Intersectional mapping of multi-transmitter neurons and other cell types in the brain.

Recent developments in intersectional strategies have greatly advanced our ability to precisely target brain cell types based on unique co-expression patterns. To accelerate the application of intersectional genetics, we perform a brain-wide characterization of 13 Flp and tTA mouse driver lines and selected seven for further analysis based on expression of vesicular neurotransmitter transporters. Using selective Cre driver lines, we created more than 10 Cre/tTA combinational lines for cell type targeting and circuit analysis. We then used VGLUT-Cre/VGAT-Flp combinational lines to identify and map 30 brain regions containing neurons that co-express vesicular glutamate and gamma-aminobutyric acid (GABA) transporters, followed by tracing their projections with intersectional viral vectors. Focusing on the lateral habenula (LHb) as a target, we identified glutamatergic, GABAergic, or co-glutamatergic/GABAergic innervations from ∼40 brain regions. These data provide an important resource for the future application of intersectional strategies and expand our understanding of the neuronal subtypes in the brain.

Methodological Issues and the Impact of Age Stratification on the Proportion of Participants with Low Appendicular Lean Mass When Adjusting for Height and Fat Mass Using Linear Regression: Results from the Canadian Longitudinal Study on Aging.

BACKGROUND: Using residual values calculated from models regressing appendicular lean mass on fat mass and height is one of several suggested strategies for adjusting appendicular lean mass for body size when measuring sarcopenia. However, special consideration is required when using this technique in different subgroups in order to capture the correct individuals as sarcopenic. OBJECTIVES: To provide guidance about how to conduct stratified analyses for the regression adjustment technique using age groups as an example. DESIGN: Cross-sectional study. SETTING: Data collected at baseline (2012-2015) for the Canadian Longitudinal Study on Aging. PARTICIPANTS: Community dwelling participants of European descent aged 45 to 85 years (n=25,399). MEASUREMENTS: Appendicular lean mass, height, and weight were measured. Sex-specific residuals were calculated in participants before and after stratifying participants by age group (45-54, 55-64, 65-74, 75-85 years). Cut offs corresponding to the sex-specific 20th percentile residual values in participants ≥65 years were determined first in the residuals calculated in all participants and residuals calculated in only those aged ≥65 years. For each set of cut offs, the percentage of age and sex-stratified participants with low appendicular lean mass were compared for the residuals calculated in all participants and the residuals calculated after stratifying by age. RESULTS: In 12,622 males and 12,737 females, regardless of the cut off used, the percentage of participants with low appendicular lean mass decreased with age when residuals were calculated after age stratification. When the residuals were calculated in all participants, the percentage of participants with sarcopenia increased from the youngest to the oldest age groups. CONCLUSIONS: Sex-specific residuals in all participants should be calculated prior to stratifying the sample by age group, or other stratification variables, for the purposes of developing appendicular lean mass cut offs or subgroup analyses.

Proceedings of the Canadian Frailty Network Workshop: Identifying Biomarkers of Frailty to Support Frailty Risk Assessment, Diagnosis and Prognosis. Toronto, January 15, 2018.

The Canadian Frailty Network (CFN), a pan-Canadian not-for-profit organization funded by the Government of Canada through the Networks of Centres of Excellence Program, is dedicated to improving the care of older Canadians living with frailty. The CFN has partnered with the Canadian Longitudinal Study on Aging (CLSA) to measure potential frailty biomarkers in biological samples (whole blood, plasma, urine) collected in over 30,000 CLSA participants. CFN hosted a workshop in Toronto on January 15 2018, bringing together experts in the field of biomarkers, aging and frailty. The overall objectives of the workshop were to start building a consensus on potential frailty biomarker domains and identify specific frailty biomarkers to be measured in the CLSA biological samples. The workshop was structured with presentations in the morning to frame the discussions for the afternoon session, which was organized as a free-flowing discussion to benefit from the expertise of the participants. Participants and speakers were from Canada, Italy, Spain, United Kingdom and the United States. Herein we provide pertinent background information, a summary of all the presentations with key figures and tables, and the distillation of the discussions. In addition, moving forward, the principles CFN will use to approach frailty biomarker research and development are outlined. Findings from the workshop are helping CFN and CLSA plan and conduct the analysis of biomarkers in the CLSA samples and which will inform a follow-up data access competition.

Point Dose Measurement for Verification of Treatment Planning System using an Indigenous Heterogeneous Pelvis Phantom for Clarkson, Convolution, Superposition, and Fast Superposition Algorithms.

BACKGROUND: Nowadays, advanced radiotherapy equipment includes algorithms to calculate dose. The verification of the calculated doses is important to achieve accurate results. Mostly homogeneous dosimetric phantoms are available commercially which do not mimic the actual patient anatomy; therefore, an indigenous heterogeneous pelvic phantom mimicking actual human pelvic region has been used to verify the doses calculated by different algorithms. OBJECTIVE: This study aims to compare the planed dose using different algorithms with measured dose using an indigenous heterogeneous pelvic phantom. MATERIAL AND METHODS: In this experimental study, various three dimensional conformal radiotherapy (3D-CRT) plans were made using different doses calculated by algorithms. The plans were delivered by medical linear accelerator and doses were measured by ion chamber placed in the indigenous pelvic phantom. Planned and measured doses were compared with together and analyzed. RESULTS: The relative electron densities of different parts in the pelvic phantom were found to be in good agreement with that of actual pelvic parts, including bladder, rectum, fats and bones. The highest percentage deviations between planned and measured dose were calculated in the single field for Superposition algorithm (3.09%) and single field with 45˚wedge for Superposition (3.04%). The least percentage deviation was calculated in the opposite field for Convolution which was - 0.08%. The results were within the range of ±5% as recommended by International Commission on Radiation Units and Measurement. CONCLUSION: The cost-effective indigenous heterogeneous pelvic phantom has the density pattern similar to the actual pelvic region; thus, it can be used for routine patient-specific quality assurance.

The prevalence of sarcopenia in community-dwelling older adults, an exploration of differences between studies and within definitions: a systematic review and meta-analyses.

Background: sarcopenia in ageing is a progressive decrease in muscle mass, strength and/or physical function. This review aims to summarise the definitions of sarcopenia in community-dwelling older adults and explore similarities and differences in prevalence estimates by definition. Methods: a systematic review was conducted to identify articles which estimated sarcopenia prevalence in older populations using search terms for sarcopenia and muscle mass. Overall prevalence for each sarcopenia definition was estimated stratified by sex and ethnicity. Secondary analyses explored differences between studies and within definitions, including participant age, muscle mass measurement techniques and thresholds for muscle mass and gait speed. Results: in 109 included articles, eight definitions of sarcopenia were identified. The lowest pooled prevalence estimates came from the European Working Group on Sarcopenia/Asian Working Group on Sarcopenia (12.9%, 95% confidence interval: 9.9-15.9%), International Working Group on Sarcopenia (9.9%, 3.2-16.6%) and Foundation for the National Institutes of Health (18.6%, 11.8-25.5%) definitions. The highest prevalence estimates were for the appendicular lean mass (ALM)/weight (40.4%, 19.5-61.2%), ALM/height (30.4%, 20.4-40.3%), ALM regressed on height and weight (30.4%, 20.4-40.3%) and ALM / body mass index (24.2%, 18.3-30.1%) definitions. Within definitions, the age of study participants and the muscle mass cut points used were substantive sources of between-study differences. Conclusion: estimates of sarcopenia prevalence vary from 9.9 to 40.4%, depending on the definition used. Significant differences in prevalence exist within definitions across populations. This lack of agreement between definitions needs to be better understood before sarcopenia can be appropriately used in a clinical context.

Evaluation of subacute toxicity of methanolic/aqueous preparation of aerial parts of O. sanctum in Wistar rats: Clinical, haematological, biochemical and histopathological studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Ocimum sanctum, commonly known as Holy Basil or Tulsi has been used in Ayurveda as a demulcent, stimulant, expectorant; in the treatment of bronchitis, skin infections, malaria, diarrhoea, dysentery, arthritis, gastric and inflammatory disorders. We have previously shown that methanolic/aqueous extract of O. sanctum did not induce genotoxicity and other toxic effects in acute oral toxicity study. In the present report, we have performed sub-acute toxicity of methanolic/aqueous preparation of O. sanctum in Wistar rats to evaluate whether it induced any chronic toxic effects. MATERIALS AND METHODS: In subacute toxicity study, animals received O. sanctum extract (OSE) by oral gavage at the doses of 250, 500 and 1000 mg/kg/day (n=5/group/sex) for 28 days. At the end of the study, the animals were sacrificed and evaluated for the effect of OSE on clinical, haematological, biochemical and histopathological parameters. RESULTS: The rats treated with OSE did not show any change in body weight, food and water consumption, motor activity, sensory reactivity and foot splay measurements. There were no significant changes in haematological, pathological and biochemical parameters; and histopathology of tissues (liver, kidney, spleen, heart, and testis/ovary) among rats of either sex. OSE at a dose of 1000 mg/kg showed significant increase of Mean corpuscular hemoglobin (MCH) (19.8 ± 0.8; 18.7 ± 0.5) and mean corpuscular hemoglobin concentration (MCHC) (41.8 ± 1.1; 39.3 ± 0.7) in male and female rats in comparison to their respective controls (MCH: 17.7 ± 0.3; 17.4 ± 0.3; MCHC: 37.8 ± 0.5; 36.1 ± 0.2). Urine parameters (appearance, blood, nitrate, leucocyte, glucose, ketone, pH, protein and specific gravity) in both the male and female rats were comparable to their respective controls. In addition, no changes were observed in the vital organs of rats at macroscopic and microscopic levels. CONCLUSIONS: Our results showed that oral administration of OSE was not toxic to male and female Wistar rats upto the highest dose tested, thereby suggesting its clinical usefulness.

A comparison study of adults with intellectual disability and psychiatric disorder with and without forensic involvement.

The current study describes and compares profiles of patients in the same specialized hospital program for patients with intellectual disability with and without forensic involvement. A retrospective chart review of 78 individuals (39 forensic and 39 non-forensic) served between 2006 and 2008 was completed. The forensic sample was more likely to have a diagnosis of borderline to mild IQ and psychotic disorder was more common. Forensic patients were also more likely to have previously used drugs or alcohol. Forensic inpatients had significantly longer lengths of stay, and were more likely to change residence from admission to discharge than the non-forensic inpatients but the GAF scores did not differ between the two groups at admission or discharge. Although there are many similarities between the two groups, there are also some important differences that exist which should be considered in the design of inpatient and outpatient mental health and intellectual disability services.

An ethnography of low-income mothers' safeguarding efforts.

PROBLEM: Children living in lower-income environments are at greater risk for unintentional injuries. However, little is known about the safety practices of mothers living in low-income situations. METHOD: This ethnographic study explored the child safeguarding experiences of low-income mothers using in-home interviews and observations. RESULTS: Mothers' safeguarding efforts included cognitive and emotional work, child directed work, and work directed at the physical and social environments. Factors that influenced the women's safeguarding included the quality of the indoor space, availability of safe play space, traffic hazards, sibling interactions, child care supports, relationships with neighbors, and trust in community services. DISCUSSION: These findings have implications for the conceptualization of safeguarding practices and provide insight about the experiences of mothers living on low-incomes. IMPACT ON INDUSTRY: When developing safety interventions, program planners should consider the views and practices of mothers as well as contextual factors in the physical and social environments.

A randomized trial to assess the effectiveness of an infant home safety programme.

The aim of this study was to test an intervention aimed at addressing the risk of injury in infants 2 - 12 months of age. A non-blinded, randomized controlled trial was conducted, whereby parents were randomly assigned to either a control or one of two intervention groups. Parents completed questionnaires regarding safety behaviours and injuries at the 2 (baseline), 6 and 12 month immunization visit at the community health unit. During the 2 month visit to the health unit, the two intervention groups received a home safety kit containing nine items, an instructional brochure and a risk assessment checklist. Subjects randomized to the safety kit plus home visit group also received a standardized home visit from a community health nurse. Two of the 14 parental safety behaviours showed a significant increase in use among parents in the intervention groups. Neither of the interventions was associated with a reduction in parent-reported injuries among children. It was concluded that home visitation may provide a beneficial adjunct to the provision of safety devices and may increase use by parents.

Risk factors for unintentional injuries due to falls in children aged 0-6 years: a systematic review.

OBJECTIVE: To identify risk factors for unintentional injuries due to falls in children aged 0-6 years. DESIGN: A systematic review of the literature. METHODS: Electronic databases from 1966 to March 2005 were comprehensively searched to identify empirical research that evaluated risk factors for unintentional injuries due to falls in children aged 0-6 years and included a comparison group. RESULTS: 14 studies met the inclusion criteria. Studies varied by the type of fall injury that was considered (ie, bunk bed, stairway, playground or infant walker) and with respect to the quality of evidence. In general, major risk factors for the incidence or severity of injuries due to falls in children included age of the child, sex, height of the fall, type of surface, mechanism (dropped, stairway or using a walker), setting (day care v home care) and socioeconomic status. CONCLUSION: Despite a high burden, few controlled studies have examined the risk and protective factors for injuries due to falls in children aged 0-6 years. The only study to examine falls from a population health perspective suggests that age, sex and poverty are independent risk factors for injuries due to falls in children.

Severity of alcohol-related motor vehicle crashes in British Columbia: case - control study.

The objective of the present study was to compare the injury severity and vehicle damage severity rates of alcohol-related crashes with rates of non-alcohol-related crashes in British Columbia (BC). Injury severity rates and vehicle damage severity rates were taken from 2002 Insurance Corporation of British Columbia traffic collision data. The data were computed in order to compare the differences in injury severity and vehicle damage severity rates of alcohol-related vs. non-alcohol-related motor vehicle crashes. Case - control methods were used in this study to analyse the risk of alcohol-related crashes compared to non-alcohol-related crashes in BC. Odds ratios (OR) and 95% CI were calculated to estimate relative risks. In the case - control analysis, the risk of fatal collision was increased for those drinking and driving compared with those driving sober (OR 4.70; 95% CI 3.15 - 7.01). Risk of injury collision was increased for those drinking and driving compared with those driving sober (OR 1.32; 95% CI 1.19 - 1.37). Importantly, the risk of vehicle damage severity was increased for those drinking and driving compared with those driving sober (write-off vehicle OR 4.24; 95% CI 3.70 - 4.86, severely damaged vehicles OR 1.98; 95% CI 1.77 - 2.21). The study reinforces existing literature to suggest that current evidence is sufficient to show an increased risk of injury and fatality to drivers and occupants in alcohol-related crashes. This paper not only emphasizes this well-known relationship, but also such consequences as increased vehicle damage severity. The connection between drinking and severity of motor vehicle crashes is popularly believed and has now received substantial scientific support. There is strong justification for injury prevention experts and policy-makers to step up motor vehicle crash injury prevention advocacy by implementing evidence-based policies to reduce rates of alcohol-impaired driving in the province of BC. Most unintentional injuries in BC are related to motor vehicle crashes. Significant improvements can be made in these statistics by: increasing the use of occupant protection (safety belt and child restraint seats); reducing alcohol-related injuries through multiple strategies including corrections in the physical environment, extensive enforcement of drinking and driving laws and health promotion/education.

Modulatory effect of dietary factors on iron-induced in vivo lipid peroxidation in liver and serum of albino rats.

Effect of a computed diet based on cereals and spices incorporated with either crude palm oil (CPO)/soybean oil (SBO)/cod liver oil (CLO) at 10% level in the diet in modulating iron-induced in vivo lipid peroxidation was carried out during a 12 week study in albino rats. Three groups of rats, each divided into three sets were fed diets based on casein/ragi/jowar incorporated with CPO or SBO or CLO. The casein group of rats did not receive any spice mixture, while the ragi and jowar groups received spice mixture at 2.5% level. Serum lipid analysis showed significant increase in cholesterol, LDL-c + VLDL-c and decrease in HDL-c levels in all the iron treated group of animals. In liver, non-significant increase in total cholesterol triglyceride and decrease in phospholipid levels were noted. Fatty acid profile of liver tissue exhibited low 18:2 levels in various experimental groups due to peroxidation of membrane lipids. Histopathological examination of liver tissue in particular showed mild cytoplasmic vacuolation in control group of rats fed ragi/jowar and moderate vacuolation in all the iron-treated groups. The results demonstrate that different dietary components can beneficially modulate free radical mediated oxidative stress induced by lipid peroxidation.

Testing for BNP and NT-proBNP in the diagnosis and prognosis of heart failure.

OBJECTIVES: The purpose of this systematic review was to evaluate BNP and NT-proBNP to: (a) identify determinants, (b) establish their diagnostic performance in heart failure (HF) patients, (c) determine their predictive ability with respect to mortality and other cardiac endpoints, and (d) determine their value in monitoring HF treatment. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Central, and AMED from 1989 to February 2005 were searched for primary studies. REVIEW METHODS: Standard systematic review methodology, including meta-analysis, was employed. All study designs were included. Eligibility criteria included English-only studies and restricted the number of test methods to maximize generalizability. Outcomes for prognosis were limited to mortality and specific cardiac events. Further specific criteria were developed for each research question. RESULTS: Determinants: There were 103 determinants identified including age, gender, disease, treatment, as well as biochemical and physiological measures. Few studies reported independent associations and of those that did age, female gender and creatinine levels were positively associated with BNP and NT-proBNP. DIAGNOSIS: Pooled sensitivity and specificity values were 94 and 66 percent for BNP and 92 and 65 percent for NT-proBNP; there was minimal difference among settings (emergency, specialized clinics, and primary care). B-type natriuretic peptides also added independent diagnostic information above traditional measures for HF. PROGNOSIS: Both BNP and NT-proBNP were found to be independent predictors of mortality and other cardiac composite endpoints in patients with risk of coronary artery disease (CAD) (risk estimate range = 1.10 to 5.40), diagnosed CAD (risk estimate range = 1.50 to 3.00), and diagnosed HF patients (risk estimate range = 2.11 to 9.35). With respect to screening, the AUC values (range = 0.57 to 0.88) suggested poor performance. Monitoring Treatment: Studies showed therapy reduced BNP and NT-proBNP, however, relationship to outcome was limited and not consistent. CONCLUSIONS: Determinants: The importance of the identified determinants for clinical use is not clear. DIAGNOSIS: In all settings both BNP and NT-proBNP show good diagnostic properties as a rule out test for HF. PROGNOSIS: BNP and NT-proBNP are consistent independent predictors of mortality and other cardiac composite endpoints for populations with risk of CAD, diagnosed CAD, and diagnosed HF. There is insufficient evidence to determine the value of B-type natriuretic peptides for screening of HF. Monitoring Treatment: There is insufficient evidence to demonstrate that BNP and NT-proBNP levels show change in response to therapies to manage stable chronic HF patients.

Diffusion and dissemination of evidence-based dietary strategies for the prevention of cancer.

We used a systematic review to identify strategies that have been evaluated for disseminating cancer control interventions that promote the uptake of a healthy diet in adults. Studies were identified by contacting technical experts and by searching MEDLINE, PreMedline, CANCERLIT, EMBASE/Excerpta Medica, Psycinfo, cinahl, the Cochrane Database of Systematic Reviews, and reference lists. English-language primary studies were selected if they evaluated the dissemination of healthy diet interventions to individuals, health care providers, or institutions. Studies involving only children or adolescents were excluded.We retrieved 101 articles for full-text screening, and identified nine reports of seven distinct studies. Four of the studies were randomized trials, one was a cohort design, and three were descriptive studies. Six of the studies were rated methodologically weak, and one was rated moderate. Because of heterogeneity, low methodological quality, and incomplete data reporting, the studies were not pooled for meta-analysis. No beneficial dissemination strategies were found. One strategy involving the use of peer educators at the work site, which led to a short-term increase in fruit and vegetable intake, looks promising.Overall, the quality of the evidence is not strong, and the evidence that exists is more descriptive than evaluative. No clear conclusions can be drawn from these data. Controlled studies are needed to evaluate dissemination strategies and to compare dissemination and diffusion strategies that communicate different messages and target different audiences.

Looking for the evidence: a systematic review of prevention strategies addressing sport and recreational injury among children and youth.

OBJECTIVES: To examine evidence on the effectiveness of current injury prevention strategies in selected sport and recreational activities, determine the applicability of the evidence to children and youth and discuss the implications related to policy, programming and future research. METHODS: Research questions and relevance criteria were developed a priori. Potentially relevant studies were located through electronic and hand searches. Two independent assessors assessed articles for first relevance and then quality. Relevant articles were abstracted and synthesised for activities that had three or more relevant articles. RESULTS: A total of 21,499 articles identified through database and manual searching yielding 117 that met inclusion criteria. The majority of the studies (93 or 89%) involved eight activities: baseball, basketball, cycling, football, ice hockey, rugby, alpine skiing and soccer. Children and youth were identified as the specific target group in 45% of the studies and another 12% included children in their sample. Studies addressed a range of intervention strategies and varied on quality of evidence. CONCLUSIONS: Surprisingly few well-designed and controlled studies investigating strategies to prevent injuries were found and an even smaller number evaluated strategies to reduce injury in children and youth. As governments in developed countries continue to focus on increasing physical activity among children and youth, thought must be given to the issue of risk of injury and the relative lack of evidence of effective preventive measures.

Strategies for prevention of soccer related injuries: a systematic review.

OBJECTIVES: To examine evidence on the effectiveness of current injury prevention strategies in soccer, determine the applicability of the evidence to children and youth, and make recommendations on policy, programming, and future research. METHODS: Standard systematic review methodology was modified and adopted for this review. Research questions and relevance criteria were developed a priori. Potentially relevant studies were located through electronic and hand searches. Articles were assessed for relevance and quality by two independent assessors, and the results of relevant articles were abstracted and synthesised. RESULTS: A total of 44 potentially relevant articles from electronic (n = 37) and hand (n = 7) searches yielded four that met inclusion criteria. These four studies addressed a range of intervention strategies and varied with respect to results and quality of evidence. CONCLUSIONS: Some of the strategies look promising but lack adequate evaluation or require further research among younger players. Practice, policy, and research recommendations are provided as a result of the synthesis.

Long-term feeding effects of heated and fried oils on hepatic antioxidant enzymes, absorption and excretion of fat in rats.

Long-term feeding effect of heated and fried peanut (PNO), rice bran (RBO) and palm oil (PO) in the diet on the hepatic antioxidant enzyme status and absorption and excretion of fats were studied in laboratory rats. The rats were fed oils heated to 180 degrees C continuously for a period of 72 h or laboratory fried at 20% level in the diet for 18 weeks. The results of the study indicated a significant increase in the catalase activity in HO groups and decrease in the FRO groups. The GPx activity while significantly low in HO groups was high in FRO groups, whereas, significant decrease in GST activity was observed in both PNO-HO/FRO groups. Increased activity was noted in RBO-FRO and PO-HO/FRO groups. The SOD activity showed a mixed response in different heated/fried oils and a marginal increase in the levels of fecal fat excretion was observed in some of the heated/fried oil groups. The results indicated no appreciable damage with respect to these antioxidant enzymes. Also, feeding heated fats as high as 20% in the diet for long duration does not result either in reduced food intake or excess fecal fat excretion.