Preventing foot ulceration in diabetes:systematic review and meta-analyses of RCT data

Aims/hypothesis: Foot ulceration is a serious complication for people with diabetes that results in high levels of morbidity for individuals and significant costs for health and social care systems. Nineteen systematic reviews of preventative interventions have been published, but none provides a reliable numerical summary of treatment effects. The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to make the best possible use of the currently available data. Methods: We conducted a systematic review and meta-analysis of RCTs of preventative interventions for foot ulceration. OVID MEDLINE and EMBASE were searched to February 2019 and the Cochrane Central Register of Controlled Trials to October 2018. RCTs of interventions to prevent foot ulcers in people with diabetes who were free from foot ulceration at trial entry were included. Two independent reviewers read the full-text articles and extracted data. The quality of trial reporting was assessed using the Cochrane Risk of Bias tool. The primary outcome of foot ulceration was summarised using pooled relative risks in meta-analyses. Results: Twenty-two RCTs of eight interventions were eligible for analysis. One trial of digital silicone devices (RR 0.07 [95% CI 0.01, 0.55]) and meta-analyses of dermal infrared thermometry (RR 0.41 [95% CI 0.19, 0.86]), complex interventions (RR 0.59 [95% CI 0.38, 0.90], and custom-made footwear and offloading insoles (RR 0.53 [95% CI 0.33, 0.85]) showed beneficial effects for these interventions. Conclusions/interpretation: Four interventions were identified as being effective in preventing foot ulcers in people with diabetes, but uncertainty remains about what works and who is most likely to benefit

Secular evolution versus hierarchical merging: galaxy evolution along the Hubble sequence, in the field and rich environments

In the current galaxy formation scenarios, two physical phenomena are invoked to build disk galaxies: hierarchical mergers and more quiescent external gas accretion, coming from intergalactic filaments. Although both are thought to play a role, their relative importance is not known precisely. Here we consider the constraints on these scenarios brought by the observation-deduced star formation history on the one hand, and observed dynamics of galaxies on the other hand: the high frequency of bars and spirals, the high frequency of perturbations such as lopsidedness, warps, or polar rings. All these observations are not easily reproduced in simulations without important gas accretion. N-body simulations taking into account the mass exchange between stars and gas through star formation and feedback, can reproduce the data, only if galaxies double their mass in about 10 Gyr through gas accretion. Warped and polar ring systems are good tracers of this accretion, which occurs from cold gas which has not been virialised in the system's potential. The relative importance of these phenomena are compared between the field and rich clusters. The respective role of mergers and gas accretion vary considerably with environment.Comment: 18 pages, 8 figures, review paper to "Penetrating Bars through Masks of Cosmic Dust: the Hubble Tuning Fork Strikes a New Note", Pilanesberg, ed. D. Block et al., Kluwe

Amputation-free survival in 17,353 people at high risk for foot ulceration in diabetes:a national observational study

Acknowledgements Some of the data were presented as an abstract at the Diabetes UK Professional Conference in 2017. Diabetes data for Scotland are available for analysis by members of the Scottish Diabetes Research Network (SDRN) thanks to the hard work and dedication of NHS staff across Scotland who enter the data and people and organisations (the Scottish Care Information –Diabetes Collaboration (SCI-DC) Steering Group, the Scottish Diabetes Group, the Scottish Diabetes Survey Group, the managed clinical network managers and staff in each Health Board) involved in setting up, maintaining and overseeing SCI-DC. The SDRN receives core support from the Chief Scientist’s Office at the Scottish Government Health Department. Members of the Scottish Diabetes Research Network Epidemiology Group who do not qualify for authorship but who contributed to data collection include R. Lindsay (Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK); J. McKnight (Western General Hospital, Edinburgh, UK); S. Philip (Institute of Applied Health Sciences, University of Aberdeen, UK); Members of the Scottish Diabetes Research Network Epidemiology Group who do not qualify for authorship but who contributed to data management include L. Blackbourn (Institute of Genetics and Molecular Medicine, University of Edinburgh, UK); B. Farran (Institute of Genetics and Molecular Medicine, University of Edinburgh, UK); D. McAllister (Institute of Health and Wellbeing, University of Glasgow, UK); P. McKeigue (Usher Institute of Population Health Sciences, University of Edinburgh, UK); S. Read (Usher Institute of Population Health Sciences, University of Edinburgh, UK).Peer reviewedPublisher PD

A unique androgen excess signature in idiopathic intracranial hypertension is linked to cerebrospinal fluid dynamics

Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology, characterized by elevated intracranial pressure frequently manifesting with chronic headaches and visual loss. Similar to polycystic ovary syndrome (PCOS), IIH predominantly affects obese women of reproductive age. In this study, we comprehensively examined the systemic and cerebrospinal fluid (CSF) androgen metabolome in women with IIH in comparison with sex-, BMI-, and age-matched control groups with either simple obesity or PCOS (i.e., obesity and androgen excess). Women with IIH showed a pattern of androgen excess distinct to that observed in PCOS and simple obesity, with increased serum testosterone and increased CSF testosterone and androstenedione. Human choroid plexus expressed the androgen receptor, alongside the androgen-activating enzyme aldoketoreductase type 1C3. We show that in a rat choroid plexus cell line, testosterone significantly enhanced the activity of Na+/K+-ATPase, a surrogate of CSF secretion. We demonstrate that IIH patients have a unique signature of androgen excess and provide evidence that androgens can modulate CSF secretion via the choroid plexus. These findings implicate androgen excess as a potential causal driver and therapeutic target in IIH

Myoblast sensitivity and fibroblast insensitivity to osteogenic conversion by BMP-2 correlates with the expression of Bmpr-1a

<p>Abstract</p> <p>Background</p> <p>Osteoblasts are considered to primarily arise from osseous progenitors within the periosteum or bone marrow. We have speculated that cells from local soft tissues may also take on an osteogenic phenotype. Myoblasts are known to adopt a bone gene program upon treatment with the osteogenic bone morphogenetic proteins (BMP-2,-4,-6,-7,-9), but their osteogenic capacity relative to other progenitor types is unclear. We further hypothesized that the sensitivity of cells to BMP-2 would correlate with BMP receptor expression.</p> <p>Methods</p> <p>We directly compared the BMP-2 sensitivity of myoblastic murine cell lines and primary cells with osteoprogenitors from osseous tissues and fibroblasts. Fibroblasts forced to undergo myogenic conversion by transduction with a MyoD-expressing lentiviral vector (LV-MyoD) were also examined. Outcome measures included alkaline phosphatase expression, matrix mineralization, and expression of osteogenic genes <it>(alkaline phosphatase, osteocalcin </it>and <it>bone morphogenetic protein receptor-1A) </it>as measured by quantitative PCR.</p> <p>Results</p> <p>BMP-2 induced a rapid and robust osteogenic response in myoblasts and osteoprogenitors, but not in fibroblasts. Myoblasts and osteoprogenitors grown in osteogenic media rapidly upregulated <it>Bmpr-1a </it>expression. Chronic BMP-2 treatment resulted in peak <it>Bmpr-1a </it>expression at day 6 before declining, suggestive of a negative feedback mechanism. In contrast, fibroblasts expressed low levels of <it>Bmpr-1a </it>that was only weakly up-regulated by BMP-2 treatment. Bioinformatics analysis confirmed the presence of myogenic responsive elements in the proximal promoter region of human and murine <it>BMPR-1A/Bmpr-1a</it>. Forced myogenic gene expression in fibroblasts was associated with a significant increase in <it>Bmpr-1a </it>expression and a synergistic increase in the osteogenic response to BMP-2.</p> <p>Conclusion</p> <p>These data demonstrate the osteogenic sensitivity of muscle progenitors and provide a mechanistic insight into the variable response of different cell lineages to BMP-2.</p

Sediment properties as important predictors of carbon storage in zostera marina meadows: a comparison of four European areas

Seagrass ecosystems are important natural carbon sinks but their efficiency varies greatly depending on species composition and environmental conditions. What causes this variation is not fully known and could have important implications for management and protection of the seagrass habitat to continue to act as a natural carbon sink. Here, we assessed sedimentary organic carbon in Zostera marina meadows (and adjacent unvegetated sediment) in four distinct areas of Europe (Gullmar Fjord on the Swedish Skagerrak coast, Asko in the Baltic Sea, Sozopol in the Black Sea and Ria Formosa in southern Portugal) down to similar to 35 cm depth. We also tested how sedimentary organic carbon in Z. marina meadows relates to different sediment characteristics, a range of seagrass-associated variables and water depth. The seagrass carbon storage varied greatly among areas, with an average organic carbon content ranging from 2.79 +/- 0.50% in the Gullmar Fjord to 0.17 +/- 0.02% in the area of Sozopol. We found that a high proportion of fine grain size, high porosity and low density of the sediment is strongly related to high carbon content in Z. marina sediment. We suggest that sediment properties should be included as an important factor when evaluating high priority areas in management of Z. marina generated carbon sinks

Mitochondrial respiratory states and rate

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminologyconcerning mitochondrial respiratory states and rates has become increasingly apparent. Thechemiosmotic theoryestablishes the mechanism of energy transformationandcoupling in oxidative phosphorylation. Theunifying concept of the protonmotive force providestheframeworkfordeveloping a consistent theoretical foundation ofmitochondrial physiology and bioenergetics.We followguidelines of the International Union of Pure and Applied Chemistry(IUPAC)onterminology inphysical chemistry, extended by considerationsofopen systems and thermodynamicsof irreversible processes.Theconcept-driven constructive terminology incorporates the meaning of each quantity and alignsconcepts and symbols withthe nomenclature of classicalbioenergetics. We endeavour to provide a balanced view ofmitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes.Uniform standards for evaluation of respiratory states and rates will ultimatelycontribute to reproducibility between laboratories and thussupport the development of databases of mitochondrial respiratory function in species, tissues, and cells.Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Psychological and Biomechanical Aspects of Patient Adaptation to Diabetic Neuropathy and Foot Ulceration

© 2017, Springer Science+Business Media, LLC. Purpose of Review: The purpose of this review was to elucidate how psychological and biomechanical factors interrelate in shaping patients’ experience with diabetic symmetric polyneuropathy (DSPN) and its sequela-diabetic foot ulceration (DFU). Recent Findings: Recent findings emphasize the importance not only of neuropathic pain but also of other DSPN symptoms, such as unsteadiness. We highlight the negative spiral between unsteadiness, falls, and psychological distress. Moreover, unsteadiness is a key determinant of non-adherence to offloading resulting in the delayed DFU healing. While depression is an established predictor of incident DFU, findings linking depression and DFU healing remain inconclusive. Examination of physical activity in DFU development and healing represents the most recent application of research to this field. Summary: Research evidence indicates that DSPN markedly impairs physical and emotional functioning and suggests that there is an unmet need for the development of multifaceted interventions that address both psychological distress and biomechanical challenges experienced by patients with this debilitating complication of diabetes