With the ageing of the global population, China is projected to be impacted significantly by the rising number of patients with Alzheimer's disease (AD). A cure for AD is not yet available, so ...society should be prepared for an increasing AD-related burden. In this review, we examine this impending problem and provide overviews on (a) the magnitude of the problem of AD in Hong Kong/China in the near future; (b) the genetic and lifestyle risk factors that contribute to AD; (c) current diagnostic approaches and the potential of newly discovered genetic biomarkers for early detection; (d) medications, non-pharmacological interventions, and possible preventive measures; and (e) the need for social and psychological care from the community. In Hong Kong, primary care and AD-related support for at-risk individuals, patients, and caregivers are inadequate. A joint effort from the medical community, government, universities, non-governmental organisations/charities, and industry should initiate the development of a long-term programme for AD. Finally, we outline recommendations for the relevant parties to consider.
The objective of this study was to estimate the prevalence and identify correlates of four sexually transmitted infections (STIs) among HIV-infected Russians reporting heavy alcohol use and recent ...unprotected sex, we conducted a cross-sectional analysis of baseline data from the HERMITAGE study. The primary outcome was any current STI, based on urine tests for Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis and serological testing for infection with Treponema pallidum. Data on potential demographic and behavioural predictors of STI were obtained from surveys administered at study entry. Of 682 participants, 12.8% (95% confidence interval CI 10.3, 15.3) tested positive for at least one STI. In a multivariable model adjusted for gender, age and marital status, only sex trade involvement over the last three months was significantly associated with an increased odds of STI (adjusted odds ratio AOR 2.00, 95% CI 1.13, 3.55). Given that STIs were common in this HIV-infected cohort, and that few patient characteristics predicted STI, the current practice of screening HIV-infected Russians for syphilis alone merits re-evaluation.
BackgroundThe Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and ...non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood.MethodsThis multicenter observational cohort study will enroll at least 600 patients <21 years old who meet the Centers for Disease Control and Prevention case definition of MIS-C across multiple North American centers over 2 years. The study will collect detailed hospital and follow-up data for up to 5 years, and optional genetic testing. Cardiac imaging at specific time points includes standardized echocardiographic assessment (all participants) and cardiac magnetic resonance imaging (CMR) in those with left ventricular ejection fraction (LVEF) <45% during the acute illness. The primary outcomes are the worst LVEF and the highest coronary artery z-score of the left anterior descending or right coronary artery. Other outcomes include occurrence and course of non-cardiac organ dysfunction, inflammation, and major medical events. Independent adjudication of cases will classify participants as definite, possible, or not MIS-C. Analysis of the outcomes will include descriptive statistics and regression analysis with stratification by definite or possible MIS-C. The MUSIC study will provide phenotypic data to support basic and translational research studies.ConclusionThe MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.
The development of reliable and safe high‐energy‐density lithium‐ion batteries is hindered by the structural instability of cathode materials during cycling, arising as a result of detrimental phase ...transformations occurring at high operating voltages alongside the loss of active materials induced by transition metal dissolution. Originating from the fundamental structure/function relation of battery materials, the authors purposefully perform crystallographic‐site‐specific structural engineering on electrode material structure, using the high‐voltage LiNi0.5Mn1.5O4 (LNMO) cathode as a representative, which directly addresses the root source of structural instability of the Fd3¯m structure. By employing Sb as a dopant to modify the specific issue‐involved 16c and 16d sites simultaneously, the authors successfully transform the detrimental two‐phase reaction occurring at high‐voltage into a preferential solid‐solution reaction and significantly suppress the loss of Mn from the LNMO structure. The modified LNMO material delivers an impressive 99% of its theoretical specific capacity at 1 C, and maintains 87.6% and 72.4% of initial capacity after 1500 and 3000 cycles, respectively. The issue‐tracing site‐specific structural tailoring demonstrated for this material will facilitate the rapid development of high‐energy‐density materials for lithium‐ion batteries.
Crystallographic‐site‐specific structural engineering is performed on the cathode material structure for lithium‐ion batteries, aiming at the root causes of the instability based on the fundamental structure/function relationship. The high‐voltage spinel LiNi0.5Mn1.5O4 (LNMO) cathode with Fd3¯m space group symmetry is employed as a representative, of which two issue‐involved crystallographic sites are directly and simultaneously addressed, contributing to an extraordinarily excellent battery performance.
Nephrogenic adenoma is a benign lesion composed of small glandular structures that develops along the urothelium with uncertain pathogenesis. Some investigators believe that nephrogenic adenoma ...develops by a metaplastic process in response to injury to the urothelium, while others believe that it arises from detached renal tubules. Nephrogenic adenoma may be present in the prostatic urethra and morphologically mimic prostatic adenocarcinoma. Alpha-methylacyl-coenzyme A racemase (AMACR), a recently identified prostate cancer marker, is typically negative in normal urothelium and prostatic glands, and positive in distal convoluted renal tubules in addition to prostatic adenocarcinomas. Therefore, evaluation of AMACR expression in nephrogenic adenoma will have significance in the pathologic diagnosis and in understanding pathogenesis of this lesion. We studied 38 nephrogenic adenomas by clinical, histologic, and immunohistochemical analyses for AMACR (P504S) and high molecular weight cytokeratin (34betaE12). Twenty-two of 38 nephrogenic adenomas (58%) demonstrated strong cytoplasmic positivity for AMACR, ranging from patchy, focal to diffuse staining. In addition, 16 of 26 (62%) nephrogenic adenomas were negative for 34betaE12. To our knowledge, this is one of the first report of a completely benign lesion, which can be found in the prostate, showing strong AMACR immunoreactivity. Our findings suggest using caution when interpreting positive AMACR immunostaining in prostatic specimens. These findings could be explained by possible renal tubular origin or renal differentiation, at least in a subset, of nephrogenic adenomas.
Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID).
To evaluate elbasvir-grazoprevir in treating HCV infection in PWID.
Randomized, placebo-controlled, double-blind trial. ...(ClinicalTrials.gov: NCT02105688).
Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States.
301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT).
The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks.
The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events.
The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and 89.5% (95% CI, 81.5% to 94.8%) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0% (CI, 89.8% to 96.9%) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebo-phase DTG (1 of 100) discontinued treatment because of an adverse event.
These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID.
Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT.
Merck & Co.
Oxides composed of an oxygen framework and interstitial cations are promising cathode materials for lithium‐ion batteries. However, the instability of the oxygen framework under harsh operating ...conditions results in fast battery capacity decay, due to the weak orbital interactions between cations and oxygen (mainly 3d–2p interaction). Here, a robust and endurable oxygen framework is created by introducing strong 4s–2p orbital hybridization into the structure using LiNi0.5Mn1.5O4 oxide as an example. The modified oxide delivers extraordinarily stable battery performance, achieving 71.4 % capacity retention after 2000 cycles at 1 C. This work shows that an orbital‐level understanding can be leveraged to engineer high structural stability of the anion oxygen framework of oxides. Moreover, the similarity of the oxygen lattice between oxide electrodes makes this approach extendable to other electrodes, with orbital‐focused engineering a new avenue for the fundamental modification of battery materials.
Strong molecular bonding formed by Ge 4s and O 2p orbitals contributes to a robust and endurable metal–oxygen framework of the spinel oxide structure, which is not achievable via common 3d–2p orbital hybridization alone, making the oxide cathodes exhibit extraordinarily stable electrochemical performance in lithium‐ion batteries.
Background & Aims Persons with hepatitis C virus (HCV) infection are at risk of progressive liver disease, cirrhosis, and decompensation. We analyzed the effects of the direct-acting antiviral agents ...elbasvir and grazoprevir in patients with HCV infection and compensated cirrhosis, combining data from 6 clinical trials. Methods We performed an integrated analysis of 402 patients with HCV genotype 1, 4, or 6 infection and Child-Pugh A compensated cirrhosis enrolled in 6 clinical trials. All patients received elbasvir/grazoprevir 50 mg/100 mg once daily, with or without ribavirin, for 12−18 weeks. The primary end point was sustained virologic response 12 weeks after completion of therapy (SVR12), defined as a level of HCV RNA <15 IU/mL. Results Among treatment-naïve and treatment-experienced patients receiving elbasvir/grazoprevir for 12 weeks, 97.8% (135 of 138) and 88.9% (48 of 54) achieved SVR12, respectively. Among patients receiving elbasvir/grazoprevir for 12 weeks, addition of ribavirin did not increase the proportion of treatment-naïve patients who achieved an SVR12 (90.3%, 28 of 31) or treatment-experienced patients who achieved an SVR12 (91.4%, 74 of 81). All (49 of 49) treatment-experienced patients receiving elbasvir/grazoprevir with ribavirin for 16 or 18 weeks achieved SVR12, and 93.9% (46 of 49) of patients receiving elbasvir/grazoprevir without ribavirin for 16 or 18 weeks achieved SVR12. Virologic failure was higher among patients with HCV genotype 1a infections compared with patients with genotype 1b or 4 infections—particularly in patients who had not responded to previous interferon therapy. Baseline tests for resistance-associated variants (RAVs) led to an individualized approach for selecting treatment duration and established a need for ribavirin for patients with HCV genotype 1a infection and RAVs, regardless of treatment history. Among patients with HCV genotype 1a infection with and without baseline RAVs in HCV nonstructural protein 5A who received elbasvir/grazoprevir for 12 weeks, 73% (8 of 11) and 98% (96 of 98) achieved SVR12, respectively. Both patients with HCV genotype 1a infection with baseline RAVs who received 16 or 18 weeks of elbasvir/grazoprevir and ribavirin achieved SVR12. Grade 3 or 4 increases in levels of alanine aminotransferase and aspartate aminotransferase, which did not cause symptoms, were reported in 2.3% of patients (6 of 264) receiving elbasvir/grazoprevir. Serious adverse events were reported in 3.0% of patients (8 of 264) and no patient had a decompensation-related event. Conclusions In an analysis of data from 6 clinical trials, we found rates of SVR12 to range from 89% to 100% in patients with HCV genotype 1, 4, or 6 infections and compensated cirrhosis treated with elbasvir/grazoprevir, with or without ribavirin. Addition of ribavirin to a 12-week regimen of elbasvir/grazoprevir had little effect on proportion of treatment-naïve or treatment-experienced patients who achieved an SVR12. However, virologic failure did not occur in any treatment-experienced patients when the duration of elbasvir/grazoprevir and ribavirin therapy was extended to 16 or 18 weeks. Baseline analysis of RAVs (or in the absence of this test, a history of nonresponse to interferon) can be used to determine treatment duration and need for ribavirin in patients with HCV genotype 1a infection. Clinicaltrials.gov ID: NCT02092350 , NCT02105662 , NCT02105467 , NCT02105701 , NCT01717326 , and NCT02105454.
Brain development and function depend on the precise regulation of gene expression. However, our understanding of the complexity and dynamics of the transcriptome of the human brain is incomplete. ...Here we report the generation and analysis of exon-level transcriptome and associated genotyping data, representing males and females of different ethnicities, from multiple brain regions and neocortical areas of developing and adult post-mortem human brains. We found that 86 per cent of the genes analysed were expressed, and that 90 per cent of these were differentially regulated at the whole-transcript or exon level across brain regions and/or time. The majority of these spatio-temporal differences were detected before birth, with subsequent increases in the similarity among regional transcriptomes. The transcriptome is organized into distinct co-expression networks, and shows sex-biased gene expression and exon usage. We also profiled trajectories of genes associated with neurobiological categories and diseases, and identified associations between single nucleotide polymorphisms and gene expression. This study provides a comprehensive data set on the human brain transcriptome and insights into the transcriptional foundations of human neurodevelopment.
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