Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture.

BACKGROUND: Trans-differentiation of human-induced pluripotent stem cells into neurons via Ngn2-induction (hiPSC-N) has become an efficient system to quickly generate neurons a likely significant advance for disease modeling and in vitro assay development. Recent single-cell interrogation of Ngn2-induced neurons, however, has revealed some similarities to unexpected neuronal lineages. Similarly, a straightforward method to generate hiPSC-derived astrocytes (hiPSC-A) for the study of neuropsychiatric disorders has also been described. RESULTS: Here, we examine the homogeneity and similarity of hiPSC-N and hiPSC-A to their in vivo counterparts, the impact of different lengths of time post Ngn2 induction on hiPSC-N (15 or 21 days), and the impact of hiPSC-N/hiPSC-A co-culture. Leveraging the wealth of existing public single-cell RNA-seq (scRNA-seq) data in Ngn2-induced neurons and in vivo data from the developing brain, we provide perspectives on the lineage origins and maturation of hiPSC-N and hiPSC-A. While induction protocols in different labs produce consistent cell type profiles, both hiPSC-N and hiPSC-A show significant heterogeneity and similarity to multiple in vivo cell fates, and both more precisely approximate their in vivo counterparts when co-cultured. Gene expression data from the hiPSC-N show enrichment of genes linked to schizophrenia (SZ) and autism spectrum disorders (ASD) as has been previously shown for neural stem cells and neurons. These overrepresentations of disease genes are strongest in our system at early times (day 15) in Ngn2-induction/maturation of neurons, when we also observe the greatest similarity to early in vivo excitatory neurons. We have assembled this new scRNA-seq data along with the public data explored here as an integrated biologist-friendly web-resource for researchers seeking to understand this system more deeply: https://nemoanalytics.org/p?l=DasEtAlNGN2&g=NES . CONCLUSIONS: While overall we support the use of the investigated cellular models for the study of neuropsychiatric disease, we also identify important limitations. We hope that this work will contribute to understanding and optimizing cellular modeling for complex brain disorders.

Impact of weight loss and weight gain trajectories on body composition in a population at high risk of type 2 diabetes: A prospective cohort analysis.

AIM: In a primary care population at high risk of type 2 diabetes, 24-month weight change trajectories were used to investigate the impact of weight cycling on fat mass (FM) and fat-free mass (FFM). MATERIALS AND METHODS: Cohort data from the Walking Away from Type 2 Diabetes trial was used, which recruited adults at-risk of type 2 diabetes from primary care in 2009/10. Annual weight change trajectories based on weight loss/gain of ≥5% were assessed over two 24-month periods. Body composition was measured by bioelectrical impedance analysis. Repeated measures were analysed using generalized estimating equations with participants contributing up to two 24-month observation periods. RESULTS: In total, 622 participants were included (average age = 63.6 years, body mass index = 32.0 kg/m2 , 35.4% women), contributing 1163 observations. Most observations (69.2%) were from those that maintained their body weight, with no change to FM or FFM. A minority (4.6% of observations) lost over 5% of body weight between baseline and 12 months, which was then regained between 12 and 24 months. These individuals regained FM to baseline levels, but lost 1.50 (0.66, 2.35) kg FFM, adjusted for confounders. In contrast, those that gained weight between baseline and 12 months but lost weight between 12 and 24 months (5.5% of observations) had a net gain in FM of 1.70 (0.27, 3.12) kg with no change to FFM. CONCLUSION: Weight cycling may be associated with a progressive loss in FFM and/or gain in FM in those with overweight and obesity at-risk of type 2 diabetes.

Ethnic differences in complement system biomarkers and their association with metabolic health in men of Black African and White European ethnicity.

Inflammation plays a fundamental role in the development of several metabolic diseases, including obesity and type 2 diabetes (T2D); the complement system has been implicated in their development. People of Black African (BA) ethnicity are disproportionately affected by T2D and other metabolic diseases but the impact of ethnicity on the complement system has not been explored. We investigated ethnic differences in complement biomarkers and activation status between men of BA and White European (WE) ethnicity and explored their association with parameters of metabolic health. We measured a panel of 15 complement components, regulators, and activation products in fasting plasma from 89 BA and 96 WE men. Ethnic differences were statistically validated. Association of complement biomarkers with metabolic health indices (BMI, waist circumference, insulin resistance, and HbA1c) were assessed in the groups. Plasma levels of the key complement components C3 and C4, the regulators clusterin and properdin and the activation marker iC3b were significantly higher in BA compared to WE men after age adjustment, while FD levels were significantly lower. C3 and C4 levels positively correlated with some or all markers of metabolic dysfunction in both ethnic groups while FD was inversely associated with HbA1c in both groups, and clusterin and properdin were inversely associated with some markers of metabolic dysfunction only in the WE group. Our findings of increased levels of complement components and activation products in BA compared to WE men suggest differences in complement regulation that may impact susceptibility to poor metabolic health.

Golgi staining-like retrograde labeling of brain circuits using rabies virus: Focus onto the striatonigral neurons.

BACKGROUND: The introduction of viral transneuronal tracers in the toolbox of neural tract-tracing methods has been an important addition in the field of connectomics for deciphering circuit-level architecture of the nervous system. One of the added values of viral compared to conventional retrograde tracers, in particular of rabies virus, is to provide a Golgi staining-like view of the infected neurons, revealing the thin dendritic arborizations and the spines that are major post-synaptic seats of neuronal connections. NEWMETHOD: Here, we comparatively illustrate the characteristics of the labeling obtained in the same model system, the basal ganglia circuitry, by different retrograde viral tracing approaches, using the Bartha strain of pseudorabies virus, the SAD and CVS strains of rabies virus and by the conventional retrograde tracer cholera toxin B. To best contrast the differences in the capacity of these tracers to reveal the dendritic morphology in details, we focused on one population of first-order infected neurons in the striatum, which exhibit high spine density, after tracer injection in the substantia nigra. RESULTS AND CONCLUSION: None of the viruses tested allowed to detect as many neurons as with cholera toxin B, but the SAD and CVS strains of rabies virus had the advantage of enabling detailed Golgi-like visualisation of the dendritic trees, the best numerical detection being offered by the transneuronal rCVS-N2c-P-mCherry while poor labeling was provided by rCVS-N2c-M-GFP. Results also suggest that, besides different viral properties, technical issues about constructs and detection methods contribute to apparently different efficiencies among the viral approaches.

[Ocular syphilis, a re-emergent pathology: Series of 12 patients in one Hospital, 2017]. / La syphilis oculaire, une pathologie ré-émergente : série de 12 patients au CHU de Marseille en 2017.

INTRODUCTION: Syphilis is a sexually transmitted disease. All organs might be affected, but ocular syphilis only occurs in 0.6 percent of patients. We collected all cases of ocular syphilis requiring hospitalization at the University Hospital Center (UHC) in Marseille in 2017. PATIENTS AND METHODS: This was a retrospective monocentric study. The diagnosis of ocular syphilis was based on the combination of ocular inflammation with a positive syphilitic serology. For each patient, sex, age, HIV status, ocular and extraocular symptoms, initial visual acuity, syphilis serology, cerebrospinal fluid (CSF) analysis if done, treatment and clinical response were collected. RESULTS: Ten men and two women, aged 28 to 86 years, were hospitalized. Two patients were HIV-positive. Ophtalmological lesions were heterogeneous the posterior structures were most affected. Anterior uveitis was isolated in one patient. Five patients had extraocular signs with cutaneous and/or mucosal involvement. No patient had neurological symptoms. Diagnosis of neurosyphilis through CSF analysis was definite for one patient, probable for 5 patients and ruled out for 2 patients. Six patients received treatment with penicillin G and six with ceftriaxone. Visual acuity improved in all cases. DISCUSSION: Ophtalmic cases of syphilis have become more frequent over the past few years in France. The diagnosis should be suspected in cases of eye inflammation even in the absence of favourable clinical presentation or anamnesis. Search for HIV co-infection should be systematic. Our study shows that ceftriaxone remains an effective alternative to penicillin G.

Reducing risk of Type 2 diabetes in HIV: a mixed-methods investigation of the STOP-Diabetes diet and physical activity intervention.

AIM: To conduct a mixed-methods feasibility study of the effectiveness and acceptability of an individualized diet and physical activity intervention designed to reduce the risk of Type 2 diabetes experienced by people living with HIV. METHODS: Participants with impaired fasting glucose and HIV were invited to take part in a 6-month diet and physical activity intervention. Individualized advice to achieve 10 lifestyle goals was delivered monthly. Diabetes risk was assessed pre- and post-intervention by measurement of the glucose and insulin response to a 3-h meal tolerance test. Six-month change was analysed using paired t-tests. Research interviews exploring the acceptability of the intervention and factors influencing behaviour change were conducted with those who participated in the intervention, and those who declined participation. RESULTS: The intervention (n=28) significantly reduced the following: glucose and insulin, both fasting and postprandial incremental area under the curve (glucose 7.9% and 17.6%; insulin 22.7% and 31.4%, respectively); weight (4.6%); waist circumference (6.2%); systolic blood pressure (7.4%); and triglycerides (36.7%). Interview data demonstrated the acceptability of the intervention. However, participants expressed concern that deliberate weight loss might lead to disclosure of HIV status or association with AIDS-related illness. The belief that antiretroviral medications drove diabetes risk was associated with declining study participation or achieving fewer goals. CONCLUSIONS: We have demonstrated the beneficial effects of a lifestyle intervention in mitigating the increased risk of Type 2 diabetes associated with HIV. Future interventions should be designed to further reduce the unique barriers that prevent successful outcomes in this cohort.

A Systematic Review of Beta Cell Function in Adults of Black African Ethnicity.

BACKGROUND: Understanding ethnic differences in beta cell function has important implications for preventative and therapeutic strategies in populations at high risk of type 2 diabetes (T2D). The existing literature, largely drawn from work in children and adolescents, suggests that beta cell function in black African (BA) populations is upregulated when compared to white Europeans (WE). METHODS: A systematic literature search was undertaken in June 2018 to identify comparative studies of beta cell function between adults (>age 18 years) of indigenous/diasporic BA and WE ethnicity. All categories of glucose tolerance and all methodologies of assessing beta cell function in vivo were included. RESULTS: 41 studies were identified for inclusion into a qualitative synthesis. The majority were studies in African American populations (n = 30) with normal glucose tolerance (NGT)/nondiabetes (n = 25), using intravenous glucose stimulation techniques (n = 27). There were fewer studies in populations defined as only impaired fasting glucose/impaired glucose tolerance (IFG/IGT) (n = 3) or only T2D (n = 3). Although BA broadly exhibited greater peripheral insulin responses than WE, the relatively small number of studies which measured C-peptide to differentiate between beta cell insulin secretion and hepatic insulin extraction (n = 14) had highly variable findings. In exclusively IGT or T2D cohorts, beta cell insulin secretion was found to be lower in BA compared to WE. CONCLUSIONS: There is inconsistent evidence for upregulated beta cell function in BA adults, and they may in fact exhibit greater deficits in insulin secretory function as glucose intolerance develops.

Ethnicity and Type 2 diabetes in the UK.

Type 2 diabetes is a major UK public health priority. Among minority ethnic communities, the prevalence is alarmingly high, approximately three to five times higher than in the white British population. Particularly striking is the earlier onset of Type 2 diabetes, which occurs some 10-12 years younger, with a significant proportion of cases being diagnosed before the age of 40 years. This review focuses on the UK context and Type 2 diabetes in adult populations, exploring the available evidence regarding the complex interplay of biological, lifestyle, social, clinical and healthcare system factors that are known to drive these disparities.

Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes.

A summary of the latest evidence-based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes-related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non-nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted 'GRADE' methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes.org.uk/nutrition-guidelines.

The DPYSL2 gene connects mTOR and schizophrenia.

We previously reported a schizophrenia-associated polymorphic CT di-nucleotide repeat (DNR) at the 5'-untranslated repeat (UTR) of DPYSL2, which responds to mammalian target of Rapamycin (mTOR) signaling with allelic differences in reporter assays. Now using microarray analysis, we show that the DNR alleles interact differentially with specific proteins, including the mTOR-related protein HuD/ELAVL4. We confirm the differential binding to HuD and other known mTOR effectors by electrophoretic mobility shift assays. We edit HEK293 cells by CRISPR/Cas9 to carry the schizophrenia risk variant (13DNR) and observe a significant reduction of the corresponding CRMP2 isoform. These edited cells confirm the response to mTOR inhibitors and show a twofold shortening of the cellular projections. Transcriptome analysis of these modified cells by RNA-seq shows changes in 12.7% of expressed transcripts at a false discovery rate of 0.05. These transcripts are enriched in immunity-related genes, overlap significantly with those modified by the schizophrenia-associated gene, ZNF804A, and have a reverse expression signature from that seen with antipsychotic drugs. Our results support the functional importance of the DPYSL2 DNR and a role for mTOR signaling in schizophrenia.

Pilot-Scale Pulsed UV Light Irradiation of Experimentally Infected Raspberries Suppresses Cryptosporidium parvum Infectivity in Immunocompetent Suckling Mice.

Cryptosporidium spp., a significant cause of foodborne infection, have been shown to be resistant to most chemical food disinfectant agents and infective for weeks in irrigation waters and stored fresh vegetal produce. Pulsed UV light (PL) has the potential to inactivate Cryptosporidium spp. on surfaces of raw or minimally processed foods or both. The present study aimed to evaluate the efficacy of PL on viability and in vivo infectivity of Cryptosporidium parvum oocysts present on raspberries, a known source of transmission to humans of oocyst-forming apicomplexan pathogens. The skin of each of 20 raspberries was experimentally inoculated with five 10-µl spots of an oocyst suspension containing 6 × 10(7) oocysts per ml (Nouzilly isolate). Raspberries were irradiated by PL flashes (4 J/cm(2) of total fluence). This dose did not affect colorimetric or organoleptic characteristics of fruits. After immunomagnetic separation from raspberries, oocysts were bleached and administered orally to neonatal suckling mice. Seven days after infection, mice were euthanized, and the number of oocysts in the entire small intestine was individually assessed by immunofluorescence flow cytometry. Three of 12 and 12 of 12 inoculated mice that received 10 and 100 oocysts isolated from nonirradiated raspberries, respectively, were found infected. Four of 12 and 2 of 12 inoculated mice that received 10(3) and 10(4) oocysts from irradiated raspberries, respectively, were found infected. Oocyst counts were lower in animals inoculated with 10(3) and 10(4) oocysts from irradiated raspberries (92 ± 144 and 38 ± 82, respectively) than in animals infected with 100 oocysts from nonirradiated raspberries (35,785 ± 66,221, P = 0.008). PL irradiation achieved oocyst reductions of 2 and 3 log for an inoculum of 10(3) and 10(4) oocysts, respectively. The present pilot-scale evaluation suggests that PL is an effective mode of decontamination for raspberries and prompts further applicability studies in industrial contexts.

Plasma free fatty acids do not provide the link between obesity and insulin resistance or ß-cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings (RISCK) study.

AIMS: To investigate the relationship between adiposity and plasma free fatty acid levels and the influence of total plasma free fatty acid level on insulin sensitivity and ß-cell function. METHODS: An insulin sensitivity index, acute insulin response to glucose and a disposition index, derived from i.v. glucose tolerance minimal model analysis and total fasting plasma free fatty acid levels were available for 533 participants in the Reading, Imperial, Surrey, Cambridge, Kings study. Bivariate correlations were made between insulin sensitivity index, acute insulin response to glucose and disposition index and both adiposity measures (BMI, waist circumference and body fat mass) and total plasma free fatty acid levels. Multivariate linear regression analysis was performed, controlling for age, sex, ethnicity and adiposity. RESULTS: After adjustment, all adiposity measures were inversely associated with insulin sensitivity index (BMI: ß = -0.357; waist circumference: ß = -0.380; body fat mass: ß = -0.375) and disposition index (BMI: ß = -0.215; waist circumference: ß = -0.248; body fat mass: ß = -0.221) and positively associated with acute insulin response to glucose [BMI: ß = 0.200; waist circumference: ß = 0.195; body fat mass ß = 0.209 (P values <0.001)]. Adiposity explained 13, 4 and 5% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. After adjustment, no adiposity measure was associated with free fatty acid level, but total plasma free fatty acid level was inversely associated with insulin sensitivity index (ß = -0.133), acute insulin response to glucose (ß = -0.148) and disposition index [ß = -0.218 (P values <0.01)]. Plasma free fatty acid concentration accounted for 1.5, 2 and 4% of the variation in insulin sensitivity index, acute insulin response to glucose and disposition index, respectively. CONCLUSIONS: Plasma free fatty acid levels have a modest negative association with insulin sensitivity, ß-cell secretion and disposition index but no association with adiposity measures. It is unlikely that plasma free fatty acids are the primary mediators of obesity-related insulin resistance or ß-cell dysfunction.

Dietary intakes of HIV-infected adults in urban UK.

Maintaining a good nutritional status is important for immune health and for managing metabolic comorbidities in adults with HIV infection. Little is known about the dietary habits of adults living with HIV infection in the United Kingdom. The aims of this study were to characterise their dietary intakes, and to identify subgroups of patients who may require nutritional counselling and/or food support services. An observational study of adults attending a London HIV out-patient clinic who completed a demographics questionnaire and a structured 24 h diet recall interview was conducted. In all, 196 (162 men, 34 women) adults participated. Forty-three percent (n=66) of men and thirty-six percent (n=11) of women did not consume enough energy to meet their basal metabolic requirements and activity factor. The majority of both men (64%) and women (56%) consumed more than the recommended amount of saturated fat. Self-report of lipodystrophy (B coefficient -2.27 (95% CI -3.92 to -0.61), P=0.008) was associated with lower dietary fibre intake/1000 kcal per day, and a more recent diagnosis of HIV (B coefficient -0.11 (95% CI -0.20 to -0.02), P=0.013) was associated with a higher dietary fibre/1000 kcal intake per day. Recreational drug use was associated with a higher overall calorie (P=0.003) and protein (P=0.001) intake than non-usage after adjusting for basal metabolic requirements and weight, respectively. Our data describe the dietary intakes of a diverse group of adults with HIV infection in the United Kingdom. These dietary habits may have an impact on their overall health and development of other metabolic comorbidities common in people with HIV.

Low glycaemic index diets and blood lipids: a systematic review and meta-analysis of randomised controlled trials.

AIMS: Low glycaemic index (GI) diets are beneficial in the management of hyperglycemia. Cardiovascular diseases are the major cause of mortality in diabetes therefore it is important to understand the effects of GI on blood lipids. The aim was to systematically review randomised controlled trials (RCTs) of low GI diets on blood lipids. DATA SYNTHESIS: We searched OVID Medline, Embase and Cochrane library to March 2012. Random effects meta-analyses were performed on twenty-eight RCTs comparing low- with high GI diets over at least 4 weeks (1272 participants; studies ranged from 6 to 155 participants); one was powered on blood lipids, 3 had adequate allocation concealment. Low GI diets significantly reduced total (-0.13 mmol/l, 95%CI -0.22 to -0.04, P = 0.004, 27 trials, 1441 participants, I(2) = 0%) and LDL-cholesterol (-0.16 mmol/l, 95%CI -0.24 to -0.08, P < 0.0001, 23 trials, 1281 participants, I(2) = 0%) compared with high GI diets and independently of weight loss. Subgroup analyses suggest that reductions in LDL-C are greatest in studies of shortest duration and greatest magnitude of GI reduction. Furthermore, lipid improvements appear greatest and most reliable when the low GI intervention is accompanied by an increase in dietary fibre. Sensitivity analyses, removing studies without adequate allocation concealment, lost statistical significance but retained suggested mean falls of ~0.10 mmol/l in both. There were no effects on HDL-cholesterol (MD -0.03 mmol/l, 95%CI -0.06 to 0.00, I(2) = 0%), or triglycerides (MD 0.01 mmol/l, 95%CI -0.06 to 0.08, I(2) = 0%). CONCLUSIONS: This meta-analysis provides consistent evidence that low GI diets reduce total and LDL-cholesterol and have no effect on HDL-cholesterol or triglycerides.

Self-reported reading and writing skills in elderly who never attended school influence cognitive performances: results from the Coyoacán cohort study.

OBJECTIVES: Beyond the well-known effect of educational level on cognitive performances, the present study investigates the specific effect of literacy acquisition independently of education. DESIGN: A sample of 175 unschooled elderly participants was selected from a larger Mexican population-based cohort study. PARTICIPANTS: The sample of 175 subjects who never went to school was divided in two groups: 109 who never acquired literacy skills and 66 who declared having acquired reading and writing abilities. MEASUREMENTS: Cognitive performances on commonly used tests (mini mental state examination, Isaacs set test, free and cued selective reminding test and clock-drawing test) were compared between the two groups taking into account several potentially confounding factors. RESULTS: The participants with reading and writing skills performed better than their counterparts in most tests, even though no difference was observed for the Isaacs Set Test and the delayed recall of the free and cued selective reminding test. CONCLUSION: Writing and reading skills in elderly people with no formal education influence performances in very commonly used test. Not only educational level but also literacy acquisition should be taken into account when conducting cognitive assessment in very low educated elderly people.

Estimating energy requirements in hospitalised underweight and obese patients requiring nutritional support: a survey of dietetic practice in the United Kingdom.

BACKGROUND: Many methods are available to determine energy requirements, however, all have limitations, particularly when used for the obese. OBJECTIVES: The aim of this survey was to investigate current practice in the estimation of energy requirements in an underweight and obese hospitalised patient in a large cohort of UK dietitians. SUBJECT/METHODS: A cross-sectional anonymous online survey of UK registered dietitians was performed. RESULTS: A total of 672 responses were received. Underweight patient: prediction equations with adjustment for metabolic stress and physical activity were most commonly used (90%). The median estimated energy requirement was 2079 kcals/day. The estimated energy requirement using calorie per kilogram method was significantly lower compared with equations (P<0.001). The median target volume of feed prescribed was 2000 mls/day. A significant reduction in feed prescribed compared with estimated energy requirements was found (P<0.001). Obese patient: prediction equations to estimate the basal metabolic rate alone were most commonly used (51%). Nutrition support dietitians used a lower stress factor compared with non-nutrition support dietitians (P=0.016). Method used to estimate the energy requirements was associated with years in clinical practice and place of work (P<0.001, 0.001). Calorie per kilogram used in the obese case study (median: 25 kcal/kg) was significantly lower than calorie per kilogram used in the underweight case study (median: 30 kcal/kg; P=0.014). CONCLUSIONS: A significant variation in the methods used by dietitians to estimate the energy requirements was found, particularly in the obese patient group. In an age of rapidly increasing rates of obesity a professional consensus of treatment of this patient group is needed.

Clinical guidelines and enteral nutrition support: a survey of dietetic practice in the United Kingdom.

BACKGROUND: Artificial nutrition support is used in treating hospital patients and has been shown to reduce hospital stays. The NICE (National Collaborating Centre for Acute Care) guidelines are the first national consensus guidelines for dietetic practice in artificial nutrition. The aim of the current survey was to explore the influence of local and national guidelines, and clinical experience on enteral tube feeding practices in a large cohort of UK dietitians. METHODS: A cross-sectional anonymous online survey of UK registered dietitians was performed. RESULTS: A total of 681 responses were received. In all, 85% deemed 'clinical experience' to be of greatest influence when initiating a tube feeding regimen; the influence of 'clinical experience' was significantly associated with the number of years in practice (P=<0.001). A total of 70% of respondents were aware of a department feeding protocol with 67% of protocols using a start rate of 24-49 ml/h; furthermore, 65% of respondents reported most commonly using a feeding start rate of 24-49 ml/h and 75% of them reported that their department had a protocol for preventing refeeding syndrome; 23% had mandatory implementation of NICE guidelines. CONCLUSIONS: Enteral feeding practice varies among practitioners. Clinical experience and published clinical guidelines have a pivotal role when treating adult patients that require enteral tube feeding.

Different experiences and perspectives between head and neck cancer patients and their care-givers on their daily impact of a gastrostomy tube.

BACKGROUND: Gastrostomy feeding in head and neck cancer patients is recognised standard practice in some cancer centres with beneficial effects on outcomes for appropriately selected patients. However, the impact on patients and care-givers needs consideration. The present study aimed to understand the daily impact of gastrostomy feeding on head and neck cancer patients and their care-givers to identify improvements to services. METHODS: Twenty-one adult patients were randomly selected from the Head and Neck centre at University College London Hospital. Six head and neck cancer patients and three care-givers participated in focus groups. The sessions were recorded, fully transcribed and qualitatively thematically analysed, and the resulting data were tabulated. RESULTS: Patients and care-givers expressed opposite experiences within knowledge and understanding of why the tube was necessary; their personal perceptions and objectives of nutritional support. Themes expressing similar experiences included: developing positive coping strategies; preventing nutritional decline; tube dependency; dentures; finance; active care; and psychological support. Furthermore, both groups expressed the benefits of retaining a support network for rehabilitation with the hospital-based specialist team. Also patients and carers recognised that the gastrostomy tube helped patient survival and, with timely dietetic management, helped them wean off the tube reliance with more confidence. CONCLUSIONS: It is essential that patients and care-givers attend pretreatment clinics to discuss nutritional support via the artificial route; their quality of life can be enhanced if guided through a specialist support pathway based at the clinical site where they initiated their care, with links to key agencies.

Effects of octreotide on jejunal hypersensitivity triggered by Cryptosporidium parvum intestinal infection in an immunocompetent suckling rat model.

BACKGROUND: Similar to other bacterial or protozoan infections, human cryptosporidiosis may trigger postinfectious irritable bowel syndrome (IBS)-like symptoms, a condition in which enhanced visceral perception of pain during intestinal distension plays a pivotal role. In an immunocompetent suckling rat model which mimicks features of postinfectious IBS, Cryptosporidium parvum infection induces long-lasting jejunal hypersensitivity to distension in association with intestinal activated mast cell accumulation. The aim of the present study was to explore in this model whether octreotide, a somatostatin agonist analog, could prevent the development of jejunal hypersensitivity and intestinal mast cell/nerve fiber accumulation. METHODS: Five-day-old Sprague-Dawley rats were infected with C. parvum and treated 10 days later with octreotide (50 g kg(-1) day(-1), i.p.) for 7 days. KEY RESULTS: Compared with untreated infected rats, octreotide treatment of infected rats resulted in increased weight gain [day 23 postinfection (PI)], decreased food intake (day 16 PI), and a reduction in jejunal villus alterations (day 14 PI), CD3(+) IEL (day 37 PI) and mast cell (days 37 and 50 PI) accumulations, nerve fiber densities (day 50 PI), and hypersensitivity to distension (day 120 PI). In uninfected rats, the effects of octreotide treatment were limited to higher weight gain (days 16 and 23 PI) and decreased food intake (day 23 PI) compared with uninfected-untreated rats. CONCLUSIONS & INFERENCES: Data confirms the relevance of the present rat model to postinfectious IBS studies and prompt further investigation of somatostatin-dependent regulatory interactions in cryptosporidiosis.