Milling plant and soil material in plastic tubes over-estimates carbon and under-estimates nitrogen concentrations

Peer reviewedPostprin

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses

Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach

BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions. METHODS: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs. Overall, 17 women shared their experiences of diabetes, pregnancy, and health services in group discussions and 28 women gave individual narrative interviews, facilitated by multilingual researchers, audiotaped, translated, and transcribed. Data were analysed using the constant comparative method, drawing on sociological and narrative theories. RESULTS: Key storylines (over-arching narratives) recurred across all ethnic groups studied. Short-term storylines depicted the experience of diabetic pregnancy as stressful, difficult to control, and associated with negative symptoms, especially tiredness. Taking exercise and restricting diet often worsened these symptoms and conflicted with advice from relatives and peers. Many women believed that exercise in pregnancy would damage the fetus and drain the mother's strength, and that eating would be strength-giving for mother and fetus. These short-term storylines were nested within medium-term storylines about family life, especially the cultural, practical, and material constraints of the traditional South Asian wife and mother role and past experiences of illness and healthcare, and within longer-term storylines about genetic, cultural, and material heritage - including migration, acculturation, and family memories of food insecurity. While peer advice was familiar, meaningful, and morally resonant, health education advice from clinicians was usually unfamiliar and devoid of cultural meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and managing diabetes in South Asian women before and during pregnancy are likely to be ineffective if delivered in a socio-cultural vacuum. Individual education should be supplemented with community-level interventions to address the socio-material constraints and cultural frames within which behavioural 'choices' are made

Cross-sectional and longitudinal construct validity of two rotator cuff disease-specific outcome measures

BACKGROUND: Disease-specific Quality Of Life (QOL) measures are devised to assess the impact of a specific disease across a spectrum of important domains of life. The purpose of this study was to examine the cross-sectional and longitudinal construct validity (sensitivity to change) of two rotator cuff disease-specific measures, the Rotator Cuff-Quality Of Life (RC-QOL) and the Western Ontario Rotator Cuff (WORC) index, in relation to one another and to other joint and limb specific measures in the same population of the patients suffering from rotator cuff pathology. METHODS: Participants enrolled were consecutive patients who received physical therapy for management of impingement syndrome or received treatment following rotator cuff repair, acromioplasty or decompression surgeries. All subjects received physical therapy treatment and completed four outcome measures at 3 single points (initial, interim, and final). Cross-sectional convergent validity was assessed at each of the 3 time-points by correlating the WORC and RC-QOL's scores to each other and to two alternative scales; a joint-specific scale, the American Shoulder and Elbow Surgeons (ASES) standardized shoulder assessment form and a limb-specific measure, the Upper Extremity Functional Index (UEFI). Non-parametric statistics (Spearman's rho and Wilcoxon-Mann-Whitney tests) examined the construct validity. The standardized response mean (SRM) was used to examine sensitivity to change. RESULTS: Forty-one participants entered the study and their scores were compared at 3 cross sectional single points. The correlation coefficients among the 4 measures varied from 0.60 to 0.91. Correlation between corresponding domains of the WORC and RC-QOL varied from 0.45 to 0.85. The known group validity was not significantly different among individual sub-scores and total scores. The final SRMs were (1.42), (1.43), (1.44), and (1.54) for the ASES, RCQOL, WORC, and UEFI respectively. CONCLUSION: The WORC and RC-QOL exhibit similar cross-sectional convergent validity in patients suffering from rotator cuff pathology. The sensitivity to change was very close among all scores, with the UEFI having the highest sensitivity. Further research is needed to examine the extent to which each physical or emotional domain contributes to prognostic or therapeutic decision-making

The effect of high tibial osteotomy on the results of total knee arthroplasty: a matched case control study

BACKGROUND: We performed a matched case control study to assess the effect of prior high tibia valgus producing osteotomy on results and complications of total knee arthroplasty (TKA). METHODS: From 1996 until 2003 356 patients underwent all cemented primary total knee replacement in our institution. Twelve patients with a history of 14 HTO were identified and matched to a control group of 12 patients with 14 primary TKA without previous HTO. The match was made for gender, age, date of surgery, body mass index, aetiology and type of prosthesis. Clinical and radiographic outcome were evaluated after a median duration of follow-up of 3.7 years (minimum, 2.3 years). The SPSS program was used for statistical analyses. RESULTS: The index group had more perioperative blood loss and exposure difficulties with one tibial tuberosity osteotomy and three patients with lateral retinacular releases. No such procedures were needed in the control group. Mid-term HSS, KSS and WOMAC scores were less favourable for the index group, but these differences were not significant. The tibial slope of patients with prior HTO was significantly decreased after this procedure. The tibial posterior inclination angle was corrected during knee replacement but posterior inclination was significantly less compared to the control group. No deep infection or knee component loosening were seen in the group with prior HTO. CONCLUSION: We conclude that TKA after HTO seems to be technically more demanding than a primary knee arthroplasty, but clinical outcome was almost identical to a matched group that had no HTO previously

A Bayesian approach to modelling heterogeneous calcium responses in cell populations

Calcium responses have been observed as spikes of the whole-cell calcium concentration in numerous cell types and are essential for translating extracellular stimuli into cellular responses. While there are several suggestions for how this encoding is achieved, we still lack a comprehensive theory. To achieve this goal it is necessary to reliably predict the temporal evolution of calcium spike sequences for a given stimulus. Here, we propose a modelling framework that allows us to quantitatively describe the timing of calcium spikes. Using a Bayesian approach, we show that Gaussian processes model calcium spike rates with high fidelity and perform better than standard tools such as peri-stimulus time histograms and kernel smoothing. We employ our modelling concept to analyse calcium spike sequences from dynamically-stimulated HEK293T cells. Under these conditions, different cells often experience diverse stimuli time courses, which is a situation likely to occur in vivo. This single cell variability and the concomitant small number of calcium spikes per cell pose a significant modelling challenge, but we demonstrate that Gaussian processes can successfully describe calcium spike rates in these circumstances. Our results therefore pave the way towards a statistical description of heterogeneous calcium oscillations in a dynamic environmen

Disabling knee pain – another consequence of obesity: Results from a prospective cohort study

BACKGROUND: Obesity is linked to knee osteoarthritis (OA) and knee pain. These are disabling problems that are more prevalent in older adults. No prospective study has estimated the impact of excess weight avoidance on the occurrence of knee pain in the general older population. The aim of this study was to investigate the influence of overweight and obesity on the onset and progression of knee pain and disability in older adults living in the community. METHODS: A prospective cohort study of people aged 50 and over registered with three general practices in North Staffordshire, UK. 5784 people who had responded to a survey in March 2000 were mailed a follow-up questionnaire in March 2003. The main outcome measures were self-reported knee pain and severe knee pain and disability at 3 years measured by the Western Ontario and McMaster Universities Osteoarthritis index. RESULTS: Adjusted response to follow-up was 75%. Among responders with no knee pain at baseline, obesity predicted onset of severe knee pain (relative risk 2.8; 95% CI 1.8, 4.5 compared to normal body mass index (BMI) category). Considering overweight and obese categories together, 19% of new cases of severe knee pain over a 3-year period could potentially be avoided by a one-category shift downwards in BMI; this includes almost half of the new cases that arose in the obese group. CONCLUSION: Obesity accounts for a substantial proportion of severe disabling knee pain. As knee pain is a common disabling condition in older adults living in the community, effective public health interventions about avoidance of excess weight could have a major impact on future lower limb disability in older adults

Identifying postpartum intervention approaches to prevent type 2 diabetes in women with a history of gestational diabetes

<p>Abstract</p> <p>Background</p> <p>Women who develop gestational diabetes mellitus (GDM) have an increased risk for the development of type 2 diabetes. Despite this "window of opportunity," few intervention studies have targeted postpartum women with a history of GDM. We sought perspectives of women with a history of GDM to identify a) barriers and facilitators to healthy lifestyle changes postpartum, and b) specific intervention approaches that would facilitate participation in a postpartum lifestyle intervention program.</p> <p>Methods</p> <p>We used mixed methods to gather data from women with a prior history of GDM, including focus groups and informant interviews. Analysis of focus groups relied on grounded theory and used open-coding to categorize data by themes, while frequency distributions were used for the informant interviews.</p> <p>Results</p> <p>Of 38 women eligible to participate in focus groups, only ten women were able to accommodate their schedules to attend a focus group and 15 completed informant interviews by phone. We analyzed data from 25 women (mean age 35, mean pre-pregnancy BMI 28, 52% Caucasian, 20% African American, 12% Asian, 8% American Indian, 8% refused to specify). Themes from the focus groups included concern about developing type 2 diabetes, barriers to changing diet, and barriers to increasing physical activity. In one focus group, women expressed frustration about feeling judged by their physicians during their GDM pregnancy. Cited barriers to lifestyle change were identified from both methods, and included time and financial constraints, childcare duties, lack of motivation, fatigue, and obstacles at work. Informants suggested facilitators for lifestyle change, including nutrition education, accountability, exercise partners/groups, access to gyms with childcare, and home exercise equipment. All focus group and informant interview participants reported access to the internet, and the majority expressed interest in an intervention program delivered primarily via the internet that would include the opportunity to work with a lifestyle coach.</p> <p>Conclusion</p> <p>Time constraints were a major barrier. Our findings suggest that an internet-based lifestyle intervention program should be tested as a novel approach to prevent type 2 diabetes in postpartum women with a history of GDM.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01102530">NCT01102530</a></p