Are older people putting themselves at risk when using their walking frames?

Background Walking aids are issued to older adults to prevent falls, however, paradoxically their use has been identified as a risk factor for falling. To prevent falls, walking aids must be used in a stable manner, but it remains unknown to what extent associated clinical guidance is adhered to at home, and whether following guidance facilitates a stable walking pattern. It was the aim of this study to investigate adherence to guidance on walking frame use, and to quantify user stability whilst using walking frames. Additionally, we explored the views of users and healthcare professionals on walking aid use, and regarding the instrumented walking frames (‘Smart Walkers’) utilized in this study. Methods This observational study used Smart Walkers and pressure-sensing insoles to investigate usage patterns of 17 older people in their home environment; corresponding video captured contextual information. Additionally, stability when following, or not, clinical guidance was quantified for a subset of users during walking in an Activities of Daily Living Flat and in a gait laboratory. Two focus groups (users, healthcare professionals) shared their experiences with walking aids and provided feedback on the Smart Walkers. Results Incorrect use was observed for 16% of single support periods and for 29% of dual support periods, and was associated with environmental constraints and a specific frame design feature. Incorrect use was associated with reduced stability. Participants and healthcare professionals perceived the Smart Walker technology positively. Conclusions Clinical guidance cannot easily be adhered to and self-selected strategies reduce stability, hence are placing the user at risk. Current guidance needs to be improved to address environmental constraints whilst facilitating stable walking. The research is highly relevant considering the rising number of walking aid users, their increased falls-risk, and the costs of falls. Trial Registration Not applicable

Conservation of energy and momenta in nonholonomic systems with affine constraints

We characterize the conditions for the conservation of the energy and of the components of the momentum maps of lifted actions, and of their `gauge-like' generalizations, in time-independent nonholonomic mechanical systems with affine constraints. These conditions involve geometrical and mechanical properties of the system, and are codified in the so-called reaction-annihilator distribution

Pharmacy practice research priorities during the COVID-19 pandemic: Recommendations of a panel of experts convened by FIP Pharmacy Practice Research Special Interest Group

Across the globe, pharmacists on the frontline continue to fight COVID-19 and its continuously evolving physical, mental, and economic consequences armed by their knowledge, professionalism, and dedication. Their need for credible scientific evidence to inform their practice has never been more urgent. Despite the exponentially increasing number of publications since the start of the pandemic, questions remain unanswered, and more are created, than have been resolved by the increasing number of publications. A panel of leading journal editors was convened by the International Pharmaceutical Federation (FIP) Pharmacy Practice Research Special Interest Group to discuss the current status of COVID-19 related research, provide their recommendations, and identify focal points for pharmacy practice, social pharmacy, and education research moving forward. Key priorities identified spanned a wide range of topics, reflecting the need for good quality research to inform practice and education. The panel insisted that a foundation in theory and use of rigorous methods should continue forming the basis of inquiry and its resultant papers, regardless of topic area. From assessing the clinical and cost effectiveness of COVID-19 therapies and vaccines to assessing different models of pharmaceutical services and education delivery, these priorities will ensure that our practice is informed by the best quality scientific evidence at this very challenging time

Acute treatment of migraine. Breaking the paradigm of monotherapy

BACKGROUND: Migraine is a highly prevalent disorder. The disability provoked by its attacks results in suffering as well as considerable economic and social losses. The objective of migraine acute treatment is to restore the patient to normal function as quickly and consistently as possible. There are numerous drugs available for this purpose and despite recent advances in the understanding of the mechanisms and different biological systems involved in migraine attacks, with the development of specific 5-HT agonists known as triptans, current options for acute migraine still stand below the ideal. DISCUSSION: Monotherapeutic approaches are the rule but up to one third of all patients discontinue their medications due to lack of efficacy, headache recurrence, cost and/or side effects. In addition, a rationale has been suggested for the development of polytherapeutic approaches, simultaneously aiming at some of the biological systems involved. This paper reviews the fundamentals for this changing approach as well as the evidence of its better efficacy. CONCLUSION: As a conclusion, most of the patients with a past history of not responding (no pain-free at 2 hours and/or no sustained pain-free at 24 hours) in at least 5 previous attacks should undergo a combination therapy suiting to their individual profile, which must include analgesics or non-steroidal anti-inflammatory agents plus a triptan or a gastro kinetic drug. The three-drug regimen may also be considered. In addition, changing the right moment to take it and the choice for formulations other than oral has also to be determined individually and clearly posted to the patient

Hydrogen Sulfide Is a Novel Protector of the Retinal Glycocalyx and Endothelial Permeability Barrier

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: The original contributions presented in the study are included in the article/supplementary material. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Significantly reduced levels of the anti-inflammatory gaseous transmitter hydrogen sulfide (H2S) are observed in diabetic patients and correlate with microvascular dysfunction. H2S may protect the microvasculature by preventing loss of the endothelial glycocalyx. We tested the hypothesis that H2S could prevent or treat retinal microvascular endothelial dysfunction in diabetes. Bovine retinal endothelial cells (BRECs) were exposed to normal (NG, 5.5 mmol/L) or high glucose (HG, 25 mmol/L) ± the slow-release H2S donor NaGYY4137 in vitro. Glycocalyx coverage (stained with WGA-FITC) and calcein-labeled monocyte adherence were measured. In vivo, fundus fluorescein angiography (FFA) was performed in normal and streptozotocin-induced (STZ) diabetic rats. Animals received intraocular injection of NaGYY4137 (1 μM) or the mitochondrial-targeted H2S donor AP39 (100 nM) simultaneously with STZ (prevention) or on day 6 after STZ (treatment), and the ratio of interstitial to vascular fluorescence was used to estimate apparent permeability. NaGYY4137 prevented HG-induced loss of BREC glycocalyx, increased monocyte binding to BRECs (p ≤ 0.001), and increased overall glycocalyx coverage (p ≤ 0.001). In rats, the STZ-induced increase in apparent retinal vascular permeability (p ≤ 0.01) was significantly prevented by pre-treatment with NaGYY4137 and AP39 (p < 0.05) and stabilized by their post-STZ administration. NaGYY4137 also reduced the number of acellular capillaries (collagen IV + /IB4-) in the diabetic retina in both groups (p ≤ 0.05). We conclude that NaGYY4137 and AP39 protected the retinal glycocalyx and endothelial permeability barrier from diabetes-associated loss of integrity and reduced the progression of diabetic retinopathy (DR). Hydrogen sulfide donors that target the glycocalyx may therefore be a therapeutic candidate for DR.Medical Research Council (MRC)British Heart FoundationRoyal SocietyBrian Ridge ScholarshipNational Eye Research CentreMasonic Charitable Foundatio

Common-path interferometric label-free protein sensing with resonant dielectric nanostructures

Research toward photonic biosensors for point-of-care applications and personalized medicine is driven by the need for high-sensitivity, low-cost, and reliable technology. Among the most sensitive modalities, interferometry offers particularly high performance, but typically lacks the required operational simplicity and robustness. Here, we introduce a common-path interferometric sensor based on guided-mode resonances to combine high performance with inherent stability. The sensor exploits the simultaneous excitation of two orthogonally polarized modes, and detects the relative phase change caused by biomolecular binding on the sensor surface. The wide dynamic range of the sensor, which is essential for fabrication and angle tolerance, as well as versatility, is controlled by integrating multiple, tuned structures in the field of view. This approach circumvents the trade-off between sensitivity and dynamic range, typical of other phase-sensitive modalities, without increasing complexity. Our sensor enables the challenging label-free detection of procalcitonin, a small protein (13 kDa) and biomarker for infection, at the clinically relevant concentration of 1 pg mL−1, with a signal-to-noise ratio of 35. This result indicates the utility for an exemplary application in antibiotic guidance, and opens possibilities for detecting further clinically or environmentally relevant small molecules with an intrinsically simple and robust sensing modality

The Role of DNA Barcodes in Understanding and Conservation of Mammal Diversity in Southeast Asia

Southeast Asia is recognized as a region of very high biodiversity, much of which is currently at risk due to habitat loss and other threats. However, many aspects of this diversity, even for relatively well-known groups such as mammals, are poorly known, limiting ability to develop conservation plans. This study examines the value of DNA barcodes, sequences of the mitochondrial COI gene, to enhance understanding of mammalian diversity in the region and hence to aid conservation planning.DNA barcodes were obtained from nearly 1900 specimens representing 165 recognized species of bats. All morphologically or acoustically distinct species, based on classical taxonomy, could be discriminated with DNA barcodes except four closely allied species pairs. Many currently recognized species contained multiple barcode lineages, often with deep divergence suggesting unrecognized species. In addition, most widespread species showed substantial genetic differentiation across their distributions. Our results suggest that mammal species richness within the region may be underestimated by at least 50%, and there are higher levels of endemism and greater intra-specific population structure than previously recognized.DNA barcodes can aid conservation and research by assisting field workers in identifying species, by helping taxonomists determine species groups needing more detailed analysis, and by facilitating the recognition of the appropriate units and scales for conservation planning

Widespread range expansions shape latitudinal variation in insect thermal limits

I thank the authors of previous studies on global variation in insect thermal tolerances who have generously provided open access use of their data sets.Peer reviewedPostprin

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS