The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation

Football fans in training: the development and optimization of an intervention delivered through professional sports clubs to help men lose weight, become more active and adopt healthier eating habits

<p>Background: The prevalence of obesity in men is rising, but they are less likely than women to engage in existing weight management programmes. The potential of professional sports club settings to engage men in health promotion activities is being increasingly recognised. This paper describes the development and optimization of the Football Fans in Training (FFIT) programme, which aims to help overweight men (many of them football supporters) lose weight through becoming more active and adopting healthier eating habits.</p> <p>Methods: The MRC Framework for the design and evaluation of complex interventions was used to guide programme development in two phases. In Phase 1, a multidisciplinary working group developed the pilot programme (p-FFIT) and used a scoping review to summarize previous research and identify the target population. Phase 2 involved a process evaluation of p-FFIT in 11 Scottish Premier League (SPL) clubs. Participant and coach feedback, focus group discussions and interviews explored the utility/acceptability of programme components and suggestions for changes. Programme session observations identified examples of good practice and problems/issues with delivery. Together, these findings informed redevelopment of the optimized programme (FFIT), whose components were mapped onto specific behaviour change techniques using an evidence-based taxonomy.</p> <p>Results: p-FFIT comprised 12, weekly, gender-sensitised, group-based weight management classroom and ‘pitch-side’ physical activity sessions. These in-stadia sessions were complemented by an incremental, pedometer-based walking programme. p-FFIT was targeted at men aged 35-65 years with body mass index ≥ 27 kg/m2. Phase 2 demonstrated that participants in p-FFIT were enthusiastic about both the classroom and physical activity components, and valued the camaraderie and peer-support offered by the programme. Coaches appreciated the simplicity of the key healthy eating and physical activity messages. Suggestions for improvements that were incorporated into the optimized FFIT programme included: more varied in-stadia physical activity with football-related components; post-programme weight management support (emails and a reunion session); and additional training for coaches in SMART goal setting and the pedometer-based walking programme.</p> <p>Conclusions: The Football Fans in Training programme is highly acceptable to participants and SPL coaches, and is appropriate for evaluation in a randomised controlled trial.</p&gt

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators

Entomological Surveillance of Behavioural Resilience and Resistance in Residual Malaria Vector Populations.

The most potent malaria vectors rely heavily upon human blood so they are vulnerable to attack with insecticide-treated nets (ITNs) and indoor residual spraying (IRS) within houses. Mosquito taxa that can avoid feeding or resting indoors, or by obtaining blood from animals, mediate a growing proportion of the dwindling transmission that persists as ITNs and IRS are scaled up. Increasing frequency of behavioural evasion traits within persisting residual vector systems usually reflect the successful suppression of the most potent and vulnerable vector taxa by IRS or ITNs, rather than their failure. Many of the commonly observed changes in mosquito behavioural patterns following intervention scale-up may well be explained by modified taxonomic composition and expression of phenotypically plastic behavioural preferences, rather than altered innate preferences of individuals or populations. Detailed review of the contemporary evidence base does not yet provide any clear-cut example of true behavioural resistance and is, therefore, consistent with the hypothesis presented. Caution should be exercised before over-interpreting most existing reports of increased frequency of behavioural traits which enable mosquitoes to evade fatal contact with insecticides: this may simply be the result of suppressing the most behaviourally vulnerable of the vector taxa that constituted the original transmission system. Mosquito taxa which have always exhibited such evasive traits may be more accurately described as behaviourally resilient, rather than resistant. Ongoing national or regional entomological monitoring surveys of physiological susceptibility to insecticides should be supplemented with biologically and epidemiologically meaningfully estimates of malaria vector population dynamics and the behavioural phenotypes that determine intervention impact, in order to design, select, evaluate and optimize the implementation of vector control measures

Longitudinal analysis of vertebral fracture and BMD in a Canadian cohort of adult cystic fibrosis patients

<p>Abstract</p> <p>Background</p> <p>Vertebral fractures in patients with cystic fibrosis (CF) may contribute to an accelerated decline in lung function and can be a contraindication to lung transplantation. In this study, we examined longitudinal change in bone mineral density (BMD) and the prevalence of vertebral fractures in adult CF patients, without lung-transplant, attending a Canadian specialty clinic.</p> <p>Methods</p> <p>Retrospective chart review of all patients attending an Adult Cystic Fibrosis Clinic at Hamilton Health Sciences in Hamilton, Canada. Forty-nine of 56 adults met inclusion criteria. Chest radiographs were graded by consensus approach using Genant's semi-quantitative method to identify and grade fractured vertebrae. Dual x-ray absorptiometry (DXA) scans were also reviewed.</p> <p>Results</p> <p>The mean age of the cohort was 25.2 years (SD 9.4), 43% were male. The mean body mass index (BMI) was 19.8 (2.8) for males and 21.7 (5.1) for females. At baseline, the rate of at least one vertebral fracture was 16.3%; rising to 21.3% (prevalent and incident) after a 3-year follow-up. The mean BMD T-or Z-scores at baseline were -0.80 (SD 1.1) at the lumbar spine, -0.57 (SD 0.97) at the proximal femur, and -0.71 (SD 1.1) at the whole body. Over approximately 4-years, the mean percent change in BMD was -1.93% at the proximal femur and -0.73% at the lumbar spine.</p> <p>Conclusion</p> <p>Approximately one in five CF patients demonstrated at least one or more vertebral fractures. Moderate declines in BMD were observed. Given the high rate of vertebral fractures noted in this cohort of adult CF patients, and the negative impact they have on compromised lung functioning, regular screening for vertebral fractures should be considered on routine chest radiographs.</p

Nutrition aspects in children receiving maintenance hemodialysis: impact on outcome

Children with end-stage renal disease (ESRD) have rates of mortality estimated to be 30-times higher than expected for age compared with those of healthy children. Physical manifestations of under-nutrition, such as body mass index (BMI) and low height standard deviation score (SDS), have been associated with increased risk of mortality. Traditional measures, such as height, weight and serum albumin concentration, may not be accurate indicators to assess the nutritional status of children receiving maintenance hemodialysis. Normalized protein catabolic rate (nPCR) has emerged as a better marker of nutritional status of such children. Meeting the special nutritional needs of these children often requires nutritional supplementation, by either the enteral or the parenteral route. Recently, in children receiving maintenance hemodialysis who are malnourished, intradialytic parenteral nutrition (IDPN) has been utilized as a means to provide additional protein and calories. This article is a state-of-the-art review of malnutrition in children receiving maintenance hemodialysis, with special focus on outcome, nPCR and IDPN

Effect of Longâ Term Oral Bisphosphonates on Implant Wound Healing: Literature Review and a Case Report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141603/1/jper0584.pd

Evaluation of antibody response to Plasmodium falciparum in children according to exposure of Anopheles gambiae s.l or Anopheles funestus vectors

<p>Abstract</p> <p>Background</p> <p>In sub-Saharan areas, malaria transmission was mainly ensured by <it>Anopheles. gambiae </it>s.l. and <it>Anopheles. funestus </it>vectors. The immune response status to <it>Plasmodium falciparum </it>was evaluated in children living in two villages where malaria transmission was ensured by dissimilar species of <it>Anopheles </it>vectors (<it>An. funestus vs An. gambiae </it>s.l.).</p> <p>Methods</p> <p>A multi-disciplinary study was performed in villages located in Northern Senegal. Two villages were selected: Mboula village where transmission is strictly ensured by <it>An. gambiae </it>s.l. and Gankette Balla village which is exposed to several <it>Anopheles </it>species but where <it>An. funestus </it>is the only infected vector found. In each village, a cohort of 150 children aged from one to nine years was followed during one year and IgG response directed to schizont extract was determined by ELISA.</p> <p>Results</p> <p>Similar results of specific IgG responses according to age and <it>P. falciparum </it>infection were observed in both villages. Specific IgG response increased progressively from one-year to 5-year old children and then stayed high in children from five to nine years old. The children with <it>P. falciparum </it>infection had higher specific antibody responses compared to negative infection children, suggesting a strong relationship between production of specific antibodies and malaria transmission, rather than protective immunity. In contrast, higher variation of antibody levels according to malaria transmission periods were found in Mboula compared to Gankette Balla. In Mboula, the peak of malaria transmission was followed by a considerable increase in antibody levels, whereas low and constant anti-malaria IgG response was observed throughout the year in Gankette Balla.</p> <p>Conclusion</p> <p>This study shows that the development of anti-malaria antibody response was profoundly different according to areas where malaria exposure is dependent with different <it>Anopheles </it>species. These results are discussed according to i) the use of immunological tool for the evaluation of malaria transmission and ii) the influence of <it>Anopheles </it>vectors species on the regulation of antibody responses to <it>P. falciparum</it>.</p

The Early Positive Approaches to Support (E-PAtS) study: study protocol for a feasibility cluster randomised controlled trial of a group programme (E-PAtS) for family caregivers of young children with intellectual disability

Background: Children with intellectual disability have an IQ < 70, associated deficits in adaptive skills and are at increased risk of having clinically concerning levels of behaviour problems. In addition, parents of children with intellectual disability are likely to report high levels of mental health and other psychological problems. The Early Positive Approaches to Support (E-PAtS) programme for family caregivers of young children (5 years and under) with intellectual and developmental disabilities is a group-based intervention which aims to enhance parental psychosocial wellbeing and service access and support positive development for children. The aim of this study is to assess the feasibility of delivering E-PAtS to family caregivers of children with intellectual disability by community parenting support service provider organisations. The study will inform a potential, definitive RCT of the effectiveness and cost-effectiveness of E-PAtS. Methods: This study is a feasibility cluster randomised controlled trial, with embedded process evaluation. Up to 2 family caregivers will be recruited from 64 families with a child (18 months to 5 years) with intellectual disability at research sites in the UK. Participating families will be allocated to intervention: control on a 1:1 basis; intervention families will be offered the E-PAtS programme immediately, continuing to receive usual practice, and control participants will be offered the opportunity to attend the E-PAtS programme at the end of the follow-up period and will continue to receive usual practice. Data will be collected at baseline, 3 months post-randomisation and 12 months post-randomisation. The primary aim is to assess feasibility via the assessment of: recruitment of service provider organisations; participant recruitment; randomisation; retention; intervention adherence; intervention fidelity and the views of participants, intervention facilitators and service provider organisations regarding intervention delivery and study processes. The secondary aim is preliminary evaluation of a range of established outcome measures for individual family members, subsystem relationships and overall family functioning, plus additional health economic outcomes for inclusion in a future definitive trial. Discussion: The results of this study will inform a potential future definitive trial, to evaluate the effectiveness and cost-effectiveness of the E-PAtS intervention to improve parental psychosocial wellbeing. Such a trial would have significant scientific impact internationally in the intellectual disability field

Evaluation of a group based cognitive behavioural therapy programme for menstrual pain management in young women with intellectual disabilities: protocol for a mixed methods controlled clinical trial

BACKGROUND: Menstrual pain which is severe enough to impact on daily activities is very common amongst menstruating females. Research suggests that menstrual pain which impacts on daily functioning may be even more prevalent amongst those with intellectual disabilities. Despite this, little research attention has focused on pain management programmes for those with intellectual disabilities. The aims of this pilot study were to develop and evaluate a theory-based cognitive behavioural therapy (CBT) programme for menstrual pain management in young women with intellectual disabilities. METHODS/DESIGN: The study utilised a mixed methods controlled clinical trial to evaluate elements from a CBT programme called Feeling Better (McGuire & McManus, 2010). The Feeling Better programme is a modular, manualised intervention designed for people with an intellectual disability and their carers. The programme was delivered to 36 young women aged 12 – 30 years who have a Mild - Moderate Intellectual Disability, split between two conditions. The treatment group received the Feeling Better intervention and the control group received treatment as usual. To evaluate the effectiveness of the programme, measures were taken of key pain variables including impact, knowledge, self-efficacy and coping. Process evaluation was conducted to examine which elements of the programme were most successful in promoting change. DISCUSSION: Participants in the intervention group were expected to report the use of a greater number of coping strategies and have greater knowledge of pain management strategies following participation in the intervention and at three month follow-up, when compared to control group participants. A significant advantage of the study was the use of mixed methods and inclusion of process evaluation to determine which elements of a cognitive behavioural therapy programme work best for individuals with intellectual disabilities. TRIAL REGISTRATION: Current Controlled Trials ISRCTN7556775