Dairy Foods, Weight Change, and Risk of Obesity During the Menopausal Transition.

BACKGROUND: Weight gain during the menopausal transition is common. Dairy consumption may impact weight change during this critical period, and different dairy foods may have different effects. OBJECTIVES: This study aimed to investigate the associations of different types of dairy foods with weight gain and risk of obesity in perimenopausal women from the Nurses' Health Study II cohort. METHODS: The examination at menopause was selected as the exam closest to the reported age at menopause. Weight change during 12 y surrounding menopause was derived from self-reported weight data for 3 exams before and 3 after menopause. The mean age of the first weight measure was 45.8 y and the average BMI was 25.0 kg/m2. Dairy food intakes were estimated as mean intakes over the same 12 y. Generalized linear models were used to assess the association between dairy foods and annualized weight change. Cox proportional hazard models were used to estimate the adjusted relative risks for becoming obese over 12 y surrounding menopause. RESULTS: In longitudinal analyses, those with the highest yogurt intakes had the lowest weight gain at every exam. This was not the case for other forms of dairy. After adjusting for potential covariates, those consuming ≥2.0 servings/wk of yogurt (compared with <1.0 serving/month) had a 31% (RR: 0.69; 95% CI: 0.64, 0.74) lower risk of obesity. The highest total dairy intake (≥2.0 servings/d compared with <1.0) was associated with only a 12% (RR: 0.88; 95% CI: 0.82, 0.95) reduction in obesity risk. Higher activity levels and alternative healthy eating index scores were independently associated with statistically significant reductions in risk of obesity, but higher intakes of yogurt strengthened these beneficial associations. CONCLUSION: Yogurt intake was associated with less weight gain and lower obesity risk in women during the menopausal transition.

Measurement of polarization observables T, P, and H in π0 and η photoproduction off quasi-free nucleons.

The target asymmetry T, recoil asymmetry P, and beam-target double polarization observable H were determined in exclusive π0 and η photoproduction off quasi-free protons and, for the first time, off quasi-free neutrons. The experiment was performed at the electron stretcher accelerator ELSA in Bonn, Germany, with the Crystal Barrel/TAPS detector setup, using a linearly polarized photon beam and a transversely polarized deuterated butanol target. Effects from the Fermi motion of the nucleons within deuterium were removed by a full kinematic reconstruction of the final state invariant mass. A comparison of the data obtained on the proton and on the neutron provides new insight into the isospin structure of the electromagnetic excitation of the nucleon. Earlier measurements of polarization observables in the γp→π0p and γp→ηp reactions are confirmed. The data obtained on the neutron are of particular relevance for clarifying the origin of the narrow structure in the ηn system at W=1.68GeV. A comparison with recent partial wave analyses favors the interpretation of this structure as arising from interference of the S11(1535) and S11(1650) resonances within the S11-partial wave.

Measurement of the helicity asymmetry E for the reaction γ p → π 0 p : The CBELSA/TAPS Collaboration.

A measurement of the double-polarization observable E for the reaction γ p → π 0 p is reported. The data were taken with the CBELSA/TAPS experiment at the ELSA facility in Bonn using the Bonn frozen-spin butanol (C 4 H 9 OH) target, which provided longitudinally-polarized protons. Circularly-polarized photons were produced via bremsstrahlung of longitudinally-polarized electrons. The data cover the photon energy range from E γ = 600 to 2310 MeV and nearly the complete angular range. The results are compared to and have been included in recent partial wave analyses.

Observation of the pη

Data on the beam asymmetry Σ in the photoproduction of η mesons off protons are reported for tagged photon energies from 1130 to 1790 MeV (mass range from W=1748 MeV to W=2045 MeV). The data cover the full solid angle that allows for a precise moment analysis. For the first time, a strong cusp effect in a polarization observable has been observed that is an effect of a branch-point singularity at the pη^{'} threshold [E_{γ}=1447 MeV (W=1896 MeV)]. The latest BnGa partial wave analysis includes the new beam asymmetry data and yields a strong indication for the N(1895)1/2^{-} nucleon resonance, demonstrating the importance of including all singularities for a correct determination of partial waves and resonance parameters.

Influence of orthopedic examination on lameness scores and interobserver and intraobserver agreement in dogs with naturally occurring elbow osteoarthritis.

OBJECTIVE: To determine the influence of orthopedic examination on numerical rating score (NRS) and visual analog score (VAS) when scoring lameness in dogs with elbow osteoarthritis (OA) and to evaluate interobserver and intraobserver agreement in NRS and VAS on the basis of video-graphic gait analysis. DESIGN: Prospective blinded study. ANIMALS: Eighteen client-owned dogs with radiographically confirmed elbow OA. METHODS: Videos were obtained for all dogs at a walk and at a trot both prior to and immediately after orthopedic examination. All videos were randomly sequenced. Six observers, unaware of the timing of the video, independently assigned both NRS and VAS twice, with at least a 2-week interval. Scores were evaluated with mixed analysis of variance, and the agreement among observers was accessed by intraclass correlation coefficient (ICC). RESULTS: No difference was detected between NRS and VAS at walk or at trot before and after orthopedic examination. Numeric rating score and VAS at walk were lower than those at trot before an orthopedic examination by scores of 0.17 (P = .0018) and 3.54 (P = .0019), respectively. The ICC for both scores for all observers was >0.9. CONCLUSION: An orthopedic examination did not exacerbate the NRS and the VAS for dogs with elbow OA. Interobserver and intraobserver agreement was high for both lameness scores. CLINICAL SIGNIFICANCE: Lameness may be scored after gait evaluation in dogs with elbow OA irrespective of the timing of a comprehensive orthopedic examination.

Nutritional status of Ugandan school-children: The effect of age imprecision.

OBJECTIVES: To analyze the nutritional status of Ugandan school-children in a cross-sectional and longitudinal perspective, considering the effect of age imprecision. MATERIALS AND METHODS: Anthropometric measurements of 831 school-children (381 males and 450 females) were analyzed. A subsample of 246 children was measured in July 2014 and 2015. Stunting (based on height-for-age Z-scores), underweight (weight-for-age), and thinness (body mass index-for-age) prevalence were calculated. Three different ages were used: declared (from schools registers), attributed (based on multiple information sources), and bootstrap (from 10,000 replicates). Significant differences among malnutrition prevalence calculated with different ages and in different groups were assessed by means of bootstrap analysis. Longitudinal analysis was conducted using a paired t test. RESULTS: The mean prevalence of malnutrition calculated with declared, attributed, or bootstrap ages were very similar: stunting (11.9-12.7); underweight (5.4-5.9); thinness (3.3-3.7); and obesity (0.7). Undernutrition was more prevalent among older children, while obesity was mostly associated with young age. Obesity was equally distributed among sexes, while undernutrition was more prevalent among females of up to 10 years of age and males above 10 years. The longitudinal analysis indicated a reduction in underweight and thinness, and an increase in stunting, especially among older children. DISCUSSION: Age imprecision did not significantly affect malnutrition estimates. Despite the decline in the prevalence of thinness and underweight observed over a 1-year period, undernutrition persists, with an observed rise in stunting. On the other hand, obesity is starting to appear. Public health efforts are required to eliminate stunting and address the emerging burden of obesity.

Structural Characterization and Ligand/Inhibitor Identification Provide Functional Insights into the Mycobacterium tuberculosis Cytochrome P450 CYP126A1.

The Mycobacterium tuberculosis H37Rv genome encodes 20 cytochromes P450, including P450s crucial to infection and bacterial viability. Many M. tuberculosis P450s remain uncharacterized, suggesting that their further analysis may provide new insights into M. tuberculosis metabolic processes and new targets for drug discovery. CYP126A1 is representative of a P450 family widely distributed in mycobacteria and other bacteria. Here we explore the biochemical and structural properties of CYP126A1, including its interactions with new chemical ligands. A survey of azole antifungal drugs showed that CYP126A1 is inhibited strongly by azoles containing an imidazole ring but not by those tested containing a triazole ring. To further explore the molecular preferences of CYP126A1 and search for probes of enzyme function, we conducted a high throughput screen. Compounds containing three or more ring structures dominated the screening hits, including nitroaromatic compounds that induce substrate-like shifts in the heme spectrum of CYP126A1. Spectroelectrochemical measurements revealed a 155-mV increase in heme iron potential when bound to one of the newly identified nitroaromatic drugs. CYP126A1 dimers were observed in crystal structures of ligand-free CYP126A1 and for CYP126A1 bound to compounds discovered in the screen. However, ketoconazole binds in an orientation that disrupts the BC-loop regions at the P450 dimer interface and results in a CYP126A1 monomeric crystal form. Structural data also reveal that nitroaromatic ligands "moonlight" as substrates by displacing the CYP126A1 distal water but inhibit enzyme activity. The relatively polar active site of CYP126A1 distinguishes it from its most closely related sterol-binding P450s in M. tuberculosis, suggesting that further investigations will reveal its diverse substrate selectivity.

Linking communities to formal health care providers through village health teams in rural Uganda: lessons from linking social capital.

BACKGROUND: Community-based programmes, particularly community health workers (CHWs), have been portrayed as a cost-effective alternative to the shortage of health workers in low-income countries. Usually, literature emphasises how easily CHWs link and connect communities to formal health care services. There is little evidence in Uganda to support or dispute such claims. Drawing from linking social capital framework, this paper examines the claim that village health teams (VHTs), as an example of CHWs, link and connect communities with formal health care services. METHODS: Data were collected through ethnographic fieldwork undertaken as part of a larger research program in Luwero District, Uganda, between 2012 and 2014. The main methods of data collection were participant observation in events organised by VHTs. In addition, a total of 91 in-depth interviews and 42 focus group discussions (FGD) were conducted with adult community members as part of the larger project. After preliminary analysis of the data, we conducted an additional six in-depth interviews and three FGD with VHTs and four FGD with community members on the role of VHTs. Key informant interviews were conducted with local government staff, health workers, local leaders, and NGO staff with health programs in Luwero. Thematic analysis was used during data analysis. RESULTS: The ability of VHTs to link communities with formal health care was affected by the stakeholders' perception of their roles. Community members perceive VHTs as working for and under instructions of "others", which makes them powerless in the formal health care system. One of the challenges associated with VHTs' linking roles is support from the government and formal health care providers. Formal health care providers perceived VHTs as interested in special recognition for their services yet they are not "experts". For some health workers, the introduction of VHTs is seen as a ploy by the government to control people and hide its inability to provide health services. Having received training and initial support from an NGO, VHTs suffered transition failure from NGO to the formal public health care structure. As a result, VHTs are entangled in power relations that affect their role of linking community members with formal health care services. We also found that factors such as lack of money for treatment, poor transport networks, the attitudes of health workers and the existence of multiple health care systems, all factors that hinder access to formal health care, cannot be addressed by the VHTs. CONCLUSIONS: As linking social capital framework shows, for VHTs to effectively act as links between the community and formal health care and harness the resources that exist in institutions beyond the community, it is important to take into account the power relationships embedded in vertical relationships and forge a partnership between public health providers and the communities they serve. This will ensure strengthened partnerships and the improved capacity of local people to leverage resources embedded in vertical power networks.

Chronic Exposure to Excess Nutrients Left-shifts the Concentration Dependence of Glucose-stimulated Insulin Secretion in Pancreatic ß-Cells.

Hyperinsulinemia (HI) is elevated plasma insulin at basal glucose. Impaired glucose tolerance is associated with HI, although the exact cause and effect relationship remains poorly defined. We tested the hypothesis that HI can result from an intrinsic response of the ß-cell to chronic exposure to excess nutrients, involving a shift in the concentration dependence of glucose-stimulated insulin secretion. INS-1 (832/13) cells were cultured in either a physiological (4 mm) or high (11 mm) glucose concentration with or without concomitant exposure to oleate. Isolated rat islets were also cultured with or without oleate. A clear hypersensitivity to submaximal glucose concentrations was evident in INS-1 cells cultured in excess nutrients such that the 25% of maximal (S0.25) glucose-stimulated insulin secretion was significantly reduced in cells cultured in 11 mm glucose (S0.25 = 3.5 mm) and 4 mm glucose with oleate (S0.25 = 4.5 mm) compared with 4 mm glucose alone (S0.25 = 5.7 mm). The magnitude of the left shift was linearly correlated with intracellular lipid stores in INS-1 cells (r(2) = 0.97). We observed no significant differences in the dose responses for glucose stimulation of respiration, NAD(P)H autofluorescence, or Ca(2+) responses between left- and right-shifted ß-cells. However, a left shift in the sensitivity of exocytosis to Ca(2+) was documented in permeabilized INS-1 cells cultured in 11 versus 4 mm glucose (S0.25 = 1.1 and 1.7 µm, respectively). Our results suggest that the sensitivity of exocytosis to triggering is modulated by a lipid component, the levels of which are influenced by the culture nutrient environment.

Phosphoinositide signalling in type 2 diabetes: a ß-cell perspective.

Type 2 diabetes is a complex disease. It results from a failure of the body to maintain energy homoeostasis. Multicellular organisms have evolved complex strategies to preserve a relatively stable internal nutrient environment, despite fluctuations in external nutrient availability. This complex strategy involves the co-ordinated responses of multiple organs to promote storage or mobilization of energy sources according to the availability of nutrients and cellular bioenergetics needs. The endocrine pancreas plays a central role in these processes by secreting insulin and glucagon. When this co-ordinated effort fails, hyperglycaemia and hyperlipidaemia develops, characterizing a state of metabolic imbalance and ultimately overt diabetes. Although diabetes is most likely a collection of diseases, scientists are starting to identify genetic components and environmental triggers. Genome-wide association studies revealed that by and large, gene variants associated with type 2 diabetes are implicated in pancreatic ß-cell function, suggesting that the ß-cell may be the weakest link in the chain of events that results in diabetes. Thus, it is critical to understand how environmental cues affect the ß-cell. Phosphoinositides are important 'decoders' of environmental cues. As such, these lipids have been implicated in cellular responses to a wide range of growth factors, hormones, stress agents, nutrients and metabolites. Here we will review some of the well-established and potential new roles for phosphoinositides in ß-cell function/dysfunction and discuss how our knowledge of phosphoinositide signalling could aid in the identification of potential strategies for treating or preventing type 2 diabetes.

The first mile: community experience of outbreak control during an Ebola outbreak in Luwero District, Uganda.

BACKGROUND: A major challenge to outbreak control lies in early detection of viral haemorrhagic fevers (VHFs) in local community contexts during the critical initial stages of an epidemic, when risk of spreading is its highest ("the first mile"). In this paper we document how a major Ebola outbreak control effort in central Uganda in 2012 was experienced from the perspective of the community. We ask to what extent the community became a resource for early detection, and identify problems encountered with community health worker and social mobilization strategies. METHODS: Analysis is based on first-hand ethnographic data from the center of a small Ebola outbreak in Luwero Country, Uganda, in 2012. Three of this paper's authors were engaged in an 18 month period of fieldwork on community health resources when the outbreak occurred. In total, 13 respondents from the outbreak site were interviewed, along with 21 key informants and 61 focus group respondents from nearby Kaguugo Parish. All informants were chosen through non-probability sampling sampling. RESULTS: Our data illustrate the lack of credibility, from an emic perspective, of biomedical explanations which ignore local understandings. These explanations were undermined by an insensitivity to local culture, a mismatch between information circulated and the local interpretative framework, and the inability of the emergency response team to take the time needed to listen and empathize with community needs. Stigmatization of the local community--in particular its belief in amayembe spirits--fuelled historical distrust of the external health system and engendered community-level resistance to early detection. CONCLUSIONS: Given the available anthropological knowledge of a previous outbreak in Northern Uganda, it is surprising that so little serious effort was made this time round to take local sensibilities and culture into account. The "first mile" problem is not only a question of using local resources for early detection, but also of making use of the contextual cultural knowledge that has already been collected and is readily available. Despite remarkable technological innovations, outbreak control remains contingent upon human interaction and openness to cultural difference.

Traditional birth attendants (TBAs) as potential agents in promoting male involvement in maternity preparedness: insights from a rural community in Uganda.

BACKGROUND: Since the 1994 International Conference on Population and Development, male involvement in reproductive health issues has been advocated as a means to improve maternal and child health outcomes, but to date, health providers have failed to achieve successful male involvement in pregnancy care especially in rural and remote areas where majority of the underserved populations live. In an effort to enhance community participation in maternity care, TBAs were trained and equipped to ensure better care and quick referral. In 1997, after the advent of the World Health Organization's Safe Motherhood initiative, the enthusiasm turned away from traditional birth attendants (TBAs). However, in many developing countries, and especially in rural areas, TBAs continue to play a significant role. This study explored the interaction between men and TBAs in shaping maternal healthcare in a rural Ugandan context. METHODS: This study employed ethnographic methods including participant observation, which took place in the process of everyday life activities of the respondents within the community; 12 focus group discussions, and 12 in-depth interviews with community members and key informants. Participants in this study were purposively selected to include TBAs, men, opinion leaders like village chairmen, and other key informants who had knowledge about the configuration of maternity services in the community. Data analysis was done inductively through an iterative process in which transcribed data was read to identify themes and codes were assigned to those themes. RESULTS: Contrary to the thinking that TBA services are utilized by women only, we found that men actively seek the services of TBAs and utilize them for their wives' healthcare within the community. TBAs in turn sensitize men using both cultural and biomedical health knowledge, and become allies with women in influencing men to provide resources needed for maternity care. CONCLUSION: In this study area, men trust and have confidence in TBAs; closer collaboration with TBAs may provide a suitable platform through which communities can be sensitized and men actively brought on board in promoting maternal health services for women in rural communities.

Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients.

Purpose. Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization of CMCs has been limited due to the lack of a robust methodology capable of identifying them in a format suitable for downstream characterization. Here, we have developed a methodology to detect intact CMCs that enables phenotypic, morphometric and genomic analysis at the single cell level. Experimental design. Blood samples from 40 metastatic melanoma patients and 10 normal blood donors were prospectively collected. A panel of 7 chondroitin sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibodies (mAbs) was used to immunocytochemically label CMCs. Detection was performed by automated digital fluorescence microscopy and multi-parametric computational analysis. Individual CMCs were captured by micromanipulation for whole genome amplification and copy number variation (CNV) analysis. Results. Based on CSPG4 expression and nuclear size, 1-250 CMCs were detected in 22 (55%) of 40 metastatic melanoma patients (0.5-371.5 CMCs ml(-1)). Morphometric analysis revealed that CMCs have a broad spectrum of morphologies and sizes but exhibit a relatively homogeneous nuclear size that was on average 1.5-fold larger than that of surrounding PBMCs. CNV analysis of single CMCs identified deletions of CDKN2A and PTEN, and amplification(s) of TERT, BRAF, KRAS and MDM2. Furthermore, novel chromosomal amplifications in chr12, 17 and 19 were also found. Conclusions. Our findings show that CSPG4 expressing CMCs can be found in the majority of advanced melanoma patients. High content analysis of this cell population may contribute to the design of effective personalized therapies in patients with melanoma.

Measurements of double-polarized compton scattering asymmetries and extraction of the proton spin polarizabilities.

The spin polarizabilities of the nucleon describe how the spin of the nucleon responds to an incident polarized photon. The most model-independent way to extract the nucleon spin polarizabilities is through polarized Compton scattering. Double-polarized Compton scattering asymmetries on the proton were measured in the Δ(1232) region using circularly polarized incident photons and a transversely polarized proton target at the Mainz Microtron. Fits to asymmetry data were performed using a dispersion model calculation and a baryon chiral perturbation theory calculation, and a separation of all four proton spin polarizabilities in the multipole basis was achieved. The analysis based on a dispersion model calculation yields γ(E1E1)=-3.5±1.2, γ(M1M1)=3.16±0.85, γ(E1M2)=-0.7±1.2, and γ(M1E2)=1.99±0.29, in units of 10(-4) fm(4).

Selection and performance of village health teams (VHTs) in Uganda: lessons from the natural helper model of health promotion.

BACKGROUND: Community health worker (CHW) programmes have received much attention since the 1978 Declaration of Alma-Ata, with many initiatives established in developing countries. However, CHW programmes often suffer high attrition once the initial enthusiasm of volunteers wanes. In 2002, Uganda began implementing a national CHW programme called the village health teams (VHTs), but their performance has been poor in many communities. It is argued that poor community involvement in the selection of the CHWs affects their embeddedness in communities and success. The question of how selection can be implemented creatively to sustain CHW programmes has not been sufficiently explored. In this paper, our aim was to examine the process of the introduction of the VHT strategy in one rural community, including the selection of VHT members and how these processes may have influenced their work in relation to the ideals of the natural helper model of health promotion. METHODS: As part of a broader research project, an ethnographic study was carried out in Luwero district. Data collection involved participant observation, 12 focus group discussions (FGDs), 14 in-depth interviews with community members and members of the VHTs and four key informant interviews. Interviews and FGD were recorded, transcribed and coded in NVivo. Emerging themes were further explored and developed using text query searches. Interpretations were confirmed by comparison with findings of other team members. RESULTS: The VHT selection process created distrust, damaging the programme's legitimacy. While the Luwero community initially had high expectations of the programme, local leaders selected VHTs in a way that sidelined the majority of the community's members. Community members questioned the credentials of those who were selected, not seeing the VHTs as those to whom they would go to for help and support. Resentment grew, and as a result, the ways in which the VHTs operated alienated them further from the community. Without the support of the community, the VHTs soon lost morale and stopped their work. CONCLUSION: As the natural helper model recommends, in order for CHW programmes to gain and maintain community support, it is necessary to utilize naturally existing informal helping networks by drawing on volunteers already trusted by the people being served. That way, the community will be more inclined to trust the advice of volunteers and offer them support in return, increasing the likelihood of the sustainability of their service in the community.

Severe intraocular pressure response to periocular or intravitreal steroid treatment in Australia and New Zealand: data from the Australian and New Zealand Ophthalmic Surveillance Unit.

BACKGROUND: Increase in intraocular pressure is a recognized complication of corticosteroid treatment via intravitreal or periocular injections for treatment of a range of conditions including macular oedema and retinal neovascularization. DESIGN: This surveillance study was designed to determine the incidence and nature of severe intraocular pressure elevation as a complication of intravitreal or periocular corticosteroid injections in Australia and New Zealand. PARTICIPANTS: Seventeen cases meeting the defined criteria of severe intraocular pressure elevation, above 35 mmHg, following an intravitreal or periocular corticosteroid injection were included in the study. METHODS: Over an 18-month period, ophthalmologists were invited to report cases to the Australian and New Zealand Ophthalmic Surveillance Unit. After reporting, further demographic and clinical information was sought via a follow-up questionnaire. MAIN OUTCOME MEASURES: Intraocular pressure elevation above 35 mmHg. RESULTS: Follow-up questionnaires were received for 20 cases of 34 initially reported to the unit. Seventeen met the defined criteria. Triamcinolone acetonide was used in all 17 cases, with 16 delivered as a 4-mg intravitreal injection. There was an absence of identified underlying risk factors in the majority of cases with personal history of glaucoma in 2 of 17 cases. No cases reported a positive family history of glaucoma. Trabeculectomy was performed in 8 of 17 patients (47%) for intraocular pressure management. CONCLUSIONS: Severe intraocular pressure elevation following intravitreal or periocular corticosteroid injection can occur in the absence of risk factors such as personal and family history of glaucoma. The severe intraocular pressure elevation may ultimately require trabeculectomy.

Measurement of the 1H(γ, p)π0 reaction using a novel nucleon spin polarimeter.

We report the first large-acceptance measurement of polarization transfer from a polarized photon beam to a recoiling nucleon. The measurement pioneers a novel polarimetry technique, which can be applied to many other nuclear and hadron physics experiments. The commissioning reaction of 1H(γ, p)π0 in the range 0.4

Photoproduction of π0 mesons off neutrons in the nucleon resonance region.

Precise angular distributions have been measured for the first time for the photoproduction of π0 mesons off neutrons bound in the deuteron. The effects from nuclear Fermi motion have been eliminated by a complete kinematic reconstruction of the final state. The influence of final-state-interaction effects has been estimated by a comparison of the reaction cross section for quasifree protons bound in the deuteron to the results for free protons and then applied as a correction to the quasifree neutron data. The experiment was performed at the tagged photon facility of the Mainz Microtron MAMI with the Crystal Ball and TAPS detector setup for incident photon energies between 0.45 and 1.4 GeV. The results are compared to the predictions from reaction models and partial-wave analyses based on data from other isospin channels. The model predictions show large discrepancies among each other and the present data will provide much tighter constraints. This is demonstrated by the results of a new analysis in the framework of the Bonn-Gatchina coupled-channel analysis which included the present data.