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The Food Resource Equity and Sustainability for Health (“FRESH”) study is an Indigenous-led intervention to increase vegetable and fruit intake among Native American children. As part of this study, we developed a hybrid (online and in-person) food sovereignty and nutrition education curriculum for the parents of these children. This 16-week curriculum was developed to promote household- and community-level healthy eating and food sovereignty practices to parents of preschool-aged children residing in Osage Nation, Oklahoma. A total of 81 parent/caregivers participated in the curriculum component of the FRESH study, with a median age of 34 years (range: 23–54 years). Most study participants were female (88.9%) and less than half (45.7%) had an annual household income of more than US$50,000. Most were married or had a significant other (76.5%) and worked full-time (65.4%). The median total number of children in the home

Very low food security among children (VLFS-C), often referred to as child hunger, can profoundly hinder child development, family well-being, and community health. Food pantries are important community resources that routinely serve at-risk families. This study investigated the influence of various candidate risk factors for VLFS-C within a food pantry population to inform the development of the "Pantry Assessment Tool against Child Hunger (PATCH)." We collected standardized surveys among a representative sample of households with children accessing food pantry services in Oklahoma (n = 188). Weighted analyses revealed a large majority of households experienced child-level food insecurity (70.6%), with nearly half reporting low food security and nearly one-quarter reporting VLFS-C. We then used logistic regression to identify factors associated with VLFS-C, followed by chi-square automatic interaction detection (CHAID) to assess if, and in what progression, significant risk factors predicted VLFS-C. In unadjusted models, annual household income

BackgroundOver the past four decades, advances in HIV treatment have contributed to a longer life expectancy for people living with HIV (PLWH). With these gains, the prevention and management of chronic co-morbidities, such as diabetes, are now central medical care goals for this population. In the United States, food insecurity disproportionately impacts PLWH and may play a role in the development of insulin resistance through direct and indirect pathways. The Nutrition to Optimize, Understand, and Restore Insulin Sensitivity in HIV for Oklahoma (NOURISH-OK) will use a novel, multi-level, integrated framework to explore how food insecurity contributes to insulin resistance among PLWH. Specifically, it will explore how food insecurity may operate as an intermediary risk factor for insulin resistance, including potential linkages between upstream determinants of health and downstream consequences of poor diet, other behavioral risk factors, and chronic inflammation.Methods/designThis paper summarizes the protocol for the first aim of the NOURISH-OK study, which involves purposeful cross-sectional sampling of PLWH (n=500) across four levels of food insecurity to test our conceptual framework. Developed in collaboration with community stakeholders, this initial phase involves the collection of anthropometrics, fasting blood samples, non-blood biomarkers, 24-hour food recall to estimate the Dietary Inflammatory Index (DII®) score, and survey data. A 1-month, prospective observational sub-study (total n=100; n=25 for each food security group) involves weekly 24-hour food recalls and stool samples to identify temporal associations between food insecurity, diet, and gut microbiome composition. Using structural equation modeling, we will explore how upstream risk factors, including early life events, current discrimination, and community food access, may influence food insecurity and its potential downstream impacts, including diet, other lifestyle risk behaviors, and chronic inflammation, with insulin resistance as the ultimate outcome variable. Findings from these analyses of observational data will inform the subsequent study aims, which involve qualitative exploration of significant pathways, followed by development and testing of a low-DII® food as medicine intervention to reverse insulin resistance among PLWH (ClinicalTrials.gov Identifier: NCT05208671).DiscussionThe NOURISH-OK study will address important research gaps to inform the development of food as medicine interventions to support healthy aging for PLWH.

ObjectiveTo increase vegetable and fruit intake, reduce body mass index (BMI), and improve parental blood pressure among American Indian families.DesignRandomized, wait-list controlled trial testing a multi-level (environmental, community, family, and individual) multi-component intervention with data collection at baseline and 6 months post-intervention.SettingTribally owned and operated Early Childhood Education (ECE) programs in the Osage Nation in Oklahoma.ParticipantsAmerican Indian families (at least one adult and one child in a ECE program). A sample size of 168 per group will provide power to detect differences in fruit and vegetable intake.InterventionThe 6-month intervention consisted of a (1) ECE-based nutrition and gardening curriculum; (2) nutrition education and food sovereignty curriculum for adults; and (3) ECE program menu modifications.Main Outcome MeasuresThe primary outcome is increase in fruit and vegetable intake, assessed with a 24-h recall for adults and plate weight assessments for children. Secondary outcomes included objective measures of BMI among adults and children and blood pressure among adults.

Food preferences begin in early childhood, and a child’s willingness to try (WTT) new vegetables is an important determinant of vegetable intake. Young children living in rural communities are at increased risk for food insecurity, which may limit exposure to and consumption opportunities for vegetables. This manuscript describes the validation of the Farfan-Ramirez WTT (FR-WTT) measure using baseline data from the FRESH study, a gardening intervention for Native American families with preschool-aged children in Osage Nation, Oklahoma. Individually weighed vegetable containers were prepared with six types of vegetables and ranch dip. Researchers presented children (n = 164; M = 4.3 years, SD = 0.8) with these vegetables preceding a snack- or lunch time and recorded the child’s FR-WTT for each vegetable using a 5-point scale, ranging from “did not remove food (0)” to “put food in mouth and swallowed (4)”. After the presentation period, contents were re-weighed to calculate vegetable consumption. Household parents/guardians completed the Child Food Neophobia Scale (CFNS) for their child. FR-WTT scores were positively correlated with consumption weights of all vegetables (r = 0.7613, p < 0.0001) and each vegetable individually (r = 0.2016–0.7664). The total FR-WTT score was inversely correlated with the CFNS score (r = 0.3268, p < 0.0001). Sensitivity analyses demonstrated similar relationships by BMI, food security, and age. In conclusion, the FR-WTT is a valid method for assessing young children’s vegetable eating behavior and intake.

Due to the high prevalence of Hepatitis C virus (HCV) infection among individuals born between 1945 and 1965, in 2012 the Centers for Disease Control and Prevention began recommending HCV screening for this birth cohort. As adherence to HCV treatment is essential for sustained virologic response, identifying factors influencing medication adherence is important. The validated Adherence to Refills and Medications Scale (ARMS) is used to study recent medication adherence in those with chronic disease. This cross-sectional pilot study assesses factors associated with reduced adherence, indicated by higher ARMS scores, among individuals in this birth cohort. To elucidate factors associated with medication adherence, measured by the ARMS score, among a birth cohort at higher risk for HCV to guide future treatment and improve adherence. Patients born between 1945 and 1965, accessing care at an academic family medicine clinic, were recruited between April and June 2019. Demographics, prior HCV diagnosis, HCV risk factors (prior imprisonment, tattoos, and intravenous drug use), depression assessment (Patient Health Questionnaire-9), adverse childhood experiences (ACEs), and ARMS scores were collected. Mean ARMS scores were compared using t tests and analysis of variance (α = 0.05), while multiple variable models were performed using linear regression. Women comprised 58% of participants (n = 76), 52% reported depression and 37% 4 or more ACEs. The mean ARMS score was 16.3 (SD = 3.43) and 10% reported prior diagnosis of HCV. In the final multiple variable model, ARMS scores were 2.3 points higher in those with mild depression (95% CI: 0.63, 4.04), 2.0 in those with at least 4 ACEs (95% CI: 0.55, 3.49), and 1.8 in those with tattoos (95% CI: 0.30, 3.28). ACEs and food insecurity were identified as confounding variables in those with moderate to severe depression. This study found medication adherence was related to depression, ACEs, tattoos, and food insecurity among patients in this birth cohort at higher risk for HCV.

Background US medical schools are increasingly integrating lifestyle medicine competencies into their academic programs. Yet, physician assistant (PA) academic programs have been slower to respond. Methods We developed, implemented, and evaluated a nutrition-centered lifestyle medicine curriculum for 2nd-year PA students (n = 24). The 4-week hybrid, 2-credit hour course activities aligned with the American College of Lifestyle Medicine competencies for primary care providers and reinforced four of the Accreditation Standards for PA Education. We combined didactic lectures with weekly hands-on cooking modules from the “Health meets Food” courseware for medical students. We employed a pre-post evaluation design including a comparison group of 2nd-year PA students in a separate program. We assessed changes in personal nutrition behaviors and knowledge and confidence for counseling in nutrition, exercise/physical activity, weight, smoking, and alcohol, using the modified 5A’s framework (assess, advise, agree, assist, and arrange) for lifestyle counseling. Results Students receiving the intervention demonstrated significantly higher gains in both knowledge and confidence for the 5A’s of nutrition counseling compared to the control group. Self-reported knowledge and confidence for the 5A’s of counseling for the other lifestyle behaviors similarly improved among the intervention group compared to the control group, but to a lesser extent. Conclusion A nutrition-centered lifestyle medicine course can demonstrate PA academic program adherence to accreditation standards, while also introducing students to nutrition and lifestyle medicine competencies. Hands-on experiences that reinforce didactic instruction may maximize student knowledge and self-efficacy for implementing lifestyle medicine into their practice.

Background American Indians (AIs) have significantly higher rates of diet-related chronic diseases than other racial/ethnic groups, and many live in environments with limited access to healthy food. Objective As part of the Tribal Resilience in Vulnerable Environments (THRIVE) study, we examined the relations between the perceived food environment, utilization of food retailers, fruit and vegetable intake, and chronic diseases, including obesity, hypertension, and type 2 diabetes among AI adults. Methods Through a community-based participatory research partnership, we surveyed a cross-sectional sample of 513 AIs living within the Chickasaw Nation and the Choctaw Nation of Oklahoma. Results Only 57% of participants reported that it was easy to purchase fruits and vegetables in their town, and fewer (35%) reported that available fruits and vegetables were of high quality. Additionally, over half (56%) reported traveling ≥20 miles round trip to shop for food. Few participants met the recommended daily intake for fruit (44%) or vegetables (25%). Obesity (55%), hypertension (49%), and diabetes (25%) were commonly reported. Obesity was significantly higher among participants who reported that the price of fruits and vegetables were cost-prohibitive (prevalence proportion ratio (PPR): 1.24; 95% CI: 1.02, 1.50) and those who shopped frequently for food at nontraditional food retailers, such as Dollar Stores (PPR: 1.35; 95% CI: 1.08, 1.69) and small markets (PPR: 1.38; 95% CI: 1.02, 1.86). Diabetes was significantly higher among participants who frequently shopped at convenience stores/gas stations (PPR: 2.26; 95% CI: 1.22, 4.19). Conclusions Our study found that the use of nontraditional food retailers, including convenience stores, gas stations, and Dollar Stores, as a regular source of food was associated with obesity and diabetes. These results underscore the importance of interventions to improve rural Tribal food environments. Healthy retail interventions in nontraditional retail settings, such as those implemented through the THRIVE study, may contribute to reducing AI health disparities.

Purpose The purpose of this study is to explore the associations between food insecurity (FI) and coping strategies of relevance to diabetes self-management among households of people with diabetes (HHDM) who access US food pantry programs. Methods The authors conducted a secondary data analysis of HHDM accessing US food pantry programs from the Hunger in America 2014 study ( n = 16 826). Weighted analyses included descriptive statistics for household sociodemographics, food pantry service utilization, FI, and coping behaviors. The authors used chi-square and logistic regression to estimate the relationship between FI and coping behaviors. Results Nearly one-half of HHDM reported visiting food pantries at least 6 times in the past year. Most HHDM were FI, with the majority experiencing the most severe form of FI. Over one-fifth of households reported lacking health insurance. The majority of HHDM reported purchasing inexpensive unhealthy foods to ensure household food adequacy, and many reported watering down food and beverages. The odds of reporting these behaviors significantly increased as FI worsened. Conclusion Food pantries represent an opportunity for the delivery of community-based diabetes self-management education and support programs. These programs should be adapted to address population barriers to self-management and to support access to healthful foods and medical care.

The efficacy of tobacco treatment delivered by state quitlines in diverse populations is well-supported, yet little is known about associations between treatment dose and cessation outcomes following the implementation of Ask-Advise-Connect (AAC), an electronic health record-based systematic referral process that generates a high volume of proactive calls from the state quitline to smokers. The current study is a secondary analysis of a 34-month implementation trial evaluating ACC in 13 safety-net clinics in Houston, TX. Treatment was delivered by a quitline and comprised up to five proactive, telephone-delivered multi-component cognitive-behavioral treatment sessions. Associations between treatment dose and abstinence were examined. Abstinence was assessed by phone six months after treatment enrollment, and biochemically confirmed via mailed saliva cotinine. Among smokers who enrolled in treatment and agreed to follow-up (n = 3704), 29.2% completed no treatment sessions, 35.5% completed one session, 16.4% completed two sessions, and 19.0% completed ≥three sessions. Those who completed one (vs. no) sessions were no more likely to report abstinence (OR: 0.98). Those who completed two (vs. no) sessions were nearly twice as likely to report abstinence (OR: 1.83). Those who completed ≥three (vs. no) sessions were nearly four times as likely to report abstinence (OR: 3.70). Biochemically-confirmed cessation outcomes were similar. Most smokers received minimal or no treatment, and treatment dose had a large impact on abstinence. Results highlight the importance of improving engagement in evidence-based treatment protocols following enrollment. Given that motivation to quit fluctuates, systematically offering enrollment to all smokers at all visits is important., Highlights • The majority of smokers received minimal or no evidence-based tobacco treatment. • Smokers who completed 0 or 1 treatment sessions were unlikely to achieve abstinence. • Completion of 2 calls doubled the likelihood of abstinence at 6 months. • Completion of ≥3 calls was associated with a near quadrupling of abstinence rates. • Improving engagement in evidence-based treatment protocols is a research priority.

This cohort study evaluates the first 22 months of implementation of the Cherokee Nation Heath Services community-based program designed to eliminate hepatitis C virus (HCV) infection., Key Points Question Can a community-based tribal hepatitis C virus (HCV) elimination program be implemented successfully in a rural setting? Findings In this cohort study, first-time HCV screening coverage increased from 20.9% to 38.2% from 3 years before to 22 months into implementation of the Cherokee Nation Health Services HCV elimination program. Identification, treatment, and cure of newly identified current HCV infections increased. Meaning In this study, implementation of a community-based HCV elimination program was associated with an improved cascade of care; this information may serve other organizations planning to implement similar programs in large rural areas., Importance In 2019, hepatitis C virus (HCV) infection contributed to more deaths in the US than 60 other notifiable infectious diseases combined. The incidence of and mortality associated with HCV infection are highest among American Indian and Alaska Native individuals. Objective To evaluate the association of the Cherokee Nation (CN) HCV elimination program with each element of the cascade of care: HCV screening, linkage to care, treatment, and cure. Design, Setting, and Participants This cohort study used data from the CN Health Services (CNHS), which serves approximately 132 000 American Indian and Alaska Native individuals residing in the 14-county CN reservation in rural northeastern Oklahoma. Data from the first 22 months of implementation (November 1, 2015, to August 31, 2017) of an HCV elimination program were compared with those from the pre–elimination program period (October 1, 2012, to October 31, 2015). The analysis included American Indian and Alaska Native individuals aged 20 to 69 years who accessed care through the CNHS between October 1, 2012, and August 31, 2017. Cure data were recorded through April 15, 2018. Exposure The CN HCV elimination program. Main Outcomes and Measures The main outcomes were the proportions of the population screened for HCV, diagnosed with current HCV infection, linked to care, treated, and cured during the initial 22 months of the elimination program period and the pre–elimination program period. Data from electronic health records and an HCV treatment database were analyzed. The cumulative incidence of HCV infection in this population was estimated using bayesian analyses. Results Among the 74 039 eligible individuals accessing care during the elimination program period, the mean (SD) age was 36.0 (13.5) years and 55.9% were women. From the pre–elimination program period to the elimination program period, first-time HCV screening coverage increased from 20.9% to 38.2%, and identification of current HCV infection and treatment in newly screened individuals increased from a mean (SD) of 170 (40) per year to 244 (4) per year and a mean of 95 (133) per year to 215 (9) per year, respectively. During the implementation period, of the 793 individuals with current HCV infection accessing the CNHS, 664 were evaluated (83.7%), 394 (59.3%) initiated treatment, and 335 (85.0%) had documented cure. In less than 2 years, the 85% 3-year goal was reached for cure (85.0%), and the goal for linkage to care was nearly reached (83.7%), whereas screening (44.1%) and treatment initiation (59.3%) required more time and resources. Conclusions and Relevance This cohort study found that after 22 months of implementation, the CNHS community-based HCV elimination program was associated with an improved cascade of care. The facilitators and lessons learned in this program may be useful to other organizations planning similar programs.

Administrative health databases have been used to monitor trends in infective endocarditis hospitalization related to nonprescription injection drug use (IDU) using International Classification of Diseases (ICD) code algorithms. Because no ICD code for IDU exists, drug dependence and hepatitis C virus (HCV) have been used as surrogate measures for IDU, making misclassification error (ME) a threat to the accuracy of existing estimates. In a serial cross-sectional analysis, we compared the unadjusted and ME-adjusted prevalences of IDU among 70,899 unweighted endocarditis hospitalizations in the 2007–2016 National Inpatient Sample. The unadjusted prevalence of IDU was estimated with a drug algorithm, an HCV algorithm, and a combination algorithm (drug and HCV). Bayesian latent class models were used to estimate the median IDU prevalence and 95% Bayesian credible intervals and ICD algorithm sensitivity and specificity. Sex- and age group-stratified IDU prevalences were also estimated. Compared with the misclassification-adjusted prevalence, unadjusted estimates were lower using the drug algorithm and higher using the combination algorithm. The median ME-adjusted IDU prevalence increased from 9.7% (95% Bayesian credible interval (BCI): 6.3, 14.8) in 2008 to 32.5% (95% BCI: 26.5, 38.2) in 2016. Among persons aged 18–34 years, IDU prevalence was higher in females than in males. ME adjustment in ICD-based studies of injection-related endocarditis is recommended.

PURPOSE: Little is known about the contribution of social support to physical activity (PA) behavior among American Indians (AIs). This community‐based participatory research study examined the prevalence of and associations between different types of PA social support and PA among AIs in rural Oklahoma. METHODS: Our tribal‐academic partnership surveyed AI adults (N = 513) living within the tribal jurisdictional areas of 2 tribal nations. We used the Physical Activity Social Support (PASS) scale to assess 3 types of PA social support and Poisson regression to investigate associations between PASS types and self‐reported PA behavior. FINDINGS: Over a third of participants perceived high levels of PA social support from friends (37%), family (35%), and overall (34%), yet only 29% reported regular PA (ie, 150 minutes or more weekly). Participants who exercised with pets/other were significantly more likely to achieve regular PA than those who exercised alone (PR 2.0, 95% CI: 1.4‐2.9). Although not significant, compared with those reporting no/low support, participants with high friend PASS (PR 1.2, 95%: CI 0.9‐1.6), medium family PASS (PR 1.2, 95% CI: 0.9‐1.7), and overall PASS (PR 1.1, 95% CI: 0.8‐1.6) were more likely to report regular PA. CONCLUSIONS: The majority of participants did not meet current recommendations for PA behavior, which underscores the ongoing need for PA effective interventions among AIs living in rural areas. Results suggest that exercising with pets/other could be an important factor for future intervention. Further research is needed to elucidate determinants of PA and test interventions to increase PA among AIs.

Food pantries serve populations with high rates of chronic disease and thus may be ideal settings for community-based health promotion programs. This study aimed to describe the readiness of food p...

In rural Native American communities, access to healthy foods is limited and diet-related disparities are significant. Tribally owned and operated convenience stores, small food stores that sell ready-to-eat foods and snacks primarily high in fat and sugar, serve as the primary and, in some areas, the only food stores. The Tribal Health and Resilience in Vulnerable Environments or “THRIVE” study, implemented between 2013 and 2018, is the first healthy retail intervention study implemented in tribally owned and operated convenience stores. THRIVE aims to increase vegetable and fruit intake among Native Americans living within the Chickasaw and Choctaw Nation of Oklahoma. The study comprises three phases: 1) formative research assessing tribal community food environments and associated health outcomes; 2) intervention development to assess convenience stores and tailor healthy retail product, pricing, promotion, and placement strategies; and 3) intervention implementation and evaluation. In this paper we share the participatory research process employed by our tribal-university partnership to develop this healthy retail intervention within the unique contexts of tribal convenience stores. We summarize our methods to engage tribal leaders across diverse health, government, and commerce sectors and adapt and localize intervention strategies that test the ability of tribal nations to increase fruit and vegetable purchasing and consumption among tribal members. Study processes will assist in developing a literature base for policy and environmental strategies that intervene broadly to improve Native community food environments and eliminate diet-related disparities among Native Americans., Highlights • The process of designing and implementing the first healthy retail study in tribal convenience stores is described. • Community-based participatory research engaged diverse tribal leaders across health, government, and commerce sectors. • Findings will elucidate relationships between Native community food environments and disease.

In rural American Indian (AI) communities, access to affordable, healthy foods is often limited. Understanding AI food choice considerations when selecting foods, such as sensory appeal, cost, or health, is an important yet understudied topic for eliminating persistent AI health disparities. In partnership with the Chickasaw Nation and Choctaw Nation of Oklahoma, we administered a modified version of the Food Choice Values (FCV) Questionnaire to a cross-sectional sample of 83 AI patrons shopping at tribally-owned convenience stores ≥3 times per week. The FCV Questionnaire uses 25 items to assess eight FCV subscales related to buying and eating food, including sensory appeal; safety; accessibility; convenience; health/ weight control; organic; tradition; and comfort. We compared mean scores for each FCV subscale by demographic groups using t-tests and ANOVA. We used confirmatory factor analysis (CFA) to examine how well the data from this population fit FCV subscale constructs. We then used cluster analysis, MANOVA, and discriminant analysis to characterize distinct segments of the population based on patterns of FCV endorsement. Appeal, safety, and access FCVs were most strongly endorsed across the sample. Prioritization of FCVs varied by age, gender, income, and education. Our cluster analysis identified four groups, or segments, each with distinct patterns of FCV endorsement: limited endorsement of any FCVs (23.3%); safety and sensory appeal (32.9%); health/weight control (17.8%); and broad endorsement of FCVs (26.0%). These groups varied by age and employment status. Findings from this analysis informed the design and implementation of a healthy retail intervention comprised of new healthful foods and beverages, product placement and marketing strategies within four tribally-owned and operated convenience stores. Public health interventions aimed at reducing nutrition-related disparities in rural AI populations may benefit from assessing food choice considerations.

New Child and Adult Care Food Program (CACFP) meal patterns and best practices were implemented nationally in 2017 to address the shift in dietary need from ensuring essential nutrient consumption to chronic disease prevention. Young American Indian (AI) children have disproportionately higher risk of chronic disease. Some AI tribes operate early care and education (ECE) programs and have the opportunity to participate in the CACFP. The purpose of this paper is to describe a CACFP best-practice menu and training developed and implemented as part of the Food Resource Equity and Sustainability for Health (FRESH) study, a community-based participatory research (CBPR) intervention implemented within ECE programs in the Osage Nation of Oklahoma. Site managers and cooks from each of the nine ECE programs attended meetings and provided investigators with feedback that shaped the best-practice menu and training. Each site participated in a three-hour training in January 2018 to discuss the best-practice menu and ways to overcome implementation barriers. Goals of the menu aimed to increase intake of fruit and vegetables and whole grains and reduce pre-fried and processed foods without increasing cook burden. Training included application activities individually and in small and large groups. Though the project is still underway, lessons learned, including the need for technical assistance, improved communication between ECE program staff and food supply vendors, and infrastructure barriers (e.g., limited space, lack of supplies) that challenge workflow, have emerged. Efforts to improve menus in rural and low-income ECE programs must consider these issues in developing feasible intervention strategies. Keywords: Native American, Early childhood, Community-based participatory research, Nutrition, Preschool

Background The Tribal Health Resilience in Vulnerable Environments (THRIVE) study aimed to increase healthy food access in 2 rural American Indian communities. The intervention sought to increase fruit and vegetable availability, variety, and convenience through placement, promotion, and pricing of healthy foods and beverages in tribal convenience stores. Objective The aim of this study was to describe the development and implementation of the study process evaluation tool to assess intervention fidelity as part of this cluster-controlled trial. Methods Eight stores (2 intervention and 2 control stores per Nation) participated in the study, implemented from May 2016 to May 2017. A web-based survey tailored to store layouts and intervention components assessed how often intervention items were available, approximate quantity available, and whether placement of healthier food items and promotional materials were implemented as designed. After pilot testing the survey, tribal staff members implemented it to collect process evaluation data in the 8 stores during a period of 9–12 mo, assessing study implementation and potential changes in control stores. Results Promotional materials were available ≥75% of the time for most intervention locations. Fruit availability was similar in Nation A and Nation B intervention stores (79–100% compared with 70–100%), whereas fresh vegetable availability was higher in Nation B compared with Nation A (95–96% compared with 55–75%). Both control stores in Nation A and 1 control store in Nation B had moderate fruit and vegetable availability, ranging from 45% to 52%. No control stores in either Nation used intervention promotional materials. Conclusions Process evaluation data indicate that the study was implemented with moderate to high fidelity. The development and implementation of the tool can inform future healthy retail interventions that aim to improve rural and tribal food environments.

Background Native American (NA) children have a high prevalence of obesity contributing to lifespan health disparities. Dietary intake is important to promote healthy weight gain, growth, and development. In 2017, the USDA enforced changes to the Child and Adult Care Food Program (CACFP). The CACFP provides reimbursement to qualifying Early Care and Education (ECE) programs that serve foods that uphold the program's nutrition requirements. Objective This study had the following 2 objectives: 1) Describe a novel index to evaluate ECE menus based on revised CACFP requirements (accounting for food substitutions) and best practices for 3- to-5-y-old children, and 2) analyze CACFP requirement and best practice compliance and nutrient changes in 9 NA ECE programs before and after enforcement of the revised CACFP requirements. Methods This longitudinal study is within a larger community-based participatory research study. Menus and meals served were evaluated for 1 wk at each of 9 programs before and after enforcement of the revised meal patterns. Nutrient analysis, CACFP requirement and best practice compliance, and substitution quality were evaluated. Differences were determined using a paired t-test or Wilcoxon matched test. This trial was registered at clinicaltrials.gov as NCT03251950. Results Total grams of fiber consumed increased (5.0 ± 1.2 compared with 5.9 ± 0.8 g, P = 0.04) and total grams of sugar consumed decreased (53.8 ± 12.6 compared with 48.4 ± 7.9 g, P = 0.024), although room for further improvement exists. Although total grams of fat remained unchanged, grams of saturated fat significantly increased (7.8 ± 1.4 compared with 10.5 ± 3.4, P = 0.041). Other nutrients remained unchanged. Overall CACFP requirement and best practice compliance scores improved, although this finding was not statistically significant. No significant changes in food quality associated with substitutions occurred. Conclusions This study provides early evidence to support the beneficial impact of the revised CACFP requirements. Understanding barriers to compliance within rural NA communities would be an important next step in enhancing the health of vulnerable children.

“Sickle cell anemia: tracking down a mutation” is a full-day, inquiry-based, biology experience for high school students enrolled in genetics or advanced biology courses. In the experience, students use restriction endonuclease digestion, cellulose acetate gel electrophoresis, and microscopy to discover which of three putative patients have the sickle cell genotype/phenotype using DNA and blood samples from wild-type and transgenic mice that carry a sickle cell mutation. The inquiry-based, problem-solving approach facilitates the students' understanding of the basic concepts of genetics and cellular and molecular biology and provides experience with contemporary tools of biotechnology. It also leads to students' appreciation of the causes and consequences of this genetic disease, which is relatively common in individuals of African descent, and increases their understanding of the first principles of genetics. This protocol provides optimal learning when led by well-trained facilitators (including the classroom teacher) and carried out in small groups (6:1 student-to-teacher ratio). This high-quality experience can be offered to a large number of students at a relatively low cost, and it is especially effective in collaboration with a local science museum and/or university. Over the past 15 yr, >12,000 students have completed this inquiry-based learning experience and demonstrated a consistent, substantial increase in their understanding of the disease and genetics in general.

Background International Classification of Diseases (ICD) code algorithms are routinely used to estimate the frequency of illicit injection drug use (IDU)-associated hospitalizations in administrative health datasets despite a lack of evidence regarding their validity. We aimed to measure the sensitivity and specificity of ICD code algorithms used to estimate the prevalence of current/recent IDU among infective endocarditis (IE) hospitalizations without a reference standard. Methods We reviewed medical records of 321 patients aged 18–64 years old from an urban academic hospital with an IE diagnosis between 2007 and 2017. Diagnostic tests for IDU included self-reported IDU in medical records; a drug use, abuse and dependence (UAD) ICD algorithm; a Hepatitis C Virus (HCV) ICD algorithm; and a combination drug UAD/HCV ICD algorithm. Sensitivity, specificity and the misclassification error (ME)-adjusted IDU prevalence were estimated using Bayesian latent class models. Results The combination algorithm had the highest sensitivity and lowest specificity. Sensitivity increased for the drug UAD algorithm in the ICD-10 period compared to the ICD-9 period. The ME-adjusted current/recent IDU prevalence estimated using the drug UAD and HCV algorithms was 23 % (95 % Bayesian credible interval: 16 %, 31 %). The unadjusted prevalence estimate from the drug UAD algorithm underestimated the ME-adjusted prevalence, while the combination algorithm overestimated it. Conclusion The validity of ICD code algorithms for IDU among IE hospitalizations is imperfect and differs between ICD-9 and ICD-10. Commonly used ICD-based algorithms could lead to substantially biased prevalence estimates in IDU-associated hospitalizations when using administrative health data.

Objectives. To assess a healthy retail intervention in Tribal convenience stores in Oklahoma. Methods. We adapted healthy retail strategies to the context of 8 Tribally owned stores. We assessed individual- and store-level outcomes in a cluster-controlled intervention trial (April 2016–June 2017). We measured fruit and vegetable intake, store environment perceptions, and purchases before and after the intervention among a cohort of 1637 Native American shoppers. We used mixed-effects linear regression to estimate pre- to postintervention changes in and between groups. Results. We followed 74% of participants (n = 1204) 9 to 12 months. Intervention and control participants perceived healthier stores after intervention. Higher shopping frequency was related to purchases of fruits, vegetables, and healthy items. Conclusions. Intervention exposure was associated with healthy purchasing but not fruit and vegetable intake. Research is needed to further assess impacts of environmental interventions on intake. Public Health Implications. As the first healthy retail intervention in Tribally owned stores, our results contribute evidence for environmental and policy interventions to address obesity in Tribal Nations. Multicomponent interventions, led by Tribal leaders from diverse sectors, are needed to create healthy environments and sustainable improvements in Native American health.

In rural American Indian (AI) communities, where supermarkets are rare, tribally owned and operated convenience stores are an important food source. Food environment measures for these settings are needed to understand and address the significant diet-related disparities among AIs. Through a tribal-university partnership that included tribal health and commerce representatives from two Native Nations in rural southeastern Oklahoma, we developed the Nutrition Environment Measures Survey for Tribal Convenience Stores (NEMS-TCS) to inform the development and evaluation of a healthy food retail intervention. The NEMS-TCS assessed four scored domains of the rural convenience store food environment—food availability, pricing, quality, and placement—and included 11 food categories that emphasized ready-to-eat food items. Trained raters administered the NEMS-TCS using a sample of 18 rural convenience stores (primarily ranging between 2,400 and 3,600 square feet). We assessed interrater reliability with kappa statistics for dichotomized variables and intraclass correlation coefficients (ICC) for continuous variables. NEMS-TCS demonstrated high inter-rater reliability for all food categories (>85% agreement), subscores (ICC = 0.73-1.00), and the total score (ICC = 0.99). The NEMS-TCS responds to recent calls for reliable measures for rural food environments and may be valuable for studying food environments of large convenience stores in other Native Nations as well as other rural settings.

Background The Oklahoma Communities of Excellence in Tobacco Control (CX) program was established in 2004. Thirty-three CX grants have been funded to implement comprehensive tobacco control programs in 50 counties and one tribal nation. Purpose To describe local tobacco policy gains within CX counties and short-term and intermediate outcomes such as Oklahoma Tobacco Helpline registration and awareness, quit attempts, and home smoking bans among adults. Methods A before-and-after study design examined outcomes within CX counties and among CX urban and rural counties. Comparisons were made with non-funded counties when possible. Local policy tracking databases were reviewed for the number of policies implemented from 2004 to 2013 in CX counties. Population-level tobacco indicators, using Helpline registration and 2004–2010 Behavioral Risk Factor Surveillance System data, quantified changes over time. Data were collected in 2003–2013 and analyzed in 2013. Results Eight hundred thirty-one legislated and voluntary policies were implemented in CX counties and high levels of Helpline registration were maintained. Statistically significant increases were observed in CX counties for the proportion of smokers making a quit attempt, Helpline awareness, and home smoking bans among smokers. These observed increases were greater in rural CX counties than urban. Non-CX counties only experienced a statistically significant increase in Helpline awareness. Conclusions Using community-based best practices in tobacco control while focusing on social norm change, CX counties experienced positive changes in smoking-related attitudes and behaviors. This study expands the evidence base for statewide tobacco control programming and underscores the value of community-based tobacco control programs.

OBJECTIVES: New Child and Adult Care Food Program (CACFP) meal patterns and best-practices were implemented nationally in 2017 to address the need to prevent chronic diseases. Young Native American children have disproportionately higher risk of chronic disease. Some Native American tribes operate early care and education (ECE) programs and have the opportunity to participate in the CACFP. The purpose of this paper is to describe a CACFP best-practice menu and training developed and implemented as part of the Food Resource Equity and Sustainability for Health (FRESH) study. METHODS: FRESH is a community-based participatory research (CBPR) intervention implemented within ECE programs in the Osage Nation of Oklahoma. Site managers and cooks from each of the nine ECE programs attended meetings and provided feedback to investigators which shaped the best-practice menu and training. Each site participated in a three-hour training in January 2018 to discuss the best-practice menu and ways to overcome implementation barriers. Goals of the menu aimed to increase intake of fruit and vegetables and whole grains and reduce pre-fried and processed foods without increasing cook burden. Training included application activities individually and in small and large groups. RESULTS: Though the project is still underway, lessons learned have emerged including the need for technical assistance, improved communication between ECE program staff and food supply vendors, and infrastructure barriers (e.g., limited space, lack of supplies) that challenge work-flow. CONCLUSIONS: Efforts to improve menus in rural and low-income ECE programs must consider these issues in developing feasible intervention strategies. Collaboration with the site manager and cook is essential to fully understand perceived and actual barriers to provide training that can provide necessary background rationale for nutrition recommendations as well as beneficial and productive activities and hands-on training to effect change outside the training. FUNDING SOURCES: This study was funded by the National Institute on Minority Health and Health Disparities (R01MD011266). The funding agency did not participate in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.

Although the majority of smokers attempting to quit do so without assistance, research in the area of unassisted quit behaviors is limited. The aim of this study was to investigate whether population-level policies and programs, such as smoke-free air policies and tobacco control programs, contribute to unassisted quit attempts and cessation.The current study used the 2003 Tobacco Use Supplement to the Current Population Survey (TUS-CPS) special Cessation Supplement (CS) to estimate unassisted quit attempt and success rates by state. Linear regression was used to examine whether state-level unassisted quit attempt and success rates were related to state-level policies and social norms. State-level factors investigated were tobacco control program funding, tobacco taxes, smoke-free air policies, state anti-smoking sentiment and recent change in smoking prevalence.Consistent with previous studies, this study found the majority of smokers who attempted to quit did so without assistance. This study also found unassisted quit attempt rates were higher than assisted attempt rates in every state and DC. Additionally, unassisted quit success rates were higher than assisted quit success rates in most states; however, some states had higher assisted quit success rates. State-level factors associated with unassisted quit attempt rates included anti-smoking sentiment and tobacco taxes; however, no significant relationships were uncovered between unassisted quit success rates and state-level factors.These results suggest that state-level factors may be more important in motivating smokers to attempt quitting, and other individual factors or unmeasured state factors may be related to quit success.

The relationship between alcohol use prior to suicide was explored among American Indian decedents in New Mexico for the years 1980 through 1998. The suicide data were collected from New Mexico Vital Statistics and toxicology reports from the New Mexico Office of the Medical Investigator and matched on a case-by-case basis. Detailed analyses were undertaken for all cases of resident New Mexico Indians from the Navajo, Pueblo, and Apache cultures. Alcohol was detected in 69% of all suicides of American Indians with some variance by major tribal cultural groups (range = 62.1% to 84.4%). This is higher than in suicides among the overall New Mexico population (44.3%). The mean blood alcohol concentration (BAC) of the drinking Indian decedents at suicide was 0.198 (+/- SD of .088). Mean BACs were high for both males (0.199) and females (0.180) who had been drinking. Over 90% of the Indian decedents who had been drinking had BACs greater than the legal intoxication level of 0.08. The Navajo had the lowest percentage of cases that were alcohol involved, and their mean BAC was lower than the other two cultural groups. Alcohol use for completed suicides also varied somewhat by age, sex, method of suicide, and place of occurrence, but very little by whether the decedent was an on or off reservation resident. Analyses indicated that alcohol use prior to suicide was significantly more associated with male suicides than for females, and it was negatively correlated for those who died by overdose and also those using other drugs at suicide. Otherwise, alcohol use did not significantly differentiate American Indian suicides by age, use of firearms, hanging, use of other methods, or residence, for the presence of alcohol was a factor very commonly associated with all of these variables. Heavy alcohol consumption is, therefore, an important factor in over two thirds of all completed suicides among the Indians of New Mexico.

Objective To describe the design, implementation, and consumer response to a coupon-style intervention aimed to increase Supplemental Nutrition Assistance Program (SNAP) use at a farmers' market (FM) among Temporary Assistance for Needy Families (TANF) participants. Design A quasi-experimental trial to evaluate redemption response to 2 coupon interventions; baseline surveys characterized coupon redeemers and non-redeemers. Setting Urban. Participants The TANF recipients were assigned to either a plain (n = 124) or targeted marketing coupon intervention (n = 130). Intervention(s) Both groups received 10 $2 coupons to double fruit and vegetable SNAP purchases at the FM. The targeted marketing group also received an oral presentation designed to reduce perceived barriers to FM use. Main Outcome Measure Coupon redemption. Analysis The researchers used t tests and chi-square/Fisher exact tests to examine associations between redeemers and non-redeemers; logistic regression was used to adjust for the intervention. Results No male and few female participants redeemed coupons (6.3%). Among women, those with knowledge of vegetable preparation were 3 times more likely to redeem coupons than were those with little or no knowledge (odds ratio = 3.77; 95% confidence interval, 1.03–13.77). Conclusions and Implications Stand-alone coupon incentive programs may not be a high-reach strategy for encouraging FM use among the population using TANF. Complementary strategies to build vegetable preparation knowledge and skills are needed.

The Oklahoma Communities of Excellence in Tobacco Control (CX) program was established in 2004. Thirty-three CX grants have been funded to implement comprehensive tobacco control programs in 50 counties and one tribal nation.To describe local tobacco policy gains within CX counties and short-term and intermediate outcomes such as Oklahoma Tobacco Helpline registration and awareness, quit attempts, and home smoking bans among adults.A before-and-after study design examined outcomes within CX counties and among CX urban and rural counties. Comparisons were made with non-funded counties when possible. Local policy tracking databases were reviewed for the number of policies implemented from 2004 to 2013 in CX counties. Population-level tobacco indicators, using Helpline registration and 2004-2010 Behavioral Risk Factor Surveillance System data, quantified changes over time. Data were collected in 2003-2013 and analyzed in 2013.Eight hundred thirty-one legislated and voluntary policies were implemented in CX counties and high levels of Helpline registration were maintained. Statistically significant increases were observed in CX counties for the proportion of smokers making a quit attempt, Helpline awareness, and home smoking bans among smokers. These observed increases were greater in rural CX counties than urban. Non-CX counties only experienced a statistically significant increase in Helpline awareness.Using community-based best practices in tobacco control while focusing on social norm change, CX counties experienced positive changes in smoking-related attitudes and behaviors. This study expands the evidence base for statewide tobacco control programming and underscores the value of community-based tobacco control programs.

Background. The current study describes concurrent use of cigarettes and smokeless tobacco (CiST) among males and females and evaluates factors associated with CiST use.Methods. Cross-sectional data were drawn from the 2010 Behavioral Risk Factor Surveillance System (BRFSS). Weighted stratified analyses were performed to find associations between CiST use and sociodemographic factors by gender. CiST users were compared to three different tobacco use groups: nonusers, exclusive smokers, and exclusive ST users.Results. Younger age and heavy alcohol consumption were consistently associated with increased odds of CiST use among both males and females, and regardless of comparison group. Among males, education was inversely related to CiST use, and these findings were consistent in all three comparisons. Among women, those unable to work or out of work were more likely to be CiST users, which was consistent across comparisons. American Indian females had higher odds of CiST use than White females when nontobacco users or smokers were the comparison group.Conclusion. This study identified sociodemographic characteristics associated with CiST use, and differences in these associations among women and men. Additionally, this study highlights the need to carefully consider what comparison groups should be used to examine factors associated with CiST use.

The mRNA levels of four immediate early genes (IEG) were measured in rat brain regions 60 min after administration of pilocarpine (30 mg/kg) to lithium-treated (3 mmol/kg) rats, during generalized convulsive status epilepticus. Northern blots demonstrated induction of the genes in the order of c-fos = jun-B > c-jun > jun-D with large increases in the cerebral cortex, hippocampus, and striatum, a smaller increase in the cerebellum, and less in the brainstem. The mRNA levels of these four IEG were measured in rat cerebral cortex and hippocampus at several times after administration of the cholinergic agonist pilocarpine (5 or 30 mg/kg) with or without lithium pretreatment (3 mmol/kg, 16 h prior, or chronic 4 week dietary administration). Treatment with pilocarpine (30 mg/kg) alone increased mRNA levels in the order of c-fos > jun-B > c-jun but did not change the jun-D mRNA level, and maximal c-fos and jun-B mRNA levels occurred earlier (30 min) in the cortex than in the hippocampus. Treatment with the lower dose of pilocarpine (5 mg/kg) alone caused only small increases in c-fos and jun-B mRNA levels and these responses were unaffected by lithium pretreatment. Lithium pretreatment potentiated IEG expression induced by 30 mg/kg pilocarpine, likely as a result of the seizures caused by this combination of drugs because pretreatment with anticonvulsants (diazepam or MK-801) blocked seizures and the enhanced IEG mRNA levels. The mRNA levels were increased during seizures in the order of c-fos > jun-B > c-jun > jun-D in the hippocampus and jun-B > c-fos > c-jun > jun-D in the cortex, and were increased for a longer duration as well as to a greater extent than after administration of pilocarpine alone. Administration of pilocarpine (30 mg/kg) to rats treated chronically with lithium caused increases similar to those measured with acute lithium pretreatment. Thus the induction of IEG by cholinergic stimulation varied with dose, time, and brain region, and unique responses were observed for each of the IEG. Lithium pretreatment did not impair IEG expression induced by the lower dose of pilocarpine and greatly enhanced expression of IEG after administration of the higher dose of pilocarpine concomitant with seizure activity.

Endogenous ADP-ribosylation of proteins was measured in homogenates, membranes, and cytosol from rat brain regions. Several proteins were ADP-ribosylated in homogenates, especially a 49 kDa protein. Sodium nitroprusside, a source of nitric oxide, particularly enhanced the ADP-ribosylation of 47 kDa and 39 kDa proteins. Levels of basal and sodium nitroprusside-stimulated ADP-ribosylated proteins were similar, but not identical, in homogenates from the cerebral cortex, hippocampus, striatum, thalamus and cerebellum. In neonatal cerebral cortex, ADP-ribosylation of an additional 110 kDa protein was detected and this was also enhanced by sodium nitroprusside. ADP-ribosylation of the 110 kDa protein was evident one and two days after birth, but not at five days and later. Each protein demonstrated unique sensitivities to sodium nitroprusside and rates of ADP-ribosylation. Cyclic GMP did not mimic the effects of sodium nitroprusside. Mg2+ inhibited ADP-ribosylation of the 49 kDa and 47 kDa proteins but had a smaller effect on the 39 kDa protein. ADP-ribosylation in the cytosol predominantly affected only a single protein of 39 kDa, and this was stimulated by sodium nitroprusside and by addition of cofactors necessary for activation of nitric oxide synthase. Several proteins in membranes were ADP-ribosylated and the 49 and 47 kDa proteins were released from the membranes coincidentally with ADP-ribosylation. The predominate substrates of endogenous ADP-ribosylation did not appear to be substrates for pertussis toxin-induced ADP-ribosylation. These and previously published results indicate that nitric oxide generated from sodium nitroprusside or endogenous sources may have modulatory effects through regulation of the endogenous ADP-ribosylation of proteins.

The concentration of Na+ in the incubation medium significantly influenced phosphoinositide hydrolysis induced by some, but not all, agonists in rat cerebral cortical slices. Reductions of the Na+ concentration below 120 mM resulted in incremental increases in basal and norepinephrine-stimulated accumulation of [3H]inositol monophosphate in cortical slices that had been prelabelled with [3H]inositol, and maximal responses were obtained with 0 and 5 mM Na+. In contrast, the responses to carbachol and ibotenate were similar in medium containing 120 or 5 mM Na+. In medium with 120 mM Na+, quisqualate has two effects on phosphoinositide hydrolysis in cortical slices, including a relatively weak stimulatory effect and an inhibitory modulation of the stimulation induced by norepinephrine. These two responses to quisqualate were differentially modulated by Na+; in 5 mM compared with 120 mM Na+ the stimulatory response was greatly increased and the inhibitory effect was mostly eliminated. That these were two separate events was confirmed by the use of L-BOAA (beta-N-oxalyl-L-alpha, beta-diaminopropionic acid), which reproduces the inhibitory, but not the stimulatory effect of quisqualate on phosphoinositide hydrolysis. In 5 mM Na+, inhibition by L-BOAA of norepinephrine-stimulated phosphoinositide hydrolysis was completely eliminated. These results demonstrate that a physiological concentration of Na+ maintains phosphoinositide hydrolysis at a submaximal level of sensitivity to some, but not all, agonists. The differential effects of Na+ on the stimulatory and inhibitory effects of quisqualate further substantiate the suggestion that these are two separate processes and indicate that alterations of the Na+ concentration may influence the effects of quisqualate, and other agonists, on phosphoinositide hydrolysis.

Hippocampal and cortical EEG recordings in rats were used to monitor the in vivo modulation by lithium of responses to agonists for 5HT2/5HT1c serotonergic (DOI) and cholinergic (pilocarpine) receptors and the influence of inositol administration. Administration of DOI (8 mg/kg) or pilocarpine (30 mg/kg) to rats pretreated with lithium acutely (3 mmol/kg) or chronically (dietary, 4 weeks) resulted in seizures, whereas these doses did not cause seizures without lithium pretreatment. This indicated that lithium most likely affects a signal transduction process common to both systems, which is the phophoinositide second messenger system. To examine the potential influence of altered inositol levels on these responses, we tested the effects of infusions (10 mg, i.c.v.) of myo-inositol, a precursor of phosphoinositide synthesis, and of epi-inositol, an isomer not used for phosphoinositede synthesis. Administration of myo-inositol (10 mg) slightly reduced the incidence of seizures induced by acute lithium plus DOI but almost completely blocked seizures induced by acute lithium plus pilocarpine. This was surprising since seizures induced by acute lithium plus DOI were less severe than those after acute lithium plus pilocarpine, but myo-inositol was more effective in blocking the latter. Epi-inositol also blocked seizures under both conditions but it was less effective than myo-inositol after treatment with acute lithium plus pilocarpine. the latencies to seizures and/or severity of seizures were potentiated more by chronic than acute lithoum pretreatment with both DOI and pilocarpine, but attenuation by myo-inositol was less with each agonist after chronic lithium compared with acute lithium treatment. Peripheral administration of a high dose of myo-inositol blocked seizures induced by acute lithium plus pilocarpine, but the inositol treatment itself was toxic and caused seizures prior to pilocarpine administration, so the mechanism of action cannot simply be attributed to increased brain inositol levels. These results demonstrate that lithium modulates the in vivo responses to DOI and pilocarpine, most probably through an effect on the phosphoinositide signal transduction system. They also show that centrally administered myo-inositol modifies responses to these agents, but the effectiveness of epi-inositol and other results have leave unclear the mechanistic basis of its actions.

The effects of two protein synthesis inhibitors, cycloheximide and anisomycin, were tested on seizures induced by coadministration of lithium and pilocarpine to rats. Systemic cycloheximide (2 mg/kg, s.c.) and centrally administered anisomycin (300 micrograms/10 microliters, i.c.v.) doubled the latency to initiation of seizures and to status epilepticus, while peripherally administered anisomycin (50 mg/kg, s.c.) completely blocked lithium-pilocarpine seizures. These results indicate that protein synthesis is required for initiation of seizures.

The therapeutic effect of lithium in manic-depressive illness may involve alterations in the activity of the phosphoinositide second messenger system. Lithium administration to rats potentiates responses to cholinergic agonists, as evidenced by the production of seizures in lithium-treated rats after normally nonconvulsant doses of cholinergic agonists. We now report that lithium also potentiates the response to a serotonin (5-HT) agonist, DOI, that activates 5-HT2/5-HT1C receptors coupled to phosphoinositide hydrolysis. EEG recordings showed that administration of DOI (8 mg kg-1) to lithium-treated, but not to lithium-naive, rats caused seizures which were blocked by ritanserin pretreatment. These results demonstrate that lithium pretreatment causes a normally subconvulsive dose of serotonergic, in addition to cholinergic, agonists to induce seizures. Since DOI, like cholinergic agonists, activates receptors coupled with phosphoinositide hydrolysis and lithium potentiates responses to each, this second messenger system is likely to be involved in this effect of lithium.

Lithium inhibits inositol monophosphatase of the phosphoinositide (PI) pathway, an effect which was suggested to be responsible for lithium's therapeutic action (Berridge et al, 1982). Lithium reduced inositol levels in rat brain following some treatment regimens and supplemental inositol reversed some of lithium's effects, including seizures resulting from lithium potentiating the response to cholinergic agonists (Tricklebank et al, 1991; Kofman et al, 1993). We used EEG measurements in rats to determine the effect of inositol on seizures induced by pilocarpine (30 mg/kg, sc) following pretreatment with acute (3 mmol/kg, ip, 20 hrs) or chronic (4 weeks) lithium. Myo-inositol (0-55 mmole, icv) dose-dependently attentuated lithium plus pilocarpine seizures when an acute but not a chronic lithium treatment was used. Epi-inositol, which is not utilized for PI synthesis blocked acute lithium and pilocarpine-induced seizures in 50% of tested rats. Similarly to its effect on muscarinic agonists, lithium increased the response to DOI, a selective 5-HT2/5-TH1C (PI-linked) agonist (Williams and Jope, 1994). While R-(-)DOI (8 mg/kg, ip) alone was not convulsive, lithium plus DOI evoked seizures. In some rats tested, myo-inositol blocked the effect of lithium on DOI-induced seizures.

Mary B. Wi I iams Mary B. Williams (Center for Science and Culture, University of Delaware, Newark, DE 19716) is an associate professor of life and health sciences and of philosophy at the University of Delaware. She received her Ph.D. in mathematical biology at the University of London, and has published articles in mathematical biology and in philosophy of biology. Her specialty is evolutionary theory.

This paper shows that species are individuals with respect to evolutionary theory in the sense that the laws of the theory deal with species as irreducible wholes rather than as sets of organisms. ‘Species X’ is an instantiation of a primitive term of the theory. I present a sketch of a proof that it cannot be defined within the theory as a set of organisms; the proof relies not on details of my axiomatization but rather on a generally accepted property of speciation; hence the same argument should work for any axiomatization which captures this generally accepted property of speciation.

Many philosophers have asserted that evolutionary theory is unfalsifiable. In this paper I refute these assertions by detailing some falsifiable predictions of the theory and the evidence used to test them. I then analyze both these predictions and evidence cited to support assertions of unfalsifiability in order to show both what type of predictions are possible and why it has been so difficult to spot them. The conclusion is that the apparent logical peculiarity of evolutionary theory is not a property of evolutionary theory; it is a property of our human-sized perspective on evolutionary theory.

Sufficient evidence of a correlation between infrequent coitus and Down syndrome (DS) has now accumulated to warrant reevaluation of the suggested biological mechanisms. The evidence provides no support for delayed fertilization as the mechanism responsible for this correlation, as was originally proposed by German [Nature 217:516-519, 1968]. A better explanation of this association is provided by the sperm aging hypothesis, which gains its support from both animal studies and chromosomal findings of a paternal contribution to DS. The animal studies supporting this hypothesis show an increased incidence of sperm-derived trisomies resulting from sperm stored for prolonged periods in the male tract. The chromosomal findings show a paternal origin in 20% of DS infants; the sperm aging hypothesis concerns the biological mechanism in this 20%. In addition to explaining the excess of DS for older mothers, the sperm aging hypothesis explains the excess for teenage unwed mothers and indicates that sperm aging from decreased ejaculatory frequency may be a cause of DS in all age groups. Testable directly in humans against German's delayed fertilization hypothesis, the sperm aging hypothesis has immediate clinical implications. It suggests 1) an approach to reduce the incidence of DS and miscarriages and 2) clinical research that will increase knowledge of the circumstances indicating a need for antenatal monitoring.

In the 1950's and 60's there arose a plethora of claims that the structure of evolutionary theory was intrinsically different from the structures of the theories of physics—and thus from the structure that philosophers of science claimed to be the structure of scientific theories. There were claims:1)that evolutionary theory had no laws (Smart 1963);2)that evolutionary concepts were so peculiar that their definitions violated the ordinary standards for definitions (Beckner 1959);3)that evolutionary theory was not axiomatizable (Beckner 1959);4)that evolutionary theory made no falsifiable predictions (Scriven 1959, Manser 1965, Smart 1963);5)that evolutionary biology relied on teleological explanations which violated the deductive-nomological explanation form (Hempel 1965); and6)that evolutionary biology made significant use of narrative explanations which also violated the deductive-nomological explanation form (Goudge 1961)

An apparently peculiar form of explanation is found in evolutionary biology (and other historical fields); it is called a genetic explanation by Beckner (1959) (and, in a more general discussion, by Hempel (1965)), a narrative explanation by Goudge (1961), and a Darwinian history by Kitcher (1985). Kitcher, assuming that the Darwinian history has some kind of logically respectable structure, is primarily concerned with arguing that it is the cornerstone of Darwin’s historical methodology; Beckner and Goudge, on the other hand, assuming that the genetic (or narrative) explanation is an important part of evolutionary biology, are primarily concerned with the difficulty of fitting this form of explanation into a logically respectable structure. Adopting the narrative explanation terminology, and assuming that the narrative explanation is central to Darwin’s historical methodology and to the methodology of contemporary evolutionary biology, I will in this paper delineate its logically respectable structure.

The use of cautionary tales to inculcate appropriate professional moral standards into professionals in various fields is described, and application to computer science professionals is suggested. The wider moral aspects of the computer's impact on society are then discussed.Because the computer gives us fundamentally new power, we are faced with decisions for which our experiences may give little guidance. The danger of applying old standards to a fundamentally new situation is well illustrated by the law, passed soon after the production of the first automobiles, which required automobiles traveling the roads to be preceded by a man on foot carrying a red flag. This law reduced danger, but robbed the auto of its intrinsic power.Similarly we could stop one type of computer crime by outlawing electronic fund transfer, or prevent a potentially dangerous accumulation of governmental power by outlawing the interconnection of computers storing different sets of information about individuals, or prevent robots from taking workers' jobs by outlawing robotization. It is possible to respond to every danger by cutting off the power that leads to that danger. But it is more productive to respond by analyzing the particular situation in order to determine whether our fundamental values are better served by changing our expectations or rules than by denying ourselves the use of the power. Such an analysis requires some understanding both of the problems which may be caused in our society by the computer and of the nature of our values.This paper begins with some computerization problems that are essentially problems of inculcating the proper professional morals into computer professionals (and into those amateurs who are deeply involved with computers). We point out that other professions inculcate professional moral standards by the use of cautionary tales, and we indicate how the computer profession can develop the cautionary tales it needs. We then turn to the problems to the computer's impact on society, discussing some of the issues that must be addressed if the negative impacts of computerization are to be minimized.

This paper describes a type of fitness indicating trait which is particularly likely to be exaggerated because of sexual selection on fitness-faking modifier genes, describes the selection process which tends to exaggerate such traits, and indicates by citing examples from different taxa the wide range of traits which can be explained as resulting from this type of selection.

The philosophical literature is heavy with discussions of the logical structure of various proposed schema of functional explanation (most of which are modifications of Hempel's schema [7]) but it is very light on detailed analysis of the way in which these schema actually work or the way in which they apply to the instances in which functional explanations are used by scientists. These papers use statements by scientists ascribing particular functions to particular traits, along with intuitions about the way in which ‘function’ is used in ordinary language, to ascertain the referents of the term and thus to determine the class of uses against which any schema should be tested; but such examples only show whether the schema under discussion refer to the same things as those the scientists’ refer to; they do not show whether the logical structure of the schema really captures the logical structure underlying the scientists’ use.

The rarity of Malthusian overexploitation has long puzzled naturalists. Nicholson has given an important proximate explanation of how population size is limited, but his discussion of density governing traits does not tackle the ultimate question of how populations acquired these traits which prevent overexploitation. This paper shows that Darwinian theory can explain the evolution of density governing limitation mechanisms which prevent overexploitation; they are a predictable by-product of selection for adaptation to the early growth phase of a population with recurrent population crashes. In this situation Darwinian selection, instead of maximizing the number of offspring of the ultimately favored allele, maximizes the number of its descendants in the comparable portion of the next growth cycle.