The aetiology of obesity has been attributed to several factors (environmental, dietary, lifestyle, host, and genetic factors); however none of these fully explain the increase in the prevalence of obesity worldwide. Gut microbiota located at the interface of host and environment in the gut are a new area of research being explored to explain the excess accumulation of energy in obese individuals and may be a potential target for therapeutic manipulation to reduce host energy storage. Several mechanisms have been suggested to explain the role of gut microbiota in the aetiology of obesity such as short chain fatty acid production, stimulation of hormones, chronic low-grade inflammation, lipoprotein and bile acid metabolism, and increased endocannabinoid receptor system tone. However, evidence from animal and human studies clearly indicates controversies in determining the cause or effect relationship between the gut microbiota and obesity. Metagenomics based studies indicate that functionality rather than the composition of gut microbiota may be important. Further mechanistic studies controlling for environmental and epigenetic factors are therefore required to help unravel obesity pathogenesis.

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IntroductionDietary zinc (Zn) deficiency is a global problem, particularly in low-income and middle-income countries where access to rich, animal-source foods of Zn is limited due to poverty. In Pakistan, Zn deficiency affects over 40% of the adult female population, resulting in suboptimal immune status and increased likelihood of complications during pregnancy.Methods and analysisWe are conducting a double-blind, randomised controlled feeding study with cross-over design in a low-resource setting in Pakistan. Households were provided with flour milled from genetically and agronomically biofortified grain (Zincol-2016/NR-421) or control grain (Galaxy-2013). Fifty households were recruited. Each household included a woman aged 16–49 years who is neither pregnant nor breastfeeding, and not currently consuming nutritional supplements. These women were the primary study participants. All households were provided with control flour for an initial 2-week baseline period, followed by an 8-week intervention period where 25 households receive biofortified flour (group A) and 25 households receive control flour (group B). After this 8-week period, groups A and B crossed over, receiving control and biofortified flour respectively for 8 weeks. Tissue (blood, hair and nails) have been collected from the women at five time points: baseline, middle and end of period 1, and middle and end of period 2.Ethics and disseminationEthical approval was granted from the lead university (reference no. STEMH 697 FR) and the collaborating institution in Pakistan. The final study methods (including any modifications) will be published in peer-reviewed journals, alongside the study outcomes on completion of the data analysis. In addition, findings will be disseminated to the scientific community via conference presentations and abstracts and communicated to the study participants through the village elders at an appropriate community forum.Registration detailsThe trial has been registered with the ISRCTN registry, study ID ISRCTN83678069.

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IntroductionMicronutrient deficiencies, commonly referred to as ‘hidden hunger’, affect more than two billion people worldwide, with zinc and iron-deficiency frequently reported. The aim of this study is to examine the impact of consuming zinc biofortified flour (Zincol-2016) on biochemical and functional measures of status in adolescent girls and children living in a low-resource setting in Pakistan.Methods and analysisWe are conducting a pragmatic, cluster-randomised, double-blind, controlled trial. A total of 482 households have been recruited from two catchment areas approximately 30–40 km distance from Peshawar. Household inclusion criteria are the presence of both an adolescent girl, aged 10–16 years, and a child aged 1–5 years. The study duration is 12 months, divided into two 6-month phases. During phase 1, all households will be provided with locally procured flour from standard varieties of wheat. During phase 2, clusters will be paired, and randomised to either the control or intervention arm of the study. The intervention arm will be provided with zinc biofortified wheat flour, with a target zinc concentration of 40 mg/kg. The control arm will be provided with locally procured wheat flour from standard varieties with an expected zinc concentration of 20 mg/kg. The primary outcome measure is plasma zinc concentration. Secondary outcomes include anthropometric measurements, biomarkers of iron and zinc status, and the presence and duration of respiratory tract infections and diarrhoea.Ethics and disseminationEthical approval was granted from the University of Central Lancashire STEMH Ethics Committee (reference number: STEMH 1014) and Khyber Medical University Ethics Committee (DIR/KMU-EB/BZ/000683). The final study methods will be published in peer-reviewed journals, alongside the study outcomes. In addition, findings will be disseminated to the scientific community via conference presentations and abstracts and communicated to the study participants through the village elders at an appropriate community forum.Trial registration numberISRCTN17107812; Pre-results.

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Consuming a diverse diet is essential to ensure an adequate intake of micronutrients. The aim of this study was to assess the nutritional status and dietary diversity of women of reproductive age (WRA) living in a marginalized community in rural Pakistan. Forty-seven WRA (35 ± 7 years old) who were not pregnant or lactating at enrollment, were recruited to participate in the study. Twenty-four-hour dietary recall interviews were conducted by the study nutritionist, and the data collected were used to create a minimum dietary diversity for women score (MDD-W) on five occasions during the monsoon and winter seasons (October to February). Nutritional status was assessed using anthropometry and biochemical markers of micronutrient status. Height and weight were used to determine body mass index (BMI), and mid-upper-arm circumference was measured. Plasma zinc, iron, and selenium concentrations were measured using inductively coupled mass spectrometry, and iron status was assessed using serum ferritin and blood hemoglobin concentrations. The mean (±SD) food group diversity score was 4 ± 1 with between 26% and 41% of participants achieving an MDD-W of 5. BMI was 27.2 ± 5.5 kg/m2 with 28% obese, 34% overweight, and 6% underweight. The prevalence of zinc deficiency, based on plasma zinc concentration, was 29.8%; 17% of the participants had low plasma selenium levels; 8.5% were iron deficient; and 2% were suffering from iron deficiency anemia. The findings indicate that the women living in this community consume a diet that has a low diversity, consistent with a diet low in micronutrients, and that zinc deficiency is prevalent. Public health interventions aimed at increasing the dietary diversity of WRA are needed to improve the micronutrient intake, particularly of zinc, in this population.

This study investigated the effects of a range of pharmaceutical drugs with ion channel-blocking activity on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the blockade of the I(Kr)/hERG channel, that is highly important for the normal functioning of the embryonic rat heart, would cause bradycardia and arrhythmia. Concomitant blockade of other channels was expected to modify the effects of hERG blockade. Fourteen drugs with varying degrees of specificity and affinity toward potassium, sodium, and calcium channels were tested over a range of concentrations. The rat embryos were maintained for 2 hr in culture, 1 hr to acclimatize, and 1 hr to test the effect of the drug. All the drugs caused a concentration-dependent bradycardia except nifedipine, which primarily caused a negative inotropic effect eventually stopping the heart. A number of drugs induced arrhythmias and these appeared to be related to either sodium channel blockade, which resulted in a double atrial beat for each ventricular beat, or I(Kr)/hERG blockade, which caused irregular atrial and ventricular beats. However, it is difficult to make a precise prediction of the effect of a drug on the embryonic heart just by looking at the polypharmacological action on ion channels. The results indicate that the use of the tested drugs during pregnancy could potentially damage the embryo by causing periods of hypoxia. In general, the effects on the embryonic heart were only seen at concentrations greater than those likely to occur with normal therapeutic dosing.