Dendritic Branching of Olfactory Bulb Mitral and Tufted Cells: Regulation by TrkB

Projection neurons of mammalian olfactory bulb (OB), mitral and tufted cells, have dendrites whose morphologies are specifically differentiated for efficient odor information processing. The apical dendrite extends radially and arborizes in single glomerulus where it receives primary input from olfactory sensory neurons that express the same odor receptor. The lateral dendrites extend horizontally in the external plexiform layer and make reciprocal dendrodendritic synapses with granule cells, which moderate mitral/tufted cell activity. The molecular mechanisms regulating dendritic development of mitral/tufted cells is one of the unsolved important problems in the olfactory system. Here, we focused on TrkB receptors to test the hypothesis that neurotrophin-mediate mechanisms contributed to dendritic differentiation of OB mitral/tufted cells.With immunohistochemical analysis, we found that the TrkB neurotrophin receptor is expressed by both apical and lateral dendrites of mitral/tufted cells and that expression is evident during the early postnatal days when these dendrites exhibit their most robust growth and differentiation. To examine the effect of TrkB activation on mitral/tufted cell dendritic development, we cultured OB neurons. When BDNF or NT4 were introduced into the cultures, there was a significant increase in the number of primary neurites and branching points among the mitral/tufted cells. Moreover, BDNF facilitated filopodial extension along the neurites of mitral/tufted cells.In this report, we show for the first time that TrkB activation stimulates the dendritic branching of mitral/tufted cells in developing OB. This suggests that arborization of the apical dendrite in a glomerulus is under the tight regulation of TrkB activation

Multiple pelvic insufficiency fractures in rheumatoid patients with mutilating changes

Multiple insufficiency fractures occurred in two patients with mutilating rheumatoid arthritis (RA), leading to substantial disabilities. Both patients received long-term oral glucocorticoid therapy and underwent multiple lower-extremity surgeries such as total hip arthroplasty (THA) or Total knee arthroplasty (TKA). The multiple fractures were located in the pelvis and lumbosacral region. Fractures in both patients were treated conservatively. Although bony union and resumption of activities were achieved in one patient, the other patient was not able to resume ambulation. For RA patients with combined risk factors for insufficiency fractures, aggressive preventive intervention and careful clinical assessment for early detection and management are warranted

Using nutritional survey data to inform the design of sugar-sweetened beverage taxes in low-resource contexts: a cross-sectional analysis based on data from an adult Caribbean population

Funder: Robinson College, University of CambridgeFunder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Funder: British Heart Foundation; FundRef: http://dx.doi.org/10.13039/501100000274Funder: UKCRC Public Health Research Centre of ExcellenceFunder: Economic and Social Research Council; FundRef: http://dx.doi.org/10.13039/501100000269Funder: Cancer Research UK; FundRef: http://dx.doi.org/10.13039/501100000289Funder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100004440Funder: Yates Unilever FundFunder: The Ministry of Health of the Government of BarbadosFunder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Funder: Gates Cambridge PhD ScholarshipFunder: Smuts Memorial Fund, University of Cambridge; FundRef: http://dx.doi.org/10.13039/501100000710Funder: Global Food Security FundFunder: Luca D’Agliano ScholarshipObjective: Sugar-sweetened beverage (SSB) taxes have been implemented widely. We aimed to use a pre-existing nutritional survey data to inform SSB tax design by assessing: (1) baseline consumption of SSBs and SSB-derived free sugars, (2) the percentage of SSB-derived free sugars that would be covered by a tax and (3) the extent to which a tax would differentiate between high-sugar SSBs and low-sugar SSBs. We evaluated these three considerations using pre-existing nutritional survey data in a developing economy setting. Methods: We used data from a nationally representative cross-sectional survey in Barbados (2012–2013, prior to SSB tax implementation). Data were available on 334 adults (25–64 years) who completed two non-consecutive 24-hour dietary recalls. We estimated the prevalence of SSB consumption and its contribution to total energy intake, overall and stratified by taxable status. We assessed the percentage of SSB-derived free sugars subject to the tax and identified the consumption-weighted sugar concentration of SSBs, stratified by taxable status. Findings: Accounting for sampling probability, 88.8% of adults (95% CI 85.1 to 92.5) reported SSB consumption, with a geometric mean of 2.4 servings/day (±2 SD, 0.6, 9.2) among SSB consumers. Sixty percent (95% CI 54.6 to 65.4) of SSB-derived free sugars would be subject to the tax. The tax did not clearly differentiate between high-sugar beverages and low-sugar beverages. Conclusion: Given high SSB consumption, targeting SSBs was a sensible strategy in this setting. A substantial percentage of free sugars from SSBs were not covered by the tax, reducing possible health benefits. The considerations proposed here may help policymakers to design more effective SSB taxes

Dietary quality among men and women in 187 countries in 1990 and 2010: a systematic assessment

Background Healthy dietary patterns are a global priority to reduce non-communicable diseases. Yet neither worldwide patterns of diets nor their trends with time are well established. We aimed to characterise global changes (or trends) in dietary patterns nationally and regionally and to assess heterogeneity by age, sex, national income, and type of dietary pattern. Methods In this systematic assessment, we evaluated global consumption of key dietary items (foods and nutrients) by region, nation, age, and sex in 1990 and 2010. Consumption data were evaluated from 325 surveys (71·7% nationally representative) covering 88·7% of the global adult population. Two types of dietary pattern were assessed: one refl ecting greater consumption of ten healthy dietary items and the other based on lesser consumption of seven unhealthy dietary items. The mean intakes of each dietary factor were divided into quintiles, and each quintile was assigned an ordinal score, with higher scores being equivalent to healthier diets (range 0–100). The dietary patterns were assessed by hierarchical linear regression including country, age, sex, national income, and time as exploratory variables. Findings From 1990 to 2010, diets based on healthy items improved globally (by 2·2 points, 95% uncertainty interval (UI) 0·9 to 3·5), whereas diets based on unhealthy items worsened (–2·5, –3·3 to –1·7). In 2010, the global mean scores were 44·0 (SD 10·5) for the healthy pattern and 52·1 (18·6) for the unhealthy pattern, with weak intercorrelation (r=–0·08) between countries. On average, better diets were seen in older adults compared with younger adults, and in women compared with men (p<0·0001 each). Compared with low-income nations, high-income nations had better diets based on healthy items (+2·5 points, 95% UI 0·3 to 4·1), but substantially poorer diets based on unhealthy items (–33·0, –37·8 to –28·3). Diets and their trends were very heterogeneous across the world regions. For example, both types of dietary patterns improved in high-income countries, but worsened in some low-income countries in Africa and Asia. Middle-income countries showed the largest improvement in dietary patterns based on healthy items, but the largest deterioration in dietary patterns based on unhealthy items. Interpretation Consumption of healthy items improved, while consumption of unhealthy items worsened across the world, with heterogeneity across regions and countries. These global data provide the best estimates to date of nutrition transitions across the world and inform policies and priorities for reducing the health and economic burdens of poor diet quality

Prospective association of the Mediterranean diet with cardiovascular disease incidence and mortality and its population impact in a non-Mediterranean population: the EPIC-Norfolk study

Abstract Background Despite convincing evidence in the Mediterranean region, the cardiovascular benefit of the Mediterranean diet is not well established in non-Mediterranean countries and the optimal criteria for defining adherence are unclear. The population attributable fraction (PAF) of adherence to this diet is also unknown. Methods In the UK-based EPIC-Norfolk prospective cohort, we evaluated habitual diets assessed at baseline (1993–1997) and during follow-up (1998–2000) using food-frequency questionnaires (n = 23,902). We estimated a Mediterranean diet score (MDS) using cut-points projected from the Mediterranean dietary pyramid, and also three other pre-existing MDSs. Using multivariable-adjusted Cox regression with repeated measures of MDS and covariates, we examined prospective associations between each MDS with incident cardiovascular diseases (CVD) by 2009 and mortality by 2013, and estimated PAF for each outcome attributable to low MDS. Results We observed 7606 incident CVD events (2818/100,000 person-years) and 1714 CVD deaths (448/100,000). The MDS based on the Mediterranean dietary pyramid was significantly associated with lower incidence of the cardiovascular outcomes, with hazard ratios (95 % confidence intervals) of 0.95 (0.92–0.97) per one standard deviation for incident CVD and 0.91 (0.87–0.96) for CVD mortality. Associations were similar for composite incident ischaemic heart disease and all-cause mortality. Other pre-existing MDSs showed similar, but more modest associations. PAF due to low dietary pyramid based MDS (<95th percentile) was 3.9 % (1.3–6.5 %) for total incident CVD and 12.5 % (4.5–20.6 %) for CVD mortality. Conclusions Greater adherence to the Mediterranean diet was associated with lower CVD incidence and mortality in the UK. This diet has an important population health impact for the prevention of CVD

Physical Activity, Physical Fitness, and Leukocyte Telomere Length: The Cardiovascular Health Study.

INTRODUCTION: The influence of physical activity (PA) and physical fitness (PF) at older ages on changes in telomere length (TL)--repetitive DNA sequences that may mark biologic aging--is not well-established. Few prior studies (mainly cross-sectional) have been conducted in older adults, and few studies have evaluated PF. METHODS: We investigated cross-sectional and prospective associations of PA and PF with leukocyte TL among 582 older adults (mean ± SD age, 73 ± 5 yr at baseline) in the Cardiovascular Health Study, with serial TL measures and PA and PF assessed multiple times. Cross-sectional associations were assessed using multivariable repeated-measures regression, in which cumulatively averaged PA and PF measures were related to TL. Longitudinal analyses assessed cumulatively averaged PA and PF against later changes in TL, and changes in cumulatively averaged PA and PF against changes in TL. RESULTS: Cross-sectionally, greater walking distance and chair test performance, but not other PA and PF measures, were each associated with longer TL (P trend = 0.007 and 0.04, respectively). In longitudinal analyses, no significant associations of baseline PA and PF with change in TL were observed. In contrast, changes in leisure-time activity and chair test performance were each inversely associated with changes in TL. CONCLUSIONS: Cross-sectional analyses suggest that greater PA and PF are associated with longer TL. Prospective analyses show that changes in PA and PF are associated with differences in changes in TL. Even later in life, changes in certain PA and PF measures are associated with changes in TL, suggesting that leisure-time activity and fitness could reduce leukocyte telomere attrition among older adults.This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant U01HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. Luisa Soares-Miranda is supported by the Portuguese Foundation of Science and Technology (FCT), SFRH/BPD/76947/2011, PTDC/DES/099018/2008 - FCT/FCOMP-01- 0124-FEDER-009573, and The Research Centre in Physical Activity Health and Leisure is supported by UID/DTP/00617/2013. Dr Imamura received support from the Medical Research Council Epidemiology Unit Core Support (MC_UU_12015/5).This is the author accepted manuscript. The final version is available from Wolters Kluwer via http://dx.doi.org/10.1249/MSS.000000000000072

Prospective associations and population impact of sweet beverage intake and type 2 diabetes, and effects of substitutions with alternative beverages.

AIMS/HYPOTHESIS: This study aimed to evaluate the association of types of sugar-sweetened beverages (SSB) (soft drinks, sweetened-milk beverages, sweetened tea/coffee), artificially sweetened beverages (ASB) and fruit juice with incident type 2 diabetes and determine the effects of substituting non-SSB for SSB and the population-attributable fraction of type 2 diabetes due to total sweet beverages. METHODS: Beverage consumption of 25,639 UK-resident adults without diabetes at baseline (1993-1997) in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study was assessed using 7-day food diaries. During 10.8 years of follow-up 847 incident type 2 diabetes cases were verified. RESULTS: In adjusted Cox regression analyses there were positive associations (HR [95% CI] per serving/day]) for soft drinks 1.21 (1.05, 1.39), sweetened-milk beverages 1.22 (1.05, 1.43) and ASB 1.22 (1.11, 1.33), but not for sweetened tea/coffee 0.98 (0.94, 1.02) or fruit juice 1.01 (0.88, 1.15). Further adjustment for adiposity attenuated the association of ASB, HR 1.06 (0.93, 1.20). There was a positive dose-response relationship with total sweet beverages: HR per 5% energy 1.18 (1.11, 1.26). Substituting ASB for any SSB did not reduce the incidence in analyses accounting for energy intake and adiposity. Substituting one serving/day of water or unsweetened tea/coffee for soft drinks and for sweetened-milk beverages reduced the incidence by 14%-25%. If sweet beverage consumers reduced intake to below 2% energy, 15% of incident diabetes might be prevented. CONCLUSIONS/INTERPRETATION: The consumption of soft drinks, sweetened-milk beverages and energy from total sweet beverages was associated with higher type 2 diabetes risk independently of adiposity. Water or unsweetened tea/coffee appear to be suitable alternatives to SSB for diabetes prevention. These findings support the implementation of population-based interventions to reduce SSB consumption and increase the consumption of suitable alternatives.This work was supported by programme grants from the Medical Research Council (MRC) UK and Cancer Research UK. We acknowledge support from the MRC Epidemiology Unit (grant number MC_UU_12015/5).This is the final published version. It first appeared at http://link.springer.com/article/10.1007%2Fs00125-015-3572-1

Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction.

OBJECTIVES: To examine the prospective associations between consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice with type 2 diabetes before and after adjustment for adiposity, and to estimate the population attributable fraction for type 2 diabetes from consumption of sugar sweetened beverages in the United States and United Kingdom. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND ELIGIBILITY: PubMed, Embase, Ovid, and Web of Knowledge for prospective studies of adults without diabetes, published until February 2014. The population attributable fraction was estimated in national surveys in the USA, 2009-10 (n=4729 representing 189.1 million adults without diabetes) and the UK, 2008-12 (n=1932 representing 44.7 million). SYNTHESIS METHODS: Random effects meta-analysis and survey analysis for population attributable fraction associated with consumption of sugar sweetened beverages. RESULTS: Prespecified information was extracted from 17 cohorts (38,253 cases/10,126,754 person years). Higher consumption of sugar sweetened beverages was associated with a greater incidence of type 2 diabetes, by 18% per one serving/day (95% confidence interval 9% to 28%, I(2) for heterogeneity=89%) and 13% (6% to 21%, I(2)=79%) before and after adjustment for adiposity; for artificially sweetened beverages, 25% (18% to 33%, I(2)=70%) and 8% (2% to 15%, I(2)=64%); and for fruit juice, 5% (-1% to 11%, I(2)=58%) and 7% (1% to 14%, I(2)=51%). Potential sources of heterogeneity or bias were not evident for sugar sweetened beverages. For artificially sweetened beverages, publication bias and residual confounding were indicated. For fruit juice the finding was non-significant in studies ascertaining type 2 diabetes objectively (P for heterogeneity=0.008). Under specified assumptions for population attributable fraction, of 20.9 million events of type 2 diabetes predicted to occur over 10 years in the USA (absolute event rate 11.0%), 1.8 million would be attributable to consumption of sugar sweetened beverages (population attributable fraction 8.7%, 95% confidence interval 3.9% to 12.9%); and of 2.6 million events in the UK (absolute event rate 5.8%), 79,000 would be attributable to consumption of sugar sweetened beverages (population attributable fraction 3.6%, 1.7% to 5.6%). CONCLUSIONS: Habitual consumption of sugar sweetened beverages was associated with a greater incidence of type 2 diabetes, independently of adiposity. Although artificially sweetened beverages and fruit juice also showed positive associations with incidence of type 2 diabetes, the findings were likely to involve bias. None the less, both artificially sweetened beverages and fruit juice were unlikely to be healthy alternatives to sugar sweetened beverages for the prevention of type 2 diabetes. Under assumption of causality, consumption of sugar sweetened beverages over years may be related to a substantial number of cases of new onset diabetes

Contribution of Major Lifestyle Risk Factors for Incident Heart Failure in Older Adults: The Cardiovascular Health Study.

OBJECTIVES: The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure (HF) in older adults. BACKGROUND: HF incurs high morbidity, mortality, and health care costs among adults ≥65 years of age, which is the most rapidly growing segment of the U.S. METHODS: We prospectively investigated separate and combined associations of lifestyle risk factors with incident HF (1,380 cases) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study, which is a community-based cohort of older adults. Lifestyle factors included 4 dietary patterns (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an American Heart Association 2020 dietary goals score, and a Biologic pattern, which was constructed using previous knowledge of cardiovascular disease dietary risk factors), 4 physical activity metrics (exercise intensity, walking pace, energy expended in leisure activity, and walking distance), alcohol intake, smoking, and obesity. RESULTS: No dietary pattern was associated with developing HF (p > 0.05). Walking pace and leisure activity were associated with a 26% and 22% lower risk of HF, respectively (pace >3 mph vs. <2 mph; hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.63 to 0.86; leisure activity ≥845 kcal/week vs. <845 kcal/week; HR: 0.78; 95% CI: 0.69 to 0.87). Modest alcohol intake, maintaining a body mass index <30 kg/m(2), and not smoking were also independently associated with a lower risk of HF. Participants with ≥4 healthy lifestyle factors had a 45% (HR: 0.55; 95% CI: 0.42 to 0.74) lower risk of HF. Heterogeneity by age, sex, cardiovascular disease, hypertension medication use, and diabetes was not observed. CONCLUSIONS: Among older U.S. adults, physical activity, modest alcohol intake, avoiding obesity, and not smoking, but not dietary patterns, were associated with a lower risk of HF.Role of the funding source: This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. Fumiaki Imamura was supported by Medical Research Council Unit Programme number MC_UU_125015/5.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jchf.2015.02.00