The Effects of Walking or Walking-with-Poles Training on Tissue Oxygenation in Patients with Peripheral Arterial Disease

This randomized trial proposed to determine if there were differences in calf muscle StO(2) parameters in patients before and after 12 weeks of a traditional walking or walking-with-poles exercise program. Data were collected on 85 patients who were randomized to a traditional walking program (n = 40) or walking-with-poles program (n = 45) of exercise training. Patients walked for 3 times weekly for 12 weeks. Seventy-one patients completed both the baseline and the 12-week follow-up progressive treadmill tests (n = 36 traditional walking and n = 35 walking-with-poles). Using the near-infrared spectroscopy measures, StO(2) was measured prior to, during, and after exercise. At baseline, calf muscle oxygenation decreased from 56 ± 17% prior to the treadmill test to 16 ± 18% at peak exercise. The time elapsed prior to reaching nadir StO(2) values increased more in the traditional walking group when compared to the walking-with-poles group. Likewise, absolute walking time increased more in the traditional walking group than in the walking-with-poles group. Tissue oxygenation decline during treadmill testing was less for patients assigned to a 12-week traditional walking program when compared to those assigned to a 12-week walking-with-poles program. In conclusion, the 12-week traditional walking program was superior to walking-with-poles in improving tissue deoxygenation in patients with PAD

Evidence That Nasal Insulin Induces Immune Tolerance to Insulin in Adults With Autoimmune Diabetes

OBJECTIVE: Insulin in pancreatic β-cells is a target of autoimmunity in type 1 diabetes. In the NOD mouse model of type 1 diabetes, oral or nasal administration of insulin induces immune tolerance to insulin and protects against autoimmune diabetes. Evidence for tolerance to mucosally administered insulin or other autoantigens is poorly documented in humans. Adults with recent-onset type 1 diabetes in whom the disease process is subacute afford an opportunity to determine whether mucosal insulin induces tolerance to insulin subsequently injected for treatment. RESEARCH DESIGN AND METHODS: We randomized 52 adults with recent-onset, noninsulin-requiring type 1 diabetes to nasal insulin or placebo for 12 months. Fasting blood glucose and serum C-peptide, glucagon-stimulated serum C-peptide, and serum antibodies to islet antigens were monitored three times monthly for 24 months. An enhanced ELISpot assay was used to measure the T-cell response to human proinsulin. RESULTS: β-Cell function declined by 35% overall, and 23 of 52 participants (44%) progressed to insulin treatment. Metabolic parameters remained similar between nasal insulin and placebo groups, but the insulin antibody response to injected insulin was significantly blunted in a sustained manner in those who had received nasal insulin. In a small cohort, the interferon-γ response of blood T-cells to proinsulin was suppressed after nasal insulin. CONCLUSIONS: Although nasal insulin did not retard loss of residual β-cell function in adults with established type 1 diabetes, evidence that it induced immune tolerance to insulin provides a rationale for its application to prevent diabetes in at-risk individuals

Seasonal variation in diagnosis of invasive cutaneous melanoma in Eastern England and Scotland.

BACKGROUND: Worldwide, the incidence of cutaneous melanoma has been reported to be highest in the summer and lowest in the winter. Northern Irish data suggested seasonal variation for women only, especially those with thinner melanomas, sited on limbs. We interrogated two larger UK cancer registries for temporal differences in melanoma diagnosis and associated patient characteristics. METHODS: Melanomas diagnosed from 2006 to 2010 in the Eastern England and Scottish cancer registries (n=11,611) were analysed by month of diagnosis, patient demographics and melanoma characteristics, using descriptive and multivariate modelling methods. RESULTS: More patients with melanoma were diagnosed in the summer months (June 9.9%, July 9.7%, August 9.8%) than the winter months (December 7.2%, January 7.2%, February 7.1%) and this pattern was consistent in both regions. There was evidence that the seasonal patterns varied by sex (p=0.015), melanoma thickness (p=0.002), body site (p=0.006), and type (superficial spreading melanomas p=0.005). The seasonal variation was greatest for diagnosis of melanomas occurring on the limbs. CONCLUSION: This study has confirmed seasonal variation in melanoma diagnosis in Eastern England and Scotland across almost all population demographics and melanoma characteristics studied, with higher numbers diagnosed in the summer months, particularly on the limbs. Seasonal patterns in skin awareness and related help-seeking are likely to be implicated. Targeted patient interventions to increase sun awareness and encourage year-long skin inspection are warranted.The paper was materially supported by the National Institute for Health Research (NIHR-CS-012-030), supporting FMW through a Clinician Scientist award. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. During this project, GL was supported by a post-doctoral fellowship by the National Institute for Health Research (PDF-2011-04-047) to the end of 2014; and by a Cancer Research UK Clinician Scientist Fellowship award (A18180) from March 2015.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.canep.2015.06.00

Molecular Insights into Division of Single Human Cancer Cells in On-Chip Transparent Microtubes.

In vivo, mammalian cells proliferate within 3D environments consisting of numerous microcavities and channels, which contain a variety of chemical and physical cues. External environments often differ between normal and pathological states, such as the unique spatial constraints that metastasizing cancer cells experience as they circulate the vasculature through arterioles and narrow capillaries, where they can divide and acquire elongated cylindrical shapes. While metastatic tumors cause most cancer deaths, factors impacting early cancer cell proliferation inside the vasculature and those that can promote the formation of secondary tumors remain largely unknown. Prior studies investigating confined mitosis have mainly used 2D cell culture systems. Here, we mimic aspects of metastasizing tumor cells dividing inside blood capillaries by investigating single-cell divisions of living human cancer cells, trapped inside 3D rolled-up, transparent nanomembranes. We assess the molecular effects of tubular confinement on key mitotic features, using optical high- and super-resolution microscopy. Our experiments show that tubular confinement affects the morphology and dynamics of the mitotic spindle, chromosome arrangements, and the organization of the cell cortex. Moreover, we reveal that membrane blebbing and/or associated processes act as a potential genome-safety mechanism, limiting the extent of genomic instability caused by mitosis in confined circumstances, especially in tubular 3D microenvironments. Collectively, our study demonstrates the potential of rolled-up nanomembranes for gaining molecular insights into key cellular events occurring in tubular 3D microenvironments in vivo.The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 311529 (S.S.) and the Volkswagen Foundation no. 86 362 (S.S. and W.X.), a FEBS Return-to-Europe fellowship (C.K.S.), the Wellcome Trust (092096/Z/10/Z for N.L.; 094587/Z/10/Z for R.B.), and a European Research Council (ERC) Starting Researcher Grant (R.E.C.-S.; SYSGRO). O.G.S. acknowledges financial support from the DFG Research Unit 1713 “Sensorische Mikro und Nanosysteme”. D.H.G. acknowledges funding from the Alexander von Humboldt Foundation and the U.S. National Science Foundation (Grants: CMMI 1200241 and CBET-1442014). Research in the S.P.J. laboratory is funded by Cancer Research U.K., the ERC, and the European Community Seventh Framework Programme (DDResponse), with core infrastructure provided by Cancer Research U.K. and the Wellcome Trust.This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/acsnano.6b0046

Surgical need among the ageing population of Uganda

Background: Uganda’s ageing population (age 50 years and older) will nearly double from 2015 to 2050. HIV/AIDS, diabetes, stroke among other disease processes have been studied in the elderly population. However, the burden of disease from surgi- cally-treatable conditions is unknown. Objectives: To determine the proportion of adults above 50 years with unmet surgical need and deaths attributable to probable surgically-treatable conditions. Methods: A cluster randomized sample representing the national population of Uganda was enumerated. The previously vali- dated Surgeons Overseas assessment of surgical need instrument, a head-to-toe verbal interview, was used to determine any sur- gically-treatable conditions in two randomly-selected living household members. Deaths were detailed by heads of households. Weighted metrics are calculated taking sampling design into consideration and Taylor series linearization was used for sampling error estimation.   Results: The study enumerated 425 individuals above age 50 years. The prevalence proportion of unmet surgical need was 27.8% (95%CI, 22.1-34.3). This extrapolates to 694,722 (95%CI, 552,279-857,157) individuals living with one or more surgically treatable conditions. The North sub-region was observed to have the highest prevalence proportion. Nearly two out of five household deaths (37.9%) were attributed to probable surgically treatable causes.Conclusion: There is disproportionately high need for surgical care among the ageing population of Uganda with approximate- ly 700,000 consultations needed.Keywords: Surgical need, ageing population, Uganda

Patient-Centered Outcomes Measurement: Does It Require Information From Patients?

Purpose: Since collecting outcome measure data from patients can be expensive, time-consuming, and subject to memory and nonresponse bias, we sought to learn whether outcomes important to patients can be obtained from data in the electronic health record (EHR) or health insurance claims. Methods: We previously identified 21 outcomes rated important by patients who had advanced imaging tests for back or abdominal pain. Telephone surveys about experiencing those outcomes 1 year after their test from 321 people consenting to use of their medical record and claims data were compared with audits of the participants’ EHR progress notes over the time period between the imaging test and survey completion. We also compared survey data with algorithmically extracted data from claims files for outcomes for which data might be available from that source. Results: Of the 16 outcomes for which patients’ survey responses were considered to be the best information source, only 2 outcomes for back pain and 3 for abdominal pain had kappa scores above a very modest level of ≥ 0.2 for chart audit of EHR data and none for algorithmically obtained EHR/claims data. Of the other 5 outcomes for which claims data were considered to be the best information source, only 2 outcomes from patient surveys and 3 outcomes from chart audits had kappa scores ≥ 0.2. Conclusions: For the types of outcomes studied here, medical record or claims data do not provide an adequate source of information except for a few outcomes where patient reports may be less accurate

ProPIG - Organic pig health, welfare and environmental impact across Europe

Organic production is perceived by consumers as being superior in animal welfare and sustainability and the demand for organic pork products is slowly increasing. Within the past ten years a variety of husbandry and management systems have been developed across the EU, ranging from farms with pigs outdoors all year round using local breeds to farms with housed pigs having concrete outside runs and using conventional breeds (CorePIG, Rousing et al, 2011). So far, mainly clinical parameters have been used to describe the health situation on organic pig farms, identifying some key problems, such as weaning diarrhoea and piglet mortality. Organic pig production is - amongst others - characterised through a holistic approach based on the EU Regulation (EC) No 834/2007 and the IFOAM principles: ‘health, ecology, fairness and care’. This clearly states that health is more than absence of clinical symptoms and, the relation between animals and their environment is identified: ‘Health’ is defined as ‘the wholeness and integrity of living systems. It is not simply the absence of illness, but the maintenance of physical, mental, social and ecological well-being’ (IFOAM; 2006). Concepts of animal welfare include physical and mental welfare as well as the concept of naturalness (Fraser 2003), which is often interpreted as the ability to perform natural behaviour. Verhoog et al (2003) describe three main approaches within organic agriculture’s concept of nature and naturalness: the no-chemicals approach, the agro-ecology approach and the integrity approach. Applying those concepts to organic pig production can highlight potential conflicts: outdoor systems are perceived as the optimal housing system for pigs, as they allow natural behaviour such as rooting. However, this behaviour can cause damage to the grass cover and furthermore the manure fate in outdoor areas needs to be considered. A few studies on outdoor pig production have shown a clear N and P surplus and a high degree of distribution heterogeneity in outdoor areas, increasing the risk of N and P losses (Watson et al. 2003). Robust and competitive organic pig production needs to encompass low environmental impacts and good animal health and welfare. So far few studies have quantified both aspects in different pig husbandry systems. In addition, the theory that improving animal health and welfare reduces environmental impacts through decreased medicine use, improved growth rate and feed conversion efficiency has still to be verified. The aim of the CoreOrganic2 project ProPIG (2011-2014; carried out in eight European countries) is to examine the relationship between health, welfare and environmental impact. On-farm assessment protocols will be carried out on 75 farms in three pig husbandry systems (outdoor, partly outdoor, indoor with concrete outside run). Environmental impact will be assessed using both Life Cycle Assessment and calculations of nutrient balances at farm and outdoor area level. Animal health and welfare will be evaluated from animal based parameters including clinical and selected behavioural parameters. Results will be fed back and used by the farmers to decide farm specific goals and strategies to achieve these goals. As an outcome, all farms will create their individual health, welfare and environmental plan, which will be reviewed after one year to allow continuous development. This will provide the opportunity not only to investigate, but also improve the influence of organic pig farming systems on animal welfare and environmental impact. This fulfils the fourth IFOAM principle of care: ‘Organic Agriculture should be managed in a precautionary and responsible manner to protect the health and well-being of current and future generations and the environment’ (IFOAM, 2006)

Randomized Controlled Trial of Physical Exercise in Diabetic Veterans With Length-Dependent Distal Symmetric Polyneuropathy

Rationale: Physical exercise is an essential adjunct to the management of patients with type 2 diabetes mellitus. Therapeutic interventions that improve blood flow to peripheral nerves, such as exercise, may slow the progression of neuropathy in the diabetic patient.Aims: This randomized clinical trial was conducted to determine whether a structured program of aerobic, isokinetic strength, or the combination of aerobic–isokinetic strength exercise intervention alters peripheral nerve function in glycemic-controlled diabetic patients with advanced length-dependent distal symmetric polyneuropathy.Methods: Forty-five patients with type 2 diabetes mellitus exhibiting tight glycemic control (HbA1c intergroup range 7.2–8.0%) were randomized by block design across four experimental groups: sedentary controls (n = 12), aerobic exercise (n = 11), isokinetic strength (n = 11), or the combination of aerobic–isokinetic strength training (n = 11). Patients randomized to training groups exercised 3× per week for 12 weeks, whereas patients randomized to the sedentary control group received standard of care. To minimize attention and educational bias, all patients attended a 12-session health promotion educational series. At baseline, immediately following intervention, and again at 12-week post-intervention, detailed nerve conduction studies were conducted as a primary outcome measure. At these same intervals, all patients completed as secondary measures quantitative sensory testing, symptom-limited treadmill stress tests, and a Short-Form 36-Veterans Questionnaire (SF-36V).Results: Of the 45 patients randomized into this study, 37 (82%) had absent sural nerve responses, 19 (42%) had absent median sensory nerve responses, and 17 (38%) had absent ulnar sensory nerve responses. By comparison, responses from tibial nerves were absent in only three (7%) subjects while responses from peroneal nerves were absent in five (11%) subjects. Eleven (92%) of 12 patients that had volunteered to be biopsied exhibited abnormal levels of epidermal nerve fiber densities. Exercise, regardless of type, did not alter sensory or motor nerve electrodiagnostic findings among those patients exhibiting measurable responses (ANOVA). There was, however, a modest (p = 0.01) beneficial effect of exercise on sensory nerve function (Fisher’s Exact Test). Importantly, the beneficial effect of exercise on sensory nerve function was enhanced (p = 0.03) during the post-intervention interval. In addition, three of six patients that had undergone exercise intervention exhibited a marked 1.9 ± 0.3-fold improvement in epidermal nerve fiber density. By comparison, none of three sedentary patients whom agreed to be biopsied a second time showed improvement in epidermal nerve fiber density. Compared to baseline values within groups, and compared with sedentary values across groups, neither aerobic, isokinetic strength, or the combination of aerobic–isokinetic strength exercise intervention altered peak oxygen uptake. Patients that underwent aerobic or the combined aerobic–isokinetic strength exercise intervention, however, demonstrated an increase in treadmill test duration that was sustained over the 12-week post-intervention period.Conclusion: A 12-week course of physical exercise, regardless of type, does not alter sensory or motor nerve electrodiagnostic findings. In a subset of patients, a short-term structured program of aerobic exercise may selectively improve sensory nerve fiber function. Large-scale exercise lifestyle intervention trials are warranted to further evaluate the impact of aerobic exercise on sensory nerve fiber function in diabetic neuropathic patients.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT00955201

Analysis of Short Tandem Repeats by Parallel DNA Threading

The majority of studies employing short tandem repeats (STRs) require investigation of several of these genetic markers. As such, we demonstrate the feasibility of the trinucleotide threading (TnT) approach for scalable analysis of STRs. The TnT method represents a parallel amplification alternative that addresses the obstacles associated with multiplex PCR. In this study, analysis of the STR fragments was performed with capillary gel electrophoresis; however, it should be possible to combine our approach with the massive 454 sequencing platform to considerably increase the number of targeted STRs