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Tuberculous meningitis remains highly lethal. In this trial, an intensified regimen of levofloxacin and higher-dose rifampin added to standard therapy was compared with standard antituberculosis therapy alone. The intensified regimen did not result in a higher survival rate. Early treatment with antituberculosis chemotherapy and adjunctive treatment with glucocorticoids reduce the rate of death and disability from tuberculous meningitis, but the disease still kills or disables almost half the patients with the condition. 1 , 2 The current guidelines recommend treatment with four antituberculosis drugs for at least the first 2 months of therapy, followed by treatment with two drugs (rifampin and isoniazid) for an additional 7 to 10 months. 3 , 4 However, these recommendations are based on data from pulmonary tuberculosis and do not take into account the differential ability of antituberculosis drugs to penetrate the brain. Rifampin is considered to . . .

In this randomized trial, HIV-positive adults with tuberculous meningitis were assigned to receive 6 to 8 weeks of dexamethasone or placebo in addition to tuberculosis treatment. No benefit of dexamethasone was observed.

Catharanthus roseus (Vinca) is a perennial herbaceous plant that is renowned for its abundance of vincristine (VCR) and vinblastine (VBL). These vinca alkaloids possess valuable anticancer properties and have been extensively used in chemotherapy treatment for various type of cancers. However, the current supply of these vinca alkaloids is reliant on plant material with low productivity and high costs. Endophytic fungi, a category of symbiotic mycota that are capable of synthesizing their host plant-specific bioactive compounds, have gained significant attention as a bioreactor for large-scale production of vinca alkaloids. In this study, a total of 34 endophytic fungal strains were isolated from stem and root tissues of C. roseus . The isolated endophytic fungi were taxonomically characterized as Alternaria sp., Talaromyces sp., and Cladosporium sp. by morphological observation and sequence analysis of the ITS region of rDNA. Three endophytic fungal strains were identified to be capable of synthesizing VCR and VBL by UPLC/MRM-MS analysis. The fungal strain Alternaria DC1 was determined to be the most prolific producer, producing VCR and VBL at concentrations of 177.6 and 114.8 µg/L, respectively. The Talaromyces DC2 strain followed with VCR and VBL yields of 44.0 and 111.6 µg/L, respectively. While the fungal strain Cladosporium DC3 was identified as a producer of VCR (36.9 µg/L) and VBL (99.6 µg/L) for the first time. These endophytic fungi exhibit the potential to serve as viable sources for the production of vinca alkaloids on a larger scale.

Adjunctive dexamethasone reduces mortality from tuberculous meningitis (TBM) but not disability, which is associated with brain infarction. We hypothesised that aspirin prevents TBM-related brain infarction through its anti-thrombotic, anti-inflammatory, and pro-resolution properties. We conducted a randomised controlled trial in HIV-uninfected adults with TBM of daily aspirin 81 mg or 1000 mg, or placebo, added to the first 60 days of anti-tuberculosis drugs and dexamethasone (NCT02237365). The primary safety endpoint was gastro-intestinal or cerebral bleeding by 60 days; the primary efficacy endpoint was new brain infarction confirmed by magnetic resonance imaging or death by 60 days. Secondary endpoints included 8-month survival and neuro-disability; the number of grade 3 and 4 and serious adverse events; and cerebrospinal fluid (CSF) inflammatory lipid mediator profiles. 41 participants were randomised to placebo, 39 to aspirin 81 mg/day, and 40 to aspirin 1000 mg/day between October 2014 and May 2016. TBM was proven microbiologically in 92/120 (76.7%) and baseline brain imaging revealed ≥1 infarct in 40/114 (35.1%) participants. The primary safety outcome occurred in 5/36 (13.9%) given placebo, and in 8/35 (22.9%) and 8/40 (20.0%) given 81 mg and 1000 mg aspirin, respectively (p=0.59). The primary efficacy outcome occurred in 11/38 (28.9%) given placebo, 8/36 (22.2%) given aspirin 81 mg, and 6/38 (15.8%) given 1000 mg aspirin (p=0.40). Planned subgroup analysis showed a significant interaction between aspirin treatment effect and diagnostic category (P heterogeneity = 0.01) and suggested a potential reduction in new infarcts and deaths by day 60 in the aspirin treated participants with microbiologically confirmed TBM (11/32 (34.4%) events in placebo vs. 4/27 (14.8%) in aspirin 81 mg vs. 3/28 (10.7%) in aspirin 1000 mg; p=0.06). CSF analysis demonstrated aspirin dose-dependent inhibition of thromboxane A 2 and upregulation of pro-resolving CSF protectins. The addition of aspirin to dexamethasone may improve outcomes from TBM and warrants investigation in a large phase 3 trial. The deadliest form of tuberculosis is tuberculosis meningitis (TBM), which causes inflammation in the brain. Even with the best treatment available, about half of patients with TBM become disabled or die, often because they have a stroke. Strokes are caused by blood clots or other blockages in blood vessels in the brain. Aspirin is known to prevent blood clots and helps reduce inflammation. Some scientists wonder if it might help patients with TBM by preventing blockages in blood vessels. Now, Nguyen et al. show that adding aspirin to existing TBM treatments may reduce strokes in some patients. In the experiments, 120 patients with TBM were randomly assigned to receive a low dose of aspirin (81 mg/day), a high dose of aspirin (1000mg/day), or an identical tablet that contained no medication. All the patients also took the anti-tuberculosis drugs and steroids usually used to treat the condition. Both doses of aspirin appeared to be safe. Patients who received aspirin were less likely to have a stroke or die in the first two months of treatment than patients who received the fake pill. But the difference was so small it could have been caused by chance. In the 92 patients with clear evidence of tuberculosis bacteria in their brains, the benefit of aspirin was larger and unlikely to be due to chance. The benefit was greatest for those who received the higher dose of aspirin, only 10.7% of these patients died or had a stroke, compared with 14.8% of those who received a low dose of aspirin, or 34% of those who received the fake pill. Next, Nguyen et al. looked at brain fluid taken from the TBM patients before and after they received the aspirin or fake medication. The experiments showed that patients treated with high dose aspirin had much lower levels of a clot-promoting substance called thromboxane A2 and more anti-inflammatory molecules. Larger studies are needed in children and adults to confirm that aspirin helps prevent strokes or death in patients with TBM. Studies are also needed on patients who have both TBM and HIV infections. But if more studies show aspirin is safe and effective, adding this medication to TBM treatment may be an inexpensive way to prevent death or disability.

Purpose Circulating microRNAs (miRNAs) are potential diagnostic biomarkers for breast cancer (BC). The application of miRNA panels could improve the performance of screening tests. Here, we integrated bioinformatic tools and meta-analyses to select circulating miRNAs with high diagnostic accuracy and combined these markers to develop diagnostic panels for BC. Methods Analyses across databases were performed to identify potential BC-related circulating miRNAs. Next, a comprehensive meta-analysis was conducted for each miRNA following the PRISMA guidelines. An electronic and manual search for relevant literature was carried out by two reviewers through PubMed, ScienceDirect, Biomed Central, and Google Scholar. The quality of the included studies was assessed using the QUADAS-2, and the statistical analyses were performed using R software 4.1.1. Finally, the accurate biomarkers confirmed through meta-analyses were combined into diagnostic models for BC. Results Twenty-seven circulating miRNAs were identified as BC-related by bioinformatic tools. After screening, only 10 miRNAs presented in 45 studies were eligible for meta-analyses. By assessing pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, 8 miRNAs (miR-21, miR-30b, miR-125b, miR-145, miR221 miR-222, and miR-335) were revealed as promising BC diagnostic biomarkers. Two panels constructed from these miRNAs showed excellent diagnostic accuracy for BC, with areas under the SROC curve of 0.917 and 0.944. Conclusion We identified 8 potential circulating miRNAs and 2 diagnostic models that are useful for diagnosing BC. However, the established miRNA panels have not been tested in any experimental studies and thus should be validated in large case–control studies for clinical use.

Background: The COVID-19 pandemic has been disseminating fear in the community, which has affected people’s quality of life, especially those with health problems. Health literacy (HL), eHealth literacy (eHEAL), and digital healthy diet literacy (DDL) may have potential impacts on containing the pandemic and its consequences. This study aimed to examine the association between the fear of COVID-19 scale (FCoV-19S) and the health-related quality of life (HRQoL), and to examine the effect modification by HL, eHEAL, and DDL on this association. Methods: A cross-sectional study was conducted in 11 hospitals across Vietnam from 7 April to 31 May 2020. Data were collected on 4348 outpatients, including demographic characteristics, HL, eHEAL, DDL, FCoV-19S, and HRQoL. Multiple linear regression and interaction models were used to explore associations. Results: Patients with higher FCoV-19S scores had lower HRQoL scores (unstandardized coefficient, B = −0.78, p < 0.001). HL (B = 0.20, p < 0.001), eHEAL (B = 0.24, p < 0.001), and DDL (B = 0.20, p < 0.001) were positively associated with higher HRQoL scores. The negative impact of FCoV-19S on HRQoL was significantly attenuated by higher eHEAL score groups (from one standard deviation (SD) below the mean, B = −0.93, p < 0.001; to the mean, B = −0.85, p < 0.001; and one SD above the mean, B = −0.77, p < 0.001); and by higher DDL score groups (from one SD below the mean, B = −0.92, p < 0.001; to the mean, B = −0.82, p < 0.001; and one SD above the mean, B = −0.72, p < 0.001). Conclusions: eHealth literacy and digital healthy diet literacy could help to protect patients’ health-related quality of life from the negative impact of the fear of COVID-19 during the pandemic.

Gene expression regulation is one of the most effective adaptation responses to abiotic stressors. Quantitative real-time polymerase chain reaction (RT-qPCR) is the method of choice for quantifying gene expression levels. Reference genes are important factors that are required for accurate and reliable normalization of RT-qPCR-derived data, and a minimum of two stably expressed reference genes must be employed according to the Minimum Information for publication of Quantitative Real-Time PCR Experiment guidelines. To date, most gene expression studies reported in rice under salt stress have utilized a single reference gene. In addition, there has been little research into a set of reference genes that are stably expressed across tissues of different rice genotypes. In this study, twelve potential reference gene candidates were selected, including ACT11 , TIP41 , BTUB , EF1A , EIF4A , FBOX , GAPDH , PP2A , SPX , UBCE2 , UBQ10 , and CCZ1 . Their expression stability was evaluated in internode, leaf, and root tissues of six rice genotypes with different salt stress tolerances. The geNorm, NormFinder, and RefFinder statistical algorithms identified EIF4A and TIP41 as the most suitable set of reference genes for the accurate and reliable normalization of RT-qPCR data generated from eighteen tissue samples. The performance of the identified reference genes was validated for their accuracy and reliability through RT-qPCR analysis of the gene encoding the HKT1 potassium transporter. Our results highlighted the importance of identifying a suitable set of reference genes for gene expression studies in rice under salt stress in order to obtain accurate and reliable data.

The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences. 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. 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. 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. 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.