Target renal damage: the microvascular associations of increased aortic stiffness in patients with COPD

Background Although renal impairment has been described in COPD, there is opportunity to evaluate further to determine nature and consider optimal management. Increased aortic stiffness, as seen in COPD, leads to reduced buffering of pulsatile flow. We hypothesised that urinary albumin creatinine ratio (UACR) would reflect glomerular damage related to aortic stiffness. Methods Patients with COPD and controls underwent spirometry, blood pressure, arterial stiffness - aortic pulse wave velocity (PWV) and provided a spot urine sample for UACR, with other renal biomarkers measured. Results The UACR was increased in patients (n = 52): 0.80 mg/mmol compared to controls (n = 34): 0.46 mg/mmol, p < 0.05. Aortic PWV was related to log10 UACR in all subjects (r = 0.426, p < 0.001) and COPD patients alone. Aortic PWV was a significant variable for UACR with oxygen saturations, after accounting for potential confounders. Eight subjects (7 patients) reached a defined clinical microalbuminuria threshold, with aortic PWV greater in these patients compared to those patients without, although albuminuria is a continuum. Proximal tubular damage biomarkers, unlike the glomerular marker, were not different between patients and controls. Conclusions There is glomerular damage in patients with COPD evidenced by increased UACR, related to increased aortic stiffness. Besides the macrovascular prognostic implications of increased aortic stiffness, the microvascular state in COPD management should be considered

Changes in Coordination and Its Variability with an Increase in Functional Performance of the Lower Extremities

Clinical gait analysis has a long-standing tradition in biomechanics. However, the use of kinematic data or segment coordination has not been reported based on wearable sensors in “real-life” environments. In this work, the skeletal kinematics of 21 healthy and 24 neurogeriatric participants was collected in a magnetically disturbed environment with inertial measurement units (IMUs) using an accelerometer-based functional calibration method. The system consists of seven IMUs attached to the lower back, the thighs, the shanks, and the feet to acquire and process the raw sensor data. The Short Physical Performance Battery (SPPB) test was performed to relate joint kinematics and segment coordination to the overall SPPB score. Participants were then divided into three subgroups based on low (0–6), moderate (7–9), or high (10–12) SPPB scores. The main finding of this study is that most IMU-based parameters significantly correlated with the SPPB score and the parameters significantly differed between the SPPB subgroups. Lower limb range of motion and joint segment coordination correlated positively with the SPPB score, and the segment coordination variability correlated negatively. The results suggest that segment coordination impairments become more pronounced with a decreasing SPPB score, indicating that participants with low overall SPPB scores produce a peculiar inconsistent walking pattern to counteract lower extremity impairment in strength, balance, and mobility. Our findings confirm the usefulness of SPPB through objectively measured parameters, which may be relevant for the design of future studies and clinical routines

Geometry-dependent critical currents in superconducting nanocircuits

In this paper we calculate the critical currents in thin superconducting strips with sharp right-angle turns, 180-degree turnarounds, and more complicated geometries, where all the line widths are much smaller than the Pearl length $\Lambda = 2 \lambda^2/d$. We define the critical current as the current that reduces the Gibbs free-energy barrier to zero. We show that current crowding, which occurs whenever the current rounds a sharp turn, tends to reduce the critical current, but we also show that when the radius of curvature is less than the coherence length this effect is partially compensated by a radius-of-curvature effect. We propose several patterns with rounded corners to avoid critical-current reduction due to current crowding. These results are relevant to superconducting nanowire single-photon detectors, where they suggest a means of improving the bias conditions and reducing dark counts. These results also have relevance to normal-metal nanocircuits, as these patterns can reduce the electrical resistance, electromigration, and hot spots caused by nonuniform heating.Comment: 29 pages, 24 figure

A Single-Molecule Nanopore Device Detects DNA Polymerase Activity with Single-Nucleotide Resolution

The ability to monitor DNA polymerase activity with single-nucleotide resolution has been the cornerstone of a number of advanced single-molecule DNA sequencing concepts. Toward this goal, we report the first spatially-resolved observation of DNA polymerase activity with single-base resolution at the single-molecule level. We describe the design and characterization of a single-species supramolecular nanopore device capable of detecting up to nine consecutive DNA polymerase-catalyzed single nucleotide primer extensions with high sensitivity and spatial resolution (≤ 2.4 Å). The device is assembled in a suspended lipid membrane by threading and mechanically capturing a single strand of DNA-PEG copolymer inside an α-hemolysin protein pore. Single nucleotide primer extensions result in successive displacements of the template DNA strand within the protein pore, which can be monitored by the corresponding stepped changes in the ion current flowing through the pore under an applied transmembrane potential. The system described thus represents a promising advance toward nanopore-mediated single-molecule DNA sequencing concept, and in addition might be applicable to studying a number of other biopolymer-protein interactions and dynamics

Sex work and HIV in Cambodia: trajectories of risk and disease in two cohorts of high-risk young women in Phnom Penh, Cambodia

Objectives HIV prevalence among Cambodian female sex workers (FSW) is among the highest in Southeast Asia. We describe HIV prevalence and associated risk exposures in FSW sampled serially in Phnom Penh, Cambodia (Young Women's Health Study (YWHS)), before and after the implementation of a new law designed to combat human trafficking and sexual exploitation. Design Cross-sectional analysis of baseline data from two prospective cohorts. Setting Community-based study in Phnom Penh, Cambodia. Participants Women aged 15–29 years, reporting ≥2 sexual partners in the last month and/or engaged in transactional sex in the last 3 months, were enrolled in the studies in 2007 (N=161; YWHS-1), and 2009 (N=220; YWHS-2) following information sessions where 285 and 345 women attended. Primary outcomes HIV prevalence, sexual risk behaviour, amphetamine-type stimulant (ATS) and alcohol use, and work-related factors were compared in the two groups, enrolled before and after implementation of the new law. Results Participants in the two cohorts were similar in age (median 25 years), but YWHS-2 women reported fewer sex partners, more alcohol use and less ATS use. A higher proportion of YWHS-2 compared with YWHS-1 women worked in entertainment-based venues (68% vs 31%, respectively). HIV prevalence was significantly lower in the more recently sampled women: 9.2% (95% CI 4.5% to 13.8%) vs 23% (95% CI 16.5% to 29.7%). Conclusions Sex work context and risk have shifted among young FSW in Phnom Penh, following implementation of anti-prostitution and anti-trafficking laws. While both cohorts were recruited using the same eligibility criteria, more recently sampled women had lower prevalence of sexual risk and HIV infection. Women engaging more directly in transactional sex have become harder to sample and access. Future prevention research and programmes need to consider how new policies and demographic changes in FSW impact HIV transmission

Clusters of risk factors in metabolic syndrome and their influence on central blood pressure in a global study

The effect of metabolic syndrome (MetS) and clusters of its components on central blood pressure (CBP) has not been well characterized. We aimed to describe the effect of MetS and clusters of its components on CBP in a large population and to identify whether this effect differs in men and women. We studied 15,609 volunteers (43% women) from 10 cohorts worldwide who participated in the Metabolic syndrome and Artery REsearch Consortium. MetS was defined according to the NCEP-ATP III criteria (GHTBW, glucose, high-density lipoprotein cholesterol, triglyceride, blood pressure, waist circumference). CBP was measured noninvasively and acquired from pulse wave analysis by applanation tonometry. MetS was associated with a 50% greater odds of having higher CSBP. After controlling for age, male sex, non HDL cholesterol, diabetes mellitus, and mean arterial pressure, only specific clusters of MetS components were associated with a higher CSBP; and some of them were significant in women but not in men. We identified "risky clusters" of MetS variables associated with high CSBP. Future studies are needed to confirm they identify subjects at high risk of accelerated arterial aging and, thus, need more intensive clinical management

The Potential and Challenges of Nanopore Sequencing

A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore. The nanopore provides a highly confined space within which single nucleic acid polymers can be analyzed at high throughput by one of a variety of means, and the perfect processivity that can be enforced in a narrow pore ensures that the native order of the nucleobases in a polynucleotide is reflected in the sequence of signals that is detected. Kilobase length polymers (single-stranded genomic DNA or RNA) or small molecules (e.g., nucleosides) can be identified and characterized without amplification or labeling, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility. Further research and development to overcome current challenges to nanopore identification of each successive nucleotide in a DNA strand offers the prospect of ‘third generation’ instruments that will sequence a diploid mammalian genome for ~$1,000 in ~24 h.Molecular and Cellular BiologyPhysic

The properties and applications of single-molecule DNA sequencing

Single-molecule sequencing enables DNA or RNA to be sequenced directly from biological samples, making it well-suited for diagnostic and clinical applications. Here we review the properties and applications of this rapidly evolving and promising technology

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk