We introduce the antibody landscape, a method for the quantitative analysis of antibodymediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among ...pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
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.
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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.
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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 . . .
Plant viral nanoparticles (VNPs) are a novel class of nanocarriers with implications for drug delivery in cancer therapy. VNPs are characterized by their highly symmetrical nanoscale structures. ...Furthermore, plant VNPs are biocompatible, biodegradable, and non-infectious in mammals. VNPs provide a proteinaceous platform technology that can be readily engineered to carry contrast agents and therapies using chemical and genetic modifications. Of particular interest are high aspect ratio, elongated filaments such as the ones formed by potato virus X (PVX, measuring 515 × 13 nm). PVX has demonstrated enhanced tumor homing and penetration properties compared to spherical counterparts. Here, we sought to investigate the potential of PVX as a drug carrier delivering doxorubicin (DOX), a commonly used cancer chemotherapy. We synthesized therapeutic PVX nanoparticles using a simple in-solution mixing protocol; after 5 days of mixing of DOX and PVX and ultra-centrifugal purification, ∼1000 DOX per PVX were stably associated with the carrier, most likely based on hydrophobic interaction. Efficacy and drug activity of PVX-DOX were confirmed using a panel of cancer cell lines including ovarian cancer, breast cancer, and cervical cancer. Lastly, we demonstrated treatment of athymic mice bearing human MDA-MB-231 breast cancer xenografts: PVX-DOX treatment resulted in reduced tumor growth in this model. Our results open the door for further development of PVX and other high aspect ratio plant VNPs for applications in cancer therapy.
Plant viral nanoparticles (VNPs) are a novel class of nanocarriers with implications for drug delivery in cancer therapy.
Background. Tuberculous meningitis (TBM) is the most devastating form of tuberculosis, yet very little is known about the pathophysiology. We hypothesized that the genotype of leukotriene A₄ ...hydrolase (encode by LTA4H), which determines inflammatory eicosanoid expression, influences intracerebral inflammation, and predicts survival from TBM. Methods. We characterized the pretreatment clinical and intracerebral inflammatory phenotype and 9-month survival of 764 adults with TBM. All were genotyped for single-nucleotide polymorphism rs17525495, and inflammatory phenotype was defined by cerebrospinal fluid (CSF) leukocyte and cytokine concentrations. Results. LTA4H genotype predicted survival of human immunodeficiency virus (HIV)=uninfected patients, with TT-genotype patients significantly more likely to survive TBM than CC-genotype patients, according to Cox regression analysis (univariate P = .040 and multivariable P = .037). HIV-uninfected, TT-genotype patients had high CSF proinflammatory cytokine concentrations, with intermediate and lower concentrations in those with CT and CC genotypes. Increased CSF cytokine concentrations correlated with more-severe disease, but patients with low CSF leukocytes and cytokine concentrations were more likely to die from TBM, HIV infection independently predicted death due to TBM (hazard ratio, 3.94; 95% confidence interval, 2.79-5.56) and was associated with globally increased CSF cytokine concentrations, independent of LTA4H genotype. Conclusions. LTA4H genotype and HIV infection influence pretreatment inflammatory phenotype and survival from TBM. LTA4H genotype may predict adjunctive corticosteroid responsiveness in HIV-uninfected individuals.
A simple metal-free method for the synthesis of quinazolinones from commercially available 2-nitrobenzyl alcohols and tetrahydroisoquinolines is developed. The reaction conditions were tolerant of an ...array of functionalities such as halogen, tertiary amine, protected alcohol, and ester groups. Under nearly identical conditions, quinazolinethiones were obtained in the presence of elemental sulfur and suitable mediators.
Osteoporosis is a common bone health disorder in hemodialysis patients that is linked with a higher morbidity and mortality rate. While previous studies have explored the associated factors of ...osteoporosis, there is a lack of studies investigating the impacts of health literacy (HL) and digital healthy diet literacy (DDL) on osteoporosis. Therefore, we aimed to investigate the associations of HL, DDL, and other factors with osteoporosis among hemodialysis patients. From July 2020 to March 2021, a cross-sectional study was conducted on 675 hemodialysis patients in eight hospitals in Vietnam. The data were collected by using the osteoporosis self-assessment tool for Asians (OSTA) and the 12-item short form of the health literacy questionnaire (HLS-SF12) on digital healthy diet literacy (DDL) and hemodialysis dietary knowledge (HDK). In addition, we also collected information about the socio-demographics, the clinical parameters, the biochemical parameters, and physical activity. Unadjusted and adjusted multinomial logistic regression models were utilized in order to investigate the associations. The proportion of patients at low, medium, and high levels of osteoporosis risk was 39.6%, 40.6%, and 19.8%, respectively. In the adjusted models, women had a higher likelihood of osteoporosis risk than men (odds ratio, OR, 3.46; 95% confidence interval, 95% CI, 1.86, 6.44; p < 0.001; and OR, 6.86; 95% CI, 2.96, 15.88; p < 0.001). The patients with rheumatoid arthritis (OR, 4.37; 95% CI, 1.67, 11.52; p = 0.003) and stomach ulcers (OR, 1.95; 95% CI, 1.01, 3.77; p = 0.048) were more likely to have a higher likelihood of osteoporosis risk than those without. The patients who had a higher waist circumference (WC), HL, and DDL were less likely to have a medium level of osteoporosis risk (OR, 0.95; 95% CI, 0.92, 0.98; p = 0.004; OR, 0.92; 95% CI, 0.88, 0.96; p < 0.001; OR, 0.96; 95% CI, 0.93, 0.99; p = 0.017, respectively) and a high level of osteoporosis risk (OR, 0.93; 95% CI, 0.89, 0.97; p = 0.001; OR, 0.89; 95% CI, 0.84, 0.94; p < 0.001; OR, 0.95; 95% CI, 0.91, 0.99; p = 0.008, respectively) compared with a low level of osteoporosis risk and to those with a lower WC, HL, and DDL. In addition, higher levels of hemoglobin (Hb) (OR, 0.79; 95% CI, 0.66, 0.95; p = 0.014), hematocrit (Hct) (OR, 0.95; 95% CI, 0.92, 0.99; p = 0.041), albumin (OR, 0.91; 95% CI, 0.83, 0.99; p = 0.030), and education (OR, 0.37; 95% CI, 0.16, 0.88; p = 0.025) were associated with a lower likelihood of a high level of osteoporosis risk. In conclusion, osteoporosis risk is highly prevalent in hemodialysis patients. Improved HL, DDL, education, WC, albumin, Hb, and Hct levels should be considered in preventing hemodialysis patients from developing osteoporosis.
Treatment adherence (TA) is a critical issue and is under-investigated in hemodialysis patients. A multi-center study was conducted from July 2020 to March 2021 on 972 hemodialysis patients in eight ...hospitals in Vietnam to explore the factors associated with TA during the COVID-19 pandemic. Data were collected, including socio-demographics, an End-Stage Renal Disease Adherence Questionnaire (ESRD-AQ), 12-item short-form health literacy questionnaire (HLS-SF12), 4-item digital healthy diet literacy scale (DDL), 10-item hemodialysis dietary knowledge scale (HDK), 7-item fear of COVID-19 scale (FCoV-19S), and suspected COVID-19 symptoms (S-COVID19-S). Bivariate and multivariate linear regression models were used to explore the associations. Higher DDL scores were associated with higher TA scores (regression coefficient, B, 1.35; 95% confidence interval, 95%CI, 0.59, 2.12;
= 0.001). Higher FCoV-19S scores were associated with lower TA scores (B, -1.78; 95%CI, -3.33, -0.24;
= 0.023). In addition, patients aged 60-85 (B, 24.85; 95%CI, 6.61, 43.11;
= 0.008) with "very or fairly easy" medication payment ability (B, 27.92; 95%CI, 5.89, 44.95;
= 0.013) had higher TA scores. Patients who underwent hemodialysis for ≥5 years had a lower TA score than those who received <5 years of hemodialysis (B, -52.87; 95%CI, -70.46, -35.28;
< 0.001). These findings suggested that DDL and FCoV-19S, among other factors, should be considered in future interventions to improve TA in hemodialysis patients.
Background: We aimed to examine the impacts of digital healthy diet literacy (DDL) and healthy eating behaviors (HES) on fear of COVID-19, changes in mental health, and health-related quality of life ...(HRQoL) among front-line healthcare workers (HCWs). Methods: An online survey was conducted at 15 hospitals and health centers from 6–19 April 2020. Data of 2299 front-line HCWs were analyzed—including socio-demographics, symptoms like COVID-19, health literacy, eHealth literacy, DDL, HES, fear of COVID-19, changes in mental health, and HRQoL. Regression models were used to examine the associations. Results: HCWs with higher scores of DDL and HES had lower scores of FCoV-19S (regression coefficient, B, −0.04; 95% confidence interval, 95% CI, −0.07, −0.02; p = 0.001; and B, −0.10; 95% CI, −0.15, −0.06; p < 0.001); had a higher likelihood of stable or better mental health status (odds ratio, OR, 1.02; 95% CI, 1.00, 1.05; p = 0.029; and OR, 1.04; 95% CI, 1.00, 1.07; p = 0.043); and HRQoL (OR, 1.02; 95% CI, 1.01, 1.03; p = 0.006; and OR, 1.04; 95% CI, 1.02, 1.06; p = 0.001), respectively. Conclusions: DDL and HES were found as independent predictors of fear of COVID−19, changes in mental health status, and HRQoL in front-line HCWs. Improving DDL and HES should be considered as a strategic approach for hospitals and healthcare systems.
Background: Most of the world’s children and adolescents live in low- and lower-middle-income countries (LALMIC), but there is limited evidence about polyvictimization (experiences of multiple forms ...of victimization) among them. The aims of this article were to systematically review the evidence from LALMIC about the overall prevalence of polyvictimization and to identify the associations between polyvictimization and health and well-being among children and adolescents. Method: A systematic search of the English-language peer-reviewed literature to identify empirical, quantitative studies conducted in LALMIC between 2005 and 2015, assessing at least four forms of victimization among young people aged up to 19 years. Where prevalence of any victimization and of polyvictimization were reported, meta-analyses were performed. Results: A total of 30/8,496 articles were included in the review. Evidence was available from 16/84 LALMIC and methodology and quality varied. Pooled prevalence of experiences of any victimization was 76.8% (95% confidence interval (CI) 64.8%, 88.9%). Prevalence of polyvictimization ranged from 0.3% to 74.7% with an overall estimate of 38.1% (95% CI 18.3%, 57.8%). None of the studies examined the associations between polyvictimization and physical or reproductive health or quality of life. Polyvictimization was associated with increased likelihood of mental health problems and involvement in health risk behaviors. Conclusions: Experiences of polyvictimization among children and adolescents in LALMIC are more prevalent than in high- and upper-middle-income countries and contribute to the burden of poor health among children and adolescents. Most LALMIC lack local data, and research is required to address this knowledge gap.
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