its application is limited to those with higher bacterial loads. In those with lower bacterial burdens, alternative approaches need to be developed for both diagnosis and resistance detection.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Meníngea , Tuberculosis Resistente a Múltiples Medicamentos , Adulto , Humanos , Tuberculosis Meníngea/diagnóstico , Tuberculosis Meníngea/tratamiento farmacológico , Tuberculosis Meníngea/líquido cefalorraquídeo , Mycobacterium tuberculosis/genética , Pirazinamida , Sensibilidad y Especificidad , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Líquido Cefalorraquídeo , Pruebas de Sensibilidad Microbiana
7.
BMC Psychiatry ; 24(1): 213, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500115

RESUMEN

BACKGROUND: The burdens of anxiety and depression symptoms have significantly increased in the general US population, especially during this COVID-19 epidemiological crisis. The first step in an effective treatment for anxiety and depression disorders is screening. The Patient Health Questionnaire-4 (PHQ-4, a 4-item measure of anxiety/depression) and its subscales (PHQ-2 [a 2-item measure of depression] and Generalized Anxiety Disorder [GAD-2, a 2-item measure of anxiety]) are brief but effective mass screening instruments for anxiety and depression symptoms in general populations. However, little to no study examined the psychometric properties (i.e., reliability and validity) of the PHQ-4 and its subscales (PHQ-2 and GAD-2) in the general US adult population or based on US nativity (i.e., foreign-born vs. the US-born). We evaluated the psychometric properties of the PHQ-4 and its subscales in US adults, as well as the psychometric equivalence of the PHQ-4 scale based on nativity. METHODS: We conducted a cross-sectional survey of 5,140 adults aged ≥ 18 years. We examined the factorial validity and dimensionality of the PHQ-4 with confirmatory factor analysis (CFA). A multiple-group confirmatory factor analysis (MCFA) was used to evaluate the comparability of the PHQ-4 across nativity groups. Reliability indices were assessed. Also, the scales' construct validities were assessed by examining the associations of both the PHQ-4 and its subscales' scores with the sociodemographic characteristics and the 3-item UCLA Loneliness scale. RESULTS: The internal consistencies were high for the PHQ-4 scale (α = 0.92) and its subscales of PHQ-2 (α = 0.86) and GAD-2 (α = 0.90). The CFA fit indices showed evidence for the two-factor structure of the PHQ-4. The two factors (i.e., anxiety and depression) were significantly correlated (r = 0.92). The MCFA demonstrated measurement invariance of the PHQ-4 across the nativity groups, but the model fits the data better in the foreign-born group. There were significant associations of the PHQ-4 scale and its subscales' scores with the sociodemographic characteristics and the UCLA Loneliness scale (all p < 0.001). CONCLUSIONS: The PHQ-4 and its subscales are reliable and valid measures to screen anxiety and depression symptoms in the general US adult population, especially in foreign-born individuals during the COVID-19 pandemic.


Asunto(s)
COVID-19 , Cuestionario de Salud del Paciente , Adulto , Humanos , Depresión/diagnóstico , Estudios Transversales , Reproducibilidad de los Resultados , Pandemias , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Ansiedad/diagnóstico , Psicometría , COVID-19/epidemiología , Encuestas y Cuestionarios
10.
Emerg Infect Dis ; 30(3): 499-509, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38407176

RESUMEN

We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.


Asunto(s)
Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Masculino , Humanos , Vietnam/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Asia , Análisis Espacial
11.
BMC Public Health ; 24(1): 207, 2024 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-38233842

RESUMEN

BACKGROUND: Schools are a key setting for supporting youth physical activity, given their broad reach and diverse student populations. Organizational readiness is a precursor to the successful implementation of school-based physical activity opportunities. The R = MC2 heuristic (Readiness = Motivation x Innovation-Specific Capacity x General Capacity) describes readiness as a function of an organization's motivation and capacity to implement an innovation and can be applied to better understand the implementation process. The purpose of this study was to explore the barriers to and facilitators of implementing school-based physical activity opportunities in the context of organizational readiness. METHODS: We analyzed interview data from 15 elementary school staff (principals, assistant principals, physical education teachers, and classroom teachers) from a school district in Texas. We focused on factors related to adopting, implementing, and sustaining a variety of school-based physical activity opportunities. We used the Framework Method to guide the analysis and coded data using deductive (informed by the R = MC2 heuristic) and inductive approaches. Themes were generated using the frequency, depth, and richness of participant responses. RESULTS: Four themes emerged from the data: (1) implementation is aided by the presence of internal and external relationships; (2) physical activity opportunities compete with other school priorities; (3) seeing the benefits of physical activity opportunities motivates school staff toward implementation; and (4) staff buy-in is critical to the implementation process. Themes 1-3 aligned with subcomponents of the R = MC2 heuristic (intra- and inter-organizational relationships, priority, and observability), whereas Theme 4 (staff buy-in) related to multiple subcomponents within the Motivation component but was ultimately viewed as a distinct construct. CONCLUSION: Our results highlight and explain how key readiness constructs impact the implementation of school-based physical activity opportunities. They also highlight the importance of obtaining staff buy-in when implementing in the school setting. This information is critical to developing readiness-building strategies that help schools improve their capacity to deliver physical activity opportunities effectively. TRIAL REGISTRATION: Not applicable.


Asunto(s)
Ejercicio Físico , Heurística , Adolescente , Humanos , Investigación Cualitativa , Estudiantes , Motivación
12.
Am J Health Educ ; 55(1): 24-32, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38264143

RESUMEN

BACKGROUND: Physical Education is a key component to improve youth health, but there is limited information on Physical Education delivery in different formats. PURPOSE: We compared PE formats (in-person versus remote) across evaluation aspects: weekly minutes; perceived effectiveness; and student-to-teacher ratio. METHODS: We distributed questionnaires (2020-2021 school year) to school contacts who represented NFL Play 60 FitnessGram® Project (n=216) schools in multiple US cities. Questionnaires entailed learning format, weekly PE minutes, perceived effectiveness, and student-to-teacher ratio. We used linear mixed models to compare PE formats across evaluation variables. RESULTS: Among 165 schools, 10% (n=17) offered in-person instruction, 31% (n=51) offered remote instruction, and 59% offered both (n=97). Results revealed higher in-person PE minutes (77.2±7.3) compared to remote minutes (67.1±14.6), but results were not significantly different (p=0.19). School contacts reported significantly more effective in-person PE (4.0) than remote PE (2.8, p<0.001). In-person PE also had significantly smaller reported student-to-teacher ratio (16.7) compared to remote PE (23.7, p<0.001). DISCUSSION: Findings indicate PE was offered during the pandemic, but remote learning appeared less effective than in-person PE. TRANSLATION to HEALTH EDUCATION PRACTICE: Efforts are needed to improve remote PE to reinforce high-quality PE in the future.

13.
Am J Community Psychol ; 73(1-2): 66-77, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37079437

RESUMEN

Black students at predominantly White institutions (PWIs) contend with racial microaggressions that can lead to negative mental health and academic outcomes. The physical and mental health consequences of the novel coronavirus pandemic are well-known. What remains unknown is how targeted racial hate during a pandemic might have a compounded effect on Black essential workers. The current study examines how future essential workers in helping professions cope with dual crises as they navigate mostly White universities. Study participants were Black university students attending PWIs in the United States enrolled in social work, public health, or psychology programs during the 2020-2021 academic year. Participants completed an online survey that measured racial microaggressions, COVID distress, sense of belonging, engagement in activism, and well-being. Hierarchical regression models revealed COVID distress predicted poorer well-being. Also, COVID distress interacted with racial microaggressions to predict well-being. Findings have implications for developing decolonized learning communities with a liberation pedagogy in community psychology and other helping professions.


Asunto(s)
COVID-19 , Blanco , Humanos , COVID-19/epidemiología , Estudiantes , SARS-CoV-2 , Aprendizaje
14.
bioRxiv ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-37425958

RESUMEN

Internalization from the cell membrane and endosomal trafficking of receptor tyrosine kinases (RTK) are important regulators of signaling in normal cells that can frequently be disrupted in cancer. The adrenal tumour pheochromocytoma (PCC) can be caused by activating mutations of the RET receptor tyrosine kinase, or inactivation of TMEM127, a transmembrane tumour suppressor implicated in trafficking of endosomal cargos. However, the role of aberrant receptor trafficking in PCC is not well understood. Here, we show that loss of TMEM127 causes wildtype RET protein accumulation on the cell surface, where increased receptor density facilitates constitutive ligand-independent activity and downstream signaling, driving cell proliferation. Loss of TMEM127 altered normal cell membrane organization and recruitment and stabilization of membrane protein complexes, impaired assembly, and maturation of clathrin coated pits, and reduced internalization and degradation of cell surface RET. In addition to RTKs, TMEM127 depletion also promoted surface accumulation of several other transmembrane proteins, suggesting it may cause global defects in surface protein activity and function. Together, our data identify TMEM127 as an important determinant of membrane organization including membrane protein diffusability, and protein complex assembly and provide a novel paradigm for oncogenesis in PCC where altered membrane dynamics promotes cell surface accumulation and constitutive activity of growth factor receptors to drive aberrant signaling and promote transformation.

15.
Transl Behav Med ; 14(2): 89-97, 2024 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-37713255

RESUMEN

School-based physical activity (PA) opportunities can help students engage in greater amounts of daily PA, meet PA guidelines, and lead to improved health and educational outcomes. However, we do not completely understand the organizational challenges to implementing these opportunities successfully. This exploratory study examined associations between school-level determinants and the implementation of school-based PA opportunities. We analyzed cross-sectional survey data from schools (n = 46) participating in the Healthy Zone School Program (HZSP) (Dallas, Texas, USA) during 2019-2020. Respondents completed an electronic survey that included measures of school-level determinants (e.g. culture, leadership, priority) and the implementation of school-based PA opportunities. We used linear regression models to examine associations between determinants and implementation outcomes (number of PA opportunities delivered, perceived overall success of each PA program/activity used). After adjusting for campus type (i.e. elementary, middle, high, K-12), student race/ethnicity, and percentage of economically disadvantaged students, no constructs were associated with the number of PA opportunities implemented. Linear regression models suggest access to knowledge and information (ß = 0.39, P = .012, 95% CI = 0.24-1.44) and implementation climate (ß = 0.34, P = .045, 95% CI = 0.02-1.59) were positively associated with the success of school-based PA opportunities. Our findings provide suggestive evidence that access to knowledge and information and a supportive school climate may improve the overall success of PA opportunities provided to students. Future research should examine additional school-level determinants to understand their importance to implementation and inform the development of strategies to improve schools' capacity for implementing PA opportunities successfully.


School-based physical activity (PA) opportunities (e.g. programs, activities, policies) help students engage in greater amounts of daily PA, meet national PA guidelines, and lead to improved health and educational outcomes. However, we do not completely understand the organizational challenges to implementing these opportunities successfully. This study explored what factors contribute to schools' ability to provide PA opportunities throughout the school year. We administered a survey to schools participating in the Healthy Zone Schools program during the 2019­20 academic year to assess the relationship between school-level determinants (e.g. culture, leadership, priority) and implementation outcomes related to school-based PA opportunities (e.g. number of programs and activities implemented, overall success of programs/activities implemented). We found no evidence of an association between determinants and the number of PA programs and activities implemented. However, we identified implementation climate and access to knowledge and information as key drivers of implementation success. This information can be used to develop implementation strategies that improve PA opportunities offered by schools.


Asunto(s)
Ejercicio Físico , Instituciones Académicas , Humanos , Estudios Transversales , Escolaridad , Promoción de la Salud , Servicios de Salud Escolar
16.
Heliyon ; 9(11): e21861, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38053913

RESUMEN

Background & aims: Cystic Fibrosis related liver disease (CFLD) is the 3rd largest cause of death in Cystic Fibrosis (CF). As advances in pulmonary therapies have increased life-expectancy, CFLD has become more prevalent. Current guidelines may underdiagnose liver fibrosis, particularly in its early stages. Newer modalities for the assessment of fibrosis may provide a more accurate assessment. FibroScan is validated in assessing fibrosis for several aetiologies including alcohol and fatty liver, the CFLD cohort have an entirely different phenotype so the cut off values are not transferrable. We appraised fibrosis assessment tools to improve diagnosis of CFLD. Methods: A prospective cohort (n = 114) of patients from the Manchester Adult Cystic Fibrosis Centre, UK were identified at annual assessment. Demographic data including co-morbidity, CFTR genotyping, biochemistry and imaging were used alongside current guidelines to group into CFLD and CF without evidence of liver disease. All patients underwent liver stiffness measurement (LSM) and assessment of serum-based fibrosis biomarker panels. A new diagnostic criterion was created and validated in a second, independent cohort. Results: 12 of 114 patient classified as CFLD according to the European Cystic Fibrosis Society best practice guidelines. No specific risk factors for development of CFLD were identified. Liver enzymes were elevated in patients with CFLD. Serum biomarker panels did not improve diagnostic criteria. LSM accurately predicted CFLD. A new diagnostic criterion was proposed and validated in a separate cohort, accurately predicating CFLD in 10 of 32 patients (31 %). Conclusion: We present a cohort of patients with CF assessed for the presence of liver fibrosis using blood biomarkers and LSM based platforms. We propose a new, simplified diagnostic criteria, capable of accurately predicting liver disease in patients with CF.Clinical trials number: NCT04277819.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38048026

RESUMEN

BACKGROUND: The war in Ukraine has led to significant migration to neighboring countries, raising public health concerns. Notable tuberculosis (TB) incidence rates in Ukraine emphasize the immediate requirement to prioritize approaches that interrupt the spread and prevent new infections. METHODS: We conducted a prospective genomic surveillance study to assess migration's impact on TB epidemiology in the Czech Republic and Slovakia. Mycobacterium tuberculosis isolates from Ukrainian war refugees and migrants, collected from September 2021 to December 2022 were analyzed alongside 1574 isolates obtained from Ukraine, the Czech Republic, and Slovakia. RESULTS: Our study revealed alarming results, with historically the highest number of Ukrainian tuberculosis patients detected in the host countries. The increasing number of cases of multidrug-resistant TB, significantly linked with Beijing lineage 2.2.1 (p < 0.0001), also presents substantial obstacles to control endeavors. The genomic analysis identified the three highly related genomic clusters, indicating the recent TB transmission among migrant populations. The largest clusters comprised war refugees diagnosed in the Czech Republic, TB patients from various regions of Ukraine, and incarcerated individuals diagnosed with pulmonary TB specialized facility in the Kharkiv region, Ukraine, pointing to a national transmission sequence that has persisted for over 14 years. CONCLUSIONS: The data showed that most infections were likely the result of reactivation of latent disease or exposure to TB before migration rather than recent transmission occurring within the host country. However, close monitoring, appropriate treatment, careful surveillance, and social support are crucial in mitigating future risks, though there is currently no evidence of local transmission in EU countries.

18.
PLOS Glob Public Health ; 3(12): e0001788, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38117783

RESUMEN

Six lineages of Mycobacterium tuberculosis sensu stricto (which excludes M. africanum) are described. Single-country or small observational data suggest differences in clinical phenotype between lineages. We present strain lineage and clinical phenotype data from 12,246 patients from 3 low-incidence and 5 high-incidence countries. We used multivariable logistic regression to explore the effect of lineage on site of disease and on cavities on chest radiography, given pulmonary TB; multivariable multinomial logistic regression to investigate types of extra-pulmonary TB, given lineage; and accelerated failure time and Cox proportional-hazards models to explore the effect of lineage on time to smear and culture-conversion. Mediation analyses quantified the direct effects of lineage on outcomes. Pulmonary disease was more likely among patients with lineage(L) 2, L3 or L4, than L1 (adjusted odds ratio (aOR) 1.79, (95% confidence interval 1.49-2.15), p<0.001; aOR = 1.40(1.09-1.79), p = 0.007; aOR = 2.04(1.65-2.53), p<0.001, respectively). Among patients with pulmonary TB, those with L1 had greater risk of cavities on chest radiography versus those with L2 (aOR = 0.69(0.57-0.83), p<0.001) and L4 strains (aOR = 0.73(0.59-0.90), p = 0.002). L1 strains were more likely to cause osteomyelitis among patients with extra-pulmonary TB, versus L2-4 (p = 0.033, p = 0.008 and p = 0.049 respectively). Patients with L1 strains showed shorter time-to-sputum smear conversion than for L2. Causal mediation analysis showed the effect of lineage in each case was largely direct. The pattern of clinical phenotypes seen with L1 strains differed from modern lineages (L2-4). This has implications for clinical management and could influence clinical trial selection strategies.

19.
Front Public Health ; 11: 1193442, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37693726

RESUMEN

Introduction: A whole-of-school approach is best to promote physical activity before, during, and after school. However, multicomponent programming is often complex and difficult to deliver in school settings. There is a need to better understand how components of a whole-of-school approach are implemented in practice. The objectives of this mixed methods study were to: (1) qualitatively explore physical activity approaches and their implementation in elementary schools, (2) quantitatively assess implementation levels, and (3) examine associations between school-level physical activity promotion and academic ratings. Methods: We used an exploratory sequential mixed methods design. We conducted semi-structured qualitative interviews with elementary school staff from a Texas school district and used a directed content analysis to explore physical activity approaches and their implementation. Using qualitative findings, we designed a survey to quantitatively examine the implementation of physical activity approaches, which we distributed to elementary staff district wide. We used Pearson correlation coefficients to examine the association between the amount of physical activity opportunities present in individual schools and school-level academic ratings. Results: We completed 15 interviews (7 principals/assistant principals, 4 physical educators, and 4 classroom teachers). Elementary school teachers and staff indicated PE and recess implementation was driven from the top-down by state and district policies, while implementation of classroom-based approaches, before and after school programming, and active transport were largely driven from the bottom-up by teachers and school leaders. Teachers and staff also discussed implementation challenges across approaches. Survey respondents (n = 247 from 22 schools) indicated 54.6% of schools were implementing ≥135 min/week of physical education and 72.7% were implementing 30 min/day of recess. Classroom-based approaches were less common. Twenty-four percent of schools reported accessible before school programs, 72.7% reported accessible after school programs, and 27% promoted active transport. There was a direct association between the number of physical activity opportunities provided and school-level academic ratings r(22) = 0.53, p = 0.01. Conclusion: Schools provided physical activity opportunities consistent with a whole-of-school approach, although there was variability between schools and implementation challenges were present. Leveraging existing school assets while providing school-specific implementation strategies may be most beneficial for supporting successful physical activity promotion in elementary schools.


Asunto(s)
Ejercicio Físico , Instituciones Académicas , Humanos , Correlación de Datos , Educación y Entrenamiento Físico , Políticas
20.
Front Sports Act Living ; 5: 1240382, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37720079

RESUMEN

Introduction: Schools play an important role in promoting physical activity for youth. However, school-based physical activity opportunities often compete with other academic priorities, limiting their implementation. The purpose of this study was to qualitatively explore elementary school teacher and staff perspectives on providing physical activity opportunities and how they impact students and learning. Methods: We partnered with a school district in Texas to conduct semi-structured individual interviews. We used a purposeful sampling approach to recruit elementary teachers and staff knowledgeable about the physical activity opportunities provided at their school. Interviews included questions about participant opinions of providing physical activity opportunities and the types of opportunities provided. We analyzed data using a directed content analysis and iterative categorization approach. Results: Fifteen participants (4 teachers, 4 physical education teachers, 3 assistant principals, and 4 principals) completed interviews from 10 elementary schools. Participants discussed observed and perceived benefits when providing physical activity opportunities, which emerged into four themes and subthemes: (1) academic benefits (learning readiness, learning engagement, and academic performance); (2) social-emotional benefits (behavior, interpersonal and social skills, and classroom culture); (3) physical benefits (brain health, skill development, physical health); and (4) instructional benefits (quality teaching time, helpful teaching tools, and teacher-student relationships). Conclusions: Teachers and staff observed numerous benefits when students had opportunities to be physically active, including the positive impact on academic and social-emotional outcomes. Our findings highlight the alignment of physical activity with other school priorities. Physical activity programming can be used in ways to support academics, learning, behavior, and other important outcomes.

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