Guidelines recommend lifestyle modification for patients with coronary heart disease (CHD). Few data demonstrate which lifestyle modifications, if sustained, reduce recurrent CHD and mortality risk ...in cardiac patients after the postacute rehabilitation phase. We determined the association between ideal lifestyle factors and recurrent CHD and all-cause mortality in REasons for Geographic and Racial Differences in Stroke study participants with CHD (n = 4,174). Ideal lifestyle factors (physical activity ≥4 times/week, nonsmoking, highest quartile of Mediterranean diet score, and waist circumference <88 cm for women and <102 cm for men) were assessed through questionnaires and an in-home study visit. There were 447 recurrent CHD events and 745 deaths over a median 4.3 and 4.5 years, respectively. After multivariable adjustment, physical activity ≥4 versus no times/week and non-smoking versus current smoking were associated with reduced hazard ratios (HRs; 95% confidence interval CI) for recurrent CHD (HR 0.69, 95% CI 0.54 to 0.89 and HR 0.50, 95% CI 0.39 to 0.64, respectively) and death (HR 0.71, 95% CI 0.59 to 0.86 and HR 0.53, 95% CI 0.44 to 0.65, respectively). The multivariable-adjusted HRs (and 95% CIs) for recurrent CHD and death comparing the highest versus lowest quartile of Mediterranean diet adherence were 0.77 (95% CI 0.55 to 1.06) and 0.84 (95% CI 0.67 to 1.07), respectively. Neither outcome was associated with waist circumference. Comparing participants with 1, 2, and 3 versus 0 ideal lifestyle factors (non-smoking, physical activity ≥4 times/week, and highest quartile of Mediterranean diet score), the HRs (and 95% CIs) were 0.60 (95% CI 0.44 to 0.81), 0.49 (95% CI 0.36 to 0.67), and 0.38 (95% CI 0.21 to 0.67), respectively, for recurrent CHD and 0.65 (95% CI 0.51 to 0.83), 0.57 (95% CI 0.43 to 0.74), and 0.41 (95% CI 0.26 to 0.64), respectively, for death. In conclusion, maintaining smoking cessation, physical activity, and Mediterranean diet adherence is important for secondary CHD prevention.
African Americans (AAs) have an increased risk for hypertension-related cardiovascular outcomes compared with whites, which may be related to abnormal left ventricular (LV) structure. We examined the ...association of prevalent hypertension with concentric remodeling (CR; normal LV mass index LVMI and increased relative wall thickness RWT), eccentric hypertrophy (increased LVMI and normal RWT), and concentric hypertrophy (CH; increased LVMI and increased RWT) within the Jackson Heart Study. Among 4721 participants (mean ± SD, age 55.7 ± 12.7 years), 2841 (60.2%) had prevalent hypertension, defined as mean clinic blood pressure ≥140/90 mm Hg or antihypertensive medication use. Prevalent hypertension was associated with a statistically significantly increased odds for having CR (odds ratio OR = 1.78, 95% confidence interval CI = 1.42-2.24), eccentric hypertrophy (OR = 1.68; 95% CI = 1.15-2.44), and CH (OR = 3.86, 95% CI = 2.28-6.54) after multivariable adjustment. In conclusion, in a population-based sample of AAs, hypertension was associated with increased odds for having abnormal LV structure, particularly CH.
Highlights • Prescribed sleep medicine use in the past 30 days is highest in women/older adults • Side effects that can affect driving safety are drowsiness/impaired coordination • Assess zolpidem ...use and motor vehicle collisions (MVC) over 5 years in old drivers • Zolpidem use was associated with higher MVC rates in women and adults ≥80 years old • Zolpidem-related MVCs may be avoided by initiating low doses, escalating as needed
Background Bloodstream infections (BSIs) cause substantial morbidity in hemodialysis patients. In 2009, the US Centers for Disease Control and Prevention (CDC) sponsored a collaborative project to ...prevent BSIs in outpatient hemodialysis facilities. We sought to assess the impact of a set of interventions on BSI and access-related BSI rates in participating facilities using data reported to the CDC's National Healthcare Safety Network (NHSN). Study Design Quality improvement project. Setting & Participants Patients in 17 outpatient hemodialysis facilities that volunteered to participate. Quality Improvement Plan Facilities reported monthly event and denominator data to NHSN, received guidance from the CDC, and implemented an evidence-based intervention package that included chlorhexidine use for catheter exit-site care, staff training and competency assessments focused on catheter care and aseptic technique, hand hygiene and vascular access care audits, and feedback of infection and adherence rates to staff. Outcomes Crude and modeled BSI and access-related BSI rates. Measurements Up to 12 months of preintervention (January 2009 through December 2009) and 15 months of intervention period (January 2010 through March 2011) data from participating centers were analyzed. Segmented regression analysis was used to assess changes in BSI and access-related BSI rates during the preintervention and intervention periods. Results Most (65%) participating facilities were hospital based. Pooled mean BSI and access-related BSI rates were 1.09 and 0.73 events per 100 patient-months during the preintervention period and 0.89 and 0.42 events per 100 patient-months during the intervention period, respectively. Modeled rates decreased 32% ( P = 0.01) for BSIs and 54% ( P < 0.001) for access-related BSIs at the start of the intervention period. Limitations Participating facilities were not representative of all outpatient hemodialysis centers nationally. There was no control arm to this quality improvement project. Conclusions Facilities participating in a collaborative successfully decreased their BSI and access-related BSI rates. The decreased rates appeared to be maintained in the intervention period. These findings suggest that improved implementation of recommended practices can reduce BSIs in hemodialysis centers.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Although the pathogenesis of MS remains unknown, it is widely regarded as an autoimmune disease ...mediated by T-lymphocytes directed against myelin proteins and/or other oligodendrocyte epitopes.
In this study we investigated the gene expression profiles of peripheral blood cells from patients with RRMS during the relapse and the remission phases utilizing gene microarray technology. Dysregulated genes encoded in regions associated with MS susceptibility from genomic screens or previous transcriptomic studies were identified. The proximal promoter region polymorphisms of two genes were tested for association with disease and expression level.
Distinct sets of dysregulated genes during the relapse and remission phases were identified including genes involved in apoptosis and inflammation. Three of these dysregulated genes have been previously implicated with MS susceptibility in genomic screens: TGFbeta1, CD58 and DBC1. TGFbeta1 has one common SNP in the proximal promoter: -508 T>C (rs1800469). Genotyping two Australian trio sets (total 620 families) found a trend for over-transmission of the T allele in MS in females (p < 0.13). Upregulation of CD58 and DBC1 in remission is consistent with their putative roles in promoting regulatory T cells and reducing cell proliferation, respectively. A fourth gene, ALOX5, is consistently found over-expressed in MS. Two common genetic variants were confirmed in the ALOX5 putative promoter: -557 T>C (rs12762303) and a 6 bp tandem repeat polymorphism (GGGCGG) between position -147 and -176; but no evidence for transmission distortion found.
The dysregulation of these genes tags their metabolic pathways for further investigation for potential therapeutic intervention.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Multiple sclerosis (MS) is an enigmatic disease of the central nervous system resulting in sclerotic plaques with the pathological hallmarks of demyelination and axonal damage, which can be directly ...or indirectly orchestrated by cells from the peripheral circulation. The majority of patients with MS follow a relapsing-remitting course in the early stages of the disease (RRMS) but most ultimately enter a secondary progressive phase (SPMS). About 10% of patients follow a primary progressive course from the onset (PPMS). We measured gene expression in whole blood of people with and without chronic progressive MS (CPMS), PPMS and SPMS, to discover genes which may be differentially expressed in peripheral blood in active disease, and so identify pathologically significant genes and pathways; and we investigated genetic differences in the promoters of dysregulated genes encoded in genomic regions associated with MS. If SPMS and PPMS were independently compared to the controls, there was little overlap in the set of most dysregulated genes. Ribosomal protein genes, whose expression is usually associated with cell proliferation and activation, were dramatically over-represented in the set of most down-regulated genes in PPMS compared to SPMS (P < 10(-4), chi(2)). The T cell proliferation gene IL7R (CD127) was also underexpressed in PPMS, but was up-regulated in SPMS compared to the controls. One interleukin 7 receptor (IL7R) promoter single nucleotide polymorphism (SNP), -504 C, was undertransmitted in PPMS trios (P = 0.05, TDT), and carriers of this allele were under-represented in PPMS cases from two independent patient cohorts (combined P = 0.006, FE). The four known IL7R promoter haplotypes were shown to have similar expression levels in healthy controls, but not in CPMS (P < 0.01, t test). These data support the hypothesis that PPMS has significant pathogenetic differences from SPMS, and that IL7R may be a useful therapeutic target in PPMS.
Zidovudine (AZT) is a potent inhibitor of the replication of the human immunodeficiency virus (HIV), and it has been shown to improve survival in advanced HIV disease. We conducted a randomized, ...double-blind trial in adults with asymptomatic HIV infection who had CD4+ cell counts of fewer than 500 per cubic millimeter on entry into the study. The subjects (92 percent male) were randomly assigned to one of three treatment groups: placebo (428 subjects); zidovudine, 500 mg per day (453); or zidovudine, 1500 mg per day (457).
After a mean follow-up of 55 weeks (range, 19 to 107), 33 of the subjects assigned to placebo had the acquired immunodeficiency syndrome (AIDS), as compared with 11 of those assigned to receive 500 mg of zidovudine (P = 0.002; relative risk, 2.8; 95 percent confidence interval, 1.4 to 5.6) and 14 of those assigned to receive 1500 mg of zidovudine (P = 0.05; relative risk, 1.9; 95 percent confidence interval, 1.0 to 3.5). In the three treatment groups, the rates of progression (per 100 person-years) to either AIDS or advanced AIDS-related complex were 7.6, 3.6, and 4.3, respectively. As compared with those assigned to placebo, the subjects in the zidovudine groups had significant increases in the number of CD4+ cells and significant declines in p24 antigen levels. In the 1500-mg zidovudine group, severe hematologic toxicity (anemia or neutropenia) was more frequent than in the other groups (P<0.0001). In the 500-mg zidovudine group, nausea was the only toxicity that was significantly more frequent (in 3.3 percent) than in the placebo group (P = 0.001).
We conclude that zidovudine is safe and effective in persons with asymptomatic HIV infection and fewer than 500 CD4+ cells per cubic millimeter. Additional study will be required to determine whether such treatment will ultimately improve survival for persons infected with HIV. (N Engl J Med 1990; 322:941–9.)
INFECTION with the human immunodeficiency virus (HIV) causes chronic, progressive depletion of CD4+ helper/inducer T lymphocytes (CD4+ cells).
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Together with the infection of macrophages and other cells, this depletion creates an immune deficiency that leads to the cancers and opportunistic infections characteristic of the acquired immunodeficiency syndrome (AIDS). Although HIV does not usually cause clinically apparent illness for many years,
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this progression may be inevitable in untreated persons. From the time of diagnosis of AIDS, the three-year mortality rate is higher than 90 percent.
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Because of the long period of latency from the primary infection to the development of clinical . . .
The effect of bacterial‐cell centrifugation and handling on the initial stages of plasmid processing was investigated. Escherichia coli cells containing either a 6 or 20 kb plasmid were grown in 75‐ ...and 450‐litre bioreactors, and the process yield of the early recovery stages was characterized in terms of SC pDNA (supercoiled plasmid DNA) recovered. In all cases, the cells were totally recovered using either a continuous‐feed, intermittent‐solids‐discharge, disc‐stack centrifuge or a continuous‐feed, batch‐discharge, solid‐bowl centrifuge. The cells were then either processed immediately or stored frozen. The centrifugation method considerably affected the yield of SC pDNA, and there was evidence that the intermittent discharge of cells from a centrifuge operating at high speed led to a sediment containing lysed cells and degraded pDNA. This led to estimated plasmid yield losses of up to 40% as compared with cells recovered from laboratory or solid‐bowl centrifuges, where there is evidently no cell stress on discharge. By inference, the cell stress on feed to either of the continuous centrifuges studied was not implicated in product loss. Freezing of the recovered cells gives a convenient hold stage prior to further processing. In all cases, this extra freeze–thaw stage led to loss of SC pDNA, and this was in addition to the loss attributed to cell lysis during centrifugation discharge. Only average yields can be gained from pilot plant‐scale studies; separate laboratory‐based experiments indicated that this loss of SC pDNA is determined by the time and temperature for which the resuspended cells are held.
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