Genetic Variants in Nuclear-Encoded Mitochondrial Genes Influence AIDS Progression

Background: The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression. Methodology/Principal Findings: Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping array of 1,455 European American patients from five US AIDS cohorts. Successfully genotyped SNPs gave 50% or better haplotype coverage for 679 of known NEMP genes. With a Bonferroni adjustment for the number of genes and tests examined, multiple SNPs within two NEMP genes showed significant association with AIDS progression: acyl-CoA synthetase medium-chain family member 4 (ACSM4) on chromosome 12 and peroxisomal D3,D2-enoyl- CoA isomerase (PECI) on chromosome 6. Conclusions: Our previous studies on mitochondrial DNA showed that European haplogroups with presumed functional differences were associated with AIDS progression and HAART mediated adverse events. The modest influences of nuclearencoded mitochondrial genes found in the current study add support to the idea that mitochondrial function plays a role in AIDS pathogenesis

Genetic Identification of a Network of Factors that Functionally Interact with the Nucleosome Remodeling ATPase ISWI

Nucleosome remodeling and covalent modifications of histones play fundamental roles in chromatin structure and function. However, much remains to be learned about how the action of ATP-dependent chromatin remodeling factors and histone-modifying enzymes is coordinated to modulate chromatin organization and transcription. The evolutionarily conserved ATP-dependent chromatin-remodeling factor ISWI plays essential roles in chromosome organization, DNA replication, and transcription regulation. To gain insight into regulation and mechanism of action of ISWI, we conducted an unbiased genetic screen to identify factors with which it interacts in vivo. We found that ISWI interacts with a network of factors that escaped detection in previous biochemical analyses, including the Sin3A gene. The Sin3A protein and the histone deacetylase Rpd3 are part of a conserved histone deacetylase complex involved in transcriptional repression. ISWI and the Sin3A/Rpd3 complex co-localize at specific chromosome domains. Loss of ISWI activity causes a reduction in the binding of the Sin3A/Rpd3 complex to chromatin. Biochemical analysis showed that the ISWI physically interacts with the histone deacetylase activity of the Sin3A/Rpd3 complex. Consistent with these findings, the acetylation of histone H4 is altered when ISWI activity is perturbed in vivo. These findings suggest that ISWI associates with the Sin3A/Rpd3 complex to support its function in vivo

Geochemical tracers for monitoring offshore CO2 stores

Chemical tracers are proposed as an effective means of detecting, attributing and quantifying any CO2 leaks to surface from geological CO2 storage sites, a key component of Carbon Capture and Storage (CCS) technology. A significant proportion of global CO2 storage capacity is located offshore, with some regions of the world having no onshore stores. To assure regulatory bodies and the public of CO2 storage integrity it is important to demonstrate that robust offshore monitoring systems are in place. A range of chemical tracers for leakage have been tested at onshore pilot CCS projects worldwide, but to date they have not been trialled at injection projects or CO2 release experiments located offshore. Here, for the first time, we critically review the current issues surrounding commercial scale use of tracers for offshore CCS projects, and examine the constraints and cost implications posed by the marine environment. These constraints include the logistics of sampling for tracers offshore, the fate of tracers in marine environments, tracer background levels, marine toxicity and legislative barriers – with particular focus on the Europe and the UK. It is clear that chemicals that form a natural component of the CO2 stream are preferable tracers for ease of permitting and avoiding cost and risks of procuring and artificially adding a tracer. However, added tracers offer more reliability in terms of their unique composition and the ability to control and regulate concentrations. We identify helium and xenon isotopes (particularly 124,129Xe), and artificial tracers such as PFCs and deuterated methane as the most suitable added tracers. This is due to their conservative behaviour, low environmental impact and relative inexpense. Importantly, we also find that SF6 and C14 are not viable tracers for CCS due to environmental concerns, and many other potential tracers can be ruled out on the basis of cost. Further, we identify key challenges that are unique to using tracers for offshore monitoring, and highlight critical uncertainties that future work should address. These include possible adsorption or dispersion of tracer compounds during ascent through the overburden, longevity of tracers over the timeframes relevant for CCS monitoring, the permissible environmental effects of tracer leakage, and tracer behaviour in seabed CO2 bubble streams and in dissolved CO2. These uncertainties directly affect the selection of appropriate tracers, the injection programme and concentrations necessary for their reliable detection, and appropriate sampling approaches. Hence offshore tracer selection and associated expense are currently poorly constrained. Further, there is limited experience of sampling for tracers in the marine environment; current approaches are expensive and must be streamlined to enable affordable monitoring strategies. Further work is necessary to address these unknowns so as to evaluate the performance of potential tracers for CO2 leak quantitation and provide more accurate costings for effective offshore tracer monitoring programmes

Non-pharmacologic interventions to improve sleep of medicine inpatients: a controlled study

Background: Sleep quality in hospitalized medicine patients is poor, with environmental factors among the most frequently cited reasons. Objective: We tested the efficacy of a non-pharmacologic intervention on the sleep quality of medicine inpatients. Design/Methods: A controlled study to evaluate our non-pharmacologic multidisciplinary ‘TUCK-in’ protocol (which includes timed lights-off periods, minimizing night-time noise, distribution of earplugs at bedtime, cued toileting before bedtime, and identification and reduction of modifiable interruptions) was deployed on two of five identical medicine wards. Randomization was at the level of the ward. The main outcome measure was self-reported duration of night-time sleep within 48 hours prior to discharge. Additional outcome measures included the Verran–Snyder-Halpern (VSH) Sleep Score and inpatient sleep pharmaceutical use. Results: Self-reported duration of night-time sleep (median 5.0 vs. 5.0 hours, p = 0.29) and daytime sleep (1.0 versus 0.5 hours, p = 0.43) did not differ between the 40 intervention patients and the 41 control patients (p = 0.13 on multivariate analysis). Cumulative VSH sleep disturbance (median 420 versus 359, p = 0.19), efficacy (median 169 versus 192, p = 0.29), or supplementation (median 97 versus 100, p = 0.51) scales were also not different between study arms. Conclusions: Although staff reported the protocol to be achievable and worthwhile, there were no significant differences in any of the outcomes between intervention and control patients.

Sleep Quality and Factors Influencing Self-Reported Sleep Duration and Quality in the General Internal Medicine Inpatient Population.

BACKGROUND:Sleep quality in hospitalized Canadian General Internal Medicine patients is not well characterized. Our goals were to characterize hospital sleep quality in this population and identify potentially modifiable barriers to good sleep. METHODS:GIM inpatients at a quaternary centre in Edmonton, Canada completed a survey, including the Verran-Snyder Halpern (VSH) questionnaire, to characterize the previous night's sleep within 48 hours prior to discharge. A chart review was also completed to assess comorbidities, discharge diagnoses, and pharmaceutical sleep aid use. RESULTS:Patients reported significantly worse nighttime sleep duration in hospital compared with home (mean 5.5 versus 7.0 hours per night, p < 0.0001). Sleep quality was poor, as measured by the VSH disturbance (mean 371), effectiveness (190), and supplementation (115) subscales. Variables independently associated with poorer sleep duration in multivariable regression include prior diagnosis of sleep disorder and multi-patient occupancy rooms. Age, sex, admitting diagnosis, length of stay, frequency of vital checks, and use of sleep pharmaceuticals during the index hospitalization were not associated with sleep duration. The most frequently reported reasons for poor sleep included noise (59%), nursing interruptions (30%), uncomfortable beds (18%), bright lights (16%), unfamiliar surroundings (14%), and pain (9%). CONCLUSIONS:Sleep quality for GIM inpatients is significantly worse in hospital than at home. There is a need to test non-pharmacologic interventions to address the most frequently identified factors causing poor sleep hygiene for GIM inpatients

How a cloud based platform can make ambulatory blood pressure monitoring more efficient, accessible, and evidence based

Ambulatory blood pressure measurement (ABPM) is the gold-standard method for blood pressure assessment. However, it is markedly underutilized, in part because legacy software provided with ABPM devices is archaic and inefficient. Herein, we illustrate an example of a recently developed cloud-based ABPM platform. Such a platform offers several distinct advantages: (1) the ability to guide users through the testing process; (2) synchronizing inputs of the technician, patient, physician, and administrative assistant so that testing can be successful and efficient; (3) providing guideline-concordant study interpretations that can be e-signed, reducing physician interpretation times; (4) enabling central expert oversight and peripheral deployment of testing, thereby increasing accessibility of quality testing; and (5) facilitating integration into electronic medical records, improving dissemination of results. It is envisioned that increased use of cloud-based ABPM platforms will lead to the expansion of quality ABPM testing, thus improving the care of patients with known or suspected hypertension

Verran Snyder Halpern Sleep Scale scores for inpatients surveyed within 48 hours of discharge (n = 93).

<p>Verran Snyder Halpern Sleep Scale scores for inpatients surveyed within 48 hours of discharge (n = 93).</p

Patient characteristics and associations with factors that may affect sleep.

<p>SD = standard deviation; CI = confidence interval. Patient characteristic values are displayed as n (%) for binary variables and mean (SD) for continuous variables.Associations are represented by linear regression coefficients (Beta), displayed for both crude and adjusted models with corresponding 95% confidence intervals. Coefficients greater than zero represent a positive association (i.e., variable is positively correlated with sleep duration in the previous night), while coefficients less than zero represent inverse association (i.e., variable is negatively correlated with sleep duration in the previous night).</p

Effect of Cuff Design on Auscultatory and Oscillometric Blood Pressure Measurements

Two-piece blood pressure (BP) cuffs are the historical cuff standard. Use of 1-piece cuffs is increasing. Substituting 1-piece for 2-piece cuffs has an unknown effect on measurement accuracy. We compared these cuff types in a 2-phase study using auscultatory and oscillometric techniques. METHODS Consenting subjects (aged ≥18 years) with BP levels between 80 and 220mm Hg/50 and 120mm Hg and arm circumferences between 25 and 43cm were studied using the International Standards Organization (ISO) 2013 protocol (modified). A Baum 2-piece cuff was used as the refer ence standard. A 1-piece Welch Allyn cuff was the comparator. In phase 1 (2-observer auscultation with a mercury sphygmomanometer), 88 sub jects were required to obtain 255 paired BP determinations. In phase 2 (oscillometric measurement with a Spacelabs 90207 device), 85 subjects were studied. Each phase was analyzed separately using paired t-tests. RESULTS Phase 1 mean age was 54.2±20.5 years, mean arm circumference was 29.9±3.7cm, 60% were female, and 32% had hypertension. One-piece cuff mean BPs were lower than the 2-piece cuff means (115.5±15.5/66.4±9.3 vs. 117.8±15.2/67.9±9.2; difference of −2.4±3.6/−1.5±2.4; P values <0.0001 for systolic and diastolic com parisons). Phase 2 mean age was 52.8±20.8 years, mean arm circumfer ence was 29.4±3.9cm, 67% were female, and 38% had hypertension. Mean BPs were lower for the 1-piece compared to the 2-piece cuff (116.5±12.8/67.1±8.1 vs. 120.8±13.5/70.4±8.5; difference of −4.4±3.6/−3.3±2.7; P values <0.0001 for both). CONCLUSIONS Mean BP is lower with 1-piece cuffs vs. 2-piece cuffs. Differences are greater with oscillometry. When performing validation studies and measurements for clinical purposes, cuff type should be taken into account.Scopu