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1.
medRxiv ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38712173

RESUMO

Rationale: C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV (PWH). However, its performance among people without HIV and in diverse settings is unknown. Objectives: In a multi-country study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ≥90%, specificity ≥70%) for an effective TB triage test. Methods/Measurements: Consecutive outpatient adults with cough ≥2 weeks from five TB endemic countries in Africa and Asia had baseline blood collected for point-of-care CRP testing and HIV and diabetes screening. Sputum samples were collected for Xpert MTB/RIF Ultra (Xpert) testing and culture. CRP sensitivity and specificity (5 mg/L cut-point) was determined in reference to sputum test results and compared by country, sex, and HIV and diabetes status. Variables affecting CRP performance were identified using a multivariate receiver operating characteristic (ROC) regression model. Results: Among 2904 participants, of whom 613 (21%) had microbiologically-confirmed TB, CRP sensitivity was 84% (95% CI: 81-87%) and specificity was 61% (95% CI: 59-63%). CRP accuracy varied geographically, with higher sensitivity in African countries (≥91%) than Asian countries (64-82%). Sensitivity was higher among men than women (87% vs. 79%, difference +8%, 95% CI: 1-15%) and specificity was higher among people without HIV than PWH (64% vs. 45%, difference +19%, 95% CI: 13-25%). ROC regression identified country and measures of TB disease severity as predictors of CRP performance. Conclusions: Overall, CRP did not achieve the minimum accuracy targets and its performance varied by setting and in some sub-groups, likely reflecting population differences in mycobacterial load.

2.
Nat Commun ; 15(1): 4081, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744844

RESUMO

Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , COVID-19/imunologia , Feminino , Masculino , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/imunologia , Pessoa de Meia-Idade , Imunogenicidade da Vacina , Adulto Jovem , Eficácia de Vacinas , Vietnã , Adolescente , Vacinas de mRNA , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/administração & dosagem
3.
Br J Pharmacol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38751168

RESUMO

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron (MN) loss and consequent muscle atrophy, for which no effective therapies are available. Recent findings reveal that disease progression is fuelled by early aberrant neuroinflammation and the loss of oligodendrocytes with neuroprotective and remyelinating properties. On this basis, pharmacological interventions capable of restoring a pro-regenerative local milieu and re-establish proper oligodendrocyte functions may be beneficial. EXPERIMENTAL APPROACH: Here, we evaluated the in vivo therapeutic effects of montelukast (MTK), an antagonist of the oligodendroglial G protein-coupled receptor 17 (GPR17) and of cysteinyl-leukotriene receptor 1 (CysLT1R) receptors on microglia and astrocytes, in the SOD1G93A ALS mouse model. We chronically treated SOD1G93A mice with MTK, starting from the early symptomatic disease stage. Disease progression was assessed by behavioural and immunohistochemical approaches. KEY RESULTS: Oral MTK treatment significantly extended survival probability, delayed body weight loss and ameliorated motor functionalityonly in female SOD1G93A mice. Noteworthy, MTK significantly restored oligodendrocyte maturation and induced significant changes in the reactive phenotype and morphological features of microglia/macrophages and astrocytes in the spinal cord of female SOD1G93A mice, suggesting enhanced pro-regenerative functions. Importantly, concomitant MN preservation has been detected after MTK administration. No beneficial effects were observed in male mice, highlighting a sex-based difference in the protective activity of MTK. CONCLUSIONS AND IMPLICATIONS: Our results provide the first preclinical evidence indicating that repurposing of MTK, a safe and marketed anti-asthmatic drug, may be a promising sex-specific strategy for personalized ALS treatment.

4.
Scand J Public Health ; : 14034948241247612, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38679806

RESUMO

AIM: This study aimed to investigate awareness of having hypertension, diabetes and dyslipidaemia and their associated factors among US adults. METHODS: Data from the National Health and Nutrition Examination Survey, including 21,399 adults aged ⩾20 years (pregnant women excluded) collected between 2011 and 2018, were used. Blood pressure was measured using a Baumanometer calibrated mercury true gravity wall model sphygmomanometer. Serum total cholesterol levels were measured using enzymatic assays. The percentage of haemoglobin A1C (HbA1c), which reflects long-term blood glucose levels, was measured and used to identify diabetes. Participants self-reported whether they were told by a doctor that they have hypertension, dyslipidaemia and diabetes. Awareness was defined as alignment between objective and self-reported measures for having the conditions. Sampling weights and the Taylor series linearisation variance estimation method were used in the analyses. RESULTS: The findings showed that 64.06% of people with hypertension, 54.71% of those with dyslipidaemia and 78.40% of those with diabetes were aware of having the respective condition. Age, sex and health insurance were associated with awareness of having all three conditions, but marital status was not associated with any outcome. Weight status was associated with awareness of having hypertension and dyslipidaemia, whereas ethnicity was associated with awareness of having hypertension and diabetes. Relative family income was only associated with awareness of having hypertension. CONCLUSIONS: Large proportions of US adults with hypertension, dyslipidaemia and diabetes are not aware of having the conditions. Interventions targeting groups at higher risk of being unaware of these conditions are needed.

5.
Drug Alcohol Depend ; 258: 111264, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38547786

RESUMO

INTRODUCTION: Cigarettes are frequently co-used with alcohol and cannabis. However, definitions of co-use vary and the extent to which cigarette use changes on days with different patterns of co-use is unclear. We compared the number of cigarettes smoked on different days based on co-use patterns of cigarettes and alcohol or cannabis. METHODS: This study analyzed 2408 smoking days collected in a 30-day smartphone-based daily diary study among 146 young adults (aged 18-26) with an oversample from sexual minority groups. Two separate multilevel models were estimated: one for cigarette and alcohol co-use and the other for cigarette and cannabis co-use. Both models examined day-level associations between the number of cigarettes smoked and 3 different types of days (smoking-only days, same-occasion co-use days, different-occasion co-use days), controlling for demographic characteristics. RESULTS: More cigarettes were smoked on same-occasion co-use days compared to cigarette-smoking-only days for both alcohol (b=1.474, SE=0.136, t=10.8, p<.001) and cannabis (b=0.822, SE=0.209, t=3.9, p<.001). There were no significant differences in cigarettes smoked on days with co-use on the same day, but on different occasions, compared to days with smoking only. CONCLUSIONS: Compared to days with cigarette smoking only, more cigarettes are smoked on days when cigarettes are co-used with alcohol or cannabis on the same occasion, while the same is not true for days with co-use on different occasions. Conflating different definitions of co-use may impact findings on associations between co-use and smoking behavior.


Assuntos
Consumo de Bebidas Alcoólicas , Fumar Cigarros , Fumar Maconha , Humanos , Masculino , Feminino , Adulto Jovem , Consumo de Bebidas Alcoólicas/epidemiologia , Adulto , Adolescente , Fumar Cigarros/epidemiologia , Fumar Maconha/epidemiologia , Fumar/epidemiologia , Smartphone
6.
J Clin Tuberc Other Mycobact Dis ; 35: 100431, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38523706

RESUMO

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.

7.
PLoS Comput Biol ; 20(2): e1011815, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38306397

RESUMO

Clinical imaging modalities are a mainstay of modern disease management, but the full utilization of imaging-based data remains elusive. Aortic disease is defined by anatomic scalars quantifying aortic size, even though aortic disease progression initiates complex shape changes. We present an imaging-based geometric descriptor, inspired by fundamental ideas from topology and soft-matter physics that captures dynamic shape evolution. The aorta is reduced to a two-dimensional mathematical surface in space whose geometry is fully characterized by the local principal curvatures. Disease causes deviation from the smooth bent cylindrical shape of normal aortas, leading to a family of highly heterogeneous surfaces of varying shapes and sizes. To deconvolute changes in shape from size, the shape is characterized using integrated Gaussian curvature or total curvature. The fluctuation in total curvature (δK) across aortic surfaces captures heterogeneous morphologic evolution by characterizing local shape changes. We discover that aortic morphology evolves with a power-law defined behavior with rapidly increasing δK forming the hallmark of aortic disease. Divergent δK is seen for highly diseased aortas indicative of impending topologic catastrophe or aortic rupture. We also show that aortic size (surface area or enclosed aortic volume) scales as a generalized cylinder for all shapes. Classification accuracy for predicting aortic disease state (normal, diseased with successful surgery, and diseased with failed surgical outcomes) is 92.8±1.7%. The analysis of δK can be applied on any three-dimensional geometric structure and thus may be extended to other clinical problems of characterizing disease through captured anatomic changes.


Assuntos
Aorta , Dissecção Aórtica , Humanos , Aorta/diagnóstico por imagem , Aorta/cirurgia , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia
8.
Nicotine Tob Res ; 26(Supplement_1): S27-S35, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38366340

RESUMO

OBJECTIVE: Social media platforms are promising to provide smoking cessation support. This study aimed to identify baseline factors associated with cigarette smoking abstinence among young adult smokers enrolled in a real-world social media-based smoking cessation program. AIMS AND METHODS: We analyzed data from young adult smokers (aged 18-30 years) participating in a publicly available Facebook-based smoking cessation program serving the San Francisco Bay Area. The analytic sample consisted of 248 participants who completed both the baseline and follow-up surveys at 3 months. Multivariable logistic regression analysis determined baseline factors significantly associated with self-reported 7-day cigarette smoking abstinence at 3 months. RESULTS: Participants were race/ethnically diverse, well-educated, and 47.6% reported LGB + sexual identity. Those who reported dual use of cigarettes and e-cigarettes in the past 30 days (vs. cigarette use only), current alcohol users (vs. non-users), and those aged 25-30 years (vs. 18-24 years) were significantly less likely to report 7-day abstinence at 3 months. Non-daily smokers (vs. daily smokers) and those with high desire to quit smoking (vs. low to moderate desire) were more likely to report abstinence. Results also showed reduction in the percentage of e-cigarette and other tobacco product use among participants. CONCLUSIONS: Social media interventions may be more effective for young adult non-daily smokers and those with high desire to quit smoking. Smoking cessation programs may help reduce use of other tobacco products among treatment-seeking smokers. Smoking cessation interventions for young adults need to explicitly address dual use of cigarettes and e-cigarettes and use of alcohol. IMPLICATIONS: Findings of this study highlight the need for future interventions to address dual use of cigarettes and e-cigarettes and use of alcohol to improve cigarette smoking abstinence outcomes. The reduction in the use of other tobacco products among program participants indicates that social media smoking cessation programs may exert a broader positive influence on overall tobacco consumption. The large number of LGB+ smokers participating in the program suggests social media is a promising cessation channel for this hard-to-reach group, warranting further study.


Assuntos
Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar , Mídias Sociais , Humanos , Adulto Jovem , Abandono do Hábito de Fumar/métodos , Fumantes
9.
NEJM Evid ; 3(3): EVIDoa2300229, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38411454

RESUMO

Disease Odds for E-Cigarettes and Dual Use versus CigarettesE-cigarettes have been promoted as less harmful than cigarettes. In this meta-analysis, Glantz et al. show that for some diseases, e-cigarette disease risks were similar to cigarettes, and for others e-cigarettes were nearly as risky as cigarettes. The risks associated with dual use were higher than those for smoking alone.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Fumar/efeitos adversos , Fumar Tabaco , Produtos do Tabaco/efeitos adversos
10.
Addict Behav ; 152: 107971, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38281461

RESUMO

PURPOSE: Co-use of tobacco and cannabis is a common and complex behavior. The lack of harmonized measures of co-use yields confusion and inconsistencies in synthesizing evidence about the health effects of co-use. We aimed to classify co-use patterns based on temporal proximity and describe preferred products and motives for each pattern in order to improve co-use surveillance. METHODS: We conducted semi-structured interviews in a sample of 34 young adults (Mage = 22.8 years, 32.4 % female) during 2017-2019 in California, USA. We employed a qualitative thematic analysis to identify timing, reasons, and contexts for tobacco and cannabis co-use and classify co-use patterns. RESULTS: Four emergent patterns of co-use with increasing temporal proximity between tobacco use and cannabis use were: Same-month different-day co-use (Pattern 1); Same-day different-occasion co-use (Pattern 2); Same-occasion sequential co-use (Pattern 3); and Same-occasion simultaneous co-use (Pattern 4). Participants used various product combinations within each pattern. Similar motives for all patterns were socialization, product availability, and coping with stress/anxiety. Unique motive for temporally distant patterns (Patterns 1 and 2) was seeking substance-specific effects (e.g., stimulant effect from nicotine, relaxation effects from cannabis), while unique motives for temporally close patterns (Patterns 3 and 4) were seeking combined effects from both substances (e.g., more intense psychoactive effects, mitigating cannabis adverse effects) and behavioral trigger (e.g., cannabis use triggers tobacco use). CONCLUSIONS: Our classification of co-use patterns can facilitate consistency for measuring co-use and assessing its health impacts. Future research should also measure product types and motives for different patterns to inform intervention efforts.


Assuntos
Cannabis , Sistemas Eletrônicos de Liberação de Nicotina , Alucinógenos , Produtos do Tabaco , Humanos , Feminino , Adulto Jovem , Adulto , Masculino , Uso de Tabaco/epidemiologia , Nicotina
11.
Methods Mol Biol ; 2748: 267-278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38070119

RESUMO

Chimeric antigen receptor (CAR)-T cell immunotherapy emerges as an effective cancer treatment. However, significant safety concerns remain, such as cytokine release syndrome (CRS) and "on-target, off-tumor" cytotoxicity, due to a lack of precise control over conventional CAR-T cell activity. To address this issue, a nano-optogenetic approach has been developed to enable spatiotemporal control of CAR-T cell activity. This system is comprised of synthetic light-sensitive CAR-T cells and upconversion nanoparticles acting as an in situ nanotransducer, allowing near-infrared light to wirelessly control CAR-T cell immunotherapy.


Assuntos
Neoplasias , Receptores de Antígenos de Linfócitos T , Humanos , Receptores de Antígenos de Linfócitos T/genética , Imunoterapia , Neoplasias/terapia , Optogenética , Linfócitos T , Imunoterapia Adotiva
12.
BMC Public Health ; 23(1): 2372, 2023 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-38042797

RESUMO

BACKGROUND: Globally, most people with multidrug-resistant tuberculosis (MDR-TB) and their households experience catastrophic costs of illness, diagnosis, and care. However, the factors associated with experiencing catastrophic costs are poorly understood. This study aimed to identify risk factors associated with catastrophic costs incurrence among MDR-TB-affected households in Ho Chi Minh City (HCMC), Viet Nam. METHODS: Between October 2020 and April 2022, data were collected using a locally-adapted, longitudinal WHO TB Patient Cost Survey in ten districts of HCMC. Ninety-four people with MDR-TB being treated with a nine-month TB regimen were surveyed at three time points: after two weeks of treatment initiation, completion of the intensive phase and the end of the treatment (approximately five and 10 months post-treatment initiation respectively). The catastrophic costs threshold was defined as total TB-related costs exceeding 20% of annual pre-TB household income. Logistic regression was used to identify variables associated with experiencing catastrophic costs. A sensitivity analysis examined the prevalence of catastrophic costs using alternative thresholds and cost estimation approaches. RESULTS: Most participants (81/93 [87%]) experienced catastrophic costs despite the majority 86/93 (93%) receiving economic support through existing social protection schemes. Among participant households experiencing and not experiencing catastrophic costs, median household income was similar before MDR-TB treatment. However, by the end of MDR-TB treatment, median household income was lower (258 [IQR: 0-516] USD vs. 656 [IQR: 462-989] USD; p = 0.003), and median income loss was higher (2838 [IQR: 1548-5418] USD vs. 301 [IQR: 0-824] USD; p < 0.001) amongst the participant households who experienced catastrophic costs. Being the household's primary income earner before MDR-TB treatment (aOR = 11.2 [95% CI: 1.6-80.5]), having a lower educational level (aOR = 22.3 [95% CI: 1.5-344.1]) and becoming unemployed at the beginning of MDR-TB treatment (aOR = 35.6 [95% CI: 2.7-470.3]) were associated with experiencing catastrophic costs. CONCLUSION: Despite good social protection coverage, most people with MDR-TB in HCMC experienced catastrophic costs. Incurrence of catastrophic costs was independently associated with being the household's primary income earner or being unemployed. Revision and expansion of strategies to mitigate TB-related catastrophic costs, in particular avoiding unemployment and income loss, are urgently required.


Assuntos
Custos de Cuidados de Saúde , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Estudos Prospectivos , Vietnã/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Renda
13.
PLOS Glob Public Health ; 3(12): e0002439, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38055709

RESUMO

To achieve the Sustainable Development Goal's targets of universal health coverage (UHC) and poverty reduction, interventions are required that strengthen and harmonize both UHC and social protection. Vietnam is committed to achieving financial protection and over 90% of the general population has enrolled in its social health insurance (SHI) scheme. However, an estimated 63% of tuberculosis (TB)-affected households in Vietnam still face catastrophic costs and little is known about the optimal strategies to mitigate the costs of TB care for vulnerable families. This study assessed the acceptability of a social protection package containing cash transfers and SHI using individual interviews (n = 19) and focus group discussions (n = 3 groups). Interviews were analyzed through framework analysis. The study's main finding indicated that both conditional and unconditional cash transfers paired with SHI were acceptable, across six dimensions of acceptability. Cash transfers were considered beneficial for mitigating out-of-pocket expenditure, increasing TB treatment adherence, and improving mental health and general well-being, but the value provided was inadequate to fully alleviate the economic burden of the illness. The conditionality of the cash transfers was not viewed by participants as inappropriate, but it increased the workload of the TB program, which brought into question the feasibility of scale-up. SHI was viewed as a necessity by almost all participants, but people with TB questioned the quality of care received when utilizing it for auxiliary TB services. Access to multiple sources of social protection was deemed necessary to fully offset the costs of TB care. Additional research is needed to assess the impact of cash transfer interventions on health and economic outcomes in order to create an enabling policy environment for scale-up.

14.
Molecules ; 28(22)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38005345

RESUMO

Thickener, also known as a gelling agent, is a critical component of lubricating greases. The most critical property of thickener, temperature resistance, is determined by the molecular structure of the compounds. Currently, all high-temperature-resistant thickeners are based on 12-hydroxystearic acid, which is exclusively produced from castor oil. Since castor oil is also an important reagent for other processes, finding a sustainable alternative to 12-hydroxystearic acid has significant economic implications. This study synthesises an alternative thickener from abundant agricultural waste, cashew nut shell liquor (CNSL). The synthesis and separation procedure contains three steps: (i) forming and separating calcium anacardate by precipitation, (ii) forming and separating anacardic acid (iii) forming lithium anacardate. The obtained lithium anacardate can be used as a thickener for lubricating grease. It was found that the recovery of anacardic acid was around 80%. The optimal reaction temperature and time conditions for lithium anacardate were 100 °C and 1 h, respectively. The method provides an economical alternative to castor and other vegetable oils. The procedure presents a simple pathway to produce the precursor for the lubricating grease from agricultural waste. The first reaction step can be combined with the existing distillation of cashew nut shell processing. An effective application can promote CNSL to a sustainable feedstock for green chemistry. The process can also be combined with recycled lithium from the spent batteries to improve the sustainability of the battery industry.

15.
Soft Matter ; 19(47): 9206-9214, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37997177

RESUMO

While buckling is a time independent phenomenon for filaments or films bonded to soft elastic substrates, time evolution plays an important role when the substrate is a viscous fluid. Here we show that buckling instabilities in fluid-structure interactions can be reduced to the analysis of a growth function that amplifies the initial noise characterizing experimental or numerical error. The convolution between a specific growth function and noise leads to natural imperfections that emerge in the form of wave packets with a large scale modulation that can transform into localized structures depending on nonlinear effects. Specifically, we provide an experimental example where these wave packets are amplified into ridges for sufficiently low compression rates or are diluted into wrinkles for high compression rates.

16.
Front Public Health ; 11: 1231326, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37794894

RESUMO

Introduction: The outbreak of coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) had significant effects on the mental well-being in general, particularly for healthcare professionals. This study examined the prevalence of depression, anxiety, and stress, and identified the associated risk factors amongst healthcare workers during the COVID-19 outbreak in a tertiary hospital located in Vietnam. Methods: We conducted a cross-sectional study at a tertiary-level hospital, where the Depression Anxiety and Stress Scale 21 (DASS-21) web-based questionnaire was employed. We analyzed the determinant factors by employing multivariate logistic models. Results: The prevalence of depression, anxiety, and stress symptoms were 19.2%, 24.7%, and 13.9%, respectively. Factors such as engaging in shift work during the pandemic, taking care of patients with COVID-19, and staff's health status were associated with mental health issues among health professionals. In addition, having alternate rest periods was likely to reduce the risk of stress. Conclusion: The prevalence of mental health problems in healthcare workers during the COVID-19 pandemic was relatively high. Having resting periods could potentially mitigate the development of stress among health professionals. Our findings could be taken into account for improving mental health of the health professional population.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Estudos Transversais , SARS-CoV-2 , Depressão/epidemiologia , RNA Viral , Centros de Atenção Terciária , Vietnã/epidemiologia , Ansiedade/epidemiologia , Pessoal de Saúde/psicologia
17.
J Biochem ; 175(1): 57-67, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-37812440

RESUMO

The Bin-Amphiphysin-Rvs (BAR) domain of endophilin binds to the cell membrane and shapes it into a tubular shape for endocytosis. Endophilin has a Src-homology 3 (SH3) domain at their C-terminal. The SH3 domain interacts with the proline-rich motif (PRM) that is found in proteins such as neural Wiskott-Aldrich syndrome protein (N-WASP). Here, we re-examined the binding sites of the SH3 domain of endophilin in N-WASP by machine learning-based prediction and identified the previously unrecognized binding site. In addition to the well-recognized PRM at the central proline-rich region, we found a PRM in front of the N-terminal WASP homology 1 (WH1) domain of N-WASP (NtPRM) as a binding site of the endophilin SH3 domain. Furthermore, the diameter of the membrane tubules in the presence of NtPRM mutant was narrower and wider than that in the presence of N-WASP and in its absence, respectively. Importantly, the NtPRM of N-WASP was involved in the membrane localization of endophilin A2 in cells. Therefore, the NtPRM contributes to the binding of endophilin to N-WASP in membrane remodeling.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte , Proteínas de Transporte/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Sítios de Ligação , Domínios de Homologia de src , Fatores de Transcrição/metabolismo , Prolina/metabolismo , Ligação Proteica
18.
Trop Med Infect Dis ; 8(9)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37755885

RESUMO

Active case finding (ACF) is a strategy that aims to identify people with tuberculosis (TB) earlier in their disease. This outreach approach may lead to a reduction in catastrophic cost incurrence (costs exceeding 20% of annual household income), a main target of WHO's End TB Strategy. Our study assessed the socio-economic impact of ACF by comparing patient costs in actively and passively detected people with TB. Longitudinal patient cost surveys were prospectively fielded for people with drug-sensitive pulmonary TB, with 105 detected through ACF and 107 passively detected. Data were collected in four Vietnamese cities between October 2020 and March 2022. ACF reduced pre-treatment (USD 10 vs. 101, p < 0.001) and treatment costs (USD 888 vs. 1213, p < 0.001) in TB-affected individuals. Furthermore, it reduced the occurrence of job loss (15.2% vs. 35.5%, p = 0.001) and use of coping strategies (28.6% vs. 45.7%, p = 0.004). However, catastrophic cost incurrence was high at 52.8% and did not differ between cohorts. ACF did not significantly decrease indirect costs, the largest contributor to catastrophic costs. ACF reduces costs but cannot sufficiently reduce the risk of catastrophic costs. As income loss is the largest driver of costs during TB treatment, social protection schemes need to be expanded.

19.
Reprod Biol ; 23(4): 100798, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37717489

RESUMO

In the present study, we attempted to improve the developmental competence of vitrified immature porcine oocytes by the preservation of mitochondrial properties using Cyclosporin A (CsA, inhibitor of mitochondrial membrane permeability transition) and Docetaxel (stabilizer of microtubules, hence mitochondrial distribution). In Experiment 1, Mitotracker red staining revealed reduced mitochondrial activity (MA) in vitrified/warmed oocytes at 0 and 22 h of in vitro maturation (IVM) compared with fresh ones. However, by at 46 h of IVM, MA levels in vitrified oocytes were similar to those in fresh control. Treatment of oocytes with CsA or Docetaxel improved MA at 0 h and 22 h of IVM compared with non-treated vitrified oocytes. However, there were no significant differences among groups in percentages of survival, maturation and embryo development after subsequent IVM and parthenogenetic activation. Nevertheless, a pretreatment with a combination of 10 µg/mL CsA and 0.05 µM Docetaxel improved the blastocyst formation of vitrified oocytes compared with non-treatment counterparts (11.2 ± 1.6% vs 5.9 ± 1.6%, P < 0.05). In conclusion, vitrification reduced mitochondrial activity in GV-stage oocytes during 0-22 h of IVM; however, it was normalized by 46 h IVM. Docetaxel or CsA pretreatment alone did not improve development competence of vitrified oocytes. However, pretreatment with a combination of CsA and Docetaxel could improve blastocyst formation rates.


Assuntos
Ciclosporina , Vitrificação , Suínos , Animais , Ciclosporina/farmacologia , Docetaxel/farmacologia , Criopreservação/veterinária , Oócitos , Desenvolvimento Embrionário
20.
Sci Rep ; 13(1): 15209, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37709844

RESUMO

Current WHO-recommended diagnostic tools for tuberculosis infection (TBI) have well-known limitations and viable alternatives are urgently needed. We compared the diagnostic performance and accuracy of the novel QIAreach QuantiFERON-TB assay (QIAreach; index) to the QuantiFERON-TB Gold Plus assay (QFT-Plus; reference). The sample included 261 adults (≥ 18 years) recruited at community-based TB case finding events. Of these, 226 underwent Tuberculin Skin Tests and 200 returned for interpretation (TST; comparator). QIAreach processing and TST reading were completed at lower-level healthcare facilities. We conducted matched-pair comparisons for QIAreach and TST with QFT-Plus, calculated sensitivity, specificity and area under a receiver-operating characteristic curve (AUC), and analyzed concordant-/discordant-pair interferon-gamma (IFN-γ) levels. QIAreach sensitivity and specificity were 98.5% and 72.3%, respectively, for an AUC of 0.85. TST sensitivity (53.2%) at a 5 mm induration threshold was significantly below QIAreach, while specificity (82.4%) was statistically equivalent. The corrected mean IFN-γ level of 0.08 IU/ml and corresponding empirical threshold (0.05) of false-positive QIAreach results were significantly lower than the manufacturer-recommended QFT-Plus threshold (≥ 0.35 IU/ml). Despite QIAreach's higher sensitivity at equivalent specificity to TST, the high number of false positive results and low specificity limit its utility and highlight the continued need to expand the diagnostic toolkit for TBI.


Assuntos
Tuberculose Latente , Tuberculose , Adulto , Humanos , Teste Tuberculínico , Vietnã/epidemiologia , Tuberculose/diagnóstico , Tuberculose Latente/diagnóstico , Bioensaio , Interferon gama
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