Short-term effects of implemented high intensity shoulder elevation during computer work

BACKGROUND: Work-site strength training sessions are shown effective to prevent and reduce neck-shoulder pain in computer workers, but difficult to integrate in normal working routines. A solution for avoiding neck-shoulder pain during computer work may be to implement high intensity voluntary contractions during the computer work. However, it is unknown how this may influence productivity, rate of perceived exertion (RPE) as well as activity and rest of neck-shoulder muscles during computer work. The aim of this study was to investigate short-term effects of a high intensity contraction on productivity, RPE and upper trapezius activity and rest during computer work and a subsequent pause from computer work. METHODS: 18 female computer workers performed 2 sessions of 15 min standardized computer mouse work preceded by 1 min pause with and without prior high intensity contraction of shoulder elevation. RPE was reported, productivity (drawings per min) measured, and bipolar surface electromyography (EMG) recorded from the dominant upper trapezius during pauses and sessions of computer work. Repeated measure ANOVA with Bonferroni corrected post-hoc tests was applied for the statistical analyses. RESULTS: The main findings were that a high intensity shoulder elevation did not modify RPE, productivity or EMG activity of the upper trapezius during the subsequent pause and computer work. However, the high intensity contraction reduced the relative rest time of the uppermost (clavicular) trapezius part during the subsequent pause from computer work (p < 0.04). CONCLUSION: Since a preceding high intensity shoulder elevation did not impose a negative impact on perceived effort, productivity or upper trapezius activity during computer work, implementation of high intensity contraction during computer work to prevent neck-shoulder pain may be possible without affecting the working routines. However, the unexpected reduction in clavicular trapezius rest during a pause with preceding high intensity contraction requires further investigation before high intensity shoulder elevations can be recommended as an integrated part of computer work

Retinal vascular fractals predict long-term microvascular complications in type 1 diabetes mellitus:the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987)

Diabetic neuropathy, nephropathy, and retinopathy cause significant morbidity in patients with type 1 diabetes, even though improvements in treatment modalities delay the appearance and reduce the severity of these complications. To prevent or further delay the onset, it is necessary to better understand common underlying pathogenesis and to discover preclinical biomarkers of these complications. Retinal vessel calibers have been associated with the presence of microvascular complications, but their long-term predictive value has only been sparsely investigated. We examined retinal vessel calibers as 16-year predictors of diabetic nephropathy, neuropathy, and proliferative retinopathy in a young population-based Danish cohort with type 1 diabetes. We used semiautomated computer software to analyze vessel diameters on baseline retinal photos. Calibers of all vessels coursing through a zone 0.5–1 disc diameter from the disc margin were measured and summarized as the central artery and vein equivalents. In multiple regression analyses, we found wider venular diameters and smaller arteriolar diameters were both predictive of the 16-year development of nephropathy, neuropathy, and proliferative retinopathy. Early retinal vessel caliber changes are seemingly early markers of microvascular processes, precede the development of microvascular complications, and are a potential noninvasive predictive test on future risk of diabetic retinopathy, neuropathy, and nephropathy.</jats:p

Molecular Basis of Enhanced Activity in Factor VIIa-Trypsin Variants Conveys Insights into Tissue Factor-mediated Allosteric Regulation of Factor VIIa Activity

The complex of coagulation factor VIIa (FVIIa), a trypsin-like serine protease, and membrane-bound tissue factor (TF) initiates blood coagulation upon vascular injury. Binding of TF to FVIIa promotes allosteric conformational changes in the FVIIa protease domain and improves its catalytic properties. Extensive studies have revealed two putative pathways for this allosteric communication. Here we provide further details of this allosteric communication by investigating FVIIa loop swap variants containing the 170 loop of trypsin that display TF-independent enhanced activity. Using x-ray crystallography, we show that the introduced 170 loop from trypsin directly interacts with the FVIIa active site, stabilizing segment 215–217 and activation loop 3, leading to enhanced activity. Molecular dynamics simulations and novel fluorescence quenching studies support that segment 215–217 conformation is pivotal to the enhanced activity of the FVIIa variants. We speculate that the allosteric regulation of FVIIa activity by TF binding follows a similar path in conjunction with protease domain N terminus insertion, suggesting a more complete molecular basis of TF-mediated allosteric enhancement of FVIIa activity

The <i>agr</i> inhibitors solonamide B and analogues alter immune responses to <i>Staphylococccus aureus</i> but do not exhibit adverse effects on immune cell functions

Staphylococcus aureus infections are becoming increasingly difficult to treat due to antibiotic resistance with the community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 being of particular concern. The inhibition of bacterial virulence has been proposed as an alternative approach to treat multi-drug resistant pathogens. One interesting anti-virulence target is the agr quorum-sensing system, which regulates virulence of CA-MRSA in response to agr-encoded autoinducing peptides. Agr regulation confines exotoxin production to the stationary growth phase with concomitant repression of surface-expressed adhesins. Solonamide B, a non-ribosomal depsipeptide of marine bacterial origin, was recently identified as a putative anti-virulence compound that markedly reduced expression of α-hemolysin and phenol-soluble modulins. To further strengthen solonamide anti-virulence candidacy, we report the chemical synthesis of solonamide analogues, investigation of structure-function relationships, and assessment of their potential to modulate immune cell functions. We found that structural differences between solonamide analogues confer significant differences in interference with agr, while immune cell activity and integrity is generally not affected. Furthermore, treatment of S. aureus with selected solonamides was found to only marginally influence the interaction with fibronectin and biofilm formation, thus addressing the concern that application of compounds inducing an agr-negative state may have adverse interactions with host factors in favor of host colonization

Inflammatory markers as correlates of body composition and grip strength among adults with and without HIV: A cross-sectional study in Ethiopia

BACKGROUND: Changes in body composition and muscle strength are common among individuals with HIV. We investigated the associations of inflammation with body composition and grip strength in adults with and without HIV. METHODS: Cross-sectional study among Ethiopian treatment-naïve individuals with and without HIV. Fat mass and fat-free mass adjusted for height (kg/m2) were used as indicators of body composition. RESULTS: 288/100 individuals with/without HIV were included between July 2010 and August 2012. Females with HIV had lower fat mass index (FMI) and fat-free mass index (FFMI) than females without HIV, whereas no difference was seen between males with and without HIV. Males and females with HIV had lower grip strength than their counterparts without HIV. Serum alpha-1-acid glycoprotein (s-AGP) was negatively correlated with FMI (-0.71 kg/m2, 95% CI: -1.2; -0.3) among individuals with HIV, and those with HIV and serum C-reactive protein (s-CRP) ≥ 10 mg/l had 0.78 kg/m2 (95% CI -1.4; -0.2) lower FMI than those with s-CRP < 10 mg/l. In contrast, s-AGP was positively correlated with FMI (2.09 kg/m2, 95% CI 0.6; 3.6) in individuals without HIV. S-CRP and AGP were negatively associated with grip strength in individuals with HIV, while no correlation was observed among those without HIV. CONCLUSION: Inflammation was positively associated with FMI in individuals without HIV while it was negatively associated with FMI in those with HIV, indicating that inflammation may be one of the drivers of depleting energy reserves among treatment-naïve individuals with HIV. Inflammation was associated with decreased muscle quantity and functional capacity among individuals with HIV, but not in those without HIV

Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia

BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub-Saharan Africa is sparse. METHODS: HIV viral load (VL) and resistance mutations pre-ART and after 6 months were determined in a prospective cohort study of ART-naïve HIV patients initiating first-line therapy in Jimma, Ethiopia. VL measurements were done at baseline and after 3 and 6 months. Genotypic HIV drug resistance (HIVDR) was performed on patients exhibiting virological failure (>1000 copies/mL at 6 months) or slow virological response (>5000 copies/mL at 3 months and <1000 copies/mL at 6 months). RESULTS: Two hundred sixty five patients had VL data available at baseline and at 6 months. Virological failure was observed among 14 (5.3%) participants out of 265 patients. Twelve samples were genotyped and six had HIV drug resistance (HIVDR) mutations at baseline. Among virological failures, 9/11 (81.8%) harbored one or more HIVDR mutations at 6 months. The most frequent mutations were K103N and M184VI. CONCLUSIONS: Our data confirm that the currently recommended first-line ART regimen is efficient in the vast majority of individuals initiating therapy in Jimma, Ethiopia eight years after the introduction of ART. However, the documented occurrence of transmitted resistance and accumulation of acquired HIVDR mutations among failing patients justify increased vigilance by improving the availability and systematic use of VL testing to monitor ART response, and underlines the need for rapid, inexpensive tests to identify the most common drug resistance mutations

A systematic approach for evaluating the role of surface-exposed loops in trypsin-like serine proteases applied to the 170 loop in coagulation factor VIIa

Proteases play a major role in many vital physiological processes. Trypsin-like serine proteases (TLPs), in particular, are paramount in proteolytic cascade systems such as blood coagulation and complement activation. The structural topology of TLPs is highly conserved, with the trypsin fold comprising two β-barrels connected by a number of variable surface-exposed loops that provide a surprising capacity for functional diversity and substrate specificity. To expand our understanding of the roles these loops play in substrate and co-factor interactions, we employ a systematic methodology akin to the natural truncations and insertions observed through evolution of TLPs. The approach explores a larger deletion space than classical random or directed mutagenesis. Using FVIIa as a model system, deletions of 1–7 amino acids through the surface exposed 170 loop, a vital allosteric regulator, was introduced. All variants were extensively evaluated by established functional assays and computational loop modelling with Rosetta. The approach revealed detailed structural and functional insights recapitulation and expanding on the main findings in relation to 170 loop functions elucidated over several decades using more cumbersome crystallization and single deletion/mutation methodologies. The larger deletion space was key in capturing the most active variant, which unexpectedly had a six-amino acid truncation. This variant would have remained undiscovered if only 2–3 deletions were considered, supporting the usefulness of the methodology in general protease engineering approaches. Our findings shed further light on the complex role that surface-exposed loops play in TLP function and supports the important role of loop length in the regulation and fine-tunning of enzymatic function throughout evolution

Diabetes prevalence by HbA1c and oral glucose tolerance test among HIV-infected and uninfected Tanzanian adults.

BACKGROUND: The burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania. METHODS: We analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes. RESULTS: Mean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25-3.03; OGTT: RRR = 1.90, 95% CI 0.96-3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93-4.34; OGTT: RRR = 1.61, 95% CI 1.22-2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/μL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT. CONCLUSIONS: The prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes

Renal Artery Stenting in Consecutive High-Risk Patients With Atherosclerotic Renovascular Disease:A Prospective 2-Center Cohort Study

BACKGROUND: The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high‐risk clinical presentations as defined in a national protocol developed in 2015. METHODS AND RESULTS: Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high‐risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24‐hour ambulatory systolic blood pressure was 166.2 mm Hg (95% CI, 162.0–170.4), the defined daily dose of antihypertensive medication was 6.5 (95% CI, 5.8–7.3), and the estimated glomerular filtration rate was 41.1 mL/min per 1.73m(2) (95% CI, 36.6–45.6). In 96 patients with available 3‐month follow‐up data, mean 24‐hour ambulatory systolic blood pressure decreased by 19.6 mm Hg (95% CI, 15.4–23.8; P<0.001), the defined daily dose of antihypertensive medication was reduced by 52% (95% CI, 41%–62%; P<0.001), and estimated glomerular filtration rate increased by 7.8 mL/min per 1.73m(2) (95% CI, 4.5–11.1; P<0.001). All changes persisted after 24 month follow‐up. Among 17 patients with a history of hospitalization for acute decompensated heart failure, 14 patients had no new episodes after successful revascularization. CONCLUSIONS: In this prospective cohort study, we observed a reduction in blood pressure and antihypertensive medication, an increase in estimated glomerular filtration rate, and a decrease in new hospital admissions attributable to heart failure/sudden pulmonary edema after renal artery stenting. REGISTRATION: URL: https://clinicaltrials.gov. Identifier: NCT02770066