HIV-associated adipose redistribution syndrome (HARS): etiology and pathophysiological mechanisms

Human immunodeficiency virus (HIV)-associated adipose redistribution syndrome (HARS) is a fat accumulation disorder characterized by increases in visceral adipose tissue. Patients with HARS may also present with excess truncal fat and accumulation of dorsocervical fat ("buffalo hump"). The pathophysiology of HARS appears multifactorial and is not fully understood at present. Key pathophysiological influences include adipocyte dysfunction and an excessive free fatty acid release by adipocyte lipolysis. The contributory roles of free fatty acids, cytokines, hormones including cortisol, insulin and the growth hormone-adipocyte axis are significant. Other potential humoral, paracrine, endocrine, and neural influences are also discussed

Validity and reliability of a portable gait analysis system for measuring spatiotemporal gait characteristics: comparison to an instrumented treadmill

Gait analysis serves as an important tool for clinicians and other health professionals to assess gait patterns related to functional limitations due to neurological or orthopedic conditions. The purpose of this study was to assess the validity of a body-worn inertial sensor system (RehaGait®) for measuring spatiotemporal gait characteristics compared to a stationary treadmill (Zebris) and the reliability of both systems at different walking speeds and slopes.; Gait analysis was performed during treadmill walking at different speeds (habitual walking speed (normal speed); 15 % above normal walking speed; 15 % below normal walking speed) and slopes (0 % slope; 15 % slope) in 22 healthy participants twice 1 week apart. Walking speed, stride length, cadence and stride time were computed from the inertial sensor system and the stationary treadmill and compared using repeated measures analysis of variance. Effect sizes of differences between systems were assessed using Cohen's d, and limits of agreement and systematic bias were computed.; The RehaGait® system slightly overestimated stride length (+2.7 %) and stride time (+0.8 %) and underestimate cadence (-1.5 %) with small effect sizes for all speeds and slopes (Cohen's d ≤ 0.44) except slow speed at 15 % slope (Cohen's d > 0.80). Walking speed obtained with the RehaGait® system closely matched the speed set on the treadmill tachometer. Intraclass correlation coefficients (ICC) were excellent for speed, cadence and stride time and for stride length at normal and fast speed at 0 % slope (ICC: .91-1.00). Good ICC values were found for stride length at slow speed at 0 % slope and all speeds at 15 % slope (ICC: .73-.90). Both devices had excellent reliability for most gait characteristics (ICC: .91-1.00) except good reliability for the RehaGait® for stride length at normal and fast speed at 0 % slope and at slow speed at 15 % slope (ICC: .80-.87).; Larger limits of agreement for walking at 15 % slope suggests that uphill walking may influence the reliability of the RehaGait® system. The RehaGait® is a valid and reliable tool for measuring spatiotemporal gait characteristics during level and inclined treadmill walking

Performance, stride characteristics, and muscle activity while running with a traditional compared to a newly developed running shoe

A new running shoe cushioning technology has been developed intending to dampen the landing impulse during running while allowing a powerful and direct push-off. We aimed to compare this newly developed technology to traditional running shoes in regard to endurance performance, spatiotemporal stride characteristics, ground reaction forces, and muscle activity. In a randomized crossover design, 13 recreational runners (age 24.9±1.2 years, height 1.68±0.07 m, body mass 62.8±6.0 kg, weekly running distance >30 km) were tested twice, once with their own traditional shoes and (with a 2-week run-in and a 6-week wash-out period) with shoes featuring the new technology. The two-day testing procedure consisted of a graded exercise running test to assess lactate threshold (LT) on day one. On the following day, muscle activity, ground reaction forces and spatiotemporal stride characteristics at two velocities (80% and 95% LT velocity) were recorded on an instrumented treadmill. Finally, 4 km time trial performance was assessed. Magnitude-based inferences were calculated to compare the two shoe conditions. Ground reaction force was likely higher at 95% LT (+5.7%) and possibly higher at 80% LT (+2.2%) with the newly designed shoes, while muscle activity was likely reduced in the tibialis anterior and biceps femoris muscles during push-off. Spatiotemporal stride parameters, physiological markers during the graded exercise test as well as time trial performance showed trivial or unclear differences between the conditions. The observed differences between the shoe conditions in ground reaction forces and muscle activity were insufficient to elicit improvements in selected performance parameters

Comparison of the ‘11+ Kids’ injury prevention programme and a regular warmup in children’s football (soccer) : a cost effectiveness analysis

Objective: To evaluate a potential reduction in injury related healthcare costs when using the '11+ Kids' injury prevention programme compared with a usual warmup in children's football. Methods: This cost effectiveness analysis was based on data collected in a cluster randomised controlled trial over one season from football teams (under-9 to under-13 age groups) in Switzerland. The intervention group (INT) replaced their usual warmup with '11+ Kids', while the control group (CON) warmed up as usual. Injuries, healthcare resource use and football exposure (in hours) were collected prospectively. We calculated the mean injury related costs in Swiss Francs (CHF) per 1000 hours of football. We calculated the cost effectiveness (the direct net healthcare costs divided by the net health effects of the '11+ Kids' intervention) based on the actual data in our study (trial based) and for a countrywide implementation scenario (model based). Results: Costs per 1000 hours of exposure were CHF228.34 (95% CI 137.45, 335.77) in the INT group and CHF469.00 (95% CI 273.30, 691.11) in the CON group. The cost difference per 1000 hours of exposure was CHF-240.66 (95% CI -406.89, -74.32). A countrywide implementation would reduce healthcare costs in Switzerland by CHF1.48 million per year. 1002 players with a mean age of 10.9 (SD 1.2) years participated. During 76 373 hours of football, 99 injuries occurred. Conclusion: The '11+ Kids' programme reduced the healthcare costs by 51% and was dominant (ie, the INT group had lower costs and a lower injury risk) compared with a usual warmup. This provides a compelling case for widespread implementation

Predictors of recurrence and reoperation for prosthetic valve endocarditis after valve replacement surgery for native valve endocarditis

ObjectiveSurgical treatment of native valve endocarditis remains challenging, especially in cases with paravalvular destruction. Basic principles include complete debridement and reconstruction. This study is designed to evaluate the outcomes of surgical reconstruction of complex annular endocarditis using standard techniques and materials, including autologous and bovine pericardium.MethodsFrom 1975 to 2000, 358 cases (357 patients, mean age 49 ± 16 years, range 18–88 years) of native valve endocarditis were surgically managed. Bioprosthetic valves were implanted in 189 cases, and mechanical prostheses were implanted in 169 cases. A total of 78 cases of paravalvular destruction were identified: 62 annular abscesses, 8 fistulas, and 8 combined abscesses/fistulas. These were managed with 46 pericardial patches and 32 isolated suture reconstructions after radical debridement and prosthetic valve replacement.ResultsThe overall early mortality was 8.4% (n = 30). The mortality with paravalvular destruction was 17.9%, and the mortality with simple leaflet infection was 5.7% (P = .001). The unadjusted survival at 20 years was 26.4% ± 4.9% for bioprosthetic valves and 56.5% ± 8.1% for mechanical prostheses (P = .007). The freedom from recurrent prosthetic valve endocarditis was 78.9% ± 4.4% at 15 years. The freedom from reoperation for recurrent prosthetic valve endocarditis was 85.8% ± 4.2% at 15 years. The freedom from reoperation after reconstruction for paravalvular destruction was 88.2% ± 6.9% at 15 years. The freedom from mortality for recurrent prosthetic valve endocarditis was 92.7% ± 3.4% at 15 years. The independent predictors of reoperation were age (hazard ratio 0.930, P = .005) and intravenous drug use/human immunodeficiency virus plus surgical technique (hazard ratio 12.8, P = .003 for patch reconstruction plus valve and hazard ratio 3.6, P = .038 for valve replacement only). Prosthesis type was not predictive when separated from intravenous drug use/human immunodeficiency virus (hazard ratio 3.268, P = .088).ConclusionParavalvular destruction is associated with a higher operative mortality. Native valve endocarditis can be managed with reasonable long-term survival and low rates of reinfection with radical debridement and pericardial reconstruction with bioprostheses and mechanical prostheses. The type of prosthesis implanted does not influence long-term outcome. Patients with a history of intravenous drug use and human immunodeficiency virus are at increased risk for recurrent infection and reoperation

Performance, stride characteristics, and muscle activity while running with a traditional compared to a newly developed running shoe

A new running shoe cushioning technology has been developed intending to dampen the landing impulse during running while allowing a powerful and direct push-off. We aimed to compare this newly developed technology to traditional running shoes in regard to endurance performance, spatiotemporal stride characteristics, ground reaction forces, and muscle activity. In a randomized crossover design, 13 recreational runners (age 24.9±1.2 years, height 1.68±0.07 m, body mass 62.8±6.0 kg, weekly running distance >30 km) were tested twice, once with their own traditional shoes and (with a 2-week run-in and a 6-week wash-out period) with shoes featuring the new technology. The two-day testing procedure consisted of a graded exercise running test to assess lactate threshold (LT) on day one. On the following day, muscle activity, ground reaction forces and spatiotemporal stride characteristics at two velocities (80% and 95% LT velocity) were recorded on an instrumented treadmill. Finally, 4 km time trial performance was assessed. Magnitude-based inferences were calculated to compare the two shoe conditions. Ground reaction force was likely higher at 95% LT (+5.7%) and possibly higher at 80% LT (+2.2%) with the newly designed shoes, while muscle activity was likely reduced in the tibialis anterior and biceps femoris muscles during push-off. Spatiotemporal stride parameters, physiological markers during the graded exercise test as well as time trial performance showed trivial or unclear differences between the conditions. The observed differences between the shoe conditions in ground reaction forces and muscle activity were insufficient to elicit improvements in selected performance parameters

Cardiorespiratory fitness and development of childhood cardiovascular risk: The EXAMIN YOUTH follow-up study

Background: Obesity- and hypertension-related cardiovascular (CV) risk has been shown to originate in childhood. Higher body mass index (BMI) and blood pressure (BP) have been associated with increased large artery stiffness and a lower microvascular arteriolar-to-venular diameter ratio (AVR) in children. This study aimed to investigate the association of cardiorespiratory fitness (CRF) with development of BMI, BP and vascular health during childhood.Methods: In our prospective cohort study, 1,171 children aged 6–8 years were screened for CRF, BMI, BP, retinal vessel diameters and pulse wave velocity using standardized protocols. Endurance capacity was assessed by 20 m shuttle run test. After 4 years, all parameters were assessed in 664 children using the same protocols.Results: Children with a higher CRF at baseline developed a significantly lower BMI (β [95% CI] −0.09 [−0.11 to −0.06] kg/m2, p < 0.001), a lower systolic BP (β [95% CI] −0.09 [−0.15 to −0.03] mmHg, p = 0.004) and a higher AVR (β [95% CI] 0.0004 [0.00004 to 0.0007] units, p = 0.027) after 4 years. The indirect association of CRF with development of retinal arteriolar diameters was mediated by changes in BMI.Conclusion: Our results identify CRF as a key modulator for the risk trajectories of BMI, BP and microvascular health in children. Obesity-related CV risk has been shown to track into adulthood, and achieving higher CRF levels in children may help counteract the development of CV risk and disease not only in pediatric populations, but may also help reduce the burden of CVD in adulthood.Registration:http://www.clinicaltrials.gov/ (NCT02853747)

Factors influencing brightness and beam quality of conventional and distributed Bragg reflector tapered laser diodes in absence of self-heating

In this study, the authors examine some of the factors affecting the brightness and the beam quality of high-power tapered lasers. The large volume resonators required to achieve a high-power, high-brightness operation make the beam quality sensitive to carrier lensing and a multimode operation. These cause bleaching of the regions outside the ridge waveguide. The beam quality in the conventional and the distributed Bragg reflector tapered lasers is examined in the absence of the self-heating effects to investigate the effect of the carrier lensing effects. The influence of the front facet reflectivity and the taper angle on the beam quality is investigated. The beam quality was found to degrade with an increase in the front facet reflectivity and for the larger taper angles in the conventional tapered lasers, especially at low ridge waveguide currents. Finally, the performance of the conventional tapered lasers employing a beamspoiler was assessed. The beam quality was found to be comparable with that achieved in the DBR tapered lasers

Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation

As researchers begin probing deep coverage sequencing data for increasingly rare mutations and subclonal events, the fidelity of next generation sequencing (NGS) laboratory methods will become increasingly critical. Although error rates for sequencing and polymerase chain reaction (PCR) are well documented, the effects that DNA extraction and other library preparation steps could have on downstream sequence integrity have not been thoroughly evaluated. Here, we describe the discovery of novel C > A/G > T transversion artifacts found at low allelic fractions in targeted capture data. Characteristics such as sequencer read orientation and presence in both tumor and normal samples strongly indicated a non-biological mechanism. We identified the source as oxidation of DNA during acoustic shearing in samples containing reactive contaminants from the extraction process. We show generation of 8-oxoguanine (8-oxoG) lesions during DNA shearing, present analysis tools to detect oxidation in sequencing data and suggest methods to reduce DNA oxidation through the introduction of antioxidants. Further, informatics methods are presented to confidently filter these artifacts from sequencing data sets. Though only seen in a low percentage of reads in affected samples, such artifacts could have profoundly deleterious effects on the ability to confidently call rare mutations, and eliminating other possible sources of artifacts should become a priority for the research community.National Human Genome Research Institute (U.S.) (HG03067-05