Serum homocysteine is weakly associated with von Willebrand factor and soluble vascular cell adhesion molecule 1, but not with C-reactive protein in type 2 diabetic and nondiabetic subjects: the Hoorn Study.

Background: Hyperhomocysteinaemia may constitute an independent risk factor for cardiovascular disease, but it is still unclear by which pathophysiological mechanisms homocysteine (tHcy) may promote atherothrombosis. The aim of this study was firstly to examine whether tHcy is associated with endothelial dysfunction, increased adherence of leukocytes, and/or chronic low-grade inflammation, as estimated from plasma levels of von Willebrand factor (vWf), soluble vascular cell adhesion molecule 1 (sVCAM-1) and C-reactive protein (CRP), respectively. Secondly we investigated whether the presence of type 2 diabetes modifies these associations. Materials and Methods: Six hundred and ten subjects of a general population of middle-aged and elderly subjects, 170 of whom had type 2 diabetes, participated in this cross-sectional study. Linear regression analyses were used to study whether tHcy was associated with vWf, sVCAM-1 and CRP, and whether the presence of diabetes modified these associations. Results: After adjustment for confounders, tHcy was significantly but weakly associated with vWf (β=0·15, P=0·05) and sVCAM-1 (β=0·082, P=0·04). tHcy was not significantly associated with CRP (β=0·02, P=0·91). The presence of diabetes did not significantly modify these associations. Conclusions: This study provides evidence that tHcy is, at most, weakly associated with endothelial dysfunction as estimated from plasma vWf, and with leukocyte adhesion as estimated from plasma sVCAM-1. tHcy was not significantly associated with chronic low-grade inflammation as estimated from plasma CRP. Our data thus suggest that the link between tHcy and atherothrombosis cannot be explained by associations of tHcy with vWf, sVCAM-1 or CRP

The therapeutic potential of attentional bias modification training for insomnia: study protocol for a randomised controlled trial.

The efficacy of attentional bias modification (ABM) as a treatment for anxiety and depression has been extensively studied with promising results. Despite some evidence of sleep-related attentional biases in insomnia, only a small number of studies, yielding mixed results, have examined the application of ABM in insomnia. This study specifically aims to determine whether ABM can reduce (i) the presence of an attentional bias for sleep-related threatening words; (ii) insomnia symptom severity; (iii) sleep onset latency; and (iv) pre-sleep cognitive arousal amongst individuals with insomnia compared to a non-treatment control group of individuals with insomnia. We propose a randomised controlled trial of 90 individuals from the general population who meet the criteria for Insomnia Disorder. Following an initial examination for the presence of a sleep-related attentional bias using the dot-probe paradigm, participants will be randomised to an online attentional bias modification training condition, or to a standard attentional bias task (non-treatment) control condition. Both conditions will be delivered online by a web platform. All participants allocated to the non-treatment control group will be offered ABM training once the study is complete. The primary outcome will be the attentional bias indices of vigilance and disengagement and self-reported insomnia symptoms, sleep onset latency and pre-sleep cognitive arousal. Attentional bias and insomnia symptoms will be assessed at baseline (day 1) and post-treatment (2 days after the final training session: day 9). Insomnia symptoms will be again assessed at follow-up (day 16). Secondary outcomes include examining whether sleep associated monitoring and worry are related to a sleep-related attentional bias in insomnia, and whether such reports reduce following ABM. All main analyses will be carried out on completion of follow-up assessments. The trial is supported by the Department of Psychology, Sociology and Politics at Sheffield Hallam University. This study will extend the research base examining the efficacy of attentional bias modification for insomnia. ISRCTN ( ISRCTN11643569 , registered on 5 June 2018)

Exploring factors that influence the spread and sustainability of a dysphagia innovation: an instrumental case study

Background: Swallowing difficulties challenge patient safety due to the increased risk of malnutrition, dehydration and aspiration pneumonia. A theoretically driven study was undertaken to examine the spread and sustainability of a locally developed innovation that involved using the Inter-Professional Dysphagia Framework to structure education for the workforce. A conceptual framework with 3 spread strategies (hierarchical control, participatory adaptation and facilitated evolution) was blended with a processual approach to sustaining organisational change. The aim was to understand the processes, mechanism and outcomes associated with the spread and sustainability of this safety initiative. Methods: An instrumental case study, prospectively tracked a dysphagia innovation for 34 months (April 2011 to January 2014) in a large health care organisation in England. A train-the-trainer intervention (as participatory adaptation) was deployed on care pathways for stroke and fractured neck of femur. Data were collected at the organisational and clinical level through interviews (n = 30) and document review. The coding frame combined the processual approach with the spread mechanisms. Pre-determined outcomes included the number of staff trained about dysphagia and impact related to changes in practice. Results: The features and processes associated with hierarchical control and participatory adaptation were identified. Leadership, critical junctures, temporality and making the innovation routine were aspects of hierarchical control. Participatory adaptation was evident on the care pathways through stakeholder responses, workload and resource pressures. Six of the 25 ward based trainers cascaded the dysphagia training. The expected outcomes were achieved when the top-down mandate (hierarchical control) was supplemented by local engagement and support (participatory adaptation). Conclusions: Frameworks for spread and sustainability were combined to create a ‘small theory’ that described the interventions, the processes and desired outcomes a priori. This novel methodological approach confirmed what is known about spread and sustainability, highlighted the particularity of change and offered new insights into the factors associated with hierarchical control and participatory adaptation. The findings illustrate the dualities of organisational change as universal and context specific; as particular and amendable to theoretical generalisation. Appreciating these dualities may contribute to understanding why many innovations fail to become routine

Proliferation of Hydroelectric Dams in the Andean Amazon and Implications for Andes-Amazon Connectivity

Due to rising energy demands and abundant untapped potential, hydropower projects are rapidly increasing in the Neotropics. This is especially true in the wet and rugged Andean Amazon, where regional governments are prioritizing new hydroelectric dams as the centerpiece of long-term energy plans. However, the current planning for hydropower lacks adequate regional and basin-scale assessment of potential ecological impacts. This lack of strategic planning is particularly problematic given the intimate link between the Andes and Amazonian flood plain, together one of the most species rich zones on Earth. We examined the potential ecological impacts, in terms of river connectivity and forest loss, of the planned proliferation of hydroelectric dams across all Andean tributaries of the Amazon River. Considering data on the full portfolios of existing and planned dams, along with data on roads and transmission line systems, we developed a new conceptual framework to estimate the relative impacts of all planned dams. There are plans for 151 new dams greater than 2 MW over the next 20 years, more than a 300% increase. These dams would include five of the six major Andean tributaries of the Amazon. Our ecological impact analysis classified 47% of the potential new dams as high impact and just 19% as low impact. Sixty percent of the dams would cause the first major break in connectivity between protected Andean headwaters and the lowland Amazon. More than 80% would drive deforestation due to new roads, transmission lines, or inundation. We conclude with a discussion of three major policy implications of these findings. 1) There is a critical need for further strategic regional and basin scale evaluation of dams. 2) There is an urgent need for a strategic plan to maintain Andes-Amazon connectivity. 3) Reconsideration of hydropower as a low-impact energy source in the Neotropics

Fetal Growth versus Birthweight: The Role of Placenta versus Other Determinants

in utero. We aimed to study the effects of maternal characteristics on both birthweight and fetal growth in third trimester and introduce placental weight as a possible determinant of both birthweight and fetal growth in third trimester.The STORK study is a prospective cohort study including 1031 healthy pregnant women of Scandinavian heritage with singleton pregnancies. Maternal determinants (age, parity, body mass index (BMI), gestational weight gain and fasting plasma glucose) of birthweight and fetal growth estimated by biometric ultrasound measures were explored by linear regression models. Two models were fitted, one with only maternal characteristics and one which included placental weight.Placental weight was a significant determinant of birthweight. Parity, BMI, weight gain and fasting glucose remained significant when adjusted for placental weight. Introducing placental weight as a covariate reduced the effect estimate of the other variables in the model by 62% for BMI, 40% for weight gain, 33% for glucose and 22% for parity. Determinants of fetal growth were parity, BMI and weight gain, but not fasting glucose. Placental weight was significant as an independent variable. Parity, BMI and weight gain remained significant when adjusted for placental weight. Introducing placental weight reduced the effect of BMI on fetal growth by 23%, weight gain by 14% and parity by 17%.In conclusion, we find that placental weight is an important determinant of both birthweight and fetal growth. Our findings indicate that placental weight markedly modifies the effect of maternal determinants of both birthweight and fetal growth. The differential effect of third trimester glucose on birthweight and growth parameters illustrates that birthweight and fetal growth are not identical entities

Epidemiology and Clinical Features of Patients with Visceral Leishmaniasis Treated by an MSF Clinic in Bakool Region, Somalia, 2004–2006

Our paper describes the epidemiological features of visceral leishmaniasis in the Bakool region, South Central Somalia, over the years 2004 to 2006. Since 2000, Médecins Sans Frontières has been providing care for patients suffering from visceral leishmaniasis in Huddur, located in a region endemic for visceral leishmaniasis. By the end of 2005, we witnessed a dramatic increase in the number of patients admitted to the Huddur centre with visceral leishmaniasis. In our paper, we provide a description of the profile of patients admitted, thus giving an insight into the epidemiology of visceral leishmaniasis in a part of the world where relatively little has been documented and where the true magnitude of this neglected disease remains unknown

VEGFR2 pY949 signalling regulates adherens junction integrity and metastatic spread

The specific role of VEGFA-induced permeability and vascular leakage in physiology and pathology has remained unclear. Here we show that VEGFA-induced vascular leakage depends on signalling initiated via the VEGFR2 phosphosite Y949, regulating dynamic c-Src and VE-cadherin phosphorylation. Abolished Y949 signalling in the mouse mutant Vegfr2Y949F/Y949F leads to VEGFA-resistant endothelial adherens junctions and a block in molecular extravasation. Vessels in Vegfr2Y949F/Y949F mice remain sensitive to inflammatory cytokines, and vascular morphology, blood pressure and flow parameters are normal. Tumour-bearing Vegfr2Y949F/Y949F mice display reduced vascular leakage and oedema, improved response to chemotherapy and, importantly, reduced metastatic spread. The inflammatory infiltration in the tumour micro-environment is unaffected. Blocking VEGFAinduced disassembly of endothelial junctions, thereby suppressing tumour oedema and metastatic spread, may be preferable to full vascular suppression in the treatment of certain cancer forms

Depressive symptoms during rehabilitation period predict poor outcome of lumbar spinal stenosis surgery: A two-year perspective

<p>Abstract</p> <p>Background</p> <p>Previous research has shown an association between preoperative depressive symptoms and a poorer surgery outcome in lumbar spinal stenosis (LSS). It is not known whether depressive symptoms throughout the recovery period are relevant to the outcome of surgery in LSS. In this prospective clinical study the predictive value of preoperative and postoperative depressive symptoms with respect to the surgery outcome is reported.</p> <p>Methods</p> <p>96 patients (mean age 62 years) with symptomatic lumbar spinal stenosis underwent decompressive surgery. They completed the same set of questionnaires preoperatively and 3 months, 6 months, 1 year and 2 years postoperatively. Depressive symptoms were assessed with the 21-item Beck Depression Inventory. Physical functioning and pain were assessed with the Oswestry Disability Index, the Stucki Questionnaire, self-reported walking ability and VAS rating. Logistic regression analyses were used to examine the predictive value of preoperative and postoperative depressive symptoms regarding the surgery outcome. A "good" outcome was defined in two ways: first, by gaining a 30% improvement in relation to the preoperative disability and pain, and second, by having a score at or below the median value for disability and pain on 2-year follow-up.</p> <p>Results</p> <p>Having elevated depressive symptoms particularly on 3-month follow-up was predictive of a poorer surgery outcome regarding pain and disability: when the outcome was defined as less than 30% improvement from the baseline, the OR's (with 95% confidence intervals) were 2.94 (1.06-8.12), <0.05 for Oswestry and 3.33 (1.13-9.79), <0.05 for VAS. In median split approach the OR was 4.11 (1.27-13.32), <0.05 for Oswestry. Predictive associations also emerged between having depressive symptoms on 6-month and 1-year follow-ups and a poorer outcome regarding disability. The predictive value of elevated depressive symptoms particularly with respect to 2-yeard disability was evident whether the outcome was defined as a 30% improvement compared to the preoperative status or as belonging to the better scoring half of the study population on 2-year follow-up.</p> <p>Conclusions</p> <p>Preoperative and postoperative depressive symptoms may indicate those patients at greater risk of a poorer postoperative functional ability. For these patients, further clinical evaluation should be carried out, especially during postoperative stages.</p