Hayshopkins0701

Statins are a class of drugs used to lower low-density lipoprotein cholesterol and are amongst the most prescribed medications worldwide. Most statins work as a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), but statin intolerance from pleiotropic effects have been proposed to arise from non-specific binding due to poor enzyme-ligand sensitivity. Yet, research into the physicochemical properties of statins, and their interactions with off-target sites, has not progressed much over the past few decades. Here, we present a concise perspective on the role of statins in lowering serum cholesterol levels, and how their reported interactions with phospholipid membranes offer a crucial insight into the mechanism of some of the more commonly observed pleiotropic effects of statin administration. Lipophilicity, which governs hepatoselectivity, is directly related to the molecular structure of statins, which dictates interaction with and transport through membranes. The structure of statins is therefore a clinically important consideration in the treatment of hypercholesterolaemia. This review integrates the recent biophysical studies of statins with the literature on the physiological effects and provides new insights into the mechanistic cause of statin pleiotropy, and prospective means of understanding the cholesterol-independent effects of statins.Dyslipidemia is one of the important influencing factors of cardiovascular health in the youth, and thus, assessment of its etiology is important. We aimed to investigate the association of dyslipidemia with vitamin D and physical activity in Korean children and adolescents. Data of 3183 subjects aged 12-18 years in the Korea National Health and Nutrition Examination Survey were analyzed. Participants were divided into subgroups according to sex, body mass index, 25-hydroxyvitamin D levels, and lipid profile. The mean 25-hydroxyvitamin D level was 16.15 ng/mL, which was below normal. In total, 79.3% of the subjects had vitamin D deficiency. Females had lower vitamin D levels and a higher incidence of dyslipidemia compared to males. Vitamin D deficiency was significantly associated with high density lipoprotein cholesterol (HDL-C) levels. The low HDL-C group consisted of a higher proportion of subjects with vitamin D deficiency and low physical activity. This study suggests that vitamin D deficiency is prevalent in Korean children and adolescents. Vitamin D deficiency and low physical activity are related with low HDL-C levels. Maintaining sufficient vitamin D levels and physical activity may help prevent dyslipidemia.In 2015, the newborn screening (NBS) programmes in England and Wales were expanded to include four additional disorders Classical Homocystinuria, Isovaleric Acidemia, Glutaric Aciduria Type 1 and Maple Syrup Urine Disease, bringing the total number of analytes quantified to eight phenylalanine, tyrosine, leucine, methionine, isovalerylcarnitine, glutarylcarnitine, octanoylcarnitine and decanoylcarnitine. Post-implementation, population data monitoring showed that inter-laboratory variation was greater than expected, with 90th centiles varying from 17 to 59%. We evaluated the effect of stable isotope internal standard (IS) used for quantitation on inter-laboratory variation. Four laboratories analysed routine screening samples (n > 101,820) using a common IS. Inter-laboratory variation was determined for the eight analytes and compared with results obtained using an in-house common IS (n > 102,194). A linear mixed-effects model was fitted to the data. Using a common IS mix reduced the inter-laboratory variation significantly (p less then 0.05) for five analytes. For three analytes, the lack of significance was explained by use of individual laboratory "calibration factors". For screening programmes where laboratories adhere to single analyte cut-off values (COVs), it is important that inter-laboratory variation is minimised, primarily to prevent false positive results. Whilst the use of a common IS helps achieve this, it is evident that instrument set-up also contributes to inter-laboratory variation.We investigate the role of tellurite on a lithium-silicate glass 0.1 TeO2 -0.90.1 TeO2 -0.9 (Li2O-2SiO2) (LSTO) system proposed for the use in solid electrolyte for lithium ion batteries. The measurements of electrical impedance are performed in the frequency 100 Hz-30 MHz and temperature from 50 to 150 °C. The electrical conductivity of LSTO glass increases compared with that of Li2O-2SiO2 (LSO) glass due to an increase in the number of Li+ ions. The ionic hopping and relaxation processes in disordered solids are generally explained using Cole-Cole, power law and modulus representations. The power law conductivity analysis, which is driven by the modified Rayleigh equation, presents the estimation of the number of ionic charge carriers explicitly. The estimation counts for direct contribution of about a 14% increase in direct current conductivity in the case of TeO2 doping. The relaxation process by modulus analysis confirms that the cations are trapped strongly in the potential wells. Both the direct current and alternating current activation energies (0.62-0.67 eV) for conduction in the LSO glass are the same as those in the LSTO glass.Downstream neighbor of Son (DONSON) plays a crucial role in cell cycle progression and in maintaining genomic stability, but its role in prostate cancer (PCa) development and progression is still underinvestigated. Methods DONSON mRNA expression was analyzed with regard to clinical-pathological parameters and progression using The Cancer Genome Atlas (TCGA) and two publicly available Gene Expression Omnibus (GEO) datasets of PCa. Afterwards, DONSON protein expression was assessed via immunohistochemistry on a comprehensive tissue microarray (TMA). Subsequently, the influence of a DONSON-knockdown induced by the transfection of antisense-oligonucleotides on proliferative capacity and metastatic potential was investigated. DONSON was associated with an aggressive phenotype in the PCa TCGA cohort, two GEO PCa cohorts, and our PCa TMA cohort as DONSON expression was particularly strong in locally advanced, metastasized, and dedifferentiated carcinomas. Thus, DONSON expression was notably upregulated in distant and androgen-deprivation resistant metastases. In vitro, specific DONSON-knockdown significantly reduced the migration capacity in the PCa cell lines PC-3 and LNCaP, which further suggests a tumor-promoting role of DONSON in PCa. In conclusion, the results of our comprehensive expression analyses, as well as the functional data obtained after DONSON-depletion, lead us to the conclusion that DONSON is a promising prognostic biomarker with oncogenic properties in PCa.The emergence and spread of extensively drug-resistant (XDR) typhoid in Karachi, Pakistan led to an outbreak response in Lyari Town, Karachi utilizing a mass immunization campaign with typhoid conjugate vaccine (TCV), Typbar TCV®. The mass immunization campaign, targeted Lyari Town, Karachi, one of the worst affected towns during the XDR typhoid outbreak. Here we describe the strategies used to improve acceptance and coverage of Typbar TCV in Lyari Town, Karachi. The mass immunization campaign with Typbar TCV was started as a school- and hospital-based vaccination campaign targeting children between the age of 6 months to 15 years old. A dose of 0.5 mL Typbar TCV was administered intramuscularly. A mobile vaccination campaign was added to cope with high absenteeism and non-response from parents in schools and to cover children out of school. Different strategies were found to be effective in increasing the vaccination coverage and in tackling vaccine hesitancy. Community engagement was the most successful strategy to overcome refusals and helped to gain trust in the newly introduced vaccine. Community announcements and playing typhoid jingles helped to increase awareness regarding the ongoing typhoid outbreak. Mop-up activity in schools was helpful in increasing coverage. Networking with locally active groups, clubs and community workers were found to be the key factors in decreasing refusals.Biofilms are aggregates of microbial cells encased in a highly hydrated matrix made up of self-produced extracellular polymeric substances (EPS) which consist of polysaccharides, proteins, nucleic acids, and lipids. While biofilm matrix polysaccharides are unraveled, there is still poor knowledge about the identity and function of matrix-associated proteins. With this work, we performed a comprehensive proteomic approach to disclose the identity of proteins associated with the matrix of biofilm-growing Burkholderia multivorans C1576 reference strain, a cystic fibrosis clinical isolate. Transmission electron microscopy showed that B. multivorans C1576 also releases outer membrane vesicles (OMVs) in the biofilm matrix, as already demonstrated for other Gram-negative species. The proteomic analysis revealed that cytoplasmic and membrane-bound proteins are widely represented in the matrix, while OMVs are highly enriched in outer membrane proteins and siderophores. Our data suggest that cell lysis and OMVs production are the most important sources of proteins for the B. multivorans C1576 biofilm matrix. Of note, some of the identified proteins are lytic enzymes, siderophores, and proteins involved in reactive oxygen species (ROS) scavenging. These proteins might help B. multivorans C1576 in host tissue invasion and defense towards immune system assaults.Decades of research suggest that Mindfulness-Based Stress Reduction (MBSR) training supports a greater capacity to live with chronic medical conditions and contributes to lowering stress levels. This paper introduces a model for a Mindfulness-Based Recovery from Stroke (MBRfS) for promoting stroke recovery, informed by the lived experience of the author (a stroke survivor and certified MBSR instructor), the research literature regarding MBSR training, and the specific challenges of stroke recovery. Four themes emerged from the autoethnographic analysis that informed the proposed model Readiness to accept the stroke event and the acquired brain injury, navigating uncertainties of stroke recovery with awareness and self-responsibility for outcomes, trusting the inherent wisdom of the body as a stroke recovery "teacher", and increased capacity to integrate complex emotions with self-compassion, and a sense of wholeness. A four-component MBRfS model is offered, which consists of an integration amongst a modified MBSR framework, emergent attitudinal themes, and insights from the autoethnographic vignettes. The MBRfS model offers a path for providing participants with a supportive experience within stroke recovery. Recommendations and suggestions for future studies are offered to support the development of MBRfS for stroke survivors and their caregivers, as well as contributing to healthcare providers.Clonal plants usually reproduce asexually through vegetative propagation and sexually by producing seeds. Physiological integration, the translocation of essential resources between ramets, usually improves vegetative reproduction. However, how physiological integration affects sexual reproduction has been less studied in clonal grasses. Here, we chose Hierochloe glabra, a major early spring forage of the eastern Eurasian steppe, and conducted a series of field experiments, including sampling reproductive ramets connected by tillering nodes to different numbers of vegetative ramets and 15N leaf labeling of ramet pairs at the seed-filling stage. In the natural populations of H. glabra, vegetative ramets were taller, had more and larger leaves, and greater biomass than reproductive ramets. Except for reproductive ramet biomass, sexual reproductive characteristics significantly increased with an increase in the number and biomass of vegetative ramets connected to tillering nodes. 15N labeling showed that vegetative ramets supplied nutrients to reproductive ramets through tillering nodes.