Quality of Life and mortality in the general population:a systematic review and meta-analysis

Background: Quality of life (QoL) is multi-dimensional concept of an individual’ general well-being status in relation to their value, environment, cultural and social context in which they live. This study aimed to quantitatively synthesise available evidence on the association between QoL and mortality in the general population. Methods: An electronic search was conducted using three bibliographic databases, MEDLINE, EMBASE and PsycINFO. Inclusion criteria were studies that assessed QoL using standardized tools and examined mortality risk in a non-patient population. Qualitative data synthesis and meta-analyses using a random-effects model were performed. Results: Of 4184 articles identified, 47 were eligible for inclusion, involving approximately 1,200,000 participants. Studies were highly heterogeneous in terms of QoL measures, population characteristics and data analysis. In total, 43 studies (91.5%) reported that better QoL was associated with lower mortality risk. The results of four metaanalyses indicated that higher health-r

Temporal trends in pregnancy-associated stroke and its outcomes among women with hypertensive disorders of pregnancy

Funding PW is funded by a NIHR Transitional Research Fellowship. CCG is part-funded by West Midlands ARC. LCC is funded by a NIHR Professorship (RP-2014-05-019). This paper presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The funders had no involvement in the conduct of this research.Peer reviewedPublisher PD

Sex Differences in Ischemic Stroke Outcomes in Patients With Pulmonary Hypertension

Acknowledgments To the authors thank Dr Jesus A Perdomo‐Lampignano, MBChB for his assistance with the figures and also acknowledge the Healthcare Cost and Utilization Project Data Partners (https://www.hcup‐us.ahrq.gov/db/hcupdatapartners.jsp). Supplementary Material for this article is available at https://www.ahajournals.org/doi/suppl/10.1161/JAHA.120.019341 Open Access via the Jisc Wiley AgreementPeer reviewedPublisher PD

Impact of the admitting ward on care quality and outcomes in non-ST-segment elevation myocardial infarction (NSTEMI) : insights from a national registry

Peer reviewedPostprin

Dihydroartemisinin-Piperaquine Versus Chloroquine in the Treatment of Plasmodium vivax Malaria in Thailand: A Randomized Controlled Trial

The efficacy of chloroquine in the treatment of Plasmodium vivax malaria is declining on the Northwestern border of Thailand. This randomized controlled trial in 500 adults and children shows that dihydroartemisinin-piperaquine is a safe and effective alternative treatment

Design and Synthesis of High Affinity Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferases Directed by Ligand Efficiency Dependent Lipophilicity (LELP)

N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both Plasmodium falciparum and P. vivax NMT and displays activity in vivo against a rodent malaria model. Here we describe the discovery of 34c through optimization of a previously described series. Development, guided by targeting a ligand efficiency dependent lipophilicity (LELP) score of less than 10, yielded a 100-fold increase in enzyme affinity and a 100-fold drop in lipophilicity with the addition of only two heavy atoms. 34c was found to be equipotent on chloroquine-sensitive and -resistant cell lines and on both blood and liver stage forms of the parasite. These data further validate NMT as an exciting drug target in malaria and support 34c as an attractive tool for further optimization

Образование иерархических структур из функционализированных многостенных углеродных нанотрубок в растворе с аэросилом

The features and  regularities of self−assembly and  self− organization processes in the diffusion−limited conditions (method of drops) of aqueous (deionized water) colloidal solutions of multi−walled carbon nanotubes with aerosil under the influence of constant electric fields with a value varying of direct  current voltage  from 15 to 25 V have been studied. During droplet evaporation in an electric field, the processes of hierarchical structuring have been studied and the formation of linear piecewise with the sizes of 40—120 nm, fractal structures 25—45 nm and  diffusion structures 250 nm from MWCNT — COOH + aerosil  + H2ODI  have  been observed. These structures have  been analyzed by methods of confocal microscopy, X−ray powder diffraction, Raman scattering, atomic force microscopy, FT−IR spectroscopy and scanning electron microscopy. The size of micro− and nanostructures in hyperbolic dependence of d = 1/U in the  approximation d → 2R, and their growth rate  increases as U2 have been observed. Intensive ultrasonic dispersion proves to produce a centrally−axial arrangement located SWCNT after ultrasonic dispersing of functionalized MWCNT — COOH + aerosil  + H2ODI colloidal solution, as confirmed by excitation of Raman lines in the low−wavelength region, the so−called breathing mode, resulting in the existence of mixed types sp2−hybridization with π− and σ−carbon bonds, as well as metallic and semiconducting conductivity, which indicates great practical importance of this structuring for the development of nanoelectronics. Изучены особенности и закономерности процессов самосборки и самоорганизации в диффузионно−ограниченных условиях (методом из капли) водных (деионизированная вода)  коллоидных растворов многостенных углеродных нанотрубок (МУНТ) с аэросилом под воздействием постоянных электрических полей, варьируемых по величине от 15 до 25 В. В ходе испарения капли в однородном электрическом поле изучены процессы иерархического структурирования и обнаружено формирование линейно−кусочных образований размером 40—120 нм, фрактальных структур — 25—45 нм, а также диффузных структур — 250 нм из «МУНТ — COOH + аэросил + H2Oд.в». Проведены исследования структур методами конфокальной микроскопии, рентгеновской дифрактометрии, спектроскопии комбинационного рассеяния, атомно−силовой микроскопии, ИК−спектроскопии и сканирующей электронной микроскопии. Установлено,  что размеры наблюдаемых микро− и наноструктур уменьшаются по гиперболической зависимости d = 1/U в приближении d  → 2R, а скорость их роста возрастает как U2. Доказано, что интенсивное ультразвуковое диспергирование функционализированных «МУНТ — COOH + аэросил + H2Oд.в» в коллоидном растворе вызывает появление внутри одностенных углеродных нанотрубок с центрально−осевым расположением так называемых дыхательных мод. Это подтверждается возбуждением линий КРС в коротковолновой области, и обусловливает как существование смешанных типов sp2−гибридизации с π− и σ−углеродными связями, так и металлической и полупроводниковой проводимостей, что указывает на большое практическое значение такого структурирования для развития наноэлектроники

Trial of Dexamethasone for Chronic Subdural Hematoma

BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.)

Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach

Malaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation). Here, we report an integrated chemical biology approach to explore protein myristoylation in the major human parasite P. falciparum, combining chemical proteomic tools for identification of the myristoylated and glycosylphosphatidylinositol-anchored proteome with selective small-molecule N-myristoyltransferase inhibitors. We demonstrate that N-myristoyltransferase is an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and show that selective inhibition of N-myristoylation leads to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle. Our studies provide the basis for the development of new antimalarials targeting N-myristoyltransferase