Do adolescent trajectories of riding with an impaired driver and driving impaired predict similar behaviors in early adulthood?

BACKGROUND: A recent study shows four trajectories of riding with an impaired driver (RWI) and driving while impaired (DWI) from adolescence to emerging adulthood. We examined prospective associations of adolescent RWI/DWI trajectory class with early adulthood RWI/DWI behavior. METHODS: Data were from the NEXT Generation Health Study (NEXT), a nationally representative longitudinal study (N = 2783) beginning with a 10th-grade cohort completing 7 annual assessment waves (W1-W7) between 2010 and 2016 and a later follow-up mixed methods study. Four RWI and DWI trajectories derived from a recently published latent class analysis study (RWI (last 12 months); DWI (last 30 days) dichotomized as ≥ once vs. none) were used: Abstainer, Escalator, Decliner, and Persister. In the follow-up examination, a purposive subsample (N = 105, 26.3 ± 0.5 y/o, Female 50.5%) of NEXT participants were selected by trajectory (31 Abstainers, 33 Escalators, 14 Decliners, and 27 Persisters) for in-depth interviews 4 years after NEXT. In interviews, self-reported RWI events (number of times) related to alcohol (Alc-RWI) or marijuana (MJ-RWI) use in the last 12 months, and DWI events (number of times) related to alcohol (Alc-DWI) & marijuana (MJ-DWI) use in January 2020 (pre-COVID pandemic) were collected using structured surveys. General linear models were used to examine associations of adolescents' RWI/DWI trajectories with early adulthood RWI/DWI behavior, controlling for sex, health status, education attainment, and work hours. RESULTS: The mean number (SD) of Alc-RWI and MJ-RWI events reported by Escalators (3.83(2.48), 2.43(2.77)) and Persisters (3.83(2.43), 3.57(2.54)) were higher (p≤0.05) than Abstainers (0.82(1.42), 0.77(2.04)) and Decliners (1.81 (2.69), 1.38 (2.04)). Similarly, Escalators (1.61 (2.28), 1.88(2.69)) and Persisters (1.96(2.08), 1.93(2.48)) reported more Alc-DWI and MJ-DWI events than Abstainers (0.18 (0.53), 0.42(1.38)) and Decliners (0.00 (0.00), 0.08(0.28)). Linear regression models indicated membership in Escalator and Persister classes compared to Abstainer class was associated (p≤0.01) with higher engagement in RWI/DWI in early adulthood. CONCLUSION: Adolescents with escalating and persistent high RWI/DWI may continue these health risking behaviors into their mid-twenties. Decliners during the transition maintained low RWI/DWI into their mid-twenties. Taken together, these findings suggest that earlier reduction may have long-term effects. Our findings can be used to inform the precision tailoring of prevention efforts aimed at effectively reducing alcohol/drug impairment crash injuries and related deaths among those in early adulthood.

All-cause mortality among males living with and without HIV initiating long-term opioid therapy, and its association with opioid dose, opioid interruption and other factors.

BACKGROUND: While the relationship between long-term opioid therapy (LTOT) dose and overdose is well-established, LTOT's association with all-cause mortality is less understood, especially among people living with HIV (PLWH). There is also limited information regarding the association of LTOT cessation or interruption with mortality. METHODS: Among PLWH and matched uninfected male veterans in care, we identified those who initiated LTOT. Using time-updated cox regression, we examined the association between all-cause mortality, unnatural death, and overdose, and opioid use categorized as 1-20 (reference group), 21-50, 51-90, and ≥ 91 mg morphine equivalent daily dose (MEDD). RESULTS: There were 22,996 patients on LTOT, 6,578 (29 %) PLWH and 16,418 (71 %) uninfected. Among 5,222 (23 %) deaths, 12 % were unnatural deaths and 6 % overdoses. MEDD was associated with risk of all 3 outcomes; compared to patients on 1-20 mg MEDD, adjusted risk for all-cause mortality monotonically increased (Hazard Ratios (HR) [95 % CI] for 21-50 mg MEDD = 1.36 [1.21, 1.52], 51-90 mg MEDD = 2.06 [1.82, 2.35], and ≥ 91 mg MEDD = 3.03 [2.71, 3.39]). Similar results were seen in models stratified by HIV. LTOT interruption was also associated with all-cause, unnatural, and overdose mortality (HR [95 % CI] 2.30 [2.09, 2.53], 1.47 [1.13, 1.91] and 1.52 [1.04, 2.23], respectively). CONCLUSIONS: Among PLWH and uninfected patients on LTOT we observed a strong dose-response relationship with all 3 mortality outcomes. Opioid risk mitigation approaches should be expanded to address the potential effects of higher dose on all-cause mortality in addition to unnatural and overdose fatalities.

Digital health screening tool for identification of elder mistreatment.

PURPOSE: It is estimated that 15.7% of people aged 60 years and older were subjected to some form of Elder Mistreatment (EM) globally (Yon et al., 2017). In the USA, as many as 1 in 24 EM cases are left unidentified by professionals, with a 300% increased mortality risk for older adults who do not receive help (National Center on Elder Abuse, n.d.; Dong, 2009). Current methods of screening tend to miss less obvious signs of EM and may discourage older adults from disclosing EM, due to either a lack of understanding of what constitutes mistreatment or fear of retaliation from the perpetrator. METHOD: Our approach shifts the focus of EM identification to the older adults themselves through an automated tablet-based tool. The Virtual cOaching in making Informed Choices on Elder Mistreatment Self-Disclosure (VOICES) tool includes various multimedia components such as videos, audio, and animations designed to educate and enhance screening. Patients screened as positive are guided through a Brief Negotiated Interview (BNI) utilizing motivational interviewing to assist in self-identification (recognize that they are experiencing elder mistreatment) or self-disclosure (inform others about their elder mistreatment experiences). During tool development, we conducted a qualitative study to evaluate the perceived value and likelihood of adopting a tablet-based approach to facilitate screening and self-disclosure of EM in the ED. We held 3 focus groups with stakeholders, including 24 adults 60 years or over, 2 social workers, 2 caregivers, and 2 ED clinicians. We used the findings from the focus groups and User-Centered Design approach (UCD) to develop the tablet-based screening tool. Once the tool was ready, we tested its usability and acceptability with 14 older adults. RESULTS AND DISCUSSION: Focus group participants supported use of a tablet-based tool to screen for EM, indicating that digital screening benefits from feelings of privacy and anonymity. On a 7-point Likert scale ranging from "1=Very Comfortable" to "7=Very Uncomfortable", older adults scored 2.8 on average for whether they would feel comfortable using a tablet device to screen for EM. Prominent suggestions made by older adults included using a female voice for the tool narrator, larger font size, more multimedia, headphones for privacy; and having someone available during screening for assistance if needed. Participants indicated that it is difficult for older adults experiencing EM to ask for help and that any type of mistreatment screening would be helpful. They also highlighted the need to explain community resources available to older adults once EM is disclosed, especially resources offering help to the caregiver. Participants of the usability evaluation rated the tool a mean score of 86.6 (median= 88.8, iQR =18.1) on the System Usability Scale (SUS), far above the benchmark SUS score of 68, which indicates that the system is "good" or "acceptable" (Bangor et al., 2008). Shifting the focus from the provider to the older adult may encourage self-disclosure of EM by addressing major barriers to traditional screening processes. In summary, this study supported the use of self-administered automated tablet-based screening for EM. Participants generally believed that the use of digital health tools to facilitate the screening process would be beneficial in the ED setting.

Increase in migraine diagnoses and guideline-concordant treatment in veterans, 2004-2012.

Background and aim Health administrators, policy makers, and educators have attempted to increase guideline adherence of migraine medications while reducing inappropriate use of opioid- and barbiturate-containing medications. We evaluated the burden of migraine and proportion of guideline-concordant care in a large, national health care system over time. Methods We conducted a time-series study using data from the Veterans Health Administration (VHA) electronic health record. Veterans with migraines were identified by ICD-9 code (346.X). Prescriptions and comorbid conditions were evaluated before and after migraine diagnosis. Chi-square tests and logistic regression were performed. Results A total of 57,064 veterans were diagnosed with migraine headache (5.3%), with women significantly more likely diagnosed (11.6% vs. 4.4%, p < 0.0001). The number of veterans diagnosed with migraine has significantly increased over the years. By 2012, triptans were prescribed to 43% of people with migraine, with no difference by gender. However, triptan prescriptions increased from 2004 to 2012 in men, but not women, veterans. Preventive medicines showed a significant increase with the year of migraine diagnosis, after controlling for age, sex, race, and for comorbidities treated with medications used for migraine prevention. Conclusions The burden of migraines is increasing within the VHA, with a corresponding increase in the delivery of guideline-concordant acute and prophylactic migraine-specific medication.

Psychosocial predictors and moderators of weight management programme outcomes in ethnically diverse obese youth.

BACKGROUND: An important area of research in childhood obesity is the identification of factors that predict or moderate the responses to obesity intervention programmes, yet few studies have examined the impact of self-esteem and family functioning on obesity treatment outcomes. OBJECTIVES: We sought to determine whether baseline self-esteem and family functioning predicted or moderated childhood obesity intervention outcomes at 6 months. METHODS: From 2009 to 2011, seventy-five 10-16 year old, racially/ethnically diverse obese youths with abnormal glucose tolerance were randomized to 6 months of an intensive family-based obesity lifestyle intervention (Bright Bodies) or routine outpatient Clinic Care. We examined youth self-concept, parent-rated family functioning and 6-month outcomes (youths' glucose tolerance, weight, body mass index and percent fat). We set the significance threshold as P ≤ 0.05 for moderator and predictor analyzes. RESULTS: Having poor family functioning and self-concept scores indicating high anxiety and low self-esteem at baseline predicted poor 6-month outcomes overall (Bright Bodies and Clinic Care groups combined). Additionally, baseline self-esteem and family functioning moderated treatment effects such that Bright Bodies outperformed Clinic Care in youths with low self-esteem and poorly functioning families, whereas youths with high self-esteem and high-functioning families did similarly well with either intervention. DISCUSSION: Our findings suggest intensive family-based lifestyle programmes are particularly beneficial for youth with low self-esteem and poorly functioning families.

Reported health conditions in animals residing near natural gas wells in southwestern Pennsylvania.

Natural gas extraction activities, including the use of horizontal drilling and hydraulic fracturing, may pose potential health risks to both human and animal populations in close proximity to sites of extraction activity. Because animals may have increased exposure to contaminated water and air as well as increased susceptibility to contaminant exposures compared to nearby humans, animal disease events in communities living near natural gas extraction may provide "sentinel" information useful for human health risk assessment. Community health evaluations as well as health impact assessments (HIAs) of natural gas exploration should therefore consider the inclusion of animal health metrics in their assessment process. We report on a community environmental health survey conducted in an area of active natural gas drilling, which included the collection of health data on 2452 companion and backyard animals residing in 157 randomly-selected households of Washington County, Pennsylvania (USA). There were a total of 127 reported health conditions, most commonly among dogs. When reports from all animals were considered, there were no significant associations between reported health condition and household proximity to natural gas wells. When dogs were analyzed separately, we found an elevated risk of 'any' reported health condition in households less than 1km from the nearest gas well (OR = 3.2, 95% CI 1.07-9.7), with dermal conditions being the most common of canine disorders. While these results should be considered hypothesis generating and preliminary, they suggest value in ongoing assessments of pet dogs as well as other animals to better elucidate the health impacts of natural gas extraction on nearby communities.

Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial.

AIMS/HYPOTHESIS: Type 1 diabetes results from a chronic autoimmune process continuing for years after presentation. We tested whether treatment with teplizumab (a Fc receptor non-binding anti-CD3 monoclonal antibody), after the new-onset period, affects the decline in C-peptide production in individuals with type 1 diabetes. METHODS: In a randomised placebo-controlled trial we treated 58 participants with type 1 diabetes for 4-12 months with teplizumab or placebo at four academic centres in the USA. A central randomisation centre used computer generated tables to allocate treatments. Investigators, patients, and caregivers were blinded to group assignment. The primary outcome was a comparison of C-peptide responses to a mixed meal after 1 year. We explored modification of treatment effects in subgroups of patients. RESULTS: Thirty-four and 29 subjects were randomized to the drug and placebo treated groups, respectively. Thirty-one and 27, respectively, were analysed. Although the primary outcome analysis showed a 21.7% higher C-peptide response in the teplizumab-treated group (0.45 vs 0.371; difference, 0.059 [95% CI 0.006, 0.115] nmol/l) (p = 0.03), when corrected for baseline imbalances in HbA(1c) levels, the C-peptide levels in the teplizumab-treated group were 17.7% higher (0.44 vs 0.378; difference, 0.049 [95% CI 0, 0.108] nmol/l, p = 0.09). A greater proportion of placebo-treated participants lost detectable C-peptide responses at 12 months (p = 0.03). The teplizumab group required less exogenous insulin (p < 0.001) but treatment differences in HbA(1c) levels were not observed. Teplizumab was well tolerated. A subgroup analysis showed that treatment benefits were larger in younger individuals and those with HbA(1c) <6.5% at entry. Clinical responders to teplizumab had an increase in circulating CD8 central memory cells 2 months after enrolment compared with non-responders. CONCLUSIONS/INTERPRETATIONS: This study suggests that deterioration in insulin secretion may be affected by immune therapy with teplizumab after the new-onset period but the magnitude of the effect is less than during the new-onset period. Our studies identify characteristics of patients most likely to respond to this immune therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00378508 FUNDING: This work was supported by grants 2007-502, 2007-1059 and 2006-351 from the JDRF and grants R01 DK057846, P30 DK20495, UL1 RR024139, UL1RR025780, UL1 RR024131 and UL1 RR024134 from the NIH.

Long-term association between seizure outcome and depression after resective epilepsy surgery.

OBJECTIVE: This study explored the association between long-term epilepsy surgery outcome and changes in depressive symptoms. METHODS: Adults were enrolled between 1996 and 2001 in a multicenter prospective study to evaluate outcomes of resective epilepsy surgery. The extent of depressive symptoms and depression case status (none, mild, or moderate/severe) were assessed using the Beck Depression Inventory (BDI) preoperatively and 3, 12, 24, 48, and 60 months postoperatively. A mixed-model repeated-measures analysis was performed, adjusting for covariates of seizure location, gender, age, race, education, and seizure control. RESULTS: Of the total 373 subjects, 256 were evaluated at baseline and 5 years after surgery. At baseline, 164 (64.1%) were not depressed, 34 (13.3%) were mildly depressed, and 58 (22.7%) had moderate to severe depression. After 5 years, 198 (77.3%) were not depressed, 20 (7.8%) were mildly depressed, and 38 (14.8%) were moderately to severely depressed. Five years after surgery, the reduction in mean change from baseline in BDI score was greater in subjects with excellent seizure control than in the fair and poor seizure control groups (p = 0.0006 and p = 0.02 respectively). Those with good seizure control had a greater reduction in BDI score than the poor seizure control group (p = 0.02) and borderline significant reduction compared with the fair seizure control group (p = 0.055). CONCLUSION: Although study participants had initial improvement in depressive symptoms, on average, after resective surgery, only patients with good or excellent seizure control had sustained long-term improvement in mood.

Size matters: gastric pouch size correlates with weight loss after laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Over the past 20 years, there has been an ongoing discussion about the importance of gastric pouch size as a key factor influencing weight loss after bariatric surgery. This analysis aimed to determine the relationship between initial gastric pouch size and excess weight loss (EWL) after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Between August 2002 and March 2005, 320 LRYGB were performed at Yale New Haven Hospital. The patients' demographics were entered into a longitudinal, prospective database. Upper gastrointestinal series were routinely performed on postoperative day 1. Pouch size was measured as area (cm2) on an anteroposterior radiograph at maximum pouch distention. Linear regression analysis was performed to determine the association between pouch size and weight loss at 6 and 12 months postoperatively. Adjustments were made for age, gender, and preoperative body mass index (BMI). RESULTS: The mean age of the patients was 41.2 years. Of the 320 study patients, 261 were women (81.6%) and 59 were men (18.4%). The mean preoperative BMI was 51.1 kg/m2; the mean 6-month EWL was 50.5%; the mean 12-month EWL was 62.5%; and the mean pouch size was 63.9 cm2. A statistically significant, negative correlation between pouch size and EWL was found at 6 months (beta = -0.241; p < 0.01) and at 12 months (beta = -0.302; p < 0.02). The findings show that male gender (beta = 0.147; p < 0.04) and preoperative BMI (beta = 0.190; p < 0.01) are positively correlated with pouch size. CONCLUSION: The analysis demonstrates that initial gastric pouch size is not the only significant component for successful weight loss after LRYGB. Male gender and increased preoperative BMI were identified as factors predicting pouch size. Efforts to standardize small pouch size for all patients seems important to the success of surgical therapy for morbid obesity.

Ethnic differences in beta cell adaptation to insulin resistance in obese children and adolescents.

AIMS/HYPOTHESIS: The prevalence of altered glucose metabolism in obese children and adolescents is growing at a significant rate, especially in ethnic minorities. It is not clear whether young people of different ethnic backgrounds differ in their adaptive mechanisms to obesity-related insulin resistance. The aim of this study was to evaluate the early insulin response and insulin clearance in response to an oral glucose load in obese children and adolescents. METHODS: Seven hundred and nine obese children and adolescents underwent an OGTT. Indices of the early insulin response and insulin clearance were compared in participants of White European, African American and Hispanic origin. RESULTS: Participants of the three ethnic groups demonstrated similar mechanisms of adaptation to increasing insulin resistance, but with different magnitudes. African American subjects had a greater early insulin response and decreased insulin clearance than their White European and Hispanic counterparts. This happened regardless of whether the cohort was divided by glucose tolerance level or by level of insulin sensitivity. IGT across ethnic groups was characterised by a marked decline in the acute insulin response in the context of severe insulin resistance and very low insulin clearance. CONCLUSIONS/INTERPRETATION: In obese children and adolescents, mechanisms of adaptation to obesity related to insulin resistance are similar across ethnic groups. The greater early insulin response needed to maintain glucose tolerance in young people of ethnic minorities may partially explain their greater tendency to develop type 2 diabetes.

Microalbuminuria in pediatric obesity: prevalence and relation to other cardiovascular risk factors.

BACKGROUND: Microalbuminuria (MA) has emerged as a strong predictor of cardiovascular (CV) events, even in nondiabetic adults. While the mechanisms behind this association remain to be established, most studies suggest that MA is the result of increased vascular leakage denoting endothelial dysfunction associated with early vasculopathy. OBJECTIVE: To examine if a urine albumin creatinine ratio (UACR) in the microalbuminuric range is related to metabolic markers of CV risk in obese and pre-diabetic youth recruited from an obesity clinic. METHODS: MA was defined as a UACR between 2.0 and 20 mg/mmol. Subjects with gross proteinuria (UACR>20 mg/mmol) were excluded from the study. Analyses were performed to assess the relationship of MA and markers of CV risk, including body mass index (BMI), % body fat, blood pressure (BP), lipid profile, inflammatory markers, insulin sensitivity indexes and degrees of oral glucose tolerance. MA was also correlated with risk factor constellations unique to the metabolic syndrome, a distinct CV risk entity. RESULTS: Postchallenge alterations in glucose metabolism and overall loss in insulin sensitivity were strongly and positively correlated with the presence of MA (P = 0.002 and 0.01, respectively). Neither the metabolic syndrome nor any of the individual CV risk factors examined were associated with MA. CONCLUSIONS: These data suggest that early glucose toxicity, as reflected by postchallenge elevations in plasma glucose even below the diagnostic cutoff for diabetes mellitus may contribute to the presence of MA. Whether MA is equally as predictive of CV disease in youth, as in adulthood, remains to be investigated.

Changes in cholesterol and triglyceride concentrations in the Vanguard population of the Carotene and Retinol Efficacy Trial (CARET).

BACKGROUND: The Beta-Carotene and Retinol Efficacy Trial (CARET) was terminated 21 months ahead of schedule due to an excess of lung cancers. Deaths from cardiovascular disease also increased (relative risk=1.26 (95% confidence interval (CI) 0.99-1.61)) in the group assigned to a combination of 30 mg beta-carotene and 25 000 IU retinyl palmitate (vitamin A) daily. The basis for increased cardiovascular mortality is unexplained. DESIGN: We analyzed data on serum lipids, available for 1474 CARET Vanguard participants who were enrolled in the two CARET pilot studies and transitioned to the Vanguard study. Total cholesterol and triglycerides were measured 2 months prior to, 4 and 12 months following randomization, and annually thereafter for up to 7 y. INTERVENTION: In the asbestos-exposed pilot (N = 816), participants were assigned to beta-carotene and retinol or to placebo; in the smokers pilot (N = 1029), participants were assigned to beta-carotene, retinol, a combination, or placebo. RESULTS: Serum cholesterol showed a decline over time in both arms; serum triglycerides had a continuous decline over time in the placebo arm, but an initial increase that persisted in the active arm. Both serum cholesterol concentrations (P < 0.0003) and serum triglycerides (P < 0.0001) were significantly higher in the participants receiving vitamin A and/or a combination of vitamin A and beta-carotene (n = 863) as compared to the placebo group (n = 611). Those in this active intervention group had an average cholesterol concentration 5.3 mg/dl (0.137 mmol/l) higher than those in the placebo arm. CONCLUSION: The differences in cholesterol and triglyceride concentrations between the groups following randomization may account in part for the unexpected excess in cardiovascular deaths seen in the active intervention arm of CARET.

Patients with uterine papillary serous cancers may benefit from adjuvant platinum-based chemoradiation.

OBJECTIVE: The coexistence of minimal uterine disease and extrauterine metastases is common in patients with uterine papillary serous carcinoma (UPSC). Only complete surgical staging accurately depicts the extent of this disease. The purpose of this study was to evaluate different therapeutic options in surgically staged patients. METHODS: We retrospectively reviewed all patients with UPSC histologically limited in the uterus to the endometrium treated at our institution between 1987 and 2002. RESULTS: Twenty-three (45%) cases were International Federation of Gynecology and Obstetrics (FIGO) stage IA, seven (15%) were stage IIIA, one (2%) was stage IIIC, and nine (18%) stage IV. Additionally, 11 of these 51 patients (21%) were diagnosed with two cancers: a stage IA UPSC and concomitant advanced stage serous cancer of the ovary, fallopian tube, or peritoneum. Stage IA patients with no cancer in the hysterectomy specimen (defined as no residual uterine disease) had no recurrences (n = 10) regardless of treatment. There was a trend toward increased survival in stage IA patients with residual uterine disease who were treated with chemoradiation (concomitant vaginal brachytherapy and platinum-based chemotherapy). There were no recurrences in patients with locoregional disease (stages IA-IIIA) who received chemoradiation. All patients with advanced stage UPSC (stage IIIC or IV or two primary cancers) did poorly regardless of treatment. CONCLUSION: Our findings suggest that stage IA patients with no residual uterine disease may be observed. Stage IA patients with residual uterine disease may benefit from chemoradiation. More effective treatment needs to be identified for advanced stage UPSC.

Estimated change in physical activity level (PAL) and prediction of 5-year weight change in men: the Aerobics Center Longitudinal Study.

OBJECTIVE: To determine the relation between the average daily physical activity level (PAL) and the trajectory of weight change in men at risk for weight gain. DESIGN AND SETTING: Clinic-based cohort study over an average of 5 y. SUBJECTS: Healthy men (N=2501) ages 20-55 y participating in the Aerobics Center Longitudinal Study who had received at least four medical examinations at the Cooper Clinic between 1970 and 1998. MEASUREMENTS: Daily leisure-time physical activity was reported and body weight was measured at all four examinations. The average daily PAL (METs 24 h(-1)) was estimated from all activities, as well as from other incidental active and passive activities. Weight change over four examinations was regressed on the change in PAL between the first and third examinations. RESULTS: Random coefficient regression modeling indicated a curvilinear slope for weight gain over the follow-up among those maintaining the same PAL between the first and third examinations. Weight gain was further accelerated among men who decreased their activity. A shift from a low PAL (<1.45 METs 24 h(-1)) to a moderate (1.45-1.60 METs 24 h(-1)) or high (>1.60 METs 24 h(-1)) PAL was necessary for weight loss over time. Men with initially the lowest PAL had the greatest benefit from increasing activity. CONCLUSIONS: Daily PAL was inversely related to weight gain in this cohort. Increasing to or maintaining a daily PAL at least 60% above the resting metabolic rate (ie, PAL >1.60 METs 24 h(-1)) may be necessary to maintain body weight in middle-age and can be achieved by incorporating 45-60 min of brisk walking, gardening/yardwork, or cycling into the daily routine.

Brain glucose levels are elevated in chronically hyperglycemic diabetic rats: no evidence for protective adaptation by the blood brain barrier.

Recent evidence suggests that brain function may be impaired by prolonged elevations of blood glucose, such as those that occur in poorly controlled diabetes. However, little is known about the effects of such hyperglycemia on brain metabolic substrate levels. Using microdialysis in awake, freely moving rats, we directly measured brain extracellular fluid (ECF) glucose, lactate, and beta-hydroxybutyrate (betaOHB) levels in the inferior colliculus in chronically hyperglycemic BB/wor diabetic rats and in control (Sprague-Dawley) rats during euglycemia and acute hyperglycemia. The ECF:plasma glucose ratio (0.27 to 0.34) was remarkably similar in animals from all 3 groups, resulting in proportional elevations of brain ECF glucose in the hyperglycemic groups. Moreover, brain ECF levels of lactate and beta-OHB were increased in diabetic (DM) rats as compared with controls. Our results suggest that no significant protective adaptation of the blood brain barrier (BBB) transfer of glucose occurs in chronic hyperglycemia. Hence, brain tissue may be chronically exposed to markedly elevated levels of glucose and other metabolic fuels during poorly controlled diabetes, and therefore it may be subject to the same long-term adverse effects of hyperglycemia seen in peripheral tissues.

Importance of plasma leptin in predicting future weight gain in obese children: a two-and-a-half-year longitudinal study.

OBJECTIVE: To determine whether relatively low leptin levels predict changes in adiposity in prepubertal and pubertal obese children. RESEARCH METHODS AND PROCEDURES: In a biracial cohort of 68 obese children (33 male and 35 female; 46 Caucasians and 22 African-Americans, age range 7-18 y), we measured at baseline fasting insulin and leptin levels, height and weight and calculated body mass index (kg/m(2)) and expressed body mass index as (BMI) Z-score. After a 2.5-y follow-up, anthropometric measurements were repeated and changes in weight gain were calculated as changes in BMI Z-score. RESULTS: At baseline obese preadolescent boys and girls had similar age and BMI Z-score, fasting insulin and leptin levels. After an average follow-up of 2.5 y, mean weight change calculated by changes in BMI Z-score from baseline was similar in both groups. In obese adolescent boys and girls at baseline, no significant gender differences were observed for BMI Z-score and insulin levels. In contrast, plasma leptin levels were significantly higher in obese girls compared with obese adolescent boys. At follow-up, there was no significant difference in change in BMI Z-score between obese boys and girls. Multiple linear regression analysis revealed that high basal leptin levels were positively associated with greater changes in BMI Z-score only in girls (r(2)=0.18, P<0.02), after adjusting for basal BMI Z-score, Tanner stage, years of follow-up and basal insulin. High basal leptin levels in girls explained 18% of the weight gain. CONCLUSION: High leptin levels are associated with excessive future weight gain only in girls.

The utility of the Digi-walker step counter to assess daily physical activity patterns.

PURPOSE: The Digi-Walker step counter is a promising and cost-effective tool to measure physical activity under free-living conditions. Two specific studies were conducted to evaluate the number of steps required to meet current physical activity guidelines. METHODS: Thirty-one adults (17 men, 14 women) served as participants. In study 1, we determined the number of steps to complete a mile under two different conditions and three paces. In study 2, we conducted a field trial to examine the relationship between daily step counts and other indices of physical activity. Participants in this study wore a Digi-Walker for 2 consecutive weeks and completed the 7-d physical activity recall (PAR) after each week. RESULTS: In study 1, there were no differences in step counts by site, but steps were inversely related to pace, with values ranging from 1330 to 1996. Individual step counts at a specific pace were negatively correlated with height, weight, leg length, and stride length and were positively correlated with body fatness. In study 2, participants had average daily step counts of 11,603 when structured vigorous activity was included and 8265 when only light and moderate activity were measured. Modest correlations were found between step counts and estimated energy expenditure. Similar correlations were observed when step counts were related to minutes of activity per day and minutes of sitting per day. CONCLUSIONS: Pedometers provide a useful indicator of daily step counts but variability in activity patterns make it difficult to establish step count guidelines that correspond with other public health guidelines.

Exercise: a prescription to delay the effects of aging.

Aging is associated with marked alterations in body composition. Of greater importance than the prevention of obesity for health and function in older age is the maintenance of body weight, specifically, preservation of lean muscle mass. Past the seventh decade of life, a decline in body weight occurs, which is at least partially explained by a loss of muscle mass, a process known as sarcopenia. Evidence suggests that muscle mass decreases 3% to 6% per decade after age 60.

Effects of recurrent hypoglycemia on brainstem function in diabetic BB rats: protective adaptation during acute hypoglycemia.

To determine whether antecedent recurrent hypoglycemia protects the brain from the adverse effects of a standardized hypoglycemic stimulus, we implanted electrodes in the inferior colliculi of diabetic rats to directly record inferior colliculi auditory-evoked potentials (ICEPs). Awake, chronically catheterized BB rats were studied after 2 weeks of insulin therapy designed to produce either chronic hyperglycemia (hyper-DM, glycated hemoglobin 7.6 +/- 0.4%) or recurrent hypoglycemia (hypo-DM, glycated hemoglobin 6.2 +/- 0.7%), and the results were compared with those observed in nondiabetic rats. When plasma glucose was lowered to and clamped at 2.8 mmol/l, the release of catecholamines was suppressed in the hypo-DM rats (epinephrine: 2.5 +/- 0.4 nmol/l) as compared with hyper-DM and the nondiabetic rats (9.3 +/- 2.3 and 32.7 +/- 6.1 nmol/l, respectively). ICEP latency was significantly delayed in hyper-DM and nondiabetic rats (P < 0.001), but it was unchanged in hypo-DM rats. A more pronounced reduction in plasma glucose (2.0 mmol/l), however, provoked a greater adrenergic response than that seen at 2.8 mmol/l and delayed ICEP latency by 23% in a separate group of hypo-DM animals. These data demonstrate that antecedent recurrent hypoglycemia attenuates the brainstem dysfunction associated with mild to moderate, but not severe, hypoglycemia in diabetic rats. This phenomenon may contribute to the alterations in hypoglycemia counterregulation seen in diabetic patients during intensive insulin therapy.