The role of advanced training in family planning and reproductive health in a low-income country; the experience of Ethiopia.

Low- and middle-income countries continue to experience high fertility rates and unsafe abortion. Increased access to safe abortion services and family planning are cost-effective ways to reduce maternal morbidity and mortality. With a vision of improving the reproductive health workforce of the country, St. Paul's Hospital Millennium Medical College, in partnership with a university in the United States (U.S.), launched the first family planning and reproductive health fellowship program in Ethiopia. As the premier program in the country, the fellowship has introduced several new initiatives and skills to the existing reproductive health care training options. This program is a stirring example of successful collaboration between a U.S. university and a college in a low- or middle-income country. We have summarized the process of establishing the fellowship program as the first experience in Ethiopia and East Africa.

Inferring diet, feeding behaviour and causes of mortality from prey-induced injuries in a New Zealand fur seal.

New Zealand fur seals Arctocephalus forsteri are the most abundant of the 4 otariid (eared seal) species distributed across Australasia. Analyses of stomach contents, scats and regurgitates suggest a diet dominated by bony fish and squid, with cartilaginous species (e.g. sharks and rays) either absent or underrepresented because of a lack of preservable hard parts. Here we report on a subadult specimen from south-eastern Australia, which was found ashore emaciated and with numerous puncture wounds across its lips, cheeks, throat and the inside of its oral cavity. Fish spines embedded in the carcass revealed that these injuries were inflicted by chimaeras and myliobatiform rays (stingrays and relatives), which matches reports on the diet of A. forsteri from New Zealand, but not South Australia. Shaking and tearing of prey at the surface may help to avoid ingestion of the venomous spines, perhaps contributing to their absence from scats and regurgitates. Nevertheless, the number and severity of the facial stab wounds, some of which led to local necrosis, likely affected the animal's ability to feed, and may account for its death. Despite their detrimental effects, fish spine-related injuries are difficult to spot, and may be a common, albeit cryptic, type of trauma. We therefore recommend that stranded seals be systematically examined for this potentially life-threatening pathology.

Ethnic differences in adiposity and diabetes risk - insights from genetic studies.

Type 2 diabetes is more common in non-Europeans and starts at a younger age and at lower BMI cut-offs. This review discusses the insights from genetic studies about pathophysiological mechanisms which determine risk of disease with a focus on the role of adiposity and body fat distribution in ethnic disparity in risk of type 2 diabetes. During the past decade, genome-wide association studies (GWAS) have identified more than 400 genetic variants associated with the risk of type 2 diabetes. The Eurocentric nature of these genetic studies has made them less effective in identifying mechanisms that make non-Europeans more susceptible to higher risk of disease. One possible mechanism suggested by epidemiological studies is the role of ethnic difference in body fat distribution. Using genetic variants associated with an ability to store extra fat in a safe place, which is subcutaneous adipose tissue, we discuss how different ethnic groups could be genetically less susceptible to type 2 diabetes by developing a more favourable fat distribution.

Reference range of liver corrected T1 values in a population at low risk for fatty liver disease-a UK Biobank sub-study, with an appendix of interesting cases.

PURPOSE: Corrected T1 (cT1) value is a novel MRI-based quantitative metric for assessing a composite of liver inflammation and fibrosis. It has been shown to distinguish between non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis. However, these studies were conducted in patients at high risk for liver disease. This study establishes the normal reference range of cT1 values for a large UK population, and assesses interactions of age and gender. METHODS: MR data were acquired on a 1.5 T system as part of the UK Biobank Imaging Enhancement study. Measures for Proton Density Fat Fraction and cT1 were calculated from the MRI data using a multiparametric MRI software application. Data that did not meet quality criteria were excluded from further analysis. Inter and intra-reader variability was estimated in a set of data. A cohort at low risk for NAFL was identified by excluding individuals with BMI ≥ 25 kg/m2 and PDFF ≥ 5%. Of the 2816 participants with data of suitable quality, 1037 (37%) were classified as at low risk. RESULTS: The cT1 values in the low-risk population ranged from 573 to 852 ms with a median of 666 ms and interquartile range from 643 to 694 ms. Iron correction of T1 was necessary in 36.5% of this reference population. Age and gender had minimal effect on cT1 values. CONCLUSION: The majority of cT1 values are tightly clustered in a population at low risk for NAFL, suggesting it has the potential to serve as a new quantitative imaging biomarker for studies of liver health and disease.

Dietary intake in people consuming a low-carbohydrate diet in the UK Biobank.

BACKGROUND: Low-carbohydrate diets are becoming increasingly popular, although their dietary quality outside of clinical studies is unknown. A previous study analysed the dietary intake in people consuming a reduced-carbohydrate diet (<40% calories). However, it is not clear what foods people consume when carbohydrate is reduced to below 26% of total calories. METHODS: In the present cross-sectional study, the dietary and nutrient intake collected via up to five consecutive 24-h dietary recalls and a food frequency questionnaire of 444 individuals (aged 46-79 years) consuming <26% of calories from carbohydrate (LCHO) was compared with that of 131 897 individuals consuming ≥45% calories from carbohydrate (NCHO) using the UK Biobank Dataset. Absolute cut-offs to define the low-carbohydrate group (<130 g day-1 ; n = 1953 versus ≥225 g day-1 , n = 113 036) were also used. RESULTS: Both NCHO (>45% calories and ≥225 g) groups consumed significantly more high-sugar, high-fat snacks [median 6.0, interquartile range (IQR) = 2.0-11.0 and median 6.0, IQR = 3.0-11.8, respectively) compared to the LCHO (<26% calories and <130 g) groups (median 0, IQR = 0-2.8 and median 1, IQR = 0-3.8, respectively) (P < 0.0001). Both LCHO groups reported consuming significantly more red meat, oily fish, nuts and seeds but fewer fruits, vegetables and pulses compared to the NCHO groups. In general, the consumption of oily fish, nuts, seeds and pulses was low across the whole cohort and differences in intake between the LCHO and NCHO groups were small. After adjusting for socio-economic status, most differences remained. CONCLUSIONS: Carbohydrate restriction is associated with both beneficial and potentially deleterious dietary changes compared to a normal carbohydrate intake.

Optimal nutrition and the ever-changing dietary landscape: a conference report.

The field of nutrition has evolved rapidly over the past century. Nutrition scientists and policy makers in the developed world have shifted the focus of their efforts from dealing with diseases of overt nutrient deficiency to a new paradigm aimed at coping with conditions of excess-calories, sedentary lifestyles and stress. Advances in nutrition science, technology and manufacturing have largely eradicated nutrient deficiency diseases, while simultaneously facing the growing challenges of obesity, non-communicable diseases and aging. Nutrition research has gone through a necessary evolution, starting with a reductionist approach, driven by an ambition to understand the mechanisms responsible for the effects of individual nutrients at the cellular and molecular levels. This approach has appropriately expanded in recent years to become more holistic with the aim of understanding the role of nutrition in the broader context of dietary patterns. Ultimately, this approach will culminate in a full understanding of the dietary landscape-a web of interactions between nutritional, dietary, social, behavioral and environmental factors-and how it impacts health maintenance and promotion.

Weekly Formative Exams and Creative Grading Enhance Student Learning in an Introductory Biology Course.

First-year students often become discouraged during introductory biology courses when repeated attempts to understand concepts nevertheless result in poor test scores. This challenge is exacerbated by traditional course structures that impose premature judgments on students' achievements. Repeated testing has been shown to benefit student ability to recognize and recall information, but an effective means to similarly facilitate skill with higher-order problems in introductory courses is needed. Here, we show that an innovative format that uses a creative grading scheme together with weekly formative midterm exams produced significant gains in student success with difficult items requiring analysis and interpretation. This format is designed to promote tenacity and avoid discouragement by providing multiple opportunities to attempt demanding problems on exams, detailed immediate feedback, and strong incentives to retain hope and improve. Analysis of individual performance trajectories with heat maps reveals the diversity of learning patterns and provides rational means for advising students.

Metabolic dysfunction following weight cycling in male mice.

BACKGROUND: Combatting overweight or obesity can lead to large fluctuations in an individual's body weight, often referred to as weight cycling or 'yo-yo' dieting. Current evidence regarding the potentially damaging effects of these changes is conflicting. METHODS: Here, we assess the metabolic effects of weight cycling in a murine model, comprising three dietary switches to normal or high-fat diets at 6 week intervals; male C57BL/6 mice were fed either a control (C) or high-fat (F) diet for 6 weeks (n=140/group). C and F groups were then either maintained on their initial diet (CC and FF, respectively) or switched to a high-fat (CF) or control (FC) diet (n=35/group). For the final 6 week interval, CC and CF groups were returned to the control diet (CCC and CFC groups), while FC and FF groups were placed on a high-fat diet (FCF and FFF) (n=28/group). RESULTS: For the majority of metabolic outcomes changes aligned with dietary switches; however, assessment of neuropeptides and receptors involved in appetite regulation and reward signalling pathways reveal variable patterns of expression. Furthermore, we demonstrate that multiple cycling events leads to a significant increase in internal fat deposition, even when compared with animals maintained on a high-fat diet (internal fat: FCF: 7.4±0.2 g vs FFF: 5.6±0.2 g; P<0.01). CONCLUSIONS: Increased internal adipose tissue is strongly linked to the development of metabolic syndrome associated conditions such as type 2 diabetes, cardiovascular disease and hypertension. Although further work will be required to elucidate the mechanisms underlying the neuronal control of energy homoeostasis, these studies provide a causative link between weight cycling and adverse health.

Reprogramming of hepatic fat accumulation and 'browning' of adipose tissue by the short-chain fatty acid acetate.

BACKGROUND/OBJECTIVES: Short-chain fatty acids, produced by microbiome fermentation of carbohydrates, have been linked to a reduction in appetite, body weight and adiposity. However, determining the contribution of central and peripheral mechanisms to these effects has not been possible. SUBJECTS/METHODS: C57BL/6 mice fed with either normal or high-fat diet were treated with nanoparticle-delivered acetate, and the effects on metabolism were investigated. RESULTS: In the liver, acetate decreased lipid accumulation and improved hepatic function, as well as increasing mitochondrial efficiency. In white adipose tissue, it inhibited lipolysis and induced 'browning', increasing thermogenic capacity that led to a reduction in body adiposity. CONCLUSIONS: This study provides novel insights into the peripheral mechanism of action of acetate, independent of central action, including 'browning' and enhancement of hepatic mitochondrial function.

Influence of age, reproductive cycling status, and menstruation on the vaginal microbiome in baboons (Papio anubis).

The vaginal microbiome is believed to influence host health by providing protection from pathogens and influencing reproductive outcomes such as fertility and gestational length. In humans, age-associated declines in diversity of the vaginal microbiome occur in puberty and persist into adulthood. Additionally, menstruation has been associated with decreased microbial community stability. Adult female baboons, like other non-human primates (NHPs), have a different and highly diverse vaginal microbiome compared to that of humans, which is most commonly dominated by Lactobacillus spp. We evaluated the influence of age, reproductive cycling status (cycling vs. non-cycling) and menstruation on the vaginal microbiome of 38 wild-caught, captive female olive baboons (Papio anubis) by culture-independent sequencing of the V3-V5 region of the bacterial 16S rRNA gene. All baboons had highly diverse vaginal microbial communities. Adult baboons had significantly lower microbial diversity in comparison to subadult baboons, which was attributable to decreased relative abundance of minor taxa. No significant differences were detected based on cycling state or menstruation. Predictive metagenomic analysis showed uniformity in relative abundance of metabolic pathways regardless of age, cycle stage, or menstruation, indicating conservation of microbial community functions. This study suggests that selection of an optimal vaginal microbial community occurs at puberty. Since decreased diversity occurs in both baboons and humans at puberty, this may reflect a general strategy for selection of adult vaginal microbial communities. Comparative evaluation of vaginal microbial community development and composition may elucidate mechanisms of community formation and function that are conserved across host species or across microbial community types. These findings have implications for host health, evolutionary biology, and microbe-host ecosystems.

Sexual dimorphism in relation to adipose tissue and intrahepatocellular lipid deposition in early infancy.

Sexual dimorphism in adiposity is well described in adults, but the age at which differences first manifest is uncertain. Using a prospective cohort, we describe longitudinal changes in directly measured adiposity and intrahepatocellular lipid (IHCL) in relation to sex in healthy term infants. At median ages of 13 and 63 days, infants underwent quantification of adipose tissue depots by whole-body magnetic resonance imaging and measurement of IHCL by in vivo proton magnetic resonance spectroscopy. Longitudinal data were obtained from 70 infants (40 boys and 30 girls). In the neonatal period girls are more adipose in relation to body size than boys. At follow-up (median age 63 days), girls remained significantly more adipose. The greater relative adiposity that characterises girls is explained by more subcutaneous adipose tissue and this becomes increasingly apparent by follow-up. No significant sex differences were seen in IHCL. Sex-specific differences in infant adipose tissue distribution are in keeping with those described in later life, and suggest that sexual dimorphism in adiposity is established in early infancy.

Response of a seagrass fish assemblage to improved wastewater treatment.

We compared the structure of a seagrass fish assemblage near a sewage outlet before and after improvements to wastewater treatment. To determine whether responses by the fish assemblage were due to changes in water quality or to other factors, comparisons were made with the structure of a fish assemblage from a nearby site unaffected by sewage effluent. Total species richness, density and biomass of fish, decreased at both sites over the 30-year period. An increase in mean trophic level near the sewage outlet following improvements in water quality indicated that wastewater treatment had another important effect. This result is consistent with the reductions in food webs supporting pelagic and benthic fishes that typically accompany decreases in nutrient inputs. Although improvements to wastewater treatment explained much of the variation in the structure of the fish assemblage at PC, our results also suggest that fishing and climate change, at both sites.

The association between objectively measured sitting and standing with body composition: a pilot study using MRI.

OBJECTIVE: To investigate the association between objectively measured sitting and standing, using a postural allocation technique, with MRI-assessed body composition. DESIGN: The present study was a cross-sectional pilot study. SETTING: Participants were examined at one centre located in London, UK. PARTICIPANTS: Normal weight Caucasian women (30.9±6.1 years; body mass index (BMI), 22.9±3.4 kg/m(2)) with desk-bound occupations were recruited to minimise variability in body composition outcomes. A convenience sample of 12 women was recruited in January 2014 from University College London. OUTCOME MEASURES: For each participant a number of body composition variables were attained from a single whole-body MRI session. Main outcome variables included: total and liver adiposity, visceral/subcutaneous fat ratio and BMI. Main exposure variables included: average sitting time, standing:sitting ratio and step count. Pearson correlations were carried out to examine associations between different activity categories and body composition variables. RESULTS: There were significant correlations between average daily sitting and liver adiposity and visceral/subcutaneous abdominal fat ratio (r=0.66 and 0.64, respectively); standing:sitting ratio was moderately correlated with liver adiposity and visceral/subcutaneous abdominal fat ratio (r=-0.53 and -0.45); average daily step count was moderately correlated with liver adiposity, total adiposity and visceral/subcutaneous abdominal fat ratio (r=-0.45, -0.46 and -0.51, respectively). CONCLUSIONS: This pilot study has provided preliminary evidence of relationships between objectively measured sitting and standing and precise measures of body composition.

Efficacy of increased resistant starch consumption in human type 2 diabetes.

Resistant starch (RS) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome, but its effects on human type 2 diabetes (T2DM) are unknown. This study aimed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postprandial metabolites and body fat in T2DM. Seventeen individuals with well-controlled T2DM (HbA1c 46.6±2 mmol/mol) consumed, in a random order, either 40 g of type 2 RS (HAM-RS2) or a placebo, daily for 12 weeks with a 12-week washout period in between. AT THE END OF EACH INTERVENTION PERIOD, PARTICIPANTS ATTENDED FOR THREE METABOLIC INVESTIGATIONS: a two-step euglycemic-hyperinsulinemic clamp combined with an infusion of [6,6-(2)H2] glucose, a meal tolerance test (MTT) with arterio-venous sampling across the forearm, and whole-body imaging. HAM-RS2 resulted in significantly lower postprandial glucose concentrations (P=0.045) and a trend for greater glucose uptake across the forearm muscle (P=0.077); however, there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity, or on HbA1c. Fasting non-esterified fatty acid (NEFA) concentrations were significantly lower (P=0.004) and NEFA suppression was greater during the clamp with HAM-RS2 (P=0.001). Fasting triglyceride (TG) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 (P=0.039 and P=0.027 respectively). Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption (P=0.049), postprandial GLP1 excursions during the MTT were significantly greater (P=0.009). HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM, but demonstrated beneficial effects on meal handling, possibly due to higher postprandial GLP1.

Impact of a hormone-releasing intrauterine system on the vaginal microbiome: a prospective baboon model.

BACKGROUND: Use of a levonorgestrel-releasing intrauterine system (LNG-IUS) in humans may alter vaginal microbial populations and susceptibility to pathogens. This study evaluated the time-dependent effects of an LNG-IUS on the vaginal microbiome of the baboon, a useful animal model for reproductive studies. METHODS: Levonorgestrel-releasing intrauterine systems were inserted into three reproductively mature, female baboons. The animals were evaluated for 6 months by physical examination and Gram-stained cytology. The vaginal microbiota was characterized at each timepoint by culture-independent analysis of the 16S rRNA-encoding gene. RESULTS: Each baboon harbored a diverse vaginal microbiome. Interindividual variation exceeded intra-individual variation. Diversity declined over time in one baboon and showed mild fluctuations in the other two. There were no significant community differences from early to late post-LNG-IUS placement. CONCLUSIONS: The baboon vaginal microbiome is unique to each individual and is polymicrobial. In this pilot study, the vaginal microbiome remained stable from early to late post-LNG-IUS placement.

Whole body fat: content and distribution.

Obesity and its co-morbidities, including type II diabetes, insulin resistance and cardiovascular diseases, have become one of the biggest health issues of present times. The impact of obesity goes well beyond the individual and is so far-reaching that, if it continues unabated, it will cause havoc with the economies of most countries. In order to be able to fully understand the relationship between increased adiposity (obesity) and its co-morbidity, it has been necessary to develop proper methodology to accurately and reproducibly determine both body fat content and distribution, including ectopic fat depots. Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) have recently emerged as the gold-standard for accomplishing this task. Here, we will review the use of different MRI techniques currently being used to determine body fat content and distribution. We also discuss the pros and cons of MRS to determine ectopic fat depots in liver, muscle, pancreas and heart and compare these to emerging MRI techniques currently being put forward to create ectopic fat maps. Finally, we will discuss how MRI/MRS techniques are helping in changing the perception of what is healthy and what is normal and desirable body-fat content and distribution.

A history of previous gestational diabetes mellitus is associated with adverse changes in insulin secretion and VLDL metabolism independently of increased intrahepatocellular lipid.

AIMS/HYPOTHESIS: We have previously reported a high prevalence of non-alcoholic fatty liver disease (NAFLD) among women with previous gestational diabetes mellitus (pGDM). We wanted to confirm that intrahepatocellular lipid (IHCL) is associated with pGDM independently of adiposity and determine: (1) if VLDL metabolism is dysregulated; and (2) the extent to which NAFLD and IHCL account for the dysmetabolic phenotype in pGDM. METHODS: We analysed data from a cohort of 234 women (114 with pGDM) and identified effects of pGDM on lipid and glucoregulation that were independent of ultrasound-diagnosed NAFLD. We then measured IHCL by MR spectroscopy in a representative subgroup (n = 36) and conducted detailed metabolic studies (IVGTT, VLDL apolipoprotein B [apoB] kinetics and palmitate turnover) and measurement of regional body fat by MRI to demonstrate effects of IHCL that were independent of a history of pGDM. RESULTS: pGDM was associated with increased IHCL (p = 0.04) after adjustment for adiposity. Independently of IHCL, pGDM was associated with a lower IVGTT disposition index (p = 0.02) and acute insulin response to glucose (pGDM+/NAFLD-, 50% lower; pGDM+/NAFLD+, 36% lower; effect of pGDM, p = 0.03), increased VLDL apoB pool size (pGDM+/NAFLD-, 3.1-fold higher; pGDM+/NAFLD+, 1.2-fold higher; effect of pGDM, p = 0.02) and, at borderline significance (p = 0.05), increased rate of VLDL apoB synthesis. CONCLUSIONS/INTERPRETATION: pGDM is associated with increased IHCL independently of adiposity. The increased liver fat contributes to the phenotype, but pGDM status is independently associated with diminished insulin secretion and (shown for the first time) augmented VLDL metabolism. IHCL with pGDM may compound a dysmetabolic phenotype.

Early nutritional determinants of intrahepatocellular lipid deposition in preterm infants at term age.

BACKGROUND: We have previously shown that by term age, preterm infants have elevated intrahepatocellular lipid (IHCL) content and altered regional adiposity, both of which are risk factors for cardiometabolic illness in adult life. Preterm nutritional intake is a plausible determinant of these aberrant trajectories of development. OBJECTIVE: We aimed to establish if macronutritional components of the preterm diet were determinants of IHCL deposition measured at term equivalent age, using (1)H Magnetic Resonance spectroscopy (MRS). METHODS: Prospective observational case-control study in a single UK neonatal unit. (1)H MR spectra were acquired from 18 preterm infants (<32 weeks gestational age at birth) at term age and 31 healthy term infants, who acted as a control group. Neonatal nutritional information was collected from birth to 34(+6) weeks postmenstrual age. RESULTS: IHCL (median, interquartile range) was significantly higher in preterm-at-term infants compared with term-born infants: 0.735, 0-1.46 versus 0.138, 0-0.58; P=0.003. In preterm infants, IHCL was positively correlated with lipid intake in the first week of life (r=0.52, P=0.04). CONCLUSIONS: This study confirms our previous observation of elevated IHCL in preterm infants at term and suggests that early lipid intake may be a determinant. Future work is warranted to establish the clinical relevance and the role of nutritional intervention in attenuating or exacerbating this effect in preterm infants.

Novel genital alphapapillomaviruses in baboons (Papio hamadryas anubis) with cervical dysplasia.

Genital Alphapapillomavirus (αPV) infections are one of the most common sexually transmitted human infections worldwide. Women infected with the highly oncogenic genital human papillomavirus (HPV) types 16 and 18 are at high risk for development of cervical cancer. Related oncogenic αPVs exist in rhesus and cynomolgus macaques. Here the authors identified 3 novel genital αPV types (PhPV1, PhPV2, PhPV3) by PCR in cervical samples from 6 of 15 (40%) wild-caught female Kenyan olive baboons (Papio hamadryas anubis). Eleven baboons had koilocytes in the cervix and vagina. Three baboons had dysplastic proliferative changes consistent with cervical squamous intraepithelial neoplasia (CIN). In 2 baboons with PCR-confirmed PhPV1, 1 had moderate (CIN2, n = 1) and 1 had low-grade (CIN1, n = 1) dysplasia. In 2 baboons with PCR-confirmed PhPV2, 1 had low-grade (CIN1, n = 1) dysplasia and the other had only koilocytes. Two baboons with PCR-confirmed PhPV3 had koilocytes only. PhPV1 and PhPV2 were closely related to oncogenic macaque and human αPVs. These findings suggest that αPV-infected baboons may be useful animal models for the pathogenesis, treatment, and prophylaxis of genital αPV neoplasia. Additionally, this discovery suggests that genital αPVs with oncogenic potential may infect a wider spectrum of non-human primate species than previously thought.

Adiposity in children and adolescents: correlates and clinical consequences of fat stored in specific body depots.

The 2011 Pennington Biomedical Research Center's Scientific Symposium focused on adiposity in children and adolescents. The symposium was attended by 15 speakers and other invited experts. The specific objectives of the symposium were to (i) integrate the latest published and unpublished findings on the laboratory and clinical assessment of depot-specific adiposity in children and adolescents, (ii) understand the variation in depot-specific adiposity and related health outcomes associated with age, sex, maturation, ethnicity and other factors and (iii) identify opportunities for incorporating new markers of abdominal obesity into clinical practice guidelines for obesity in children and adolescents. This symposium provided an overview of important new advances in the field and identified directions for future research. The long-term goal of the symposium is to aid in the early identification of children and adolescents who are at increased health risk because of obesity and obesity-related conditions.