Over-the-counter (OTC) drugs are ubiquitous in the US. Policymakers have long debated how to modernize the system for making determinations of safety and effectiveness and addressing safety issues with OTC drugs.

Detecting gastrointestinal (GI) infection transmission among men who have sex with men (MSM) in England is complicated by a lack of routine sexual behavioural data. We investigated whether gender distributions might generate signals for increased transmission of GI pathogens among MSM. We examined the percentage male of laboratory-confirmed patient-episodes for patients with no known travel history for 10 GI infections of public health interest in England between 2003 and 2013, stratified by age and region. An adult male excess was observed for Shigella spp. (annual maximum 71% male); most pronounced for those aged 25–49 years and living in London, Brighton and Manchester. An adult male excess was observed every year for Entamoeba histolytica (range 59.8–76.1% male), Giardia (53.1–57.6%) and Campylobacter (52.1–53.5%) and for a minority of years for hepatitis A (max. 69.8%) and typhoidal salmonella (max. 65.7%). This approach generated a signal for excess male episodes for six GI pathogens, including a characterised outbreak of Shigella among MSM. Stratified analyses by geography and age group were consistent with MSM transmission for Shigella. Optimisation and routine application of this technique by public health authorities elsewhere might help identify potential GI infection outbreaks due to sexual transmission among MSM, for further investigation.

The evidence underpinning the developmental origins of health and disease (DOHaD) is overwhelming. As the emphasis shifts more towards interventions and the translational strategies for disease prevention, it is important to capitalize on collaboration and knowledge sharing to maximize opportunities for discovery and replication. DOHaD meetings are facilitating this interaction. However, strategies to perpetuate focussed discussions and collaborations around and between conferences are more likely to facilitate the development of DOHaD research. For this reason, the DOHaD Society of Australia and New Zealand (DOHaD ANZ) has initiated themed Working Groups, which convened at the 2014–2015 conferences. This report introduces the DOHaD ANZ Working Groups and summarizes their plans and activities. One of the first Working Groups to form was the ActEarly birth cohort group, which is moving towards more translational goals. Reflecting growing emphasis on the impact of early life biodiversity – even before birth – we also have a Working Group titled Infection, inflammation and the microbiome. We have several Working Groups exploring other major non-cancerous disease outcomes over the lifespan, including Brain, behaviour and development and Obesity, cardiovascular and metabolic health. The Epigenetics and Animal Models Working Groups cut across all these areas and seeks to ensure interaction between researchers. Finally, we have a group focussed on ‘Translation, policy and communication’ which focusses on how we can best take the evidence we produce into the community to effect change. By coordinating and perpetuating DOHaD discussions in this way we aim to enhance DOHaD research in our region.

We have undertaken a study of the 3-D spatial distribution of the older (τ ≥ 1–2 Gyr) stellar population lying beyond ~ 2 kpc in projected radial distance from the centre of the SMC. The study will eventually cover 120 square degrees including six overlapping Schmidt fields. Here we present the results from an area of 80 square degrees including the western, northern and north-eastern outer parts of the SMC.

The Western diet is typically high in salt and fructose, which have pressor activity. Maternal diet can affect offspring blood pressure, but the extent to which maternal intake of excess salt and fructose may influence cardiovascular function of the offspring is unknown. We sought to determine the effect of moderate maternal dietary intake of salt and/or fructose on resting and stimulated cardiovascular function of the adult male and female offspring. Pregnant rats were fed purified diets (±4 % salt) and water (±10 % fructose) before and during gestation and through lactation. Male and female offspring were weaned onto standard laboratory chow. From 9 to 14 weeks of age, cardiovascular parameters (basal, circadian and stimulated) were assessed continuously by radiotelemetry. Maternal salt intake rendered opposite-sex siblings with a 25-mmHg difference in blood pressure as adults; male offspring were hypertensive (15 mmHg mean arterial pressure (MAP)) and female offspring were hypotensive (10 mmHg MAP) above and below controls, respectively. Sex differences were unrelated to endothelial nitric oxide activity in vivo, but isolation-induced anxiety revealed a significantly steeper coupling between blood pressure and heart rate in salt-exposed male offspring but not in female offspring. MAP of all offspring was refractory to salt loading but sensitive to subsequent dietary fructose, an effect exacerbated in female offspring from fructose-fed dams. Circadian analyses of pressure in all offspring revealed higher mean set-point for heart rate and relative non-dipping of nocturnal pressure. In conclusion, increased salt and fructose in the maternal diet has lasting effects on offspring cardiovascular function that is sex-dependent and related to the offspring’s stress–response axis.

We present a systematic review providing estimates of the overall and regional burden of infectious complications following prostate biopsy. A directly standardized prevalence estimate was used because it reflects the burden of disease more explicitly. Complications included sepsis, hospitalization, bacteraemia, bacteriuria, and acute urinary retention after biopsy. There were 165 articles, comprising 162 577 patients, included in the final analysis. Our findings demonstrate that transrectal biopsy was associated with a higher burden of hospitalization (1·1% vs. 0·9%) and sepsis (0·8% vs. 0·1%) compared to transperineal biopsy, while acute urinary retention was more prevalent after transperineal than transrectal biopsy (4·2% vs. 0·9%). The differences were statistically non-significant because of large heterogeneity across countries. We also demonstrate and discuss regional variations in complication rates, with Asian studies reporting higher rates of sepsis and hospitalization.

Drugs that kill or inhibit the sexual stages of Plasmodium in order to prevent transmission are important components of malaria control programmes. Reducing gametocyte carriage is central to the control of Plasmodium falciparum transmission as infection can result in extended periods of gametocytaemia. Unfortunately the number of drugs with activity against gametocytes is limited. Primaquine is currently the only licensed drug with activity against the sexual stages of malaria parasites and its use is hampered by safety concerns. This shortcoming is likely the result of the technical challenges associated with gametocyte studies together with the focus of previous drug discovery campaigns on asexual parasite stages. However recent emphasis on malaria eradication has resulted in an upsurge of interest in identifying compounds with activity against gametocytes. This review examines the gametocytocidal properties of currently available drugs as well as those in the development pipeline and examines the prospects for discovery of new anti-gametocyte compounds.

We assessed vascular programming in genetically identical monochorionic twin pairs with twin-to-twin transfusion syndrome (TTTS) treated differently in utero by serial amnioreduction or fetal laser arterial photocoagulation. This case–control study re-assessed four twin groups at median 11 years comprising 20 pairs of monochorionic diamniotic twins: nine treated by amnioreduction (TTTS-amnio) and eleven by laser (TTTS-laser) with seven monochorionic and six dichorionic control pairs. Outcome measures were current blood pressure (BP), brachio-radial arterial stiffness derived from pulse wave velocity (PWV), resting microcirculation (Flux) and response to heating and post-occlusive reactive hyperaemia measured using laser Doppler. Potential confounders [PWV and BP at first study, current height, weight, heart rate and twin type (ex-recipient, ex-donor or heavier/lighter of pair)] were accounted for by Mixed Linear Models statistical methodology. PWV dichorionic > monochorionic (P = 0.024); systolic and diastolic BP dichorionic > TTTS-amnio and TTTS-laser (P = 0.004, P = 0.02 and P = 0.005, P = 0.02, respectively). Within-twin pair pattern of PWV discordance was similar in laser treated and dichorionic controls (heavier-born > lighter), opposite to TTTS-amnio and monochorionic controls. Flux monochorionic > dichorionic (P = 0.044) and heavier > lighter-born (P = 0.024). TTTS-laser and dichorionic diamniotic showed greatest hyperaemic responses (dichorionic > TTTS-amnio or monochorionic controls (P = 0.007, P = 0.025). Hyperaemic responses were slower in heavier-born twins (P = 0.005). In summary, monochorionic twins had lower BP, arterial stiffness and increased resting vasodilatation than dichorionic twins implying shared fetal circulation affects vascular development. Vascular responses in laser-TTTS were similar to dichorionic and opposite to TTTS-amnio suggesting a lasting effect of fetal therapy on vascular health.

A total of 72 male weaned pigs were used in a 110-day study to investigate the effect of feeding genetically modified (GM) Bt MON810 maize on selected growth and health indicators. It was hypothesised that in pigs fed Bt maize, growth and health are not impacted compared with pigs fed isogenic maize-based diets. Following a 12-day basal period, pigs (10.7 ± 1.9 kg body weight (BW); ∼40 days old) were blocked by weight and ancestry and randomly assigned to treatments: (1) non-GM maize diet for 110 days (non-GM), (2) GM maize diet for 110 days (GM), (3) non-GM maize diet for 30 days followed by GM maize diet up to day 110 (non-GM/GM) and (4) GM maize diet for 30 days followed by non-GM maize diet up to day 110 (GM/non-GM). BW and daily feed intake were recorded on days 0, 30, 60 and 110 (n = 15). Body composition was determined by dual energy X-ray absorptiometry (n = 10) on day 80. Following slaughter on day 110, organs and intestines were weighed and sampled for histological analysis and urine was collected for biochemical analysis (n = 10). Serum biochemistry analysis was performed on days 0, 30, 60, 100 and 110. Growth performance and serum biochemistry were analysed as repeated measures with time and treatment as main factors. The slice option of SAS was used to determine treatment differences at individual time points. There was no effect of feeding GM maize on overall growth, body composition, organ and intestinal weight and histology or serum biochemistry on days 60 and 100 and on urine biochemistry on day 110. A treatment × time interaction was observed for serum urea (SU; P < 0.05), creatinine (SC; P < 0.05) and aspartate aminotransferase (AST; P < 0.05). On day 30, SU was lower for the non-GM/GM treatment compared with the non-GM, GM and GM/non-GM treatments (P < 0.05). On day 110, SC was higher for the non-GM/GM and GM/non-GM treatments compared with non-GM and GM treatments (P < 0.05). Overall, serum total protein was lower for the GM/non-GM treatment compared with the non-GM/GM treatment (P < 0.05). The magnitude of change observed in some serum biochemical parameters did not indicate organ dysfunction and the changes were not accompanied by histological lesions. Long-term feeding of GM maize to pigs did not adversely affect growth or the selected health indicators investigated.

An appropriate foetal cardiovascular (CV) response to reduced substrate supply (e.g. oxygen or other nutrients) is vital for growth and development, and may impact on CV control. The prevailing nutritional environment and associated CV changes may influence subsequent CV responses to challenges during late gestation, for example, umbilical cord occlusion (UCO). We investigated the effect of low-circulating glucose on foetal CV control mechanisms and response to UCO. Under general anaesthesia, late gestation foetal sheep (n = 7, 119 days gestational age (dGA), term ∼147 days) were implanted with vascular catheters, a bladder catheter, electrocardiogram electrodes and an umbilical cord occluder. Mean arterial pressure (MAP), heart rate (HR) and kidney function were monitored during maternal saline (MSAL, 125dGA) and insulin (MINS, 126dGA) infusion, and foetal CV responses were assessed during incremental doses of angiotensin II, a 90-s total UCO, and administration of phenylephrine to assess baroreflex function. During MINS infusion, the decrease in maternal and foetal blood glucose was associated with a small but significant decrease in foetal HR and reduced foetal baroreflex sensitivity (P < 0.05). The increase in foetal MAP during a 90-s UCO was greater during hypoglycaemia (P < 0.05). The MAP response to angiotensin II was not affected by hypoglycaemia. Decreased foetal HR and baroreflex sensitivity and increased CV responsiveness to UCO during hypoglycaemia indicates altered CV homoestatic mechanisms. The combination of altered nutrition and a CV challenge, such as UCO, during late gestation may have a cumulative effect on foetal CV function.

An improved technique for small-scale rearing of Rhodnius prolixus Stal on rabbits is described. For feeding, the bugs are presented in tubes closed with silk to the shaved stomachs of rabbits; between feeds the bugs are held in 1-lb glass jarsat 28°C. Large-scale rearing by this method was precluded by the amount of handling required. Feeding on defibrinated blood resulted in a survival rate to the adult stage of less than 10%, but sheep on which up to 6 600 fourth instar could be fed weekly proved satisfactory hosts, although they had to be replaced after 1–9 weeks as they developed a resistance which prevented the bugs feeding. A large-scale rearing technique is described in which instars 2–5 are presented to sheep in wire cages covered with nylon netting while instar 1 and adults are fed on rabbits; between feeds the bugs are housed in 3½–7-lb glass jars or in net-covered cages. A production of 4 000 fed fourth instar or larger bugs per week for 18 months was achieved, sometimes reaching 7 000 per week.

A case of acute schizophrenic psychosis developing during the treatment of hyper-thyroidism with carbimazole is described. The patient was clinically and biochemically euthyroid at the time the psychosis developed. It is suggested that an acute alteration in thyroid status, without necessarily producing hyper- or hypothyroidism, may be sufficient to induce a psychotic reaction.

Coated metacyclics of Trypanosoma vivax exist in the hypopharynges of infected tsetse flies and are extruded in low numbers when the flies are induced to probe onto warm slides or into medium. After extensive searching of T. vivax-infected proboscides, and resort to a process for the examination of single, extruded, metacyclic trypanosomes, electron micro scopic evidence is presented that, contrary to an earlier report, metacyclic T. vivaxacquire a surface coat before contact with the mammalian host. Since T. vivax exhibits antigenic variation, the role of the surface coat in this species is likely to be functionally equivalent to the surface coat of the other tsetse-transmitted trypanosome species, T. brucei and T. congolense.

To determine if, as is the case with Trypanosoma brucei and T. congolense, serodemes of T. vivax could be distinguished on the basis of immunity to the metacyclic stages of the parasite, attempts were made to immunize goats by infection with infected tsetse, followed by chemotherapy or eventual ‘self-cure’. Thirty goats were infected by tsetse with either clones or stocks of T. vivax from East or West Africa. Twenty-four goats were treated with diminazene aceturate (Berenil, Hoechst A.G.) 2–6 weeks after infection and 6 goats were allowed to self-cure. Infection, followed by treatment, induced immunity to a first homologous challenge by infected tsetse in only 2 of 24 goats (one immune to the East African stock, and the other to a clone of the West African stock). Immunity to a clone of the East African stock was induced in 3 or 4 animals after a second infection and treatment and in the fourth animal of the group following a third infection and treatment. One of 2 goats infected with the clone of the East African stock was immune to challenge at 16 weeks, following self-cure without treatment, and 1 of 4 goats infected with the parent stock was similarly immune when challenged at 40 weeks post-infection. Goats susceptible to infection with East African T. vivax showed evidence of partial immunity by delayed pre-patent periods and depressed parasitaemias after challenge. Goats infected with the relatively more virulent West African T. vivax were, however, completely susceptible to infection after homologous challenge, and showed only a slight delay in pre-patent period. A similar result was obtained in a further 8 goats primed and challenged by large numbers of tsetse (20 or 100 infected tsetse/goat) with the West African T. vivax. In further experiments using a very short treatment interval, infections following challenge were clearly shown to be the result of a lack of immunity rather than relapse following treatment. Lytic antibody activity to cultured metacyclic trypanosomes could not be detected during infection but such activity against bloodstream forms was detected after 2 weeks of infection. It is suggested that the primary reason for the erratic induction of immunity to T. vivax employing this methodology is the low number of metacyclics transmitted by infected tsetse, and thus poor antigenic stimulus encountered by goats upon tsetse challenge.

Antigenic variation in the ILDar 1 serodeme of the naturally rodent-infective stock of West African Trypanosoma vivax has been investigated following cyclical transmission. The immunofluorescent and immune lysis tests were employed with a panel of 39 variant-specific mouse antisera. When antigenically homogeneous, or mixed, populations were transmitted by tsetse flies to goats, the first peak parasitaemias arising in the goats were antigenic mixtures (up to 9 major, and several minor variants being recognized in some cases) from which the ingested variant was absent. Although first peak parasitaemias in similarly infected goats showed some variants in common, there was no obvious relationship between the VAT profiles in different goats. When these populations were expanded in irradiated mice, VAT heterogeneity was maintained with a tendency towards the development of predominant variants in some, but not all, instances. Six additional variants, derived following the growth of bloodstream form ILDat 1·9 in 37°C culture, were also represented in goat and mouse populations. Two further variants, isolated after cyclical development of ILDat 1·9-derived trypanosomes in vitro, were not present in the early parasitaemias in goats and mice.