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1.
JMIR Public Health Surveill ; 10: e50189, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564248

RESUMO

BACKGROUND: The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences. OBJECTIVE: This study focuses on assessing the prevalence and clustering of 5 unhealthy lifestyle behaviors among Vietnamese adults after recovering from COVID-19, with a specific emphasis on sex differences. METHODS: The cross-sectional data of 5890 survivors of COVID-19 in Vietnam were analyzed from December 2021 to October 2022. To examine the sex differences in 5 unhealthy lifestyle behaviors (smoking, drinking, unhealthy diet, physical inactivity, and sedentary behavior), the percentages were plotted along with their corresponding 95% CI for each behavior. Latent class analysis was used to identify 2 distinct classes of individuals based on the clustering of these behaviors: the "less unhealthy" group and the "more unhealthy" group. We examined the sociodemographic characteristics associated with each identified class and used logistic regression to investigate the factors related to the "more unhealthy" group. RESULTS: The majority of individuals (male participants: 2432/2447, 99.4% and female participants: 3411/3443, 99.1%) exhibited at least 1 unhealthy behavior, with male participants being more susceptible to multiple unhealthy behaviors. The male-to-female ratio for having a single behavior was 1.003, but it escalated to 25 for individuals displaying all 5 behaviors. Male participants demonstrated a higher prevalence of combining alcohol intake with sedentary behavior (949/2447, 38.8%) or an unhealthy diet (861/2447, 35.2%), whereas female participants tended to exhibit physical inactivity combined with sedentary behavior (1305/3443, 37.9%) or an unhealthy diet (1260/3443, 36.6%). Married male participants had increased odds of falling into the "more unhealthy" group compared to their single counterparts (odds ratio [OR] 1.45, 95% CI 1.14-1.85), while female participants exhibited lower odds (OR 0.65, 95% CI 0.51-0.83). Female participants who are underweight showed a higher likelihood of belonging to the "more unhealthy" group (OR 1.11, 95% CI 0.89-1.39), but this was not observed among male participants (OR 0.6, 95% CI 0.41-0.89). In both sexes, older age, dependent employment, high education, and obesity were associated with higher odds of being in the "more unhealthy" group. CONCLUSIONS: The study identified notable sex differences in unhealthy lifestyle behaviors among survivors of COVID-19. Male survivors are more likely to engage in unhealthy behaviors compared to female survivors. These findings emphasize the importance of tailored public health interventions targeting sex-specific unhealthy behaviors. Specifically, addressing unhealthy habits is crucial for promoting post-COVID-19 health and well-being.


Assuntos
COVID-19 , Caracteres Sexuais , Adulto , Feminino , Masculino , Humanos , Análise de Classes Latentes , Estudos Transversais , Pandemias , COVID-19/epidemiologia , Análise por Conglomerados , Estilo de Vida
2.
Cureus ; 16(3): e55792, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586804

RESUMO

In recent years, there has been an increase in the prevalence of the diagnosis of attention-deficit/hyperactivity disorder (ADHD), a cognitive and behavioral disorder in which individuals present with inattention and impulsivity, in the pediatric population. With an increase in diagnoses, there is also increasing concern regarding overdiagnosis and overtreatment with medications for ADHD. The objective of this study was to map out and compile the recent literature pertaining to alternative therapies (e.g., physical activity, diet, mindfulness, and computer-based interventions) for children and adolescents diagnosed with ADHD in an attempt to reduce or replace the use of pharmacological therapy. This scoping review searched articles from multiple databases (PubMed, ScienceDirect, Web of Science, Directory of Open Access Journals, Scopus, and CINAHL). Using search terms "children with ADHD," "alternative treatment," and "cognitive behavioral therapy," articles were identified that were specific to the research question. The inclusion criteria were patients under the age of 18 with a previous diagnosis of ADHD, no other comorbid illnesses, alternative treatments, and was limited to studies published between 2012 and 2022. After removing duplicates, screening for eligibility criteria, and conducting a critical appraisal of the articles, 16 articles were retained for the final review. The main alternative therapeutic domains that emerged were (1) physical activity, (2) diet, (3) mindfulness, (4) computer-based interventions, and (5) miscellaneous interventions. Seven articles assessed the effect of physical activity on executive and cognitive function in children and adolescents with ADHD. Most findings showed improvement with increased physical activity. Two articles explored the effect of diet on the improvement of ADHD symptoms and reported a positive impact. The two articles that evaluated the effects of mindfulness on ADHD symptoms reported a reduction in ADHD symptoms. Two studies evaluated the use of computer-based interventions as an adjunct treatment in children and adolescents with ADHD; improvements in symptoms were reported. One study each evaluated interventions based on music and nerve stimulation. These showed an improvement in attention, memory, and executive function. With the increasing prevalence of ADHD diagnosis in children and adolescents, alternative and/or adjunctive treatments may be a viable and valuable alternative to pharmaceutical interventions. The findings from this review suggest that multiple non-pharmacological interventions effectively reduce symptoms of ADHD in children and adolescents, including diet, exercise, mindfulness, computer-based interventions, music, and nerve stimulation. While there are implications for alternatives to be used in the future, more research is warranted using larger samples with controlled trials.

3.
Nat Prod Res ; : 1-10, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38600840

RESUMO

This phytochemistry investigation on the trunk of Morus alba L. resulted in the isolation of three triterpenoids, including a new gammacerane triterpenoid - morusacerane (1); along with two known compounds of betulinic acid (2) and ursolic acid (3). The structure elucidation was thoroughly conducted based on 1D, 2D-NMR and HRESIMS spectra, followed by a comparison with existing literatures. The evaluation on α-glucosidase inhibitory exhibited the great potential of the application of these isolated compounds in diabetes treatments. The results show that morusacerane (1), betulinic acid (2), and ursolic acid (3) demonstrate the strong inhibitory with the IC50 values of 106.1, 11.12, and 7.20 µM, respectively. All of these compounds interacted well with the allosteric site enzyme α-glucosidase MAL32 through H-bonds and hydrophobic interaction.

4.
Osong Public Health Res Perspect ; 15(1): 33-44, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38481048

RESUMO

BACKGROUND: The prevalence of posttraumatic stress disorder (PTSD) has increased, particularly among individuals who have recovered from coronavirus disease 2019 (COVID-19) infection. Health literacy is considered a "social vaccine" that helps people respond effectively to the pandemic. We aimed to investigate the association between long COVID-19 and PTSD, and to examine the modifying role of health literacy in this association. METHODS: A cross-sectional study was conducted at 18 hospitals and health centers in Vietnam from December 2021 to October 2022. We recruited 4,463 individuals who had recovered from COVID-19 infection for at least 4 weeks. Participants provided information about their sociodemographics, clinical parameters, health-related behaviors, health literacy (using the 12-item short-form health literacy scale), long COVID-19 symptoms and PTSD (Impact Event Scale-Revised score of 33 or higher). Logistic regression models were used to examine associations and interactions. RESULTS: Out of the study sample, 55.9% had long COVID-19 symptoms, and 49.6% had PTSD. Individuals with long COVID-19 symptoms had a higher likelihood of PTSD (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.63-2.12; p<0.001). Higher health literacy was associated with a lower likelihood of PTSD (OR, 0.98; 95% CI, 0.97-0.99; p=0.001). Compared to those without long COVID-19 symptoms and the lowest health literacy score, those with long COVID-19 symptoms and a 1-point health literacy increment had a 3% lower likelihood of PTSD (OR, 0.97; 95% CI, 0.96-0.99; p=0.001). CONCLUSION: Health literacy was found to be a protective factor against PTSD and modified the negative impact of long COVID-19 symptoms on PTSD.

5.
Am J Pathol ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38548267

RESUMO

Hepatocellular carcinoma (HCC) was associated with increased soluble CD40 levels in a previous study. This study aimed to investigate CD40's role in liver tumor progression. CD40 levels were examined in HCC patient tissues and various HCC cell lines, and their interaction with CD4+T cells was studied. RNA sequencing analysis was performed to explore the mechanisms of CD40 induction. Poorly differentiated HCC tumor tissues exhibited high membrane-bound CD40 expression, in contrast to nontumor areas. Poorly differentiated HCC cell lines showed high expression of membrane-bound CD40 with low CD40 promoter methylation, which was opposite of well-differentiated ones. Solely modulating CD40 expression in HCC cells exerted no direct consequences on cell growth or appearance. Interestingly, HLFs co-cultured with activated (CD40 ligand+) CD4+ T cells increased CD40 levels and showed a modest 3.2% dead cells, then increased to 10.9% underwent preneutralizing CD40 condition, whereas preblocking both CD40 and integrin α5ß1 concomitantly caused only 1.9% cell death. RNA sequencing of co-cultured HLFs with activated CD4+ T cells revealed the up-regulation of interferon and immune-response pathways. Increased interferon-γ levels in the activated T-cell media stimulated the Janus kinase/signal transducer and activator of transcription 3 pathway, resulting in increased CD40 expression in HLF. Collectively, CD40 expression in poorly differentiated HCC cells prevents cell death by interacting with CD40 ligand in activated T cells. Targeting CD40 may represent a promising anticancer therapy.

6.
Nat Commun ; 15(1): 1640, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388531

RESUMO

THOC6 variants are the genetic basis of autosomal recessive THOC6 Intellectual Disability Syndrome (TIDS). THOC6 is critical for mammalian Transcription Export complex (TREX) tetramer formation, which is composed of four six-subunit THO monomers. The TREX tetramer facilitates mammalian RNA processing, in addition to the nuclear mRNA export functions of the TREX dimer conserved through yeast. Human and mouse TIDS model systems revealed novel THOC6-dependent, species-specific TREX tetramer functions. Germline biallelic Thoc6 loss-of-function (LOF) variants result in mouse embryonic lethality. Biallelic THOC6 LOF variants reduce the binding affinity of ALYREF to THOC5 without affecting the protein expression of TREX members, implicating impaired TREX tetramer formation. Defects in RNA nuclear export functions were not detected in biallelic THOC6 LOF human neural cells. Instead, mis-splicing was detected in human and mouse neural tissue, revealing novel THOC6-mediated TREX coordination of mRNA processing. We demonstrate that THOC6 is required for key signaling pathways known to regulate the transition from proliferative to neurogenic divisions during human corticogenesis. Together, these findings implicate altered RNA processing in the developmental biology of TIDS neuropathology.


Assuntos
Deficiência Intelectual , RNA , Estilbenos , Ácidos Sulfônicos , Humanos , Animais , Camundongos , RNA/metabolismo , Deficiência Intelectual/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Processamento Pós-Transcricional do RNA , Transporte de RNA , Mamíferos/genética , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
7.
Eur J Med Chem ; 268: 116162, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38394930

RESUMO

Human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease with current treatments marred by severe side effects or delivery issues. To identify novel classes of compounds for the treatment of HAT, high throughput screening (HTS) had previously been conducted on bloodstream forms of T. b. brucei, a model organism closely related to the human pathogens T. b. gambiense and T. b. rhodesiense. This HTS had identified a number of structural classes with potent bioactivity against T. b. brucei (IC50 ≤ 10 µM) with selectivity over mammalian cell-lines (selectivity index of ≥10). One of the confirmed hits was an aroyl guanidine derivative. Deemed to be chemically tractable with attractive physicochemical properties, here we explore this class further to develop the SAR landscape. We also report the influence of the elucidated SAR on parasite metabolism, to gain insight into possible modes of action of this class. Of note, two sub-classes of analogues were identified that generated opposing metabolic responses involving disrupted energy metabolism. This knowledge may guide the future design of more potent inhibitors, while retaining the desirable physicochemical properties and an excellent selectivity profile of the current compound class.


Assuntos
Parasitos , Tripanossomicidas , Trypanosoma brucei brucei , Trypanosoma , Tripanossomíase Africana , Animais , Humanos , Tripanossomicidas/química , Trypanosoma brucei rhodesiense , Guanidina/farmacologia , Tripanossomíase Africana/tratamento farmacológico , Tripanossomíase Africana/parasitologia , Guanidinas/farmacologia , Metabolismo Energético , Mamíferos
9.
Ophthalmol Retina ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38403242

RESUMO

PURPOSE: To examine retinal feature dynamics in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF therapy and the relationship of these features with visual acuity. DESIGN: Post hoc analysis of the phase III, randomized, HAWK nAMD clinical trial. PARTICIPANTS: Participants randomized to the brolucizumab 6 mg or aflibercept 2 mg arms of the trial. METHODS: Spectral-domain OCT scans collected at 4-week intervals were analyzed using an automated machine learning-enhanced segmentation and feature-extraction platform with manual verification. Quantitative volumetric measures of retinal and exudative features were exported at multiple timepoints over 48 weeks. Volatility of exudative features was calculated as the standard deviation of each feature value during the maintenance phase (week 12-48) of treatment. These features were examined for their associations with anatomic and functional outcomes. MAIN OUTCOME MEASURES: Longitudinal intraretinal fluid (IRF) and subretinal fluid (SRF) volume, subretinal hyperreflective material (SHRM) volume, ellipsoid zone (EZ) integrity (EZ-retinal pigment epithelium [RPE] volume/thickness), and correlation with best-corrected visual acuity (BCVA). RESULTS: Intraretinal fluid, SRF, and SHRM demonstrated significant volumetric reduction from baseline with anti-VEGF therapy (P < 0.001 at each timepoint). Ellipsoid zone integrity measures demonstrated significant improvement from baseline (P < 0.001 at each timepoint). Both EZ integrity and SHRM measures correlated significantly with BCVA at all timepoints (EZ-RPE volume: 0.38 ≤ r ≤ 0.47; EZ-RPE central subfield thickness: 0.22 ≤ r ≤ 0.41; SHRM volume: -0.33 ≤ r ≤ -0.44). After treatment initiation, correlations of IRF and SRF volume with BCVA were weak or nonsignificant. Eyes with lower volatility of IRF, SRF, and SHRM volumes during the maintenance phase showed greater improvements in EZ integrity (all P < 0.01) and greater gains in BCVA (all P < 0.01) at week 48 compared with eyes with higher volatility in those exudative parameters. CONCLUSIONS: Quantitative measures of SHRM volume and EZ integrity correlated more strongly with BCVA than retinal fluid volumes during treatment. High volatility of exudative parameters, including SRF, during the maintenance phase of treatment was associated with loss of EZ integrity and BCVA. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

10.
Sci Adv ; 10(9): eadm7605, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38416820

RESUMO

Cerebral perfusion is critical for the early detection of neurological diseases and for effectively monitoring disease progression and treatment responses. Mouse models are widely used in brain research, often under anesthesia, which can affect vascular physiology. However, the impact of anesthesia on regional cerebral blood volume and flow in mice has not been thoroughly investigated. In this study, we have developed a whole-brain perfusion MRI approach by using a 5-second nitrogen gas stimulus under inhalational anesthetics to induce transient BOLD dynamic susceptibility contrast (DSC). This method proved to be highly sensitive, repeatable within each imaging session, and across four weekly sessions. Relative cerebral blood volumes measured by BOLD DSC agree well with those by contrast agents. Quantitative cerebral blood volume and flow metrics were successfully measured in mice under dexmedetomidine and various isoflurane doses using both total vasculature-sensitive gradient-echo and microvasculature-sensitive spin-echo BOLD MRI. Dexmedetomidine reduces cerebral perfusion, while isoflurane increases cerebral perfusion in a dose-dependent manner.


Assuntos
Anestesia , Dexmedetomidina , Isoflurano , Animais , Camundongos , Isoflurano/farmacologia , Dexmedetomidina/farmacologia , Imageamento por Ressonância Magnética/métodos , Hipóxia , Encéfalo/irrigação sanguínea , Perfusão , Circulação Cerebrovascular/fisiologia
12.
Nat Prod Res ; : 1-8, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38258412

RESUMO

Two new hopan-type triterpenoids, namely tinctoric acid A-B (1-2), were isolated from the lichen Parmotrema tinctorum (Despr. ex Nyl.) Hale. Their structures were elucidated by extensive spectroscopic analyses (1D and 2D NMR). The absolute configuration at C-22 of 1 was established through DP4 probability. Compounds 1-2 were evaluated for their inhibitory activity against α-glucosidase and found to be more potent than those of positive control (acarbose, IC50 168 µM) with values IC50 74.7 and 98.2 µM, respectively. Both of these compounds interacted well with enzyme α-glucosidase MAL32 through H-bonds and hydrophobic interaction.

13.
Arch Environ Contam Toxicol ; 86(1): 48-57, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38063883

RESUMO

The seeds of Annona glabra L., an invasive plant in Vietnam, were first employed as a new biosorbent for the adsorption of methylene blue (MB) from aqueous media. The characterizations of the material using FT-IR, SEM, nitrogen adsorption-desorption analysis, and point of zero charge reveals that it possesses a rough and irregular surface, various polar functional groups, and pHpzc of 5.5. Certain adsorption conditions including adsorbent dose, solution pH, contact time, and initial concentration of MB were found to affect adsorption efficiency. The kinetic data are well fitted with pseudo-second-order model with the adsorption rate of 0.002 g mg-1 min-1 and initial rate of 4.46 mg g-1 min-1. For the adsorption isotherm, three nonlinear models were used to analyze the experiment data, including Langmuir, Freundlich, and Temkin. The results indicate that the Langmuir model best describes the adsorption of Annona glabra L. seeds powder (AGSP) with a maximum adsorption capacity of 98.0 mg g-1. The investigation underpins the adsorption mechanism, whereby the electrostatic attraction between positively charged MB and negatively charged surface of AGSP is expected to be the predominant mechanism, together with hydrogen bonding and pi-pi interaction. These results make AGSP an interesting biosorbent concerning its environmental friendliness, cost-effectiveness, and relatively high dye adsorption capacity.


Assuntos
Annona , Poluentes Químicos da Água , Azul de Metileno/análise , Azul de Metileno/química , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio , Sementes/química , Adsorção , Cinética
14.
Am J Prev Med ; 66(5): 877-882, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38143046

RESUMO

INTRODUCTION: The often-cited Centers for Disease Control and Prevention (CDC) estimate of 480,000 annual U.S. smoking-attributable deaths (SADs), including 439,000 first-hand smoke deaths, derives from 2005 to 2009 data. Since then, adult smoking prevalence has decreased by 40%, while the population has grown and the smoking population aged. An updated estimate is presented to determine whether the CDC figure remains accurate or has changed substantially. In addition, the likely annual smoking-related mortality toll is projected through 2035. METHODS: A well-established model of smoking prevalence and health effects is employed to estimate annual SADs among individuals exposed to first-hand smoke in the U.S. for two distinct periods: 2005-2009 and 2020-2035. The estimate for 2005-2009 serves as a benchmark to evaluate the reliability of the model's estimate in comparison to CDC's. The projections for 2020-2035 provide up-to-date figures for SADs, predicting how annual SADs are likely to change in the coming years. Data were collected between 2005 and 2020. The analysis was conducted in 2023. RESULTS: This study's estimate of 420,000 first-hand smoke deaths over 2005-2009 is 95.7% of CDC's estimate during the same period. The model projections indicate that SADs among individuals who currently smoke or formerly smoked have increased modestly since 2005-2009. Beginning in 2020, annual SADs will remain relatively stable at approximately 450,000 before starting to decline around 2030. CONCLUSIONS: These findings suggest that the CDC estimate of the annual mortality burden of smoking remains valid. Despite U.S. population growth and the aging of the smoking population, substantial reductions in smoking will finally produce a steady, if gradual, decline in SADs beginning around 2030.


Assuntos
Fumar , Poluição por Fumaça de Tabaco , Humanos , Estados Unidos/epidemiologia , Adulto , Fumar/epidemiologia , Fumar/mortalidade , Fumar/tendências , Masculino , Pessoa de Meia-Idade , Feminino , Prevalência , Poluição por Fumaça de Tabaco/efeitos adversos , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Idoso , Adulto Jovem , Centers for Disease Control and Prevention, U.S. , Adolescente
15.
Mol Biotechnol ; 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102344

RESUMO

The melon (Cucumis melo L.), a fruit crop of significant economic importance, is prized for its sweet and succulent fruits. Among variations of soluble sugars, sucrose, a disaccharide composed of glucose and fructose, is a key carbohydrate present in melon fruits. The sucrose content also determines the quality and value of melon fruits. However, the accumulation of sucrose is a complex process involving the coordinated actions of multiple enzymes and pathways. In melon species, there are two types of fruit ripening modes including climacteric and non-climacteric. Due to this biological characteristic, melon is emerging as a good model for studying the ripening process. Ethylene is a well-known phytohormone regulating the ripening of climacteric fruits. Recently, a few studies have elucidated a primary ethylene-dependent signaling pathway of sucrose accumulation in melon fruits. This review aims to provide a careful overview of the sucrose biosynthesis pathways in melon. It is essential to understand the molecular mechanisms of sucrose metabolism as well as its regulation mode. The information will be useful for developing molecular marker-assisted breeding as well as genetic engineering strategies aiming to improve the sucrose content and quality of melon fruits. In addition, even though limited, the impacts of genetic background and environmental factors on sucrose accumulation in melon fruits are also discussed. These are useful for practical applications in melon cultivation and quality management.

16.
Am J Hum Genet ; 110(12): 2112-2119, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-37963460

RESUMO

Over two dozen spliceosome proteins are involved in human diseases, also referred to as spliceosomopathies. WW domain-binding protein 4 (WBP4) is part of the early spliceosomal complex and has not been previously associated with human pathologies in the Online Mendelian Inheritance in Man (OMIM) database. Through GeneMatcher, we identified ten individuals from eight families with a severe neurodevelopmental syndrome featuring variable manifestations. Clinical manifestations included hypotonia, global developmental delay, severe intellectual disability, brain abnormalities, musculoskeletal, and gastrointestinal abnormalities. Genetic analysis revealed five different homozygous loss-of-function variants in WBP4. Immunoblotting on fibroblasts from two affected individuals with different genetic variants demonstrated a complete loss of protein, and RNA sequencing analysis uncovered shared abnormal splicing patterns, including in genes associated with abnormalities of the nervous system, potentially underlying the phenotypes of the probands. We conclude that bi-allelic variants in WBP4 cause a developmental disorder with variable presentations, adding to the growing list of human spliceosomopathies.


Assuntos
Deficiência Intelectual , Malformações do Sistema Nervoso , Transtornos do Neurodesenvolvimento , Humanos , Spliceossomos/genética , Transtornos do Neurodesenvolvimento/genética , Deficiência Intelectual/genética , Deficiência Intelectual/complicações , Síndrome , Malformações do Sistema Nervoso/genética , Perda de Heterozigosidade , Fenótipo
17.
Med Mycol ; 61(11)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37994652

RESUMO

Antifungal drug resistance is an emerging cause of treatment failure in invasive fungal infections, and antifungal susceptibility testing (AFST) may inform treatment decisions. Currently, there are no established AFST guidelines for Talaromyces marneffei (Tm) or other dimorphic fungi. We developed a colorimetric AFST method using a fluorescent redox indicator alamarBlue, which changes from blue to pink in proportion to cellular metabolic activity. We determined the optimal time for alamarBlue addition to be 24 h post-inoculation and for MIC reading to be 72 h post-inoculation. Our method allows three ways to determine minimum inhibitory concentration (MIC): visual inspection of color change, optical density, and fluorescence intensity. We validated the assay by determining the MICs for seven antifungals against 32 Tm clinical isolates and assessed the essential agreement (EA) and inter-rater reliability between our alamarBlue and the Clinical Laboratory Standard Institute (CLSI) broth microdilution methods. The MIC ranges (from low to high) were: 0.008-0.025 µg/ml for itraconazole, 0.004-0.13 µg/ml for voriconazole, 0.03-0.13 µg/ml for posaconazole, 0.06-0.5 µg/ml for flucytosine, 0.5-1 µg/ml for amphotericin B, 0.5-4 µg/ml for caspofungin, and 0.5-16 µg/ml for fluconazole. The EAs were 100% between all three MIC readouts of the alamarBlue method, and 94%-100% between the alamarBlue and CLSI methods. Our alamarBlue method had substantially higher inter-rater agreement and offers a more reliable method that can be standardized across laboratories in both high- and low-resource settings compared to the established CLSI methodology.


We developed a colorimetric alamarBlue method to determine the susceptibility of antifungal drugs against Talaromyces marneffei. We observed excellent agreement between the alamarBlue method and the Clinical Laboratory Standard Institute broth microdilution method, and the alamarBlue method had substantially higher inter-rater agreement.


Assuntos
Antifúngicos , Talaromyces , Animais , Antifúngicos/farmacologia , Colorimetria/veterinária , Reprodutibilidade dos Testes , Voriconazol/farmacologia , Testes de Sensibilidade Microbiana/veterinária
18.
Front Microbiol ; 14: 1238542, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869655

RESUMO

RT-qPCR remains a key diagnostic methodology for COVID-19/SARS-CoV-2. Typically, nasal or saliva swabs from patients are placed in virus transport media (VTM), RNA is extracted at the pathology laboratory, and viral RNA is measured using RT-qPCR. In this study, we describe the use of TNA-Cifer Reagent E in a pre-clinical evaluation study to inactivate SARS-CoV-2 as well as prepare samples for RT-qPCR. Adding 1 part TNA-Cifer Reagent E to 5 parts medium containing SARS-CoV-2 for 10 min at room temperature inactivated the virus and permitted RT-qPCR detection. TNA-Cifer Reagent E was compared with established column-based RNA extraction and purification methodology using a panel of human clinical nasal swab samples (n = 61), with TNA-Cifer Reagent E showing high specificity (100%) and sensitivity (97.37%). Mixtures of SARS-CoV-2 virus and TNA-Cifer Reagent E could be stored for 3 days at room temperature or for 2 weeks at 4°C without the loss of RT-qPCR detection sensitivity. The detection sensitivity was preserved when TNA-Cifer Reagent E was used in conjunction with a range of VTM for saliva samples but only PBS (Gibco) and Amies Orange for nasal samples. Thus, TNA-Cifer Reagent E improves safety by rapidly inactivating the virus during sample processing, potentially providing a safe means for molecular SARS-CoV-2 testing outside traditional laboratory settings. The reagent also eliminates the need for column-based and/or automated viral RNA extraction/purification processes, thereby providing cost savings for equipment and reagents, as well as reducing processing and handling times.

19.
BMC Public Health ; 23(1): 2076, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875887

RESUMO

BACKGROUND: Tracking the US smoking cessation rate over time is of great interest to tobacco control researchers and policymakers since smoking cessation behaviors have a major effect on the public's health. Recent studies have employed dynamic models to estimate the US cessation rate through observed smoking prevalence. However, none of those studies has provided annual estimates of the cessation rate by age group. Hence, the primary objective of this study is to estimate annual smoking cessation rates specific to different age groups in the US from 2009 to 2017. METHODS: We employed a Kalman filter approach to investigate the annual evolution of age-group-specific cessation rates, unknown parameters of a mathematical model of smoking prevalence, during the 2009-2017 period using data from the 2009-2018 National Health Interview Surveys. We focused on cessation rates in the 25-44, 45-64 and 65 + age groups. RESULTS: The findings show that cessation rates followed a consistent u-shaped curve over time with respect to age (i.e., higher among the 25-44 and 65 + age groups, and lower among 45-64-year-olds). Over the course of the study, the cessation rates in the 25-44 and 65 + age groups remained nearly unchanged around 4.5% and 5.6%, respectively. However, the rate in the 45-64 age group exhibited a substantial increase of 70%, from 2.5% to 2009 to 4.2% in 2017. The estimated cessation rates in all three age groups tended to converge to the weighted average cessation rate over time. CONCLUSIONS: The Kalman filter approach offers a real-time estimation of cessation rates that can be helpful for monitoring smoking cessation behavior.


Assuntos
Abandono do Hábito de Fumar , Humanos , Estados Unidos/epidemiologia , Abandono do Hábito de Fumar/métodos , Fumar/epidemiologia , Fumar Tabaco , Comportamentos Relacionados com a Saúde , Prevalência , Fatores Etários
20.
JAMA Netw Open ; 6(10): e2337101, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37862018

RESUMO

Importance: The prevalence of electronic nicotine delivery systems (ENDS) use among US youths has increased significantly during the past decade. Identifying key factors highly associated with ENDS use is essential in monitoring and preventing this harmful behavior among youths. Objective: To identify the most important risk factors in wave 4.5 (ie, December 2017 to December 2018) of the Population Assessment of Tobacco and Health Study (PATH) data that are associated with ENDS use in wave 5 (ie, December 2018 to November 2019) among adolescents who were tobacco-naive at baseline. Design, Setting, and Participants: This prognostic study examined data from waves 4.5 and 5 of the PATH youth data set using machine learning techniques. The PATH study is a nationally representative longitudinal cohort study of tobacco use and health in the United States among individuals aged 12 years and older. The data analysis was carried out between January and April 2023. Main Outcomes and Measures: Wave 5 current ENDS use status of wave 4.5 adolescents who were tobacco-naive. Results: The analyzed data set comprised 7943 individuals who were tobacco-naive in wave 4.5. Among this group, 332 participants (4.2%) indicated their present use of ENDS in wave 5, 5047 (63.5%) were aged 12 to 14 years, 4066 (51.2%) were male, and 2455 (30.9%) were Hispanic. The most important risk factors of ENDS use in wave 5 among adolescents who were tobacco-naive in wave 4.5 were the likelihood of using ENDS if offered by a best friend (mean SHAP value, 0.184), the number of best friends using e-cigarettes (mean SHAP value, 0.167), household tobacco usage (mean SHAP value, 0.161), curiosity about ENDS use (mean SHAP value, 0.088), future intention to use ENDS (mean SHAP value, 0.068), youth's total average weekly earnings (mean SHAP value, 0.060), and perceptions of tobacco product safety (mean SHAP value, 0.026). Conclusions and Relevance: The findings of this study suggest that family and friends play an important role in ENDS use among adolescents. The top-ranking factors associated with ENDS use in this study are areas for further exploration, given the increasing prevalence of ENDS use among youths in recent years. Additionally, these findings highlight the important role of families and schools in shaping adolescents' tobacco-related knowledge, which can protect them from using ENDS.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Masculino , Adolescente , Estados Unidos/epidemiologia , Feminino , Estudos Longitudinais , Fatores de Risco , Uso de Tabaco/epidemiologia , Estudos de Coortes
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