Dynamic Opportunities for Medical Students to Assume the Roles of "Medical Teacher".

The traditional undergraduate medical education curriculum focuses on bolstering knowledge for practice and building clinical skills. However, as future clinicians, medical students will be tasked with teaching throughout their careers, first as residents and then as attendings. Here, we describe teaching opportunities for students that foster their development as future teachers and potential clinician educators. These offerings are diverse in their focus and duration and are offered across various levels of the curriculum - including course-based learning, longitudinal electives, and extra-curricular opportunities for medical students who have a passion for teaching.

Provider moral distress in caring for tracheostomy and ventilator dependent children: A single institution cross-sectional evaluation.

OBJECTIVE: To determine levels of moral distress in a pediatric unit caring for patients with tracheostomy/ventilator dependence. HYPOTHESIS: Moral distress will be significant in a dedicated pediatric trach/vent unit. METHODS: The Moral Distress Survey-Revised (MDS-R) is a 21-question survey measuring moral distress in pediatrics. The MDS-R was anonymously distributed to medical degree/doctor of osteopathy (MD/DOs), advanced practice practitioners (APPs), registered nurses (RNs), and respiratory therapists (RTs) in a unit caring for tracheostomy/ventilator dependent patients. Descriptive statistics, bivariate and multivariate analysis were performed. RESULTS: Response rate was 48% (61/127). Mean MDS-R score was 83 (range 43-119), which is comparable to reported levels in the pediatric intensive care unit (ICU). APPs had the highest median rate of moral distress (112, interquartile range [IQR], 72-138), while MD/DOs had the lowest median score (49, IQR, 43-77). RNs and RTs had MDS-R scores between these two groups (medians of 91 and 84, respectively). CONCLUSIONS: Moral distress levels in a unit caring for long term tracheostomy and ventilator dependent patients are high, comparable to levels in pediatric ICUs. APPs. APPs had higher levels of distress compared to other groups. This may be attributable to the constant stressors of being the primary provider for complex patients, especially in a high-volume inpatient setting.

Understanding COVID-19 Vaccine Confidence in People Living with HIV: A pan-Canadian Survey.

Understanding the roots of Covid-19 vaccine hesitancy in at-risk groups, such as persons living with HIV (PLWH), is of utmost importance. We developed a modified Vaccine Hesitancy Scale (VHS) questionnaire using items from the National Advisory Committee on Immunization Acceptability Matrix. To examine factors associated with receiving COVID-19 vaccine and the link between vaccine attitudes and beliefs with vaccine behavior, PLWH were recruited via social media and community-based organizations (February-May 2022). Descriptive statistics were used to summarize results. Total VHS score was generated by adding Likert scale scores and linear regression models used to compare results between participants who received or did not receive COVID-19 vaccines. Logistic regression models were used to identify factors associated with vaccine uptake. A total of 246 PLWH indicated whether they received a COVID-19 vaccine. 89% received ≥ 1 dose. Mean total VHS(SD) for persons having received ≥ 1 COVID-19 vaccine was 17.8(6.2) vs. 35.4(9.4) for participants not having received any COVID-19 vaccine. Persons who received ≥ 1 dose were significantly older than those who had not received any (48.4 ± 13.8 vs. 34.0 ± 7.7 years, p < 0.0001). The majority of participants considered COVID-19 vaccination important for their health(81.3%) and the health of others(84.4%). Multivariate logistic regression revealed the odds of taking ≥ 1dose were increased 2.4-fold [95% CI 1.6, 3.5] with each increase in age of 10 years (p < 0.0001). Sex and ethnicity were not different between groups. In conclusion, PLWH accept COVID-19 vaccines for both altruistic and individual reasons. With evolving recommendations and increasing numbers of booster vaccines, we must re-examine the needs of PLWH regularly.

A two-day workshop reviewing Canadian provincial and national HIV care cascade indicators, reporting, challenges, and recommendations.

BACKGROUND: The HIV care cascade is an indicators-framework used to assess achievement of HIV clinical targets including HIV diagnosis, HIV care initiation and retention, initiation of antiretroviral therapy, and attainment of viral suppression for people living with HIV. METHODS: The HIV Care Cascade Research Development Team at the CIHR Canadian HIV Trials Network Clinical Care and Management Core hosted a two-day virtual workshop to present HIV care cascade data collected nationally from local and provincial clinical settings and national cohort studies. The article summarizes the workshop presentations including the indicators used and available findings and presents the discussed challenges and recommendations. RESULTS: Identified challenges included (1) inconsistent HIV care cascade indicator definitions, (2) variability between the use of nested UNAIDS's targets and HIV care cascade indicators, (3) variable analytic approaches based on differing data sources, (4) reporting difficulties in some regions due to a lack of integration across data platforms, (5) lack of robust data on the first stage of the care cascade at the sub-national level, and (6) inability to integrate key socio-demographic data to estimate population-specific care cascade shortfalls. CONCLUSION: There were four recommendations: standardization of HIV care cascade indicators and analyses, additional funding for HIV care cascade data collection, database maintenance and analyses at all levels, qualitative interviews and case studies characterizing the stories behind the care cascade findings, and employing targeted positive-action programs to increase engagement of key populations in each HIV care cascade stage.

HISTORIQUE: La cascade des soins du VIH est un cadre d'indicateurs utilisé pour évaluer l'atteinte des cibles cliniques du VIH, y compris le diagnostic, le début et le maintien des soins, le début du traitement antirétroviral et l'obtention de la suppression virale chez les personnes qui vivent avec le VIH. MÉTHODOLOGIE: L'équipe de développement de la recherche sur la cascade des soins du VIH située au noyau de perfectionnement de la gestion clinique du Réseau canadien pour les essais VIH des IRSC a organisé un atelier virtuel de deux jours pour présenter les données sur la cascade des soins du VIH amassées dans les milieux cliniques locaux et provinciaux et les études de cohorte de tout le pays. L'article résume les présentations d'ateliers, y compris les indicateurs utilisés et les observations disponibles, et présente les défis et recommandations abordés. RÉSULTATS: Les défis mis en évidence incluaient 1) les définitions hétérogènes des indicateurs de la cascade des soins sur le VIH, 2) la variabilité entre l'utilisation des cibles d'ONUSIDA imbriquées et les indicateurs de cascade des soins du VIH, 3) des approches analytiques variables d'après diverses sources de données, 4) la déclaration des difficultés dans certaines régions à cause de l'absence d'intégration entre les plateformes de données, 5) l'absence de données vigoureuses sur la première étape de la cascade des soins infranationaux et 6) l'incapacité d'intégrer les principales données sociodémographiques pour évaluer les écueils de la cascade des soins populationnels. CONCLUSION: Quatre recommandations ont été formulées : la standardisation des indicateurs et des analyses de la cascade des soins du VIH, le financement supplémentaire de la collecte de la cascade des soins du VIH, l'entretien des bases de données et les analyses à tous les échelons, les entrevues qualitatives et les études de cas qui caractérisent les histoires qui se cachent derrière les observations tirées de la cascade des soins et le recours à des programmes d'action positive ciblés pour accroître la participation de populations clés à chaque étape de la cascade des soins du VIH.

National Food Intake Assessment: Technologies to Advance Traditional Methods.

National dietary surveillance produces dietary intake data used for various purposes including development and evaluation of national policies in food and nutrition. Since 2000, What We Eat in America, the dietary component of the National Health and Nutrition Examination Survey, has collected dietary data and reported on the dietary intake of the US population. Continual innovations are required to improve methods of data collection, quality, and relevance. This review article evaluates the strengths and limitations of current and newer methods in national dietary data collection, underscoring the use of technology and emerging technology applications. We offer four objectives for national dietary surveillance that serve as guiding principles in the evaluation. Moving forward, national dietary surveillance must take advantage of new technologies for their potential in enhanced efficiency and objectivity in data operations while continuing to collect accurate dietary information that is standardized, validated, and publicly transparent.

Comparing Two Days of Dietary Intake in What We Eat in America (WWEIA), NHANES, 2013-2016.

The objective of this research is to compare the Day 1 and Day 2 dietary intakes of adults in What We Eat in America, National Health and Nutrition Examination Survey (WWEIA, NHANES) 2013-2016. Dietary recalls of males (n = 2599) and females (n = 2624) 20+ years who had both a Day 1 and Day 2 recall and reported their intake as usual on both days in WWEIA, NHANES 2013-2016 were examined. Mean (±SE) energy intake for males was 2425 ± 26 kcal for Day 1 and 2334 ± 32 kcal for Day 2 (p = 0.004). For females, 1832 ± 18 kcal and 1775 ± 26 kcal were reported for Day 1 and 2, respectively (p = 0.020). There were no significant differences between energy intake on Day 1 and Day 2 within males and females by ten-year age groups. Comparing 20 year age groups for males and females by race/ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic) and income (<131%, 131-350%, and >350% of poverty level) also showed no significant differences in energy intake between Day 1 and Day 2. Mean energy intake of adults was not statistically different between the two days of recall by sex, race/ethnicity or income within selected age groups. Overall, the difference in energy intake was less than 4% for both males and females.

Fruit and Vegetable Consumption of US Adults by Level of Variety, What We Eat in America, NHANES 2013-2016.

BACKGROUND: Dietary guidance encourages consuming a variety of fruit and vegetables (FVs), which has been associated with higher FV intake and nutrient adequacy. Dietary intake of adults in the United States has not been described in the context of variety. OBJECTIVES: The objective of this study was to describe FV consumption of adults in the United States by level of FV variety. METHODS: One day of dietary intake data of adults aged ≥20 y (n = 10,064) in What We Eat in America, NHANES 2013-2016 were used. FV variety was the count of foods consumed that contributed to total FV intake. Each FV was counted only once; a mixed dish counted as 1. Variety levels were high (≥5 items, n = 2316); moderate (3-4 items, n = 3423); or low (1-2 items, n = 3746). Differences between each level of variety were compared by t test. RESULTS: Among the low, moderate, and high levels, total FV intakes were 1.4, 2.6, and 4.4 cup equivalents (CE), respectively. CE amounts of FVs consumed were 0.3, 0.6, and 1.4 of vegetables excluding potatoes; 0.2, 0.3, and 0.3 of potatoes; 0.3, 0.6, and 1.2 of fruit; and 0.4, 0.4, and 0.5 from mixed dishes, respectively; percentages of each level reporting intake were 34%, 64%, and 89% for vegetables excluding potatoes; 23%, 34%, and 32% for potatoes; 22%, 49%, and 75% for fruit; and 72%, 71%, and 72% for mixed dishes, respectively. CONCLUSIONS: Those with more variety of FV intake include whole FVs more frequently and in higher amounts. These results support suggestions for encouraging more FVs at snacks and as side dishes and salads at meals to increase total intake.

Sodium Content of Foods Contributing to Sodium Intake: Comparison between Selected Foods from the CDC Packaged Food Database and the USDA National Nutrient Database for Standard Reference.

The sodium concentration (mg/100g) for 23 of 125 Sentinel Foods (e.g. white bread) were identified in the 2009 CDC Packaged Food Database (PFD) and compared with data in the USDA's 2013 National Nutrient Database for Standard Reference(SR 26). Sentinel Foods are foods identified by USDA to be monitored as primary indicators to assess the changes in the sodium content of commercially processed foods from stores and restaurants. Overall, 937 products were evaluated in the CDC PFD, and between 3 (one brand of ready-to-eat cereal) and 126 products (white bread) were evaluated per selected food. The mean sodium concentrations of 17 of the 23 (74%) selected foods in the CDC PFD were 90%-110% of the mean sodium concentrations in SR 26 and differences in sodium concentration were statistically significant for 6 Sentinel Foods. The sodium concentration of most of the Sentinel Foods, as selected in the PFD, appeared to represent the sodium concentrations of the corresponding food category. The results of our study help improve the understanding of how nutrition information compares between national analytic values and the label and whether the selected Sentinel Foods represent their corresponding food category as indicators for assessment of change of the sodium content in the food supply.

A New Database Facilitates Characterization of Flavonoid Intake, Sources, and Positive Associations with Diet Quality among US Adults.

BACKGROUND: Epidemiologic studies demonstrate inverse associations between flavonoid intake and chronic disease risk. However, lack of comprehensive databases of the flavonoid content of foods has hindered efforts to fully characterize population intakes and determine associations with diet quality. OBJECTIVES: Using a newly released database of flavonoid values, this study sought to describe intake and sources of total flavonoids and 6 flavonoid classes and identify associations between flavonoid intake and the Healthy Eating Index (HEI) 2010. METHODS: One day of 24-h dietary recall data from adults aged ≥ 20 y (n = 5420) collected in What We Eat in America (WWEIA), NHANES 2007-2008, were analyzed. Flavonoid intakes were calculated using the USDA Flavonoid Values for Survey Foods and Beverages 2007-2008. Regression analyses were conducted to provide adjusted estimates of flavonoid intake, and linear trends in total and component HEI scores by flavonoid intake were assessed using orthogonal polynomial contrasts. All analyses were weighted to be nationally representative. RESULTS: Mean intake of flavonoids was 251 mg/d, with flavan-3-ols accounting for 81% of intake. Non-Hispanic whites had significantly higher (P < 0.001) intakes of total flavonoids (275 mg/d) than non-Hispanic blacks (176 mg/d) and Hispanics (139 mg/d). Tea was the primary source (80%) of flavonoid intake. Regardless of whether the flavonoid contribution of tea was included, total HEI score and component scores for total fruit, whole fruit, total vegetables, greens and beans, seafood and plant proteins, refined grains, and empty calories increased (P < 0.001) across flavonoid intake quartiles. CONCLUSIONS: A new database that permits comprehensive estimation of flavonoid intakes in WWEIA, NHANES 2007-2008; identification of their major food/beverage sources; and determination of associations with dietary quality will lead to advances in research on relations between flavonoid intake and health. Findings suggest that diet quality, as measured by HEI, is positively associated with flavonoid intake.

Sodium monitoring in commercially processed and restaurant foods.

BACKGROUND: Most sodium in the US diet comes from commercially processed and restaurant foods. Sodium reduction in these foods is key to several recent public health efforts. OBJECTIVE: The objective was to provide an overview of a program led by the USDA, in partnership with other government agencies, to monitor sodium contents in commercially processed and restaurant foods in the United States. We also present comparisons of nutrients generated under the program to older data. DESIGN: We track ∼125 commercially processed and restaurant food items ("sentinel foods") annually using information from food manufacturers and periodically by nationwide sampling and laboratory analyses. In addition, we monitor >1100 other commercially processed and restaurant food items, termed "priority-2 foods" (P2Fs) biennially by using information from food manufacturers. These foods serve as indicators for assessing changes in the sodium content of commercially processed and restaurant foods in the United States. We sampled all sentinel foods nationwide and reviewed all P2Fs in 2010-2013 to determine baseline sodium concentrations. RESULTS: We updated sodium values for 73 sentinel foods and 551 P2Fs in the USDA's National Nutrient Database for Standard Reference (releases 23-26). Sodium values changed by at least 10% for 43 of the sentinel foods, which, for 31 foods, including commonly consumed foods such as bread, tomato catsup, and potato chips, the newer sodium values were lower. Changes in the concentrations of related nutrients (total and saturated fat, total sugar, potassium, or dietary fiber) that were recommended by the 2010 Dietary Guidelines for Americans for reduced or increased consumption accompanied sodium reduction. The results of sodium reduction efforts, based on resampling of the sentinel foods or re-review of P2Fs, will become available beginning in 2015. CONCLUSION: This monitoring program tracks sodium reduction efforts, improves food composition databases, and strengthens national nutrition monitoring.

Top sources of dietary sodium from birth to age 24 mo, United States, 2003-2010.

BACKGROUND: Sodium intake is high in US children. Data are limited on the dietary sources of sodium, especially from birth to age 24 mo. OBJECTIVE: We identified top sources of dietary sodium in US children from birth to age 24 mo. DESIGN: Data from the NHANES 2003-2010 were used to examine food sources of sodium (population proportions and mean intakes) in 778 participants aged 0-5.9 mo, 914 participants aged 6-11.9 mo, and 1219 participants aged 12-23.9 mo by sociodemographic characteristics. RESULTS: Overall, mean dietary sodium intake was low in 0-5.9-mo-old children, and the top contributors were formula (71.7%), human milk (22.9%), and commercial baby foods (2.2%). In infants aged 6-11.9 mo, the top 5 contributors were formula (26.7%), commercial baby foods (8.8%), soups (6.1%), pasta mixed dishes (4.0%), and human milk (3.9%). In children aged 12-23.9 mo, the top contributors were milk (12.2%), soups (5.4%), cheese (5.2%), pasta mixed dishes (5.1%), and frankfurters and sausages (4.6%). Despite significant variation in top food categories across racial/ethnic groups, commercial baby foods were a top food contributor in children aged 6-11.9 mo, and frankfurters and sausages were a top food contributor in children aged 12-23.9 mo. The top 5 food categories that contributed to sodium intake also differed by sex. Most of the sodium consumed (83-90%) came from store foods (e.g., from the supermarket). In children aged 12-23.9 mo, 9% of sodium consumed came from restaurant foods, and 4% of sodium came from childcare center foods. CONCLUSIONS: The vast majority of sodium consumed comes from foods other than infant formula or human milk after the age of 6 mo. Although the majority of sodium intake was from store foods, after age 12 mo, restaurant foods contribute significantly to intake. Reducing the sodium content in these settings would reduce sodium intake in the youngest consumers.

Overcoming Insulin Insufficiency by Forced Follistatin Expression in ß-cells of db/db Mice.

Diabetes poses a substantial burden to society as it can lead to serious complications and premature death. The number of cases continues to increase worldwide. Two major causes of diabetes are insulin resistance and insulin insufficiency. Currently, there are few antidiabetic drugs available that can preserve or protect ß-cell function to overcome insulin insufficiency in diabetes. We describe a therapeutic strategy to preserve ß-cell function by overexpression of follistatin (FST) using an AAV vector (AAV8-Ins-FST) in diabetic mouse model. Overexpression of FST in the pancreas of db/db mouse increased ß-cell islet mass, decreased fasting glucose level, alleviated diabetic symptoms, and essentially doubled lifespan of the treated mice. The observed islet enlargement was attributed to ß-cell proliferation as a result of bioneutralization of myostatin and activin by FST. Overall, our study indicates overexpression of FST in the diabetic pancreas preserves ß-cell function by promoting ß-cell proliferation, opening up a new therapeutic avenue for the treatment of diabetes.

Escape variants of the XPR1 gammaretrovirus receptor are rare due to reliance on a splice donor site and a short hypervariable loop.

Entry determinants in the XPR1 receptor for the xenotropic/polytropic mouse leukemia viruses (XP-MLVs) lie in its third and fourth putative extracellular loops (ECLs). The critical ECL3 receptor determinant overlies a splice donor and is evolutionarily conserved in vertebrate XPR1 genes; 2 of the 3 rare replacement mutations at this site destroy this receptor determinant. The 13 residue ECL4 is hypervariable, and replacement mutations carrying an intact ECL3 site alter but do not abolish receptor activity, including replacement of the entire loop with that of a jellyfish (Cnidaria) XPR1. Because ECL4 deletions are found in all X-MLV-infected Mus subspecies, we deleted each ECL4 residue to determine if deletion-associated restriction is residue-specific or is effected by loop size. All deletions influence receptor function, although different deletions affect different XP-MLVs. Thus, receptor usage of a constrained splice site and a loop that tolerates mutations severely limits the likelihood of host escape mutations.

Difference in adult food group intake by sex and age groups comparing Brazil and United States nationwide surveys.

BACKGROUND: International comparisons of dietary intake are an important source of information to better understand food habits and their relationship to nutrition related diseases. The objective of this study is to compare food intake of Brazilian adults with American adults identifying possible dietary factors associated with the increase in obesity in Brazil. METHODS: This research used cross-national analyses between the United States and Brazil, including 5,420 adults in the 2007-2008 What We Eat In America, National Health and Nutrition Examination Survey and 26,390 adults in the 2008-2009 Brazilian Household Budget Survey, Individual Food Intake. Dietary data were collected through 24 h recalls in the U.S. and through food records in Brazil. Foods and beverages were combined into 25 food categories. Food intake means and percentage of energy contribution by food categories to the population's total energy intake were compared between the countries. RESULTS: Higher frequencies of intake were reported in the United States compared to Brazil for the majority of food categories except for meat, rice and rice dishes; beans and legumes; spreads; and coffee and tea. In either country, young adults (20-39 yrs) had greater reports of meat, poultry and fish mixed dishes; pizza and pasta; and soft drinks compared to older adults (60 + yrs). Meat, poultry and fish mixed dishes (13%), breads (11%), sweets and confections (8%), pizza and pasta (7%), and dairy products (6%) were the top five food category sources of energy intake among American adults. The top five food categories in Brazil were rice and rice dishes (13%), meat (11%), beans and legumes (10%), breads (10%), and coffee and tea (6%). Thus, traditional plant-based foods such as rice and beans were important contributors in the Brazilian diet. CONCLUSION: Although young adults had higher reports of high-calorie and nutrient-poor foods than older adults in both countries, Brazilian young adults did not consume a diet similar to Americans, indicating that it is still possible to reverse the current trends of incorporating Western dietary habits in Brazil.

Muscle and heart function restoration in a limb girdle muscular dystrophy 2I (LGMD2I) mouse model by systemic FKRP gene delivery.

Mutations in fukutin-related protein (FKRP) gene cause a wide spectrum of disease phenotypes including the mild limb-girdle muscular dystrophy 2I (LGMD2I), the severe Walker-Warburg syndrome, and muscle-eye-brain disease. FKRP deficiency results in α-dystroglycan (α-DG) hypoglycosylation in the muscle and heart, which is a biochemical hallmark of dystroglycanopathies. To study gene replacement therapy, we generated and characterized a new mouse model of LGMD2I harboring the human mutation leucine 276 to isoleucine (L276I) in the mouse alleles. The homozygous knock-in mice (L276I(KI)) mimic the classic late onset phenotype of LGMD2I in both skeletal and cardiac muscles. Systemic delivery of human FKRP gene by AAV9 vector in the L276I(KI) mice, at either neonatal age or at the age of 9 months, rendered body wide FKRP expression and restored glycosylation of α-DG in both skeletal and cardiac muscles. FKRP gene therapy ameliorated dystrophic pathology and cardiomyopathy such as muscle degeneration, fibrosis, and myofiber membrane leakage, resulting in restoration of muscle and heart contractile functions. Thus, these results demonstrated that the treatment based on FKRP gene replacement was effective.

The avian XPR1 gammaretrovirus receptor is under positive selection and is disabled in bird species in contact with virus-infected wild mice.

Xenotropic mouse leukemia viruses (X-MLVs) are broadly infectious for mammals except most of the classical strains of laboratory mice. These gammaretroviruses rely on the XPR1 receptor for entry, and the unique resistance of laboratory mice is due to two mutations in different putative XPR1 extracellular loops. Cells from avian species differ in susceptibility to X-MLVs, and 2 replacement mutations in the virus-resistant chicken XPR1 (K496Q and Q579E) distinguish it from the more permissive duck and quail receptors. These substitutions align with the two mutations that disable the laboratory mouse XPR1. Mutagenesis of the chicken and duck genes confirms that residues at both sites are critical for virus entry. Among 32 avian species, the 2 disabling XPR1 mutations are found together only in the chicken, an omnivorous, ground-dwelling fowl that was domesticated in India and/or Southeast Asia, which is also where X-MLV-infected house mice evolved. The receptor-disabling mutations are also present separately in 5 additional fowl and raptor species, all of which are native to areas of Asia populated by the virus-infected subspecies Mus musculus castaneus. Phylogenetic analysis showed that the avian XPR1 gene is under positive selection at sites implicated in receptor function, suggesting a defensive role for XPR1 in the avian lineage. Contact between bird species and virus-infected mice may thus have favored selection of mouse virus-resistant receptor orthologs in the birds, and our data suggest that similar receptor-disabling mutations were fixed in mammalian and avian species exposed to similar virus challenges.

Evolution of functional and sequence variants of the mammalian XPR1 receptor for mouse xenotropic gammaretroviruses and the human-derived retrovirus XMRV.

Genetic conflicts between retroviruses and their receptors result in the evolution of novel host entry restrictions and novel virus envelopes, and such variants can influence trans-species transmission. We screened rodents and other mammals for sequence variation in the Xpr1 receptor for the mouse xenotropic or polytropic mouse leukemia viruses (X-MLVs or P-MLVs, respectively) of the gammaretrovirus family and for susceptibility to mouse-derived X/P-MLVs and to XMRV (xenotropic murine leukemia virus-related virus), an X-MLV-like virus isolated from humans with prostate cancer and chronic fatigue syndrome. We identified multiple distinct susceptibility phenotypes; these include the four known Xpr1 variants in Mus and a novel fifth Xpr1 gene found in Mus molossinus and Mus musculus. We describe the geographic and species distribution of the Mus Xpr1 variants but failed to find the X-MLV-restrictive laboratory mouse allele in any wild mouse. We used mutagenesis and phylogenetic analysis to evaluate the functional contributions made by constrained, variable, and deleted residues. Rodent Xpr1 is under positive selection, indicating a history of host-pathogen conflicts; several codons under selection have known roles in virus entry. All non-Mus mammals are susceptible to mouse X-MLVs, but some restrict other members of the X/P-MLV family, and the resistance of hamster and gerbil cells to XMRV indicates that XMRV has unique receptor requirements. We show that the hypervariable fourth extracellular XPR1 loop (ECL4) contains three evolutionarily constrained residues that do not contribute to receptor function, we identify two novel residues important for virus entry (I579 and T583), and we describe a unique pattern of ECL4 variation in the three virus-restrictive Xpr1 variants found in MLV-infected house mice; these mice carry different deletions in ECL4, suggesting either that these sites or loop size affects receptor function.

Adaptive evolution of Mus Apobec3 includes retroviral insertion and positive selection at two clusters of residues flanking the substrate groove.

Mouse APOBEC3 (mA3) is a cytidine deaminase with antiviral activity. mA3 is linked to the Rfv3 virus resistance factor, a gene responsible for recovery from infection by Friend murine leukemia virus, and mA3 allelic variants differ in their ability to restrict mouse mammary tumor virus. We sequenced mA3 genes from 38 inbred strains and wild mouse species, and compared the mouse sequence and predicted structure with human APOBEC3G (hA3G). An inserted sequence was identified in the virus restrictive C57BL strain allele that disrupts a splice donor site. This insertion represents the long terminal repeat of the xenotropic mouse gammaretrovirus, and was acquired in Eurasian mice that harbor xenotropic retrovirus. This viral regulatory sequence does not alter splicing but is associated with elevated mA3 expression levels in spleens of laboratory and wild-derived mice. Analysis of Mus mA3 coding sequences produced evidence of positive selection and identified 10 codons with very high posterior probabilities of having evolved under positive selection. Six of these codons lie in two clusters in the N-terminal catalytically active cytidine deaminase domain (CDA), and 5 of those 6 codons are polymorphic in Rfv3 virus restrictive and nonrestrictive mice and align with hA3G CDA codons that are critical for deaminase activity. Homology models of mA3 indicate that the two selected codon clusters specify residues that are opposite each other along the predicted CDA active site groove, and that one cluster corresponds to an hAPOBEC substrate recognition loop. Substitutions at these clustered mA3 codons alter antiviral activity. This analysis suggests that mA3 has been under positive selection throughout Mus evolution, and identified an inserted retroviral regulatory sequence associated with enhanced expression in virus resistant mice and specific residues that modulate antiviral activity.

A comparison of two systems for entering and assessing dietary data for a research study.

To reduce the cost of analyzing dietary data for research studies, we evaluated the accuracy of an entry and assessment system that could be used by trained food and nutrition professionals who did not routinely perform this type of task. We compared intakes from 24-hour recalls for 175 adult women and 185 schoolchildren using two methods for entry of dietary data. For the standard method, registered dietitians who routinely evaluate dietary data entered the recalls using a professional data entry program, RapidCalc. For the second method, other food and nutrition professionals were trained by the registered dietitians to use the Pacific Tracker program, a consumer-friendly dietary assessment system. Both programs use the same food composition table. Mean food group and nutrient intakes were similar for the two methods, differing by <10% on average for both adults and children. Correlations were also high, ranging from 0.77 to 0.96 for the women and from 0.76 to 0.94 for the children. For adults and children combined, mean energy intakes were remarkably close, at 2,067 kcal/d for RapidCalc and 2,072 kcal/d for Pacific Tracker, although absolute differences in energy intakes were >300 kcal/d for 23% of the women and 30% of the children. Costs are much lower with the Pacific Tracker method, unless the fees for the standard method are subsidized. We conclude that the Pacific Tracker method provides an accurate and cost-effective method of dietary data entry for research purposes.

Contribution of dietary supplements to nutrient adequacy among children in Hawaii.

OBJECTIVES: To quantify the use of dietary supplements over a 24-hour and 1-month time frame, to determine the contribution of dietary supplements to the prevalence of dietary nutrient adequacy in the population, and to identify factors associated with supplement use, including characteristics of caregivers. DESIGN: Cross-sectional study. SUBJECTS/SETTING: Children aged 8 to 11 years from four primarily Native Hawaiian and Pacific Islander communities on Oahu (n=115) and the island of Hawaii (n=70). METHODS: A 24-hour food recall and a dietary supplement record were collected and analyzed for each child. Demographic and supplement use data were collected for each caregiver. STATISTICAL ANALYSES: Significant differences between supplement users and nonusers were determined by chi(2) analysis. Prevalence of dietary nutrient adequacy with and without intake from dietary supplements was calculated using PC-Side software (version 1.02, 2001, Department of Statistics and Center for Agricultural and Rural Development, Iowa State University, Ames). RESULTS: Use of any dietary supplement by children in the previous day and month was 26% (n=48) and 40% (n=74), respectively. Prevalence of dietary nutrient adequacy from foods alone ranged from 33% to 100%, and increased to 59% to 100% when the nutrient contribution from dietary supplements was included. The largest increases in nutrient adequacy were for vitamins A, E, and C. Use of dietary supplements was most strongly associated with use of dietary supplements by caregivers, as well as with younger age of child, and greater years of caregiver education. CONCLUSIONS: Dietary supplements are being used by a large percentage of these children in Hawaii and use is associated with use by their caregivers. The nutrient contribution from dietary supplements increased the prevalence of nutrient adequacy for several nutrients.