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BackgroundDespite the criticality of adherence to tuberculosis treatment, there is paucity of rigorous experimental research exploring the efficacy of interventions to promote adherence and a greater lack of inquiry addressing the integral role of adherence behaviour. The aim of this formative study was to examine the way in which the Wisepill evriMED Medication Event Reminder Monitor (MERM) was used among outpatients with drug susceptible pulmonary tuberculosis.MethodsIn depth interviews were conducted with 20 outpatients receiving treatment from two public healthcare facilities in Thanh Hoa, a rural province in northern Viet Nam. Patients had been enrolled in a randomized controlled trial evaluating the effect of using the MERM device upon adherence for between 1-3 months. The control group used the device without an alert, while the intervention group used the device with a daily alert and scheduled dosing history review.FindingsAll 20 patients interviewed were supportive of using the MERM device. Those able to be at home at the time that their treatment was due (50%) used the device as intended. Patients who worked all reported separating the time when the box was opened from the time at which they ingested their medication. Patients expressed fidelity to the prescribed medication taking time and concerns regarding the portability of the device. Limitations of the study surround the inclusion of a small sample population that did not experience factors that further compromise adherence.ConclusionsData recorded by the box did not always accurately reflect usage patterns. The alert in the intervention arm was able to support adherence only in patients who did not work while completing their treatment. MERM implementation can be improved by better aligning prescriber instructions with patients' daily routines, and increasing the use of adherence data to guide adherence support practices. Healthcare staff need to be aware of potential barriers to optimal use of MERM devices. A rigorous qualitative approach to formative assessment is essential to inform the scale up of new digital technologies.

ObjectiveManagement of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data.MethodWe conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence.ResultsOut of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 [1.91-37.42]), renal dysfunction (HR = 8.46 [1.91-37.42]), alcoholism (HR = 13.28 [5.04-34.99]), and a higher average daily dose of injectable drugs (HR = 1.28 [1.14-1.43]).ConclusionWhile a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.

ObjectivesVietnam is a high-prevalence country for tuberculosis (TB). Xpert MTB/RIF is a novel PCR-based diagnostic test that is substantially more sensitive for detecting M. tuberculosis than traditional smear-based techniques. However, locally-derived evidence of Xpert MTB/RIF in HIV-infected people is limited. This study evaluates the performance of the Xpert MTB/RIF in HIV-infected patients with smear-negative pulmonary TB (SNTB).MethodsThis was a cross-sectional study in 3 hospitals. The performance of Xpert MTB/RIF was compared with the reference standard of liquid culture and phenotypic drug-susceptibility testing for rifampicin (RIF) resistance.ResultsOut of 123 patients, the median age was 37.0 (IQR: 32.0-41.0) and 81.3% were male. The area under the receiver operating characteristic curve, sensitivity (Se) and specificity (Sp) of Xpert MTB/RIF for pulmonary TB diagnosis were 0.72 (95% confidence interval [CI]: 0.63-0.81), 66.7% (95%CI: 54.8-77.1) and 77.1% (95%CI: 62.7-88.0), respectively, while Se and Sp of Xpert MTB/RIF in detecting RIF resistance were 50.0 (11.8-88.2) and 86.4% (95%CI: 72.7-94.8).ConclusionThe performance of Xpert MTB/RIF in HIV-infected patients with SNTB for the diagnosis of TB and RIF-resistance was low. Further studies are required to evaluate the results of Xpert MTB/RIF assay in HIV-infected patients with SNTB and the role of Xpert repetition on the same specimens.

Nile tilapia (Oreochromis niloticus) is an African freshwater fish that displays a genetic sex determination system (XX|XY) where high temperatures (above 32°C to 36.5°C) induce masculinization. In Nile tilapia, the thermosensitive period was reported from 10 to 30 days post fertilization. In their natural environment, juveniles may encounter high temperatures that are above the optimal temperature for growth (27-30°C). The relevance of the thermal sex reversal mechanism in a natural context remains unclear. The main objective of our study is to determine whether sexually undifferentiated juveniles spontaneously prefer higher, unfavorable temperatures and whether this choice skews the sex ratio toward males. Five full-sib progenies (from 100% XX crosses) were subjected to (1) a horizontal three-compartment thermal step gradient (thermal continuum 28°C- 32°C- 36.5°C) during the thermosensitive period, (2) a control continuum (28°C- 28°C- 28°C) and (3) a thermal control tank (36.5°C). During the first days of the treatment, up to an average of 20% of the population preferred the masculinizing compartment of the thermal continuum (36.5°C) compared to the control continuum. During the second part of the treatment, juveniles preferred the lower, nonmasculinizing 32°C temperature. This short exposure to higher temperatures was sufficient to significantly skew the sex ratio toward males, compared to congeners raised at 28°C (from 5.0 ± 6.7% to 15.6 ± 16.5% of males). The proportion of males was significantly different in the thermal continuum, thermal control tank and control continuum, and it was positively correlated among populations. Our study shows for the first time that Nile tilapia juveniles can choose a masculinizing temperature during a short period of time. This preference is sufficient to induce sex reversal to males within a population. For the first time, behavior is reported as a potential player in the sex determination mechanism of this species.

[This corrects the article DOI: 10.1371/journal.pone.0212504.].

The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)ssaV(-)) ZH9 with two independently attenuating deletions. Studies in healthy adults demonstrated immunogenicity and an acceptable safety profile.We conducted a randomised placebo controlled, single-blind trial to evaluate the safety and immunogenicity of M01ZH09 in healthy Vietnamese children aged 5 to 14 years.Subjects were randomly assigned to receive either a nominal dose of 5x10(9) CFU of M01ZH09 or placebo and were followed up for 28 days. The primary safety outcome was the proportion of subjects with any adverse event attributed to M01ZH09. The primary immunogenicity endpoint was the proportion of subjects who showed a positive immune response to M01ZH09 in the Salmonella Typhi lipopolysaccharide (LPS) specific serum IgA and IgG ELISA.One hundred and fifty-one children were enrolled, 101 subjects received M01ZH09 and 50 subjects received placebo. An intention to treat analysis was conducted. There were no serious adverse events and no bacteraemias. In the M01ZH09 group, 26 (26%; 95% CI, 18-5%) of 101 subjects experienced adverse events compared to 11 (22%; 95% CI, 12-36%) of 50 subjects in the placebo group (odds ratio (OR) [95%CI] = 1.23 [0.550-2.747]; p = 0.691). Faecal shedding of S. Typhi (Ty2 aroC(-)ssaV(-)) ZH9 was detected in 51 (51%; 95% CI, 41-61%) of 100 M01ZH09 subjects. No shedding was detected beyond day 3. A positive immune response, defined as 70% increase (1.7 fold change) in LPS specific serum IgG (day 14 or 28) and/or 50% increase (1.5 fold change) in LPS specific serum IgA (day 7 or 14) from baseline was detected in 98 (97%; 95% CI, 92-99%) of 101 M01ZH09 recipients and 8 (16%; 95% CI, 7-29%) of 50 placebo recipients. Twenty-eight (100%; 95% CI, 88-100%) of 28 vaccine recipients who were evaluated in the LPS specific IgA ELISPOT assay showed a positive response compared to none of the 14 placebo recipients tested.This was the first phase II trial of a novel oral candidate typhoid vaccine in children in an endemic country. M01ZH09 had an appropriate safety profile and was immunogenic in children.Controlled-trials.com ISRCTN91111837.

Loneliness is linked to wide ranging physical and mental health problems, including increased rates of mortality. Understanding how loneliness manifests is important for targeted public health treatment and intervention. With advances in mobile sending and wearable technologies, it is possible to collect data on human phenomena in a continuous and uninterrupted way. In doing so, such approaches can be used to monitor physiological and behavioral aspects relevant to an individual's loneliness. In this study, we proposed a method for continuous detection of loneliness using fully objective data from smart devices and passive mobile sensing. We also investigated whether physiological and behavioral features differed in their importance in predicting loneliness across individuals. Finally, we examined how informative data from each device is for loneliness detection tasks. We assessed subjective feelings of loneliness while monitoring behavioral and physiological patterns in 30 college students over a 2-month period. We used smartphones to monitor behavioral patterns (e.g., location changes, type of notifications, in-coming and out-going calls/text messages) and smart watches and rings to monitor physiology and sleep patterns (e.g., heart-rate, heart-rate variability, sleep duration). Participants reported their loneliness feeling multiple times a day through a questionnaire app on their phone. Using the data collected from their devices, we trained a random forest machine learning based model to detect loneliness levels. We found support for loneliness prediction using a multi-device and fully-objective approach. Furthermore, behavioral data collected by smartphones generally were the most important features across all participants. The study provides promising results for using objective data to monitor mental health indicators, which could provide a continuous and uninterrupted source of information in mental healthcare applications., Competing Interests: Enter: The authors have declared that no competing interests exist., (Copyright: © 2024 Jafarlou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Prevalence of hepatitis C virus (HCV) infection among Vietnamese Americans is reportedly high. Understanding the profile of those at greater risk of HCV in this ethnic population is a vital step to addressing this high prevalence. We hypothesize that certain sociodemographic characteristics increase the likelihood of having HCV in Vietnamese Americans., Methods: Cross-sectional data from 2,497 Vietnamese Americans in Southern California who participated in a series of community hepatitis screening events organized by the Vietnamese American Cancer Foundation (VACF) were analyzed. Serological tests via immunoassays were used to determine whether the participant had hepatitis C antibodies (anti-HCV) to indicate a HCV infection. Sociodemographic characteristics as well as participants' reasons for screening were collected from questionnaires, and logistic regression models with odds ratios (ORs) and 95% confidence intervals (CIs) were used to quantify their associations with HCV infection., Results: Approximately 5.8% of the study population was infected with HCV. Older adults and male participants had higher odds of being infected with HCV (e.g. OR = 2.90, 95% CI 1.25-6.76 for ages 70+ versus ages <40; OR = 2.57, 95% CI 1.79-3.69 for male versus female participants) as were those with a family history of HCV infection (OR = 2.74, 95% CI 1.57-4.78). In addition, perceived self-risk as a motivation for screening was significantly associated with HCV infection (OR = 1.88, 95% CI 1.26-2.78)., Conclusions: This study identifies specific subgroups in the Vietnamese American community who would largely benefit from targeted interventions given their higher likelihood of having HCV. These interventions should emphasize improving HCV knowledge and promoting HCV self-risk assessment since awareness of one's own risk may motivate those likely to be infected to get screened., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The objective of this study was to assess the classification capability of Breast Imaging Reporting and Data System (BI-RADS) ultrasound feature descriptors targeting established commercial transcriptomic gene signatures that guide management of breast cancer., Materials and Methods: This retrospective, single-institution analysis of 219 patients involved two cohorts using one of two FDA approved transcriptome-based tests that were performed as part of the clinical care of breast cancer patients at Harbor-UCLA Medical Center between April 2008 and January 2013. BI-RADS descriptive terminology was collected from the corresponding ultrasound reports for each patient in conjunction with transcriptomic test results. Recursive partitioning and regression trees were used to test and validate classification of the two cohorts., Results: The area under the curve (AUC) of the receiver operator curves (ROC) for the regression classifier between the two FDA approved tests and ultrasound features were 0.77 and 0.65, respectively; they employed the 'margins', 'retrotumoral', and 'internal echoes' feature descriptors. Notably, the 'retrotumoral' and mass 'margins' features were used in both classification trees. The identification of sonographic correlates of gene tests provides added value to the ultrasound exam without incurring additional procedures or testing., Conclusions: The predictive capability using structured language from diagnostic ultrasound reports (BI-RADS) was moderate for the two tests, and provides added value from ultrasound imaging without incurring any additional costs. Incorporation of additional measures, such as ultrasound contrast enhancement, with validation in larger, prospective studies may further substantiate these results and potentially demonstrate even greater predictive utility., Competing Interests: The authors have declared that no competing interests exist.

Background: Depression is a common mental health problem in medical students worldwide. The association between depression and motivation in Vietnamese medical students is not well-documented., Objectives: To estimate the prevalence of self-reported depression and to identify associated risk factors among medical students at Hanoi Medical University (HMU)., Method: A cross-sectional study was conducted on medical students with clinical experience at HMU from November 2015 to January 2016. We used the multistage cluster random sampling technique to select and invite students to complete a questionnaire including demographic characteristics, Patient Health Questionnaire 9 (PHQ-9), Academic Motivation Scale (AMS), and International Physical Activity Questionnaire Short Form (IPAQ)., Results: Among 494 participants (78.8% response rate), the prevalence of self-reported depression was 15.2% (95%CI:12.0%-19.0%), and suicidal ideation was 7.7% (95%CI:6.2%-9.5%). Self-reported depression was significantly associated with perceived financial burden, physical inactivity, being senior student, perceived negative influence of night shifts, and non-self-determined motivation profile. Suicidal ideation was significantly associated with perceived financial burden and non-self-determined motivation profile. In the multivariable regression models, significant risk factors for self-reported depression were non-self-determined motivation (PR = 2.62, 95%CI:1.68-4.07), perceived financial burden (PR = 1.95, 95%CI:1.39-2.73), and vigorous level of physical activity (PR = 0.43, 95%CI:0.20-0.942). For suicidal ideation, non-self-determined motivation (PR = 2.33, 95%CI:1.13-4.80) and perceived financial burden (PR = 1.91, 95%CI:1.16-3.13) were significant risk factors., Strengths and Limitations: The strengths of our study included a representative sample, a good response rate, and using a good depression screening tool. However, the PHQ-9 only allowed us to screen for depression, and the translation of the AMS and IPAQ into Vietnamese could potentially decrease these tools' validity., Conclusion: The prevalence of self-reported depression and suicidal ideation in medical students is notably higher compared to the general population in Vietnam. Non-self-determined motivation and financial burden were the prominent risk factors for both the depression and suicidal ideation in medical students., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: Lactulose is a common food ingredient and widely used as a treatment for constipation or hepatic encephalopathy and a substrate for hydrogen breath tests. Lactulose is fermented by the colon microbiota resulting in the production of hydrogen (H2). H2 is a substrate for enteropathogens including Salmonella Typhimurium (S. Typhimurium) and increased H2 production upon lactulose ingestion might favor the growth of H2-consuming enteropathogens. We aimed to analyze effects of single-dose lactulose ingestion on the growth of intrinsic Escherichia coli (E. coli), which can be efficiently quantified by plating and which share most metabolic requirements with S. Typhimurium., Methods: 32 healthy volunteers (18 females, 14 males) were recruited. Participants were randomized for single-dose ingestion of 50 g lactulose or 50 g sucrose (controls). After ingestion, H2 in expiratory air and symptoms were recorded. Stool samples were acquired at days -1, 1 and 14. We analyzed 16S microbiota composition and abundance and characteristics of E. coli isolates., Results: Lactulose ingestion resulted in diarrhea in 14/17 individuals. In 14/17 individuals, H2-levels in expiratory air increased by ≥20 ppm within 3 hours after lactulose challenge. H2-levels correlated with the number of defecations within 6 hours. E. coli was detectable in feces of all subjects (2 x 10(2)-10(9) CFU/g). However, the number of E. coli colony forming units (CFU) on selective media did not differ between any time point before or after challenge with sucrose or lactulose. The microbiota composition also remained stable upon lactulose exposure., Conclusion: Ingestion of a single dose of 50 g lactulose does not significantly alter E. coli density in stool samples of healthy volunteers. 50 g lactulose therefore seems unlikely to sufficiently alter growth conditions in the intestine for a significant predisposition to infection with H2-consuming enteropathogens such as S. Typhimurium (www.clinicaltrials.gov NCT02397512)., Competing Interests: The authors have declared that no competing interests exist.

Background: There is growing evidence that breastfeeding has short- and long-term cardiovascular health benefits for mothers. The objectives of this systematic review were to examine the association between breastfeeding and maternal cardiovascular risk factors and outcomes that have not previously been synthesized systematically, including metabolic syndrome, hypertension and cardiovascular disease., Methods and Findings: This systematic review meets PRISMA guidelines. The MEDLINE, EMBASE and CINAHL databases were systematically searched for relevant publications of any study design from the earliest publication date to March 2016. The reference lists from selected articles were reviewed, and forward and backward referencing were conducted. The methodological quality of reviewed articles was appraised using validated checklists. Twenty-one studies meeting the inclusion criteria examined the association between self-reported breastfeeding and one or more of the following outcomes: metabolic syndrome/metabolic risk factors (n = 10), inflammatory markers/adipokines (n = 2), hypertension (n = 7), subclinical cardiovascular disease (n = 2), prevalence/incidence of cardiovascular disease (n = 3) and cardiovascular disease mortality (n = 2). Overall, 19 studies (10 cross-sectional/retrospective, 9 prospective) reported significant protective effects of breastfeeding, nine studies (3 cross-sectional/retrospective, 5 prospective, 1 cluster randomized controlled trial) reported non-significant findings and none reported detrimental effects of breastfeeding. In most studies reporting significant associations, breastfeeding remained associated with both short- and long-term maternal cardiovascular health risk factors/outcomes, even after covariate adjustment. Findings from several studies suggested that the effects of breastfeeding may diminish with age and a dose-response association between breastfeeding and several metabolic risk factors. However, further longitudinal studies, including studies that measure exclusive breastfeeding, are needed to confirm these findings., Conclusions: The evidence from this review suggests that breastfeeding is associated with cardiovascular health benefits. However, results should be interpreted with caution as the evidence gathered for each individual outcome was limited by the small number of observational studies. Additional prospective studies are needed., Prospero Registration Number: CRD42016047766.

Children are at risk for adverse health outcomes from occupant-controllable indoor airborne contaminants in their homes. Data are needed to design residential interventions for reducing low-income children's pollutant exposure. Using customized air quality monitors, we continuously measured fine particle counts (0.5 to 2.5 microns) over a week in living areas of predominantly low-income households in San Diego, California, with at least one child (under age 14) and at least one cigarette smoker. We performed retrospective interviews on home characteristics, and particle source and ventilation activities occurring during the week of monitoring. We explored the relationship between weekly mean particle counts and interview responses using graphical visualization and multivariable linear regression (base sample n = 262; complete cases n = 193). We found associations of higher weekly mean particle counts with reports of indoor smoking of cigarettes or marijuana, as well as with frying food, using candles or incense, and house cleaning. Lower particle levels were associated with larger homes. We did not observe an association between lower mean particle counts and reports of opening windows, using kitchen exhaust fans, or other ventilation activities. Our findings about sources of fine airborne particles and their mitigation can inform future studies that investigate more effective feedback on residential indoor-air-quality and better strategies for reducing occupant exposures.

LacZ is widely used as a reporter in studies of gene expression patterns. β-galactosidase, the product of LacZ gene, is usually detected by X-gal/FeCN staining. In X-gal/FeCN staining, β-galactosidase catalyzes X-gal to produce blue precipitates, which indicate the expression patterns of the gene of interest. A newer LacZ detection method using S-gal/TNBT is more sensitive but plagued by high background. Here, we describe an improved procedure that combines advantageous steps from the two methods. By comparing with X-gal/FeCN and S-gal/TNBT methods in detecting the expression patterns of miR-322/503 and miR-451 at a series of developmental stages, the improved method showed higher sensitivity and lower background. Thus, the improved method could be an alternative way of β-galactosidase staining in low gene expression situations.

Natural products are universally recognized to contribute valuable chemical diversity to the design of molecular screening libraries. The analysis undertaken in this work, provides a foundation for the generation of fragment screening libraries that capture the diverse range of molecular recognition building blocks embedded within natural products. Physicochemical properties were used to select fragment-sized natural products from a database of known natural products (Dictionary of Natural Products). PCA analysis was used to illustrate the positioning of the fragment subset within the property space of the non-fragment sized natural products in the dataset. Structural diversity was analysed by three distinct methods: atom function analysis, using pharmacophore fingerprints, atom type analysis, using radial fingerprints, and scaffold analysis. Small pharmacophore triplets, representing the range of chemical features present in natural products that are capable of engaging in molecular interactions with small, contiguous areas of protein binding surfaces, were analysed. We demonstrate that fragment-sized natural products capture more than half of the small pharmacophore triplet diversity observed in non fragment-sized natural product datasets. Atom type analysis using radial fingerprints was represented by a self-organizing map. We examined the structural diversity of non-flat fragment-sized natural product scaffolds, rich in sp3 configured centres. From these results we demonstrate that 2-ring fragment-sized natural products effectively balance the opposing characteristics of minimal complexity and broad structural diversity when compared to the larger, more complex fragment-like natural products. These naturally-derived fragments could be used as the starting point for the generation of a highly diverse library with the scope for further medicinal chemistry elaboration due to their minimal structural complexity. This study highlights the possibility to capture a high proportion of the individual molecular interaction motifs embedded within natural products using a fragment screening library spanning 422 structural clusters and comprised of approximately 2800 natural products.