The effect of aspirin and eicosapentaenoic acid on urinary biomarkers of prostaglandin E2 synthesis and platelet activation in participants of the seAFOod polyp prevention trial.

Urinary prostaglandin (PG) E metabolite (PGE-M) and 11-dehydro (d)-thromboxane (TX) B2 are biomarkers of cyclooxygenase-dependent prostanoid synthesis. We investigated (1) the effect of aspirin 300 mg daily and eicosapentaenoic acid (EPA) 2000 mg daily, alone and in combination, on urinary biomarker levels and, (2) whether urinary biomarker levels predicted colorectal polyp risk, during participation in the seAFOod polyp prevention trial. Urinary PGE-M and 11-d-TXB2 were measured by liquid chromatography-tandem mass spectrometry. The relationship between urinary biomarker levels and colorectal polyp outcomes was investigated using negative binomial (polyp number) and logistic (% with one or more polyps) regression models. Despite wide temporal variability in PGE-M and 11-d-TXB2 levels within individuals, both aspirin and, to a lesser extent, EPA decreased levels of both biomarkers (74% [P ≤ .001] and 8% [P ≤ .05] reduction in median 11-d-TXB2 values, respectively). In the placebo group, a high (quartile [Q] 2-4) baseline 11-d-TXB2 level predicted increased polyp number (incidence rate ratio [IRR] [95% CI] 2.26 [1.11,4.58]) and risk (odds ratio [95% CI] 3.56 [1.09,11.63]). A low (Q1) on-treatment 11-d-TXB2 level predicted reduced colorectal polyp number compared to placebo (IRR 0.34 [0.12,0.93] for combination aspirin and EPA treatment) compared to high on-treatment 11-d-TXB2 values (0.61 [0.34,1.11]). Aspirin and EPA both inhibit PGE-M and 11-d-TXB2 synthesis in keeping with shared in vivo cyclooxygenase inhibition. Colorectal polyp risk and treatment response prediction by 11-d-TXB2 is consistent with a role for platelet activation during early colorectal carcinogenesis. The use of urinary 11-d-TXB2 measurement for a precision approach to colorectal cancer risk prediction and chemoprevention requires prospective evaluation.

Factors influencing gastrostomy tube removal.

BACKGROUND: When commencing enteral feeding, patients and families will want to know the likelihood of returning to an oral diet. There is a paucity of data on the prognosis of patients with gastrostomies. We describe a large dataset of patients, which identifies factors influencing gastrostomy removal and assesses the likelihood of the patient having at home enteral nutrition. METHODS: Retrospective data was collected on patients from Sheffield Teaching Hospitals who had received a gastrostomy and had outpatient enteral feeding between January 2016 and December 2019. Demographic data, indication and outcomes were analysed. RESULTS: A total of 451 patients were assessed, median age: 67.7. 183/451(40.6%) gastrostomies were for head and neck cancer, 88/451 (19.5%) for stroke, 28/451 (6.2%) for Motor Neuron Disease, 32/451 (7.1%) for other neurodegenerative causes, 120/451 (26.6%) other. Of the 31.2% who had their gastrostomy removed within 3 years, head and neck cancer was the most common indication (58.3%) followed by stroke (10.2%), Motor Neuron Disease (7.1%) and other neurodegenerative diseases (3.1%). Gastrostomy removal was significantly influenced by age, place of residence, and having head and neck cancer (p < 0.05). There was the greatest likelihood of removal within the first year (24%). 70.5% had enteral feeding at home. CONCLUSION: This large cohort study demonstrates 31.2% of patients had their gastrostomy removed within 3 years. Head and neck cancer patients, younger age and residing at home can help positively predict removal. Most patients manage their feeding at home rather than a nursing home. This study provides new information on gastrostomy outcomes when counselling patients to provide realistic expectations.

A retrospective study of outcomes and the validation of the Sheffield Gastrostomy Score in PEGs, RIGs and PIGs.

INTRODUCTION: There are limited studies comparing the safety and effectiveness of Radiologically Assisted Gastrostomies (RAGs) against Percutaneous Endoscopic Gastrostomies (PEGs). The Sheffield Gastrostomy Score (SGS) can be used to help predict 30-day mortality, more information is needed on its validity in RAGs. Our aim is to compare mortality between RAGs (Radiologically Inserted Gastrostomies (RIGs) and Per-oral Image Guided Gastrostomies (PIGs)) with PEGs and validate the SGS. METHOD: Data on gastrostomies newly inserted in three hospitals from 2016-2019 were retrospectively collected. Demographics, indication, insertion date, date of death, inpatient status and blood tests (albumin, CRP and eGFR) were recorded. RESULTS: 1977 gastrostomies were performed: Gastrostomy mortality at 7 days was 1.3% and at 30 days was 6%. There was a 5% 30-day mortality for PEGs, 5.5% RIGs, 7.2% PIGs (p = 0.215). Factors increasing 30 day mortality were age ≥60 years (p = 0.039), albumin <35 g/L (p = 0.005), albumin <25 g/L (p < 0.001) and CRP ≥10 mg/L (p < 0.001). For patients who died within 30 days; 0.6% had an SGS of 0, 3.7% = 1, 10.2% = 2 and 25.5% = 3, with similar trends for RAGs and PEGs. ROC curves showed the area under the curve for all gastrostomies, RAGs and PEGs as 0.743, 0.738, 0.787 respectively. DISCUSSION: There was no significant difference between 30-day mortality for PEGs, RIGs and PIGs. Factors predicting risk include age ≥60 years, albumin <35 g/L, albumin <25 g/L and CRP ≥10 mg/L. The SGS has been validated in this study for PEGs and for the first time in RAGs as well..

Vitamin D supplementation in people with IBS has no effect on symptom severity and quality of life: results of a randomised controlled trial.

PURPOSE: Several small trials suggest a benefit of vitamin D supplementation in irritable bowel syndrome (IBS). The generalisability of these reports is limited by their design and scale. This study aimed to assess whether vitamin D supplementation improved IBS symptoms in a UK community setting. METHODS: This was a randomised, double-blind, placebo-controlled study. Participants were recruited from the community in winter months between December 2017 and March 2019. 135 participants received either vitamin D (3,000 IU p.d.) or placebo for 12 weeks. The primary outcome measure was change in IBS symptom severity; secondary outcomes included change in IBS-related quality of life. RESULTS: The participants were analysed on an intent-to-treat basis. 60% of participants were vitamin D deficient or insufficient at baseline. Although vitamin D levels increased in the intervention arm relative to placebo (45.1 ± 32.88 nmol/L vs 3.1 ± 26.15 nmol/L; p < 0.001). There was no difference in the change of IBS symptom severity between the active and placebo trial arms (- 62.5 ± 91.57 vs - 75.2 ± 84.35, p = 0.426) over time. Similarly there was no difference between trial arms in τhe change in quality of life (- 7.7 ± 25.36 vs - 11.31 ± 25.02, p = 0.427). CONCLUSIONS: There is no case for advocating use of vitamin D in the management of IBS symptoms. The prevalence of vitamin D insufficiency suggests routine screening and supplementation should be implemented in this population for general health reasons. This trial was retrospectively registered with ISRCTN (ISRCTN13277340) on 24th April 2018 after recruiting had been initiated.

Caring for the poor: Lessons learned from a simulation on social determinants of health.

Poverty is a dominant social determinant of health (SDOH). One in 10 people in the United States lives in poverty. During the pandemic unemployment increased exponentially, swelling the number of individuals and families with limited resources. Adverse health outcomes and challenges in accessing healthcare for the poor are well documented. This paper describes a simulation comprised of case study enactments to increase collaboration among future healthcare providers as they mitigate the negative impact of SDOH, with particular focus on poverty. University students from schools of nursing, public health, and medicine, joined by health care and social service providers from the community, engaged in problem solving through role playing enactments of case studies. Focus groups were conducted to explicate the process and capture challenges, triumphs, and problem solving strategies associated with SDOH, particularly poverty. Directed content analysis and thematic analysis were used to analyze the focus groups. Six themes emerged from simulation debriefings that provide critical lessons related to SDOH and caring for the poor: "When it Rains, it Pours," "Coming of Age Too Soon," Delay and Deny, "Time is Money," "When You Don't Know Your Options, You Don't Have Any," and "Walking in the Shoes of Others." Recommendations included using simulations, with focus groups as a primary methodological approach, for preparing and updating the skills of the present and future healthcare workforce in addressing SDOH especially as recovery from the pandemic takes place.

A randomized placebo-controlled trial to investigate the effect of lactolycopene on semen quality in healthy males.

PURPOSE: Poor sperm quality is a major contributor to infertility in heterosexual couples, but at present there are few empirical therapies. Several studies have examined the role of dietary factors and data from randomized controlled trials suggest that oral antioxidant therapy can improve some sperm parameters. Health benefits of lycopene supplementation have been proposed for a variety of health conditions and here we examine whether it can help improve sperm quality. This study aimed to investigate the effect of 14 mg daily lactolycopene for 12 weeks on semen quality in healthy men. METHODS: Sixty healthy male participants were recruited and randomized to this double-blind, placebo-controlled parallel study and received either 14 mg/d lactolycopene or a placebo for 12 weeks. The primary endpoint was a change in motile sperm concentration. Secondary endpoints were all other aspects of sperm quality, including the level of sperm DNA damage. RESULTS: Fifty-six men completed the intervention and the level of plasma lycopene was significantly increased in the men randomized to receive lycopene supplementation. There was no significant change in the primary endpoint (motile sperm concentration) post-intervention (p = 0.058). However, the proportion of fast progressive sperm (p = 0.006) and sperm with normal morphology (p < 0.001) did improve significantly in response to lactolycopene intervention. CONCLUSIONS: Supplementation with 14 mg/d lactolycopene improves sperm motility and morphology in young healthy men. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: ISRCTN33248724 http://www.isrctn.com/ISRCTN33248724.

Comparing supermarket loyalty card data with traditional diet survey data for understanding how protein is purchased and consumed in older adults for the UK, 2014-16.

BACKGROUND: Our ability to understand population-level dietary intake patterns is dependent on having access to high quality data. Diet surveys are common diet assessment methods, but can be limited by bias associated with under-reporting. Food purchases tracked using supermarket loyalty card records may supplement traditional surveys, however they are rarely available to academics and policy makers. The aim of our study is to explore population level patterns of protein purchasing and consumption in ageing adults (40 years onwards). METHODS: We used diet survey data from the National Diet and Nutrition Survey (2014-16) on food consumption, and loyalty card records on food purchases from a major high street supermarket retailer (2016-17) covering the UK. We computed the percentage of total energy derived from protein, protein intake per kg of body mass, and percentage of protein acquired by food type. RESULTS: We found that protein consumption (as the percentage of total energy purchased) increased between ages 40-65 years, and declined thereafter. In comparison, protein purchased in supermarkets was roughly 2-2.5 percentage points lower at each year of age. The proportion of adults meeting recommended levels of protein was lowest in age groups 55-69 and 70+. The time of protein consumption was skewed towards evening meals, with low intakes during breakfast or between main meals. Meat, fish and poultry dominated as sources of protein purchased and consumed, although adults also acquired a large share of their protein from dairy and bread, with little from plant protein. CONCLUSIONS: Our study provides novel insights into how protein is purchased and consumed by ageing adults in the UK. Supermarket loyalty card data can reveal patterns of protein purchasing that when combined with traditional sources of dietary intake may enhance our understanding of dietary behaviours.

Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial.

BACKGROUND: The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy. METHODS: In a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55-73 years who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme (BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach, adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN05926847. FINDINGS: Between Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups (176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for 163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in the EPA plus aspirin group. The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group, 61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any effect for EPA (risk ratio [RR] 0·98, 95% CI 0·87 to 1·12; risk difference -0·9%, -8·8 to 6·9; p=0·81) or aspirin (RR 0·99 (0·87 to 1·12; risk difference -0·6%, -8·5 to 7·2; p=0·88). EPA and aspirin were well tolerated (78 [44%] of 176 had ≥1 adverse event in the placebo group compared with 82 [46%] in the EPA group, 68 [39%] in the aspirin group, and 76 [45%] in the EPA plus aspirin group), although the number of gastrointestinal adverse events was increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and 68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment groups (two in the EPA group, three in the aspirin group, and one in the placebo group). INTERPRETATION: Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence. FUNDING: Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership.

Protein Valuation in Food Choice Is Positively Associated with Lean Mass in Older Adults.

BACKGROUND: Calorie for calorie, protein is more satiating than carbohydrate or fat. However, it remains unclear whether humans perceive calories derived from these macronutrients equally and whether lean mass is associated with a tendency to "value" protein when dietary decisions are made. OBJECTIVES: This study aimed to determine the test-retest reliability of a novel method for quantifying macronutrient valuations in human volunteers and to determine whether "protein valuation" is associated with a higher fat-free mass index (FFMI) in older adults. METHODS: A 2-alternative, forced-choice task in which 25 foods were compared in 300 trials was undertaken in 2 studies. In study 1, participants (age range 19-71 y, n = 92) attended 2 test sessions, spaced 1 wk apart. In study 2, older adults (age range 40-85 y; n = 91) completed the food-choice task and assessed the test foods for liking, expected satiety, and perceived healthiness. Body composition and habitual protein intake were assessed in both studies. Data were analyzed through the use of individual binomial logistic regressions and multilevel binomial logistic regressions. RESULTS: In study 1, measures of macronutrient valuation showed excellent test-retest reliability; responses in the forced-choice task were highly correlated (week 1 compared with week 2; protein, r = 0.83, P < 0.001; carbohydrate, r = 0.90, P < 0.001; fat, r = 0.90, P < 0.001). Calorie for calorie, protein and carbohydrate were stronger predictors of choice than fat (P < 0.001). In study 2, protein was a stronger predictor than both carbohydrate (P = 0.039) and fat (P = 0.003), and a positive interaction was observed between protein valuation and FFMI (OR = 1.64; 95% CI: 1.38, 1.95; P < 0.001). This was the case after controlling for age, gender, liking for foods, and habitual protein consumption. CONCLUSIONS: Together, these findings demonstrate that adult humans value calories derived from protein, carbohydrate, and fat differently, and that the tendency to value protein is associated with greater lean mass in older adults.

Dual signaling of Wamide myoinhibitory peptides through a peptide-gated channel and a GPCR in Platynereis.

Neuropeptides commonly signal by metabotropic GPCRs. In some mollusks and cnidarians, RFamide neuropeptides mediate fast ionotropic signaling by peptide-gated ion channels that belong to the DEG/ENaC family. Here we describe a neuropeptide system with a dual mode of signaling by both a peptide-gated ion channel and a GPCR. We identified and characterized a peptide-gated channel in the marine annelid Platynereis dumerilii that is specifically activated by Wamide myoinhibitory peptides derived from the same proneuropeptide. The myoinhibitory peptide-gated ion channel (MGIC) belongs to the DEG/ENaC family and is paralogous to RFamide-gated ion channels. Platynereis myoinhibitory peptides also activate a previously described GPCR, MAG. We measured the potency of all Wamides on both MGIC and MAG and identified peptides that preferentially activate one or the other receptor. Analysis of a single-cell transcriptome resource indicates that MGIC and MAG signal in distinct target neurons. The identification of a Wamide-gated ion channel suggests that peptide-gated channels are more diverse and widespread in animals than previously appreciated. The possibility of neuropeptide signaling by both ionotropic and metabotropic receptors to different target cells in the same organism highlights an additional level of complexity in peptidergic signaling networks.-Schmidt, A., Bauknecht, P., Williams, E. A., Augustinowski, K., Gründer, S., Jékely, G. Dual signaling of Wamide myoinhibitory peptides through a peptide-gated channel and a GPCR in Platynereis.

Advanced Human Immunodeficiency Virus Disease in Botswana Following Successful Antiretroviral Therapy Rollout: Incidence of and Temporal Trends in Cryptococcal Meningitis.

Background: Botswana has a well-developed antiretroviral therapy (ART) program that serves as a regional model. With wide ART availability, the burden of advanced human immunodeficiency virus (HIV) and associated opportunistic infections would be expected to decline. We performed a nationwide surveillance study to determine the national incidence of cryptococcal meningitis (CM), and describe characteristics of cases during 2000-2014 and temporal trends at 2 national referral hospitals. Methods: Cerebrospinal fluid data from all 37 laboratories performing meningitis diagnostics in Botswana were collected from the period 2000-2014 to identify cases of CM. Basic demographic and laboratory data were recorded. Complete national data from 2013-2014 were used to calculate national incidence using UNAIDS population estimates. Temporal trends in cases were derived from national referral centers in the period 2004-2014. Results: A total of 5296 episodes of CM were observed in 4702 individuals; 60.6% were male, and median age was 36 years. Overall 2013-2014 incidence was 17.8 (95% confidence interval [CI], 16.6-19.2) cases per 100000 person-years. In the HIV-infected population, incidence was 96.8 (95% CI, 90.0-104.0) cases per 100000 person-years; male predominance was seen across CD4 strata. At national referral hospitals, cases decreased during 2007-2009 but stabilized during 2010-2014. Conclusions: Despite excellent ART coverage in Botswana, there is still a substantial burden of advanced HIV, with 2013-2014 incidence of CM comparable to pre-ART era rates in South Africa. Our findings suggest that a key population of individuals, often men, is developing advanced disease and associated opportunistic infections due to a failure to effectively engage in care, highlighting the need for differentiated care models.

Conserved MIP receptor-ligand pair regulates Platynereis larval settlement.

Life-cycle transitions connecting larval and juvenile stages in metazoans are orchestrated by neuroendocrine signals including neuropeptides and hormones. In marine invertebrate life cycles, which often consist of planktonic larval and benthic adult stages, settlement of the free-swimming larva to the sea floor in response to environmental cues is a key life cycle transition. Settlement is regulated by a specialized sensory-neurosecretory system, the larval apical organ. The neuroendocrine mechanisms through which the apical organ transduces environmental cues into behavioral responses during settlement are not yet understood. Here we show that myoinhibitory peptide (MIP)/allatostatin-B, a pleiotropic neuropeptide widespread among protostomes, regulates larval settlement in the marine annelid Platynereis dumerilii. MIP is expressed in chemosensory-neurosecretory cells in the annelid larval apical organ and signals to its receptor, an orthologue of the Drosophila sex peptide receptor, expressed in neighboring apical organ cells. We demonstrate by morpholino-mediated knockdown that MIP signals via this receptor to trigger settlement. These results reveal a role for a conserved MIP receptor-ligand pair in regulating marine annelid settlement.

Feasibility study of portable technology for weight loss and HbA1c control in type 2 diabetes.

BACKGROUND: The study investigated the feasibility of conducting a future Randomised Controlled Trial (RCT) of a mobile health (mHealth) intervention for weight loss and HbA1c reduction in Type 2 Diabetes Mellitus (T2DM). METHODS: The intervention was a small wearable mHealth device used over 12 weeks by overweight people with T2DM with the intent to lose weight and reduce their HbA1c level. A 4 week maintenance period using the device followed. The device records physical activity level and information about food consumption, and provides motivational feedback based on energy balance. Twenty-seven participants were randomised to receive no intervention; intervention alone; or intervention plus weekly motivational support. All participants received advice on diet and exercise at the start of the study. Weight and HbA1c levels were recorded at baseline and weeks 6, 12, and 16. Qualitative interviews were conducted with participants who received the intervention to explore their experiences of using the device and involvement in the study including the training received. RESULTS: Overall the device was perceived to be well-liked, acceptable, motivational and easy to use by participants. Some logistical changes were required during the feasibility study, including shortening of the study duration and relaxation of participant inclusion criteria. Descriptive statistics of weight and HbA1c data showed promising trends of weight loss and HbA1c reduction in both intervention groups, although this should be interpreted with caution. CONCLUSIONS: A number of methodological recommendations for a future RCT emerged from the current feasibility study. The mHealth device was acceptable and promising for helping individuals with T2DM to reduce their HbA1c and lose weight. Devices with similar features should be tested further in larger studies which follow these methodological recommendations.

Conflicted Identification in the Sex Education Classroom: Balancing Professional Values With Organizational Mandates.

Despite enormous resources spent on sex education, the United States faces an epidemic of unplanned pregnancy and sexually transmitted infections among young people. Little research has examined the role sex educators play in alleviating or exacerbating this problem. In this study, we interviewed 50 sex educators employed by public schools throughout a Midwestern, U.S. state about their experiences in the sex education classroom. Twenty-two interviewees communicated feelings of conflicted identification and provided examples of the ways in which they experienced this subjectivity in the context of their employment. We find these interviews shed light on the as-yet-understudied communicative experience of conflicted identification by delineating key sources of such conflict and discursive strategies used in its negotiation. Our results suggest that those who experience conflicted identification and who have a sense of multiple or nested identifications within their overarching professional identity may be safeguarded to some extent from eventual organizational disidentification.

Object-based representation and analysis of light and electron microscopic volume data using Blender.

BACKGROUND: Rapid improvements in light and electron microscopy imaging techniques and the development of 3D anatomical atlases necessitate new approaches for the visualization and analysis of image data. Pixel-based representations of raw light microscopy data suffer from limitations in the number of channels that can be visualized simultaneously. Complex electron microscopic reconstructions from large tissue volumes are also challenging to visualize and analyze. RESULTS: Here we exploit the advanced visualization capabilities and flexibility of the open-source platform Blender to visualize and analyze anatomical atlases. We use light-microscopy-based gene expression atlases and electron microscopy connectome volume data from larval stages of the marine annelid Platynereis dumerilii. We build object-based larval gene expression atlases in Blender and develop tools for annotation and coexpression analysis. We also represent and analyze connectome data including neuronal reconstructions and underlying synaptic connectivity. CONCLUSIONS: We demonstrate the power and flexibility of Blender for visualizing and exploring complex anatomical atlases. The resources we have developed for Platynereis will facilitate data sharing and the standardization of anatomical atlases for this species. The flexibility of Blender, particularly its embedded Python application programming interface, means that our methods can be easily extended to other organisms.

Myoinhibitory peptide regulates feeding in the marine annelid Platynereis.

BACKGROUND: During larval settlement and metamorphosis, marine invertebrates undergo changes in habitat, morphology, behavior and physiology. This change between life-cycle stages is often associated with a change in diet or a transition between a non-feeding and a feeding form. How larvae regulate changes in feeding during this life-cycle transition is not well understood. Neuropeptides are known to regulate several aspects of feeding, such as food search, ingestion and digestion. The marine annelid Platynereis dumerilii has a complex life cycle with a pelagic non-feeding larval stage and a benthic feeding postlarval stage, linked by the process of settlement. The conserved neuropeptide myoinhibitory peptide (MIP) is a key regulator of larval settlement behavior in Platynereis. Whether MIP also regulates the initiation of feeding, another aspect of the pelagic-to-benthic transition in Platynereis, is currently unknown. RESULTS: Here, we explore the contribution of MIP to the regulation of feeding behavior in settled Platynereis postlarvae. We find that in addition to expression in the brain, MIP is expressed in the gut of developing larvae in sensory neurons that densely innervate the hindgut, the foregut, and the midgut. Activating MIP signaling by synthetic neuropeptide addition causes increased gut peristalsis and more frequent pharynx extensions leading to increased food intake. Conversely, morpholino-mediated knockdown of MIP expression inhibits feeding. In the long-term, treatment of Platynereis postlarvae with synthetic MIP increases growth rate and results in earlier cephalic metamorphosis. CONCLUSIONS: Our results show that MIP activates ingestion and gut peristalsis in Platynereis postlarvae. MIP is expressed in enteroendocrine cells of the digestive system suggesting that following larval settlement, feeding may be initiated by a direct sensory-neurosecretory mechanism. This is similar to the mechanism by which MIP induces larval settlement. The pleiotropic roles of MIP may thus have evolved by redeploying the same signaling mechanism in different aspects of a life-cycle transition.

The validation of a computer-based food record for older adults: the Novel Assessment of Nutrition and Ageing (NANA) method.

Dietary assessment in older adults can be challenging. The Novel Assessment of Nutrition and Ageing (NANA) method is a touch-screen computer-based food record that enables older adults to record their dietary intakes. The objective of the present study was to assess the relative validity of the NANA method for dietary assessment in older adults. For this purpose, three studies were conducted in which a total of ninety-four older adults (aged 65-89 years) used the NANA method of dietary assessment. On a separate occasion, participants completed a 4 d estimated food diary. Blood and 24 h urine samples were also collected from seventy-six of the volunteers for the analysis of biomarkers of nutrient intake. The results from all the three studies were combined, and nutrient intake data collected using the NANA method were compared against the 4 d estimated food diary and biomarkers of nutrient intake. Bland-Altman analysis showed a reasonable agreement between the dietary assessment methods for energy and macronutrient intake; however, there were small, but significant, differences for energy and protein intake, reflecting the tendency for the NANA method to record marginally lower energy intakes. Significant positive correlations were observed between urinary urea and dietary protein intake using both the NANA and the 4 d estimated food diary methods, and between plasma ascorbic acid and dietary vitamin C intake using the NANA method. The results demonstrate the feasibility of computer-based dietary assessment in older adults, and suggest that the NANA method is comparable to the 4 d estimated food diary, and could be used as an alternative to the food diary for the short-term assessment of an individual's dietary intake.

HPV vaccine use among African American girls: qualitative formative research using a participatory social marketing approach.

OBJECTIVE: To generate recommendations for framing messages to promote HPV vaccination, specifically for African American adolescents and their parents who have not yet made a decision about the vaccine (the "Undecided" market segment). METHODS: Focus groups and interviews were conducted with African American girls ages 11-18 (N=34) and their mothers (N=31), broken into market segments based on daughter's vaccination status and mother's intent to vaccinate. RESULTS: Findings suggested that the HPV vaccine should be presented to "Undecided" mothers and adolescents as a routine vaccine (just like other vaccines) that helps prevent cancer. Within the "Undecided" segment, we identified two sub-segments based on barriers to HPV vaccination and degree of reluctance. The "Undecided/Ready If Offered" segment would easily accept HPV vaccine if given the opportunity, with basic information and a healthcare provider recommendation. The "Undecided/Skeptical" segment would need more in-depth information to allay concerns about vaccine safety, mistrust of drug companies, and recommended age. Some mothers and girls had the erroneous perception that girls do not need the vaccine until they become sexually active. African American adolescents and their mothers overwhelmingly thought campaigns should target both girls and boys for HPV vaccination. In addition, campaigns and messages may need to be tailored for pre-teens (ages 9-12) versus teens (ages 13-18) and their parents. CONCLUSIONS: Findings pointed to the need to "normalize" the perception of HPV vaccine as just another routine vaccine (e.g., part of pre-teen vaccine package). Findings can inform social marketing campaigns targeting Undecided or ethnically diverse families.

Microalgal biofilm induces larval settlement in the model marine worm Platynereis dumerilii.

A free-swimming larval stage features in many marine invertebrate life cycles. To transition to a seafloor-dwelling juvenile stage, larvae need to settle out of the plankton, guided by specific environmental cues that lead them to an ideal habitat for their future life on the seafloor. Although the marine annelid Platynereis dumerilii has been cultured in research laboratories since the 1950s and has a free-swimming larval stage, specific environmental cues that induce settlement in this nereid worm are yet to be identified. Here, we demonstrate that microalgal biofilm is a key settlement cue for P. dumerilii larvae, inducing earlier onset of settlement and enhancing subsequent juvenile growth as a primary food source. We tested the settlement response of P. dumerilii to 40 different strains of microalgae, predominantly diatom species, finding that P. dumerilii have species-specific preferences in their choice of settlement substrate. The most effective diatom species for inducing P. dumerilii larval settlement were benthic pennate species including Grammatophora marina, Achnanthes brevipes and Nitzschia ovalis. The identification of specific environmental cues for P. dumerilii settlement enables a link between its ecology and the sensory and nervous system signalling that regulates larval behaviour and development. Incorporation of diatoms into P. dumerilii culture practices will improve the husbandry of this marine invertebrate model.