Wood cookstove use is associated with gastric cancer in Central America and mediated by host genetics.

Biomass cookstove food preparation is linked to aero-digestive cancers, mediated by ingested and inhaled carcinogens (e.g., heterocyclic amines, and polycyclic aromatic hydrocarbons). We investigated the association between gastric adenocarcinoma, wood cookstove use, H. pylori CagA infection and risk modification by variants in genes that metabolize and affect the internal dose of carcinogens. We conducted a population-based, case-control study (814 incident cases, 1049 controls) in rural Honduras, a high-incidence region with a homogeneous diet and endemic H. pylori infection, primarily with the high-risk CagA genotype. We investigated factors including wood cookstove use, H. pylori CagA serostatus, and 15 variants from 7 metabolizing genes, and the interactions between wood stove use and the genetic variants. Male sex (OR 2.0, 1.6-2.6), age (OR 1.04, 1.03-1.05), wood cookstove use (OR 2.3, 1.6-3.3), and CagA serostatus (OR 3.5, 2.4-5.1) and two SNPs in CYP1B1 (rs1800440 and rs1056836) were independently associated with gastric cancer in multivariate analysis. In the final multivariate model, a highly significant interaction (OR 3.1, 1.2-7.8) was noted between wood cookstove use and the rs1800440 metabolizing genotype, highlighting an important gene-environment interaction. Lifetime wood cookstove use associates with gastric cancer risk in the high-incidence regions of Central America, and the association is dependent on the rs1800440 genotype in CYP1B1. H. pylori CagA infection, wood cookstove use and the rs1800440 genotype, all of which are highly prevalent, informs who is at greatest risk from biomass cookstove use.

Early intervention with double balloon enteroscopy for higher yield for inpatient overt obscure gastrointestinal bleeding: A propensity matched analysis.

Background and Aim: Overt obscure gastrointestinal bleeding (OOGIB) is defined as continued bleeding with unknown source despite esophagogastroduodenoscopy (EGD) and colonoscopy evaluation. Small bowel evaluation through video capsule endoscopy (VCE) or double balloon enteroscopy (DBE) is often warranted. We studied the timing of DBE in hospitalized OOGIB patients regarding diagnostic yield, therapeutic yield, and GI rebleeding. Methods: We performed a retrospective review of DBEs performed at a tertiary medical center between November 2012 and December 2020. The inclusion criterion was first admission for OOGIB undergoing DBE. Those without previous EGD or colonoscopy were excluded. Patients were stratified into two groups: DBE performed within 72 h of OOGIB (emergent) and beyond 72 h of OOGIB (nonemergent). Propensity score matching was used to adjust for the difference in patients in the two groups. Logistic regression analysis was used to assess factors associated with diagnostic and therapeutic yield. Kaplan-Meir survival curve showed GI bleed-free survival following initial bleed and was compared using the log rank test. Results: A total of 154 patients met the inclusion criterion, of which 62 had emergent DBE and 92 had nonemergent DBE. The propensity-score-matched sample consisted of 112 patients, with 56 patients each in the emergent and nonemergent groups. Univariate and multivariable logistic regression analysis showed a significant association between VCE and emergent DBE and diagnostic and therapeutic yield (P < 0.05). Emergent DBE patients had increased GI bleed-free survival compared to those in the nonemergent group (P = 0.009). Conclusion: Our data demonstrate that emergent DBE during inpatient OOGIB can impact the overall diagnostic yield, therapeutic yield, and GI rebleeding post DBE.

Predictive models for abdominal aortic aneurysms using polygenic scores and PheWAS-derived risk factors.

Abdominal aortic aneurysms (AAA) are common enlargements of the abdominal aorta which can grow larger until rupture, often leading to death. Detection of AAA is often by ultrasonography and screening recommendations are mostly directed at men over 65 with a smoking history. Recent large-scale genome-wide association studies have identified genetic loci associated with AAA risk. We combined known risk factors, polygenic risk scores (PRS) and precedent clinical diagnoses from electronic health records (EHR) to develop predictive models for AAA, and compared performance against screening recommendations. The PRS included genome-wide summary statistics from the Million Veteran Program and FinnGen (10,467 cases, 378,713 controls of European ancestry), with optimization in Vanderbilt's BioVU and validated in the eMERGE Network, separately across both White and Black participants. Candidate diagnoses were identified through a temporally-oriented Phenome-wide association study in independent EHR data from Vanderbilt, and features were selected via elastic net. We calculated C-statistics in eMERGE for models including PRS, phecodes, and covariates using regression weights from BioVU. The AUC for the full model in the test set was 0.883 (95% CI 0.873-0.892), 0.844 (0.836-0.851) for covariates only, 0.613 (95% CI 0.604-0.622) when using primary USPSTF screening criteria, and 0.632 (95% CI 0.623-0.642) using primary and secondary criteria. Brier scores were between 0.003 and 0.023 for our models indicating good calibration, and net reclassification improvement over combined primary and secondary USPSTF criteria was 0.36-0.60. We provide PRS for AAA which are strongly associated with AAA risk and add to predictive model performance. These models substantially improve identification of people at risk of a AAA diagnosis compared with existing guidelines, with evidence of potential applicability in minority populations.

GSK3ß Regulates Brain Energy Metabolism.

GSK3ß is a serine threonine kinase implicated in the progression of Alzheimer's disease. Although the role of GSK3ß in growth and pathology has been extensively studied, little is known about the metabolic consequences of GSK3ß manipulation, particularly in the brain. Here, we show that GSK3ß regulates mitochondrial energy metabolism in human H4 neuroglioma cells and rat PC12-derived neuronal cells and that inhibition of GSK3ß in mice in vivo alters metabolism in the hippocampus in a region-specific manner. We demonstrate that GSK3ß inhibition increases mitochondrial respiration and membrane potential and alters NAD(P)H metabolism. These metabolic effects are associated with increased PGC-1α protein stabilization, enhanced nuclear localization, and increased transcriptional co-activation. In mice treated with the GSK3ß inhibitor lithium carbonate, changes in hippocampal energy metabolism are linked to increased PGC-1α. These data highlight a metabolic role for brain GSK3ß and suggest that the GSK3ß/PGC-1α axis may be important in neuronal metabolic integrity.

Addressing Stroke Risk Factors in Black and White Americans: Findings from the National Health and Nutrition Examination Survey, 2009-2010.

OBJECTIVE: Recurrent stroke affects 5%-15% of stroke survivors, is higher among Blacks, and preventable with secondary stroke prevention medications. Our study aimed to examine racial differences in risk factors being addressed (defined as either on active treatment or within guideline levels) among stroke survivors and those at risk for stroke. METHODS: A cross-sectional study using NHANES 2009-2010 standardized interviews of Whites and Blacks aged ≥18 years. Risk factors were defined as being addressed if: 1) for hypertension, SBP <140, DBP <90 (SBP<130, DBP<80 for diabetics) or using BP-lowering medications; 2) for current smoking, using cessation medications; and 3) for hyperlipidemia, LDL<100 (LDL<70 for stroke survivors) or using lipid-lowering medications. Participants were stratified by stroke history. Prevalence of addressed risk factors was compared by race. RESULTS: Among 4005 participants (mean age 48, 52% women, 15% Black), 4% reported a history of stroke. Among stroke survivors, there were no statistically significant differences in Blacks and Whites having their hypertension or hyperlipidemia addressed. Among stroke naïve participants, the prevalence of addressed hypertension (P<.01) and hyperlipidemia (P<.01) was lower in Blacks compared with Whites. CONCLUSIONS: We found that addressed hypertension and hyperlipidemia in stroke naïve participants were significantly lower in Blacks than Whites. Our observations call attention to areas that require further investigation, such as why Black Americans may not be receiving evidence-based pharmacologic therapy for hypertension and hyperlipidemia or why Black Americans are not at goal blood pressure or goal LDL. A better understanding of this information is critical to preventing stroke and other vascular diseases.

Multireader evaluation of lesion conspicuity in small pancreatic adenocarcinomas: complimentary value of iodine material density and low keV simulated monoenergetic images using multiphasic rapid kVp-switching dual energy CT.

OBJECTIVE: Perform multireader analysis of objective and subjective lesion conspicuity for small pancreatic adenocarcinomas using rapid switching dual energy CT (rsDECT). MATERIALS AND METHODS: With IRB approval, 51 abdominal multiphasic rsDECT scans in 46 subjects with small (<3 cm) pancreatic adenocarcinomas were retrospectively reviewed by three independent readers for objective and subjective lesion conspicuity. Measured variables during individual, blinded interpretive sessions of separate low (52) keV, PACS-equivalent (70) keV, and iodine material density (MD) image sets included Hounsfield units (HU) and mg/cc iodine for tumor, nontumoral pancreas, and subcutaneous fat. Objective measures included absolute lesion contrast (LC) and contrast to noise ratios (CNR). Subjective measures included image quality, lesion conspicuity, and reader confidence. Reader agreement was measured with kappa statistic; correlation with truth by Pearson coefficient, CNR with repeated mANOVA; subjective quality measures utilized Tukey-Cramer corrections for multiple testing, p < 0.05 considered significant. RESULTS: Demographics: 26 F, 20 M, mean age 68 years, weight 75 kg, tumor size of 2.3 cm. LC was highest on 52 keV images for all three readers (mean 90.1 HU). Mean CNR for iodine MD images (4.87) was significantly higher than 52 keV (4.13) or 70 keV (3.9). Very high to near-perfect kappa values were observed for all individual measured objective variables but were best for 52 keV images (52 keV 0.89-0.95, 70 keV 0.76-0.83, iodine 0.87-0.92). 70 keV images scored best for subjective image quality; iodine MD images scored best for lesion conspicuity and reader confidence. CONCLUSION: We observed very high reader agreement for independent objective rsDECT image variables and subjective rsDECT image scores in patients with small pancreatic adenocarcinomas. Maximal objective tumor to nontumoral LC was depicted on 52 keV and highest CNR on iodine MD images; readers scored the iodine MD images best for lesion conspicuity and confidence.

Quantitative perfusion- and diffusion-weighted magnetic resonance imaging of gastrointestinal cancers treated with multikinase inhibitors: a pilot study.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) are often used to detect the early response of solid tumors to an effective therapy. The early changes in intratumoral physiological parameters measured by DCE-MRI/DWI have been evaluated as surrogate biomarkers allowing a tailored treatment for the individual patient. METHODS: Patients with newly diagnosed, biopsy-proven, treatment-naïve gastrointestinal stromal tumor (GIST) or hepatocellular carcinoma (HCC) were enrolled prospectively after institutional review board (IRB)-approved informed consent (5 patients per tumor type). Patients with GIST were treated with sunitinib over 6 weeks. DCE-MRI/DWI was applied before therapy (baseline imaging) and at 2 and 6 weeks after therapy initiation. Patients with HCC were treated with radiation during the first 2 weeks and then with sorafenib for the next 6 weeks. DCE-MRI/DWI was applied in all patients with HCC before and after radiation therapy and at the end of sorafenib therapy. Tumor volume, perfusion parameters (K (trans), the forward volume-transfer constant, and k ep, the reverse reflux-rate constant) and the apparent diffusion coefficient (ADC) were measured. RESULTS: During 2 weeks of sunitinib therapy, GIST volume, K (trans), and k ep decreased 32 ± 13, 45 ± 24, and 42 ± 15%, respectively, whereas ADC increased 76 ± 24%. After 6 weeks of sunitinib therapy, GIST volume, K (trans), and k ep decreased 56 ± 7, 70 ± 7, and 50 ± 12%, respectively, whereas ADC increased 85 ± 33%. After completion of radiation therapy, HCC volume, K (trans), and k ep decreased 34 ± 14, 35 ± 12, and 4 ± 21%, respectively, but ADC increased 21 ± 9%. During the entire 10-week therapeutic period, HCC volume, K (trans), and k ep decreased 65 ± 15, 40 ± 9, and 26 ± 2%, respectively, whereas ADC increased 28 ± 10%. CONCLUSION: DCE-MRI/DWI can measure the perfusion and diffusion changes in GISTs or HCCs treated with multikinase inhibitors.

Early therapy assessment of combined anti-DR5 antibody and carboplatin in triple-negative breast cancer xenografts in mice using diffusion-weighted imaging and (1)H MR spectroscopy.

PURPOSE: To assess the early response of triple-negative breast-cancer (TNBC) following TRA-8 and carboplatin therapy using DWI and MRS in 2LMP and SUM159 mouse models. MATERIALS AND METHODS: Four groups (n = 5/group) of each model were untreated or treated with carboplatin, TRA-8, and combination, respectively. DWI and MRS were applied on 0, 3, and 7 days after therapy initiation, and all tumors were collected thereafter for terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. The changes in intratumoral apparent diffusion coefficient (ADC) and fat-water ratios (FWRs) were compared with tumor volume changes and apoptotic cell densities. RESULTS: Mean ADC values of 2LMP and SUM159 tumors significantly increased 4 ± 4% and 37 ± 11% during 7 days of combination therapy, respectively, as compared to control groups (P < 0.05). Similarly, mean FWRs of 2LMP and SUM159 tumors significantly increased 102 ± 30% and 126 ± 52%, respectively, for 7 days of combined treatment (P < 0.05). The changes of the mean ADC values for 3 days (or FWRs for 7 days) were linearly proportional to either the mean volume changes or apoptotic cell densities in both models. CONCLUSION: DWI and MRS assessed the early tumor response to TRA-8 and carboplatin in TNBC mouse models.

Antagonistic effects of anti-EMMPRIN antibody when combined with chemotherapy against hypovascular pancreatic cancers.

PURPOSE: To examine the antagonistic effects of anti-extracellular matrix metalloprotease inducer (anti-EMMPRIN) antibody when combined with chemotherapy using a hypovascular pancreatic tumor model. PROCEDURES: Severely compromised immunodeficient mice bearing orthotopic MIA PaCa-2 tumors were used (five to six animals per group). Dynamic contrast-enhanced magnetic resonance imaging was used to examine the relationship between tumor vascularity and size. Therapy was initiated when tumors were hypovascular. Treatments included: (1) gemcitabine alone, (2) anti-EMMPRIN antibody alone, and (3) combination, each for 2 weeks. Additionally, another treatment arm included ß-lapachone, an NAD(P)H/quinone 1 (NQO1) bioactivated agent. (18)F-fluoro-D-glucose-positron emission tomography/computed tomography imaging was used weekly to monitor therapeutic effects. RESULTS: Gemcitabine or anti-EMMPRIN monotherapy significantly delayed tumor growth, but the combination therapy showed an antagonistic effect. Similarly, tumor growth was significantly suppressed by ß-lapachone alone, and additive effects were noted when combined with gemcitabine, but the therapeutic efficacy was reduced when anti-EMMPRIN antibody was added. CONCLUSIONS: Anti-EMMPRIN antibody with chemotherapy in hypovascular tumors results in antagonistic effects.

Diffusion weighted imaging evaluated the early therapy effect of tamoxifen in an MNU-induced mammary cancer rat model.

PURPOSE: To assess the optimal time point of diffusion-weighted imaging (DWI) for early prognosis of breast cancer following tamoxifen therapy using a methylnitrosourea (MNU)-induced ER-positive breast-cancer model. METHODS: Two groups of Sprague-Dawley rats (n = 15 for group 1; n = 10 for group 2) were used. All animals (50 days old) were intravenously injected with MNU (50 mg/kg body weight) to induce ER-positive mammary tumors. When tumors were approximately 2 cm in diameter, DWI was performed on days 0, 3, and 7, and intratumoral apparent diffusion coefficient (ADC) values were measured. Therapy started on day 0 with tamoxifen (10 mg/kg diet) and continued for 4 weeks for group 1, but only 1 week for group 2, while tumor volume was measured by caliper twice weekly. All animals of group 2 were euthanized on day 7 after imaging, and Ki-67, TUNEL, ERα, and ERß staining were performed on tumor tissue. RESULTS: DW images of MNU-induced mammary tumors were successfully obtained with minimal motion artifact. For group 1, ADC change for 3 days after therapy initiation (ADC3D) was significantly correlated with tumor-volume change until day 11, but the significant correlation between ADC change for 7 days (ADC7D) and the tumor-volume change was observed until day 18. Similarly, for group 2, either ADC7D or ADC3D was significantly correlated with the tumor-volume change, but the higher significance was observed for ADC7D. Furthermore, ADC7D was significantly correlated with apoptotic (TUNEL stained), proliferative (Ki-67 stained), and ERß-positive cell densities, but ADC3D was not significantly correlated with any of those. CONCLUSIONS: ADC7D might be a more reliable surrogate imaging biomarker than ADC3D to assess effectiveness of tamoxifen therapy for ER-positive breast cancer, which may enable personalized treatment. The significant correlation between ADC7D and ERß-positive cell density suggests that ERß may play an important role as a therapeutic indicator of tamoxifen.

A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys.

Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using magnetic resonance imaging, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n=24, 13 males, 11 females) and standard (n=17, 8 males, 9 females) diets. Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex. A Diet X Age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR-induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species.

Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study.

Calorie restriction (CR), a reduction of 10­40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7­14 years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.

Caloric restriction delays aging-induced cellular phenotypes in rhesus monkey skeletal muscle.

Sarcopenia is the age-related loss of skeletal muscle mass and function and is characterized by a reduction in muscle mass and fiber cross-sectional area, alterations in muscle fiber type and mitochondrial functional changes. In rhesus monkeys, calorie restriction (CR) without malnutrition improves survival and delays the onset of age-associated diseases and disorders including sarcopenia. We present a longitudinal study on the impact of CR on early stage sarcopenia in the upper leg of monkeys from ~16 years to ~22 years of age. Using dual-energy X-ray absorptiometry we show that CR delayed the development of maximum muscle mass and, unlike Control animals, muscle mass of the upper leg was preserved in CR animals during early phase sarcopenia. Histochemical analyses of vastus lateralis muscle biopsies revealed that CR opposed age-related changes in the proportion of Type II muscle fibers and fiber cross-sectional area. In contrast the number of muscle fibers with mitochondrial electron transport system enzyme abnormalities (ETS(ab)) was not significantly affected by CR. Laser capture microdissection of ETS(ab) fibers and subsequent PCR analysis of the mitochondrial DNA revealed large deletion mutations in fibers with abnormal mitochondrial enzyme activities. CR did not prevent stochastic mitochondrial deletion mutations in muscle fibers but CR may have contributed to the maintenance of affected fibers.

Warfarin dosing in patients with impaired kidney function.

BACKGROUND: In patients with kidney impairment, warfarin, a drug metabolized primarily by the cytochrome P-450 system, is initiated at similar doses and managed similarly as in the general medical population. Unfortunately, few data exist to guide dose adjustment in patients with decreased kidney function. Here, we determine the degree of warfarin dose reduction associated with kidney impairment and make recommendations for warfarin dosing. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Long-term warfarin users followed up at anticoagulation clinics (n = 980); 708 participants from the University of Alabama (UAB) and 272 participants from the University of Chicago (UIC). PREDICTOR: No/mild (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2)), moderate (eGFR, 30-59 mL/min/1.73 m(2)), and severe (eGFR < 30 mL/min/1.73 m(2)) kidney impairment; CYP2C9 and VKORC1 genotype; age; race; sex; body mass; sociodemographic factors; smoking status; alcohol; vitamin K intake; comorbid conditions (eg, congestive heart failure); and drug interactions (eg, amiodarone and statins). OUTCOME & MEASUREMENT: Warfarin dose (milligrams per day) was evaluated using linear regression after adjustment for clinical, demographic, and genetic factors. RESULTS: Prevalences of moderate (31.8% and 27.6%) and severe kidney impairment (8.9% and 6.6%) were similar in the UAB and UIC cohorts. Warfarin dose requirements were significantly lower in patients with moderate and severe kidney impairment compared with those with no/mild kidney impairment in the UAB (P < 0.001) and UIC (P < 0.001) cohorts. Compared with patients with no/mild kidney impairment, patients with moderate kidney impairment required 9.5% lower doses (P < 0.001) and patients with severe kidney impairment required 19% lower doses (P < 0.001). LIMITATIONS: No measurement of warfarin, serum albumin, vitamin K, and coagulation factors; no evaluation of other markers (eg, cystatin). CONCLUSION: Moderate and severe kidney impairment were associated with a reduction in warfarin dose requirements.

A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys.

Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using MRI, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n = 24; 13 males, 11 females) and standard diets (n = 17; 8 males, 9 females). Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex. A diet x age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR-induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species.

Caloric restriction delays disease onset and mortality in rhesus monkeys.

Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established. We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research. In a population of rhesus macaques maintained at the Wisconsin National Primate Research Center, moderate CR lowered the incidence of aging-related deaths. At the time point reported, 50% of control fed animals survived as compared with 80% of the CR animals. Furthermore, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy. These data demonstrate that CR slows aging in a primate species.

Longitudinal analysis of early stage sarcopenia in aging rhesus monkeys.

We present a longitudinal study using the rhesus monkey to determine biochemical and histological changes in vastus lateralis (VL) muscle fibers and whether these changes correlate with muscle mass loss. Dual-energy X-ray absorptiometry (DXA) was used to determine body weight, body fat and to estimate upper leg muscle mass in 12 adult male rhesus monkeys over 12 years. Muscle mass (MM) was evaluated at years 6, 9 and 12 of the study. Concurrently, VL muscle biopsy samples were collected. Muscle tissue was sectioned, stained and individual muscle fibers were analyzed for fiber type, cross-sectional area (CSA) and mitochondrial electron transport system (ETS) enzyme abnormalities. The animals' body weight did not change over time, however a significant increase in DXA-measured percent body fat was observed. Significant MM loss occurred in the upper leg over 12 years. A reduction in muscle fiber CSA significantly contributed to the MM loss observed in the VL of middle-aged rhesus monkeys. An age-dependent increase in muscle fibers developing mitochondrial enzyme abnormalities due to mitochondrial DNA deletion mutations was observed. The longitudinal approach of this study demonstrated that significant muscle changes occurred during middle age in a cohort of aging rhesus monkeys.

Effectiveness evaluation of the N-O-T smoking cessation program for adolescents.

OBJECTIVE: To evaluate the effectiveness of the Not-On-Tobacco Program. METHODS: Forty-four high schools implemented the program (n=241 students), with 27 comparison schools (n=251 students). Students reported smoking in the last 7 and 30 days at baseline and follow-up. RESULTS: Those in the program had an increased likelihood of reporting 30-day abstinence at end of program (OR = 4.2) but not at 6 or 12 months. For 7-day abstinence there was no significant difference for any time point. CONCLUSIONS: In this effectiveness evaluation the N-O-T Program increased quitting during the program, but the effects were not present at 6 or 12 months.