Mutations that disable the DNA repair gene XPG in a xeroderma pigmentosum group G patient

The human XPG (ERCC5) gene encodes a large acidic protein that corrects the ultraviolet light sensitivity of cells from both xeroderma pigmentosum complementation group G and rodent ERCC group 5. Here we characterize five XPG sequence alterations and a minor splicing defect in XP-G patient XP125LO. Three of these changes are polymorphic variants whereas the remaining two, one in each XPG allele, inactivate complementation in vivo. These single point mutations provide formal proof that defects in XPG give rise to the group G form of xeroderma pigmentosum, and their locations suggest ways in which this may occu

Chronic Blood Flow Restriction Exercise Improves Objective Physical Function: A Systematic Review

Background: Blood flow restriction or KAATSU exercise training is associated with greater muscle mass and strength increases than non-blood flow restriction equivalent exercise. Blood flow restriction exercise has been proposed as a possible alternative to more physically demanding exercise prescriptions (such as high-load/high-intensity resistance training) in a range of clinical and chronic disease populations. While the maintenance of muscle mass and size with reduced musculoskeletal tissue loading appeals in many of these physically impaired populations, there remains a disconnect between some of the desired clinical measures for chronic disease populations and those commonly measured in the literature examining blood flow restriction exercise. While strength does play a vital role in physical function, task-specific objective measures of physical function indicative of activities of daily living are often more clinically relevant and applicable for evaluating the success of medical and surgical interventions or monitoring age- and disease-related physical decline. Objective: To determine whether exercise interventions utilizing blood flow restriction are able to improve objective measures of physical function indicative of activities of daily living. Methods: A systematic search of Medline, Embase, CINAHL, SPORTDiscus, and Springer identified 13 randomized control trials utilizing an exercise intervention combined with blood flow restriction, while measuring at least one objective measure of physical function. Participants were ≥18 years of age. Systematic review of the literature and quality assessment of the included studies used the Cochrane Collaboration's tool for assessing risk bias. Results: Data from 13 studies with a total of 332 participants showed blood flow restriction exercise, regardless of modality, most notably increased performance on the 30 s sit-to-stand and timed up and go tests, and generally improved physical function on other tests including walking tests, variations of sit-to-stand tests, and balance, jumping, and stepping tests. Conclusions: From the evidence available, blood flow restriction exercise of multiple modalities improved objective measures of physical function indicative of activities of daily living

3D surface-imaging for volumetric measurement in people with obesity

BACKGROUND: Current methods for tracking the progress of people with obesity towards a weight loss goal appear simple and potentially misleading. A technique to quantify change in body shape whilst visualising areas of the body where weight loss occurs would be advantageous, and has the potential to be used as a motivational tool. Three-dimensional (3D) surface-imaging would serve as a good basis for such a technique, however current systems are prohibitively expensive. OBJECTIVE: Highlight the use of a cheaper alternative 3D surface-imaging system for volumetric measurement in people with obesity. METHODS: A recently developed low-cost 3D surface-imaging system was used, having previously being validated in a healthy population. A total of 61 people with obesity, enrolled on a weight-loss programme, were surface-imaged using the system. RESULTS: The findings suggest the low-cost system can obtain 3D surface-images of an obese human body, from which numerical parameters could be calculated and further analysis conducted. CONCLUSIONS: Further studies will focus on the validity and reliability of such analyses and the potential of the system to be considered as a long-term instalment in primary healthcare settings as a weight loss aid

Domain swapping between FEN-1 and XPG defines regions in XPG that mediate nucleotide excision repair activity and substrate specificity

FEN-1 and XPG are members of the FEN-1 family of structure-specific nucleases, which share a conserved active site. FEN-1 plays a central role in DNA replication, whereas XPG is involved in nucleotide excision repair (NER). Both FEN-1 and XPG are active on flap structures, but only XPG cleaves bubble substrates. The spacer region of XPG is dispensable for nuclease activity on flap substrates but is required for NER activity and for efficient processing of bubble substrates. Here, we inserted the spacer region of XPG between the nuclease domains of FEN-1 to test whether this domain would be sufficient to confer XPG-like substrate specificity and NER activity on a related nuclease. The resulting FEN-1-XPG hybrid protein is active on flap and, albeit at low levels, on bubble substrates. Like FEN-1, the activity of FEN-1-XPG was stimulated by a double-flap substrate containing a 1-nt 3′ flap, whereas XPG does not show this substrate preference. Although no NER activity was detected in vitro, the FEN-1-XPG hybrid displays substantial NER activity in vivo. Hence, insertion of the XPG spacer region into FEN-1 results in a hybrid protein with biochemical properties reminiscent of both nucleases, including partial NER activity

Muscular Adaptations to Whole Body Blood Flow Restriction Training and Detraining

Resistance training with blood flow restriction is typically performed during single exercises for the lower- or upper-body, which may not replicate real world programming. The present study examined the change in muscle strength and mass in a young healthy population during an 8-week whole body resistance training program, as well as monitoring these adaptations following a 4-week detraining period. Thirty-nine participants (27 males, 12 females) were allocated into four groups: blood flow restriction training (BFR-T); moderate-heavy load training (HL-T), light-load training (LL-T) or a non-exercise control (CON). Testing measurements were taken at Baseline, during mid-point of training (week 4), end of training (week 8) and following four weeks of detraining (week 12) and included anthropometrics, body composition, muscle thickness (MTH) at seven sites, and maximal dynamic strength (1RM) for six resistance exercises. Whole body resistance training with BFR significantly improved lower- and upper-body strength (overall; 11% increase in total tonnage), however, this was similar to LL-T (12%), but both groups were lower in comparison with HL-T (21%) and all groups greater than CON. Some markers of body composition (e.g., lean mass) and MTH significantly increased over the course of the 8-week training period, but these were similar across all groups. Following detraining, whole body strength remained significantly elevated for both BFR-T (6%) and HL-T (14%), but only the HL-T group remained higher than all other groups. Overall, whole body resistance training with blood flow restriction was shown to be an effective training mode to increase muscular strength and mass. However, traditional moderate-heavy load resistance training resulted in greater adaptations in muscle strength and mass as well as higher levels of strength maintenance following detraining

A practical review of energy saving technology for ageing populations

Fuel poverty is a critical issue for a globally ageing population. Longer heating/cooling requirements combine with declining incomes to create a problem in need of urgent attention. One solution is to deploy technology to help elderly users feel informed about their energy use, and empowered to take steps to make it more cost effective and efficient. This study subjects a broad cross section of energy monitoring and home automation products to a formal ergonomic analysis. A high level task analysis was used to guide a product walk through, and a toolkit approach was used thereafter to drive out further insights. The findings reveal a number of serious usability issues which prevent these products from successfully accessing an important target demographic and associated energy saving and fuel poverty outcomes. Design principles and examples are distilled from the research to enable practitioners to translate the underlying research into high quality design-engineering solutions

Efficacy of blood flow restriction exercise during dialysis for end stage kidney disease patients: protocol of a randomised controlled trial

BACKGROUND: Exercise during haemodialysis improves strength and physical function. However, both patients and clinicians are time poor, and current exercise recommendations add an excessive time burden making exercise a rare addition to standard care. Hypothetically, blood flow restriction exercise performed during haemodialysis can provide greater value for time spent exercising, reducing this time burden while producing similar or greater outcomes. This study will explore the efficacy of blood flow restriction exercise for enhancing strength and physical function among haemodialysis patients. METHODS: This is a randomised controlled trial design. A total of 75 participants will be recruited from haemodialysis clinics. Participants will be allocated to a blood flow restriction cycling group, traditional cycling group or usual care control group. Both exercising groups will complete 3 months of cycling exercise, performed intradialytically, three times per week. The blood flow restriction cycling group will complete two 10-min cycling bouts separated by a 20-min rest at a subjective effort of 15 on a 6 to 20 rating scale. This will be done with pressurised cuffs fitted proximally on the active limbs during exercise at 50% of a pre-determined limb occlusion pressure. The traditional cycling group will perform a continuous 20-min bout of exercise at a subjective effort of 12 on the same subjective effort scale. These workloads and volumes are equivalent and allow for comparison of a common blood flow restriction aerobic exercise prescription and a traditional aerobic exercise prescription. The primary outcome measures are lower limb strength, assessed by a three repetition maximum leg extension test, as well as objective measures of physical function: six-minute walk test, 30-s sit to stand, and timed up and go. Secondary outcome measures include thigh muscle cross sectional area, body composition, routine pathology, quality of life, and physical activity engagement. DISCUSSION: This study will determine the efficacy of blood flow restriction exercise among dialysis patients for improving key physiological outcomes that impact independence and quality of life, with reduced burden on patients. This may have broader implications for other clinical populations with similarly declining muscle health and physical function, and those contraindicated to higher intensities of exercise.<br /