Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B ...deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking.
In this open-label, noninferiority trial, we randomly assigned 440 HIV-infected adults who had talaromycosis, confirmed by either microscopy or culture, to receive either intravenous amphotericin B deoxycholate (amphotericin) (219 patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days, followed by 400 mg per day, for 11 days; thereafter, all the patients received maintenance therapy with itraconazole. The primary outcome was all-cause mortality at week 2. Secondary outcomes included all-cause mortality at week 24, the time to clinical resolution of talaromycosis, early fungicidal activity, relapse of talaromycosis, development of the immune reconstitution inflammatory syndrome (IRIS), and the side-effect profile.
The risk of death at week 2 was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval CI, -3.9 to 5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3% in the amphotericin group and 21.0% in the itraconazole group (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with amphotericin was associated with significantly faster clinical resolution and fungal clearance and significantly lower rates of relapse and IRIS than itraconazole. The patients who received amphotericin had significantly higher rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, and anemia than patients in the itraconazole group.
Amphotericin was superior to itraconazole as initial treatment for talaromycosis with respect to 6-month mortality, clinical response, and fungicidal activity. (Funded by the Medical Research Council and others; IVAP Current Controlled Trials number, ISRCTN59144167 .).
BACKGROUND: Whether isoflavone has any effect on recurrent cardiovascular events is unknown. OBJECTIVE: To investigate the relations between isoflavone intake and the risk of stroke recurrence. ...SUBJECTS AND METHODS: We recruited 127 consecutive patients with prior history of atherothrombolic/ hemorrhagic stroke (mean age: 67 ± 11 years, 69% male) and prospectively followed up for a mean duration of 30 months. Stroke recurrence and major adverse cardiovascular events (MACE) were documented. Brachial flow-mediated dilatation (FMD) was measured using high-resolution ultrasound. Isoflavone intake was estimated using a validated food frequency questionnaire. RESULTS: Median isoflavone intake was 6.9 (range: 2.1–14.5) mg/day. Isoflavone intake was independently associated with increased FMD (Pearson R=0.23, p=0.012). At 30 months, there were 10 stroke recurrence and 12 MACE. Kaplan-Meier analysis showed that patients with isoflavone intake higher than median value had significantly longer median stroke recurrence-free survival time (19.0 range: 10.4–27.6 mth versus 5.0 range: 4.1–5.9 mth, p=0.021) and MACE-free survival time (19.0 range: 10.4–27.6 mth versus 4.0 range: 2.4–5.6 mth, p=0.013). Using multivariate cox regression, higher isoflavone intake was an independent predictor for lower risk of stroke recurrence (hazards ratio 0.18 95%CI: 0.03–0.95, risk reduction 82%, p=0.043) and MACE (hazards ratio 0.16 95%CI: 0.03–0.84, risk reduction 84%, p=0.030). CONCLUSIONS: Higher isoflavone intake in stroke patients was associated with prolonged recurrence-free survival, and reduced risk of stroke recurrence and MACE, independent of baseline vascular.function. Whether isoflavone may confer clinically significant secondary protection in stroke patients should be further investigated in a randomized controlled trial.
•Protected areas were studied as spaces for adaptation to COVID-19.•The socio-psychological model of precautionary adaptation was employed.•High perceived adaptation efficacy and low adaptation cost ...promoted adaptation.•The ability of protected areas to assist in adaptation to pandemics was highlighted.
As COVID-19 has swept across the world, governments have been prompted to order social distancing measures, from the closure of schools, restaurants and public facilities to quarantines and lockdowns. Access to and contact with nature have been suggested to help combat impacts associated with isolation measures, and a coincidental surge in the number of visitors to country parks in Hong Kong has recently been observed. The current study sought to explore the visitation of country parks as an adaptation to COVID-19 by employing the socio-psychological model of precautionary adaptation (SPMPA). Questionnaire surveys were administered in 12 country parks in Hong Kong, and a total of 600 samples were collected. A conceptual model based on the SPMPA was proposed and tested through multiple regression analysis. Significant associations between perceived severity, threat experience and adaptative behaviour were found, suggesting the possible risks of visiting country parks. However, the relationships among perceived adaptation efficacy, adaptation cost and reliance on public adaptation implied that the adaptative benefits of visiting country parks may outweigh the risks when proper visitor management measures are implemented. The findings highlighted the importance of providing accessible protected areas or other types of nature-based spaces to facilitate the adaptation of people to disease outbreaks in both the short and long run.
Observational studies usually show that moderate alcohol use is associated with better cognitive function. Such studies are vulnerable to residual confounding arising from systematic differences ...between moderate alcohol users and others. A Mendelian randomization study carried out in a suitable population, such as southern Chinese men, in which alcohol use is low to moderate and is influenced by genotype, offers an alternative and superior approach for clarifying the causal effect of moderate alcohol use on cognitive function. The authors used aldehyde dehydrogenase 2 (ALDH2) genotype (AA, GA, or GG) as an instrumental variable in 2-stage least squares analysis to obtain unbiased estimates of the relation of alcohol consumption (measured in alcohol units (10 g ethanol) per day) with cognitive function, assessed from delayed 10-word recall score (n = 4,707) and Mini-Mental State Examination (MMSE) score (n = 2,284), among men from the Guangzhou Biobank Cohort Study (2003-2008). ALHD2 genotype was strongly associated with alcohol consumption, with an F statistic of 71.0 in 2-stage least squares analysis. Alcohol consumption was not associated with delayed 10-word recall score (-0.03 words per alcohol unit, 95% confidence interval: -0.18, 0.13) or MMSE score (0.06 points per alcohol unit, 95% confidence interval: -0.22, 0.34). Moderate alcohol use is unlikely to be cognitively protective.
This study sought to examine the biomechanical effects of an in-field sensor-based gait retraining program targeting footstrike pattern modification during level running, uphill running and downhill ...running.
Quasi-experimental design.
Sixteen habitual rearfoot strikers were recruited. All participants underwent a baseline evaluation on an instrumented treadmill at their preferred running speeds on three slope settings. Participants were then instructed to modify their footstrike pattern from rearfoot to non-rearfoot strike with real-time audio biofeedback in an 8-session in-field gait retraining program. A reassessment was conducted to evaluate the post-training biomechanical effects. Footstrike pattern, footstrike angle, vertical instantaneous loading rate (VILR), stride length, cadence, and knee flexion angle at initial contact were measured and compared.
No significant interaction was found between training and slope conditions for all tested variables. Significant main effects were observed for gait retraining (p-values≤0.02) and slopes (p-values≤0.01). After gait retraining, 75% of the participants modified their footstrike pattern during level running, but effects of footstrike pattern modification were inconsistent between slopes. During level running, participants exhibited a smaller footstrike angle (p≤0.01), reduced VILR (p≤0.01) and a larger knee flexion angle (p=0.01). Similar effects were found during uphill running, together with a shorter stride length (p=0.01) and an increased cadence (p≤0.01). However, during downhill running, no significant change in VILR was found (p=0.16), despite differences found in other biomechanical measurements (p-values=0.02–0.05).
An 8-session in-field gait retraining program was effective in modifying footstrike pattern among runners, but discrepancies in VILR, stride length and cadence were found between slope conditions.
Abstract
Background
Double-stranded DNA in plasma is known to carry single-stranded ends, called jagged ends. Plasma DNA jagged ends are biomarkers for pathophysiologic states such as pregnancy and ...cancer. It remains unknown whether urinary cell-free DNA (cfDNA) molecules have jagged ends.
Methods
Jagged ends of cfDNA were detected by incorporating unmethylated cytosines during a DNA end-repair process, followed by bisulfite sequencing. Incorporation of unmethylated cytosines during the repair of the jagged ends lowered the apparent methylation levels measured by bisulfite sequencing and were used to calculate a jagged end index. This approach is called jagged end analysis by sequencing.
Results
The jagged end index of urinary cfDNA was higher than that of plasma DNA. The jagged end index profile of plasma DNA displayed several strongly oscillating major peaks at intervals of approximately 165 bp (i.e., nucleosome size) and weakly oscillating minor peaks with periodicities of approximately 10 bp. In contrast, the urinary DNA jagged end index profile showed weakly oscillating major peaks but strongly oscillating minor peaks. The jagged end index was generally higher in nucleosomal linker DNA regions. Patients with bladder cancer (n = 46) had lower jagged end indexed of urinary DNA than participants without bladder cancer (n = 39). The area under the curve for differentiating between patients with and without bladder cancer was 0.83.
Conclusions
Jagged ends represent a property of urinary cfDNA. The generation of jagged ends might be related to nucleosomal structures, with enrichment in linker DNA regions. Jagged ends of urinary DNA could potentially serve as a new biomarker for bladder cancer detection.
The evidence base for the benefit of quitting smoking as regards morbidity and mortality outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) is limited. The ...present article is a review of the existing literature. A systematic literature search in medical databases was performed until March 2006, and subsequently until September 1, 2007. The outcomes examined were COPD-related morbidity and mortality (including all-cause mortality) in COPD patients in connection with smoking cessation. A total of 21 and 27 published articles on morbidity and mortality, respectively, were identified and reviewed. For both outcomes, only a few of the studies included patients with severe COPD. Most of the studies reported a beneficial effect of smoking cessation compared with continued smoking, whereas a few found no improvement. Methodological problems, including small study sizes, poor data quality, possibility of reverse causality and incomplete ascertainment of cause of death, limit interpretation of some of the studies. The evidence as a whole supports the conclusion that, even in severe chronic obstructive pulmonary disease, smoking cessation slows the accelerated rate of lung function decline and improves survival compared with continued smoking.
This article proposes and implements a full-range soft-switching pulse frequency modulated (PFM) wireless power transfer (WPT) system, which not only offers high efficiency but also high ...controllability, selectivity, and security. Although the phase-shift control (PSC) has been widely used in various WPT applications, the high-frequency hard-switching operation will inevitably degrade the system performances in terms of power losses, and hence, efficiency during power regulation. Thus, a soft-switching PFM is newly conceived to suppress the switching frequency and power losses while maintaining full-range soft switching for effective power control, hence improving the system efficiency. In addition to realizing the controllability, the full-range soft-switching PFM can be further derived to implement the selectivity and security. The system efficiency of a multiobjective PFM-WPT system prototype can reach 86.27% at 220-W output power and 135-mm transfer distance. During wireless power control, it can effectively be improved by up to 5.68% as compared to its counterpart using the PSC. Theoretical analysis, computer simulation, and hardware experimentation are given to verify the feasibility of proposed full-range soft-switching PFM-WPT system.
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