251 research outputs found
Milling plant and soil material in plastic tubes over-estimates carbon and under-estimates nitrogen concentrations
Peer reviewedPostprin
Tumour response interpretation with new tumour response criteria vs the World Health Organisation criteria in patients with bone-only metastatic breast cancer
Prior Mating Experience Modulates the Dispersal of Drosophila in Males More Than in Females
Cues from both an animal’s internal physiological state and its local environment may influence its decision to disperse. However, identifying and quantifying the causative factors underlying the initiation of dispersal is difficult in uncontrolled natural settings. In this study, we automatically monitored the movement of fruit flies and examined the influence of food availability, sex, and reproductive status on their dispersal between laboratory environments. In general, flies with mating experience behave as if they are hungrier than virgin flies, leaving at a greater rate when food is unavailable and staying longer when it is available. Males dispersed at a higher rate and were more active than females when food was unavailable, but tended to stay longer in environments containing food than did females. We found no significant relationship between weight and activity, suggesting the behavioral differences between males and females are caused by an intrinsic factor relating to the sex of a fly and not simply its body size. Finally, we observed a significant difference between the dispersal of the natural isolate used throughout this study and the widely-used laboratory strain, Canton-S, and show that the difference cannot be explained by allelic differences in the foraging gene
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
CD36 deficiency attenuates experimental mycobacterial infection
<p>Abstract</p> <p>Background</p> <p>Members of the CD36 scavenger receptor family have been implicated as sensors of microbial products that mediate phagocytosis and inflammation in response to a broad range of pathogens. We investigated the role of CD36 in host response to mycobacterial infection.</p> <p>Methods</p> <p>Experimental <it>Mycobacterium bovis </it>Bacillus Calmette-Guérin (BCG) infection in <it>Cd36<sup>+/+ </sup></it>and <it>Cd36<sup>-/- </sup></it>mice, and <it>in vitro </it>co-cultivation of <it>M. tuberculosis</it>, BCG and <it>M. marinum </it>with <it>Cd36<sup>+/+ </sup></it>and <it>Cd36<sup>-/-</sup></it>murine macrophages.</p> <p>Results</p> <p>Using an <it>in vivo </it>model of BCG infection in <it>Cd36<sup>+/+ </sup></it>and <it>Cd36<sup>-/- </sup></it>mice, we found that mycobacterial burden in liver and spleen is reduced (83% lower peak splenic colony forming units, p < 0.001), as well as the density of granulomas, and circulating tumor necrosis factor (TNF) levels in <it>Cd36<sup>-/- </sup></it>animals. Intracellular growth of all three mycobacterial species was reduced in <it>Cd36<sup>-/- </sup></it>relative to wild type <it>Cd36<sup>+/+ </sup></it>macrophages <it>in vitro</it>. This difference was not attributable to alterations in mycobacterial uptake, macrophage viability, rate of macrophage apoptosis, production of reactive oxygen and/or nitrogen species, TNF or interleukin-10. Using an <it>in vitro </it>model designed to recapitulate cellular events implicated in mycobacterial infection and dissemination <it>in vivo </it>(i.e., phagocytosis of apoptotic macrophages containing mycobacteria), we demonstrated reduced recovery of viable mycobacteria within <it>Cd36<sup>-/- </sup></it>macrophages.</p> <p>Conclusions</p> <p>Together, these data indicate that CD36 deficiency confers resistance to mycobacterial infection. This observation is best explained by reduced intracellular survival of mycobacteria in the <it>Cd36<sup>-/- </sup></it>macrophage and a role for CD36 in the cellular events involved in granuloma formation that promote early bacterial expansion and dissemination.</p
Cannabis in medicine: a national educational needs assessment among Canadian physicians
BACKGROUND: There is increasing global awareness and interest in the use of cannabis for therapeutic purposes (CTP). It is clear that health care professionals need to be involved in these decisions, but often lack the education needed to engage in informed discussions with patients. This study was conducted to determine the educational needs of Canadian physicians regarding CTP. METHODS: A national needs assessment survey was developed based on previous survey tools. The survey was approved by the Research Ethics Board of the McGill University Health Centre Research Institute and was provided online using LimeSurvey®. Several national physician organizations and medical education organizations informed their members of the survey. The target audience was Canadian physicians. We sought to identify and rank using 5-point Likert scales the most common factors involved in decision making about using CTP in the following categories: knowledge, experience, attitudes, and barriers. Preferred educational approaches and physician demographics were collected. Gap analysis was conducted to determine the magnitude and importance of differences between perceived and desired knowledge on all decision factors. RESULTS: Four hundred and twenty six responses were received, and physician responses were distributed across Canada consistent with national physician distribution. The most desired knowledge concerned “potential risks of using CTP” and “safety, warning signs and precautions for patients using CTP”. The largest gap between perceived current and desired knowledge levels was “dosing” and “the development of treatment plans”. CONCLUSIONS: We have identified several key educational needs among Canadian physicians regarding CTP. These data can be used to develop resources and educational programs to support clinicians in this area, as well as to guide further research to inform these gaps
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
Model for individual prediction of diabetes up to 5 years after gestational diabetes mellitus
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