The alpha-7 nicotinic acetylcholine receptor agonist GTS-21 engages the glucagon-like peptide-1 incretin hormone axis to lower levels of blood glucose in db/db mice.

AIM: To establish if alpha-7 nicotinic acetylcholine receptor (α7nAChR) agonist GTS-21 exerts a blood glucose-lowering action in db/db mice, and to test if this action requires coordinate α7nAChR and GLP-1 receptor (GLP-1R) stimulation by GTS-21 and endogenous GLP-1, respectively. MATERIALS AND METHODS: Blood glucose levels were measured during an oral glucose tolerance test (OGTT) using db/db mice administered intraperitoneal GTS-21. Plasma GLP-1, peptide tyrosine tyrosine 1-36 (PYY1-36), glucose-dependent insulinotropic peptide (GIP), glucagon, and insulin levels were measured by ELISA. A GLP-1R-mediated action of GTS-21 that is secondary to α7nAChR stimulation was evaluated using α7nAChR and GLP-1R knockout (KO) mice, or by co-administration of GTS-21 with the dipeptidyl peptidase-4 inhibitor, sitagliptin, or the GLP-1R antagonist, exendin (9-39). Insulin sensitivity was assessed in an insulin tolerance test. RESULTS: Single or multiple dose GTS-21 (0.5-8.0 mg/kg) acted in a dose-dependent manner to lower levels of blood glucose in the OGTT using 10-14 week-old male and female db/db mice. This action of GTS-21 was reproduced by the α7nAChR agonist, PNU-282987, was enhanced by sitagliptin, was counteracted by exendin (9-39), and was absent in α7nAChR and GLP-1R KO mice. Plasma GLP-1, PYY1-36, GIP, glucagon, and insulin levels increased in response to GTS-21, but insulin sensitivity, body weight, and food intake were unchanged. CONCLUSIONS: α7nAChR agonists improve oral glucose tolerance in db/db mice. This action is contingent to coordinate α7nAChR and GLP-1R stimulation. Thus α7nAChR agonists administered in combination with sitagliptin might serve as a new treatment for type 2 diabetes.

Maximizing the Morning Commute: A Randomized Trial Assessing the Effect of Driving on Podcast Knowledge Acquisition and Retention.

STUDY OBJECTIVE: Emergency medicine residents use podcasts as part of their learning process, often listening while driving. It is unclear how driving while listening to a podcast affects knowledge acquisition and retention. This study evaluated the knowledge gained from listening to podcasts while driving compared to that gained from undistracted listening. METHODS: This was a multicenter, randomized, crossover trial among postgraduate year (PGY) 1 to 4 emergency medicine residents at 4 institutions. Residents were randomized with stratification by site and PGY level to listen to podcasts while driving first or sitting undistracted in a room first. Within 30 minutes of listening, they completed a 20-question test. They subsequently crossed over to the alternate intervention, serving as their own controls, and listened to a different podcast before completing a second 20-question test. Each of the podcasts was professionally recorded and based on 5 emergency medicine-relevant journal articles that had not been covered in a journal club or curriculum at any of the institutions. One month later, participants completed a delayed recall test composed of 40 new questions based on both podcasts. Questions were derived and validity evidence was collected prior to use. Data were compared using a paired-sample t test and ANOVA. RESULTS: A total of 100 residents completed the initial recall tests, and 96 residents completed the delayed recall test. There was no statistically significant difference between the driving and undistracted cohorts on the initial recall (74.2% versus 73.3%) or delayed recall (52.2% versus 52.0%). CONCLUSION: Driving while listening to a podcast does not meaningfully affect knowledge acquisition or retention when compared with undistracted podcast listening among emergency medicine residents.

Association of serum levels of antioxidant micronutrients with mortality in US adults: National Health and Nutrition Examination Survey 1999-2002.

OBJECTIVE: To examine associations between serum antioxidant levels and mortality (all-cause, cancer and CVD) among US adults. DESIGN: We examined the risk of death from all-cause and cause-specific mortality associated with serum antioxidant (vitamin E and carotenoids) and vitamin A levels using Cox regression models to estimate hazards ratios (HR) and 95 % CI. SETTING: The National Health and Nutrition Examination Survey (NHANES) 1999-2002 was followed up through 31 December 2015. PARTICIPANTS: The NHANES 1999-2002 cohort included 8758 participants aged ≥ 20 years. Serum carotenoid levels were only assessed for the 1999-2000 cycle. Therefore, sample size for each assessed antioxidant ranged from 4633 to 8758. RESULTS: Serum vitamin E level was positively associated with all-cause mortality (HR = 1·22, 95 % CI 1·04, 1·43, highest v. lowest quartile). No other antioxidants were associated with mortality in overall analysis. In race/ethnicity-specific analyses, high vitamin E and α-tocopherol levels were associated with increased risk of all-cause mortality among non-Hispanic Whites. Among non-Hispanic Blacks, serum α-tocopherol level was associated with decreased risk of cancer mortality (HR = 0·30, 95 % CI 0·12, 0·75, third v. first quartile) and total carotenoid levels with reduced risk of CVD mortality (HR = 0·26; 95 % CI 0·07, 0·97, second v. lowest quartile). Hispanics with high ß-carotene levels had reduced risk of CVD mortality. CONCLUSIONS: Serum antioxidant levels may be related to mortality; these associations may differ by race/ethnicity and appeared to be non-linear for all-cause and cause-specific mortality. Further studies are needed to confirm our results.

Therapeutic potential of α7 nicotinic acetylcholine receptor agonists to combat obesity, diabetes, and inflammation.

The cholinergic anti-inflammatory reflex (CAIR) represents an important homeostatic regulatory mechanism for sensing and controlling the body's response to inflammatory stimuli. Vagovagal reflexes are an integral component of CAIR whose anti-inflammatory effects are mediated by acetylcholine (ACh) acting at α7 nicotinic acetylcholine receptors (α7nAChR) located on cells of the immune system. Recently, it is appreciated that CAIR and α7nAChR also participate in the control of metabolic homeostasis. This has led to the understanding that defective vagovagal reflex circuitry underlying CAIR might explain the coexistence of obesity, diabetes, and inflammation in the metabolic syndrome. Thus, there is renewed interest in the α7nAChR that mediates CAIR, particularly from the standpoint of therapeutics. Of special note is the recent finding that α7nAChR agonist GTS-21 acts at L-cells of the distal intestine to stimulate the release of two glucoregulatory and anorexigenic hormones: glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Furthermore, α7nAChR agonist PNU 282987 exerts trophic factor-like actions to support pancreatic ß-cell survival under conditions of stress resembling diabetes. This review provides an overview of α7nAChR function as it pertains to CAIR, vagovagal reflexes, and metabolic homeostasis. We also consider the possible usefulness of α7nAChR agonists for treatment of obesity, diabetes, and inflammation.

The Potential Physiological Role of γ-Tocopherol in Human Health: A Qualitative Review.

Chronic aging-related diseases result in the greatest burden to the health care system, yet there is little agreement on optimal levels of vitamins or the functional significance of many other dietary molecules in disease prevention. This review presents accumulated information regarding the role of γ-tocopherol in the prevention of nitrogen oxide-mediated damage and its impact on aging-related diseases. γ-Tocopherol is ubiquitous in the diet and levels appear to be physiologically regulated such that levels rise in response to inflammation and deficiencies in certain key vitamins. The unique antioxidant properties of γ-tocopherol, whereby DNA-damaging nitrogen dioxide is rapidly converted to nitric oxide, suggest a mechanistic justification for a functional role in the prevention of DNA damage over time. Data from cell, animal, and human studies indicate that γ-tocopherol appears to have significant beneficial effects, protecting cells from inflammatory damage; however, interpretation of epidemiologic studies is complex due to the paradoxical rise in levels of γ-tocopherol in response to known etiologic risk factors. Current knowledge of its antioxidant mechanism of action, apparent physiological regulation, and impact on various enzymatic pathways suggests γ-tocopherol may have a functional role in maintaining human health. Its utility as a biomarker and the consequences of its deficiency deserve further study.

A systematic review and meta-analysis of predictors of recurrence in patients with Solid Pseudopapillary Tumors of the Pancreas.

BACKGROUND: The recurrence rates and predictors of recurrence in patients with Solid Pseudopapillary tumors (SPT) are unclear, which makes it challenging to determine the duration of follow-up. The aim of the current study was to perform a systematic review and meta-analysis to determine the recurrence rates and pathologic factors associated with recurrence in patients with SPT. METHODS: A PubMed, Scopus, and Web of Science search was conducted to identify studies of SPT published during the last 15 years: (09/2002-09/2017). Studies reporting on patients with SPT and follow-up of >5 years were included. The search strategy was conducted per 2009 PRISMA guidelines. RESULTS: A total of 103 studies reporting on 2599 non-metastatic SPT patients were identified. Sixty-nine patients (2.6%) developed recurrence during follow-up. Pooled estimates from studies with a sample size >20 (N = 33) noted an overall recurrence rate of 2% (95% CI 1-2%). Male gender (OR 1.960), positive lymph nodes (OR 11.9), R1 margins (OR 11.1), and LVI (OR 5.5), were associated with a significantly (all p < 0.05) increased risk of recurrence. CONCLUSION: Current meta-analysis suggests that only 2% of patients with SPT experience recurrence after resection. These data will guide the treating physicians and patients regarding recurrence rates and help identify patients at increased risk of recurrence during follow-up.

Protective effects of glutathione on oxidative injury induced by hydrogen peroxide in intestinal epithelial cells.

BACKGROUND: Reactive oxygen species are increased in multiple gastrointestinal diseases and contribute to their pathogenesis. glutathione (GSH) is an antioxidant that helps to prevent reactive oxygen species-mediated mucosal damage. This study examines the mechanisms by which GSH attenuates hydrogen peroxide (H2O2)-induced injury in intestinal epithelial cells. METHODS: IEC-6 cells were cultured and treated with H2O2 ± GSH. Inflammation was measured by nuclear factor kappa-B (NF-κB) P65 expression, NF-κB nuclear translocation, iκBα phosphorylation, and interleukin 1 beta secretion. Terminal deoxynucleotidyl transferase-mediated UTP end-labeling staining and cleaved caspase-3 were used to assess apoptosis. The role of P38 mitogen-activated protein kinase (P38 MAPK) signaling was examined using the P38 MAPK agonist U46619 and inhibitor SB203580 in H2O2 and GSH-treated cells. Phosphorylated and total P38 MAPKs and cleaved caspase-3 were measured by Western blot. Data are means ± standard deviation, statistical significance P < 0.05 by student's t-test, or one-way analysis of variance. RESULTS: Pretreatment with GSH attenuates the activation of NF-κB and P38 MAPK signaling pathways by H2O2. GSH also decreased H2O2-mediated increases in interleukin 1 beta secretion, cleaved caspase-3 activation, and apoptosis in IEC-6 cells. SB203580 attenuated the increase in apoptosis and cleaved caspase-3 in H2O2-treated cells. The increase in apoptotic index and cleaved caspase-3 observed in U46619-treated cells was also diminished by GSH. CONCLUSIONS: GSH appears to ameliorate oxidative injury in intestinal epithelial cells by attenuating H2O2-mediated activation of NF-κB and P38 MAPK signaling pathways that regulate intestinal inflammation and apoptosis.

The paths of Andrew A. Benson: a radio-autobiography.

Andrew A. Benson, one of the greatest biochemists of our time, is celebrated on his centennial by the authors with whom he interacted performing experiments or contemplating metabolic pathways in a wide range of biological kingdoms. He charted the chemical flow of energy in cells, tissues, organs, plants, animals, and ecosystems. Benson collaborated with hundreds of colleagues to examine the natural history of autotrophy, mixotrophy, and heterotrophy while elucidating metabolic pathways. We present here a biological perspective of his body of studies. Benson lived from September 24, 1917, to January 16, 2015. Out of over 1000 autoradiograms he produced in his life, he left a legacy of 50 labeled autoradiograms to the authors who tell the story of his life's work that resulted in Benson's Protocol (Nonomura et al., Photosynth Res 127:369-378, 2016) that has been applied, over the years, for the elucidation of major metabolic pathways by many scientists.

Dietary Red and Processed Meat Intake and Markers of Adiposity and Inflammation: The Multiethnic Cohort Study.

OBJECTIVE: The potential influence of dietary factors on inflammation is important for cancer prevention. Utilizing data from control participants (312 men, 911 women) in 2 nested case-control studies of cancer within the Multiethnic Cohort, we examined the associations of red and processed meat intake with serum levels of leptin, adiponectin, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 and the mediator effect of body mass index (BMI) on the above associations (if present). METHODS: Multivariable linear models were applied to assess the association between red and processed meat intake at cohort entry and serum biomarker levels measured 9.1 years later after adjusting for covariates and to determine the mediator effect of BMI. RESULTS: Overall red and processed meat intake was positively associated with serum leptin levels in men (ß = 0.180, p = 0.0004) and women (ß = 0.167, p < 0.0001). In women, higher red and processed meat consumption was significantly associated with higher CRP (ß = 0.069, p = 0.03) and lower adiponectin levels (ß = -0.082, p = 0.005). In mediation analyses with red and processed meat intake and BMI as predictors, the associations of red and processed meat with biomarkers decreased substantially (as indicated by percentage change in effect: leptin in men, 13.4%; leptin in women, 13.7%; adiponectin in women, -4.7%; CRP in women, 7.4%) and were no longer significant (p > 0.05), whereas BMI remained significantly associated with serum leptin (men: ß = 3.209, p < 0.0001; women: ß = 2.891, p < 0.0001), adiponectin (women: ß = -1.085, p < 0.0001), and CRP (women: ß = 1.581, p < 0.0001). CONCLUSION: The current data suggest that the amount of excess body weight or the degree of adiposity may mediate the relations between dietary red and processed meat intake and serum biomarkers associated with obesity and inflammation.

Differential susceptibility of transgenic mice expressing human surfactant protein B genetic variants to Pseudomonas aeruginosa induced pneumonia.

Surfactant protein B (SP-B) is essential for lung function. Previous studies have indicated that a SP-B 1580C/T polymorphism (SNP rs1130866) was associated with lung diseases including pneumonia. The SNP causes an altered N-linked glycosylation modification at Asn129 of proSP-B, e.g. the C allele with this glycosylation site but not in the T allele. This study aimed to generate humanized SP-B transgenic mice carrying either SP-B C or T allele without a mouse SP-B background and then examine functional susceptibility to bacterial pneumonia in vivo. A total of 18 transgenic mouse founders were generated by the DNA microinjection method. These founders were back-crossed with SP-B KO mice to eliminate mouse SP-B background. Four founder lines expressing similar SP-B levels to human lung were chosen for further investigation. After intratracheal infection with 50 µl of Pseudomonas aeruginosa solution (1 × 10(6) CFU/mouse) or saline in SP-B-C, SP-B-T mice the mice were sacrificed 24 h post-infection and tissues were harvested. Analysis of surfactant activity revealed differential susceptibility between SP-B-C and SP-B-T mice to bacterial infection, e.g. higher minimum surface tension in infected SP-B-C versus infected SP-B-T mice. These results demonstrate for the first time that human SP-B C allele is more susceptible to bacterial pneumonia than SP-B T allele in vivo.

Readmissions After Colectomy: The Upstate New York Surgical Quality Initiative Experience.

BACKGROUND: Hospital readmissions remain a major medical and financial concern to the healthcare system and have become an area of interest in health outcomes performance metrics. There is a pressing need to identify process measures that may help reduce readmissions. OBJECTIVE: Our aim was to assess the patient characteristics and surgical factors associated with 30-day readmissions for colorectal surgery in Upstate New York. DESIGN: This was a retrospective cohort study. SETTINGS: The study included colectomy cases abstracted for the National Surgical Quality Improvement Program in the Upstate New York Surgical Quality Initiative from June 2013 to June 2014. PATIENTS: The study consists of 630 colectomies. Patients with a length of stay >30 days or who died during the index admission were excluded. MAIN OUTCOME MEASURES: Readmission within 30 days of surgery was the main outcome measure. RESULTS: Of 630 colectomy patients, 76 patients (12%) were readmitted within 30 days of surgery. Major and minor complications were associated with 30-day postoperative readmission (OR = 2.99 (95% CI, 1.70-5.28) and OR = 2.19 (95% CI, 1.09-4.43)) but excluded from final analysis because they included both predischarge and postdischarge complications. Risk factors independently associated with 30-day postoperative readmission included diabetes mellitus (OR = 1.94 (95% CI, 1.02-3.67)), smoker within the past year (OR = 2.01 (95% CI, 1.12-3.60)), no scheduled follow-up (OR = 2.20 (95% CI, 1.25-3.86)), and ileostomy formation (OR = 1.97 (95% CI, 1.03-3.77)). LIMITATIONS: Limitations include the retrospective design and only 30 days of postoperative follow-up. CONCLUSIONS: Consistent with national trends, 1 in 8 patients in the Upstate New York Surgical Quality Initiative program was readmitted within 30 days after colorectal surgery. This study identified several risk factors that may act as tangible targets for intervention, including preoperative smoking cessation programs, optimization of diabetic management, mandatory scheduled follow-up appointments on discharge, and ostomy care pathways.

Depression, Anxiety, and Pharmacotherapy Around the Time of Pregnancy in Hawaii.

BACKGROUND: Depression and anxiety are common conditions among pregnant and postpartum women, but population-based information is lacking on treatments and help-seeking behaviors. PURPOSE: This study described the prevalence of depression, anxiety, pharmaceutical treatment, and help-seeking behaviors among a multiethnic population of women with recent live births in Hawaii. METHOD: Hawaii Pregnancy Risk Assessment Monitoring System data from 4735 respondents were weighted to be representative of all pregnancies resulting in live births in Hawaii in 2009-2011 and were used to estimate the prevalence of several indicators related to anxiety and depression before, during, and after pregnancy among women with recent live births. RESULTS: Of Hawaii women with live births in 2009-2011, 7.3 % reported visiting a healthcare worker to be checked or treated for depression or anxiety in the year before their most recent pregnancy, 4.9 % reported having depression in the 3 months before pregnancy, 5.9 % reported having anxiety in the same period, 9.1 % screened positive for postpartum depression, and 6.9 % reported asking a doctor, nurse, or other healthcare worker for help for anxiety postpartum. The prevalence of antianxiety and antidepressant prescription drug use was 2.3 % in the month before pregnancy and 1.4 % during pregnancy. Hawaii had lower prevalence of pre-pregnancy depression, anxiety, and depression/anxiety health visits than other US states. Pre-pregnancy depression and anxiety and postpartum anxiety help-seeking behaviors differed significantly by race/ethnicity. CONCLUSION: Depression and anxiety are common among pregnant and postpartum women in Hawaii. More research could better inform heath care professionals and patients of the treatment options available and their potential risks and benefits.

Time-related increase in urinary testosterone levels and stable semen analysis parameters after bariatric surgery in men.

The aim of this prospective cohort study was to determine the time-course in androgen and semen parameters in men after weight loss associated with bariatric surgery. Six men aged 18-40 years, meeting National Institutes of Health bariatric surgery guidelines, were followed between 2005 and 2008. Study visits took place at baseline, then 1, 3, 6 and 12 months after surgery. All men underwent Roux-en-y gastric bypass (RYGB). At each visit, biometric, questionnaire, serum, and urinary specimens and seman analysis were collected. Urinary integrated total testosterone levels increased significantly (P < 0.0001) by 3 months after surgery, and remained elevated throughout the study. Circulating testosterone levels were also higher at 1 and 6 months after surgery, compared with baseline. Serum sex hormone-binding globulin levels were significantly elevated at all time points after surgery (P < 0.01 to P = 0.02). After RYGB surgery, no significant changes occurred in urinary oestrogen metabolites (oestrone 3-glucuronide), serum oestradiol levels, serial semen parameters or male sexual function by questionnaire. A threshold of weight loss is necessary to improve male reproductive function by reversing male hypogonadism, manifested as increased testosterone levels. Further serial semen analyses showed normal ranges for most parameters despite massive weight loss.

Adherence to cancer prevention recommendations and antioxidant and inflammatory status in premenopausal women.

For cancer prevention, the World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) emphasise recommendations to improve individual behaviour, including avoidance of tobacco products, maintaining a lean body mass, participating in physical activity, consuming a plant-based diet, and minimising the consumption of energy-dense foods, such as sodas, red and processed meats and alcohol. In the present study of 275 healthy premenopausal women, we explored the association of adherence scores with levels of three biomarkers of antioxidant and inflammation status: serum C-reactive protein (CRP), serum γ-tocopherol and urinary F2-isoprostane. The statistical analysis applied linear regression across categories of adherence to WCRF/AICR recommendations. Overall, seventy-two women were classified as low ( ≤ 4), 150 as moderate (5-6), and fifty-three as high adherers ( ≥ 7). The unadjusted means for CRP were 2.7, 2.0 and 1.7 mg/l for low, moderate and high adherers (P trend= 0.03); this association was strengthened after adjustment for confounders (P trend= 0.006). The respective values for serum γ-tocopherol were 1.97, 1.63 and 1.45 µg/ml (P trend= 0.02 before and P trend= 0.03 after adjustment). Only for urinary F2-isoprostane, the lower values in high adherers (16.0, 14.5, and 13.3 ng/ml) did not reach statistical significance (P trend= 0.18). In an analysis by BMI, overweight and obese women had higher biomarker levels than normal weight women; the trend was significant for CRP (P trend< 0.001) and γ-tocopherol (P trend= 0.003) but not for F2-isoprostane (P trend= 0.14). These findings suggest that both adherence to the WCRF/AICR guidelines and normal BMI status are associated with lower levels of biomarkers that indicate oxidative stress and inflammation.

Prediagnostic circulating carotenoid levels and the risk of non-Hodgkin lymphoma: the Multiethnic Cohort.

This analysis examined the association of non-Hodgkin lymphoma (NHL) with prediagnostic carotenoid levels, a marker for a diet rich in fruits and vegetables. We conducted a nested case-control study within the Multiethnic Cohort with 271 NHL cases and 538 controls matched on sex, ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, and hours fasting before blood draw. Serum carotenoid levels were obtained by high-pressure liquid chromatography with photodiode array detection. Conditional logistic regression was used to calculate odds ratios (ORs) according to tertiles of serum carotenoids and trend tests using continuous variables. Higher total serum carotenoids (OR(T3 vs T1) = 0.66 [0.46-0.96]; P(trend) = .02), lycopene (OR = 0.54 [0.38-0.78]; P(trend) = .003), and α-cryptoxanthin (OR = 0.53 [0.36-0.78]; P(trend) = .003) were associated with a lower risk of NHL. For retinol (OR = 0.90 [0.61-1.33]; P(trend) = .04), a statistically significant inverse linear trend was detected. Risk estimates remained unchanged with adjustment for NHL risk factors and were similar in analyses stratified by sex and ethnicity; heterogeneity with NHL subtype was detected only for ß-carotene. Other carotenoids, including α-carotene, ß-carotene, lutein, ß-cryptoxanthin, and zeaxanthin, showed no association with risk. These data provide support for a protective role of carotenoid-rich fruits and vegetables in the etiology of NHL.

In vivo changes in plasma coenzyme Q10, carotenoid, tocopherol, and retinol levels in children after computer tomography.

BACKGROUND: Low dose X-irradiation (IR) from computer tomography (CT) can generate free radicals, which can damage biologically relevant molecules and ultimately lead to cancer. These effects are especially concerning for children owing to their higher radiosensitivity and longer life expectancy than adults. The lipid phase micronutrients (LPM) coenzyme Q10, carotenoids, E vitamers, and vitamin A are potent radical scavengers that can act as intracellular antioxidants. METHODS: We investigated changes in circulating levels of these LPM in 17 children (0.25-6 y) undergoing medically indicated CT scans involving relatively low IR doses. Blood was drawn before and 1h after CT scans and analyzed using HPLC with electrochemical and UV/VIS detection. RESULTS: We found significant decreases (p<0.05) in post-CT plasma levels in several LPM which suggests that these LPM can serve as biodosimeters and may protect against damage from IR during clinical procedures such as CT. The strongest predictors for pre- to post-CT changes for many LPM were their baseline levels. CONCLUSION: Future larger studies are warranted to confirm our findings and to test whether high circulating antioxidant levels protect against IR damage in vivo with an ultimate goal of establishing prophylactic modalities for CT-induced IR damage.

Plasma 25-hydroxyvitamin D3 is associated with decreased risk of postmenopausal breast cancer in whites: a nested case-control study in the multiethnic cohort study.

BACKGROUND: Higher sunlight exposure is correlated with lower incidence of breast cancer in ecological studies, but findings from prospective studies regarding the association of circulating levels of vitamin D with the risk of breast cancer have been null. The objective of this study was to examine the relation between plasma levels of vitamin D and the risk of postmenopausal breast cancer. METHODS: We conducted a nested case-control study within the Multiethnic Cohort Study of five race/ethnic groups (white, African-American, Native Hawaiian, Japanese, and Latino) from Hawaii and Los Angeles between 2001 and 2006. Pre-diagnostic plasma levels of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3] and 25(OH)D (sum of 25(OH)D2 and 25(OH)D3) were examined among 707 postmenopausal breast cancer cases and matched controls. RESULTS: Using conditional logistic regression models, 20 ng/mL increases of plasma 25(OH)D3 (odds ratio (OR) 0.28; 95% confidence interval (CI) 0.14-0.56) and 25(OH)D (OR 0.43; 95% CI 0.23-0.80) were inversely associated with breast cancer risk among white women, but not among women in other race/ethnic groups. Using two-segmented, piecewise-linear logistic regression models, the change-points of the ORs, either for 25(OH)D3 or for 25(OH)D, were detected as 20 ng/mL among whites. CONCLUSIONS: Circulating 25(OH)D3 and 25(OH)D were associated with a reduced risk of postmenopausal breast cancer among whites, but not in other ethnic groups, who reside in low latitude regions.

Serum coenzyme Q10, α-tocopherol, γ-tocopherol, and C-reactive protein levels and body mass index in adolescent and premenopausal females.

OBJECTIVE: Lipid-soluble antioxidants are associated with a lower incidence for many chronic diseases of aging, possibly by preventing damage from chronic inflammation. In the current study, we compared serum levels of coenzyme Q10 (CoQ10), α-tocopherol, γ-tocopherol, and C-reactive protein (CRP) between adolescent girls and premenopausal women to assess changes from childhood to midlife. METHODS: Baseline serum CoQ10, α-tocopherol, γ-tocopherol, and CRP levels were measured in 207 girls (13-19 years) and 183 premenopausal women (34-47 years) using standard methods and the 2 age groups were compared by t test. The influence of age, body mass index (BMI), and race/ethnicity and interaction effects on serum values were assessed using analysis of covariance. Pearson correlation coefficients were used to assess associations between pairs of lipid micronutrients. RESULTS: Overall, adolescent girls had significantly lower mean serum CoQ10, α-tocopherol, γ-tocopherol, and CRP levels relative to premenopausal women (CoQ10: 376 vs 544 ng/mL, p < 0.0001; α-tocopherol: 6.9 vs 13.5 µg/mL, p < 0.0001; γ-tocopherol: 1.3 vs 1.7 µg/mL, p < 0.0001; CRP: 1.29 vs 2.13 mg/L, p < 0.0001). The differences in CoQ10 and tocopherols remained significant after adjustment for BMI and race/ethnicity. CoQ10 was significantly and positively correlated to α- and γ-tocopherol, and BMI was positively associated with CRP and γ-tocopherol in both groups. CONCLUSIONS: Lower serum CoQ10, α-tocopherol, γ-tocopherol, and CRP levels in adolescent girls compared to women suggests that adolescents may have a reduced need for antioxidants possibly due to their lower BMI and inflammatory status as indicated by CRP.

A Randomized Trial Assessing the Effect of Exercise on Residents' Podcast Knowledge Acquisition and Retention.

PURPOSE: Podcasts are commonly used by residents as part of their learning, with many listening concomitantly with other activities (e.g., driving and exercise). The effects of exercise on learning are controversial, with some suggesting potential benefit and others suggesting impaired learning. This study examined whether exercise influences knowledge acquisition and retention among resident physicians listening to a podcast while exercising versus those with undistracted listening. METHOD: This multicenter, randomized, crossover trial assessed emergency medicine residents across 5 U.S. institutions from September 2022 to January 2023. Residents were randomized to a group that listened to one 30-minute podcast while seated or a group that listened to a 30-minute podcast while engaging in 30 minutes of continuous aerobic exercise, with stratification by site and postgraduate year. Within 30 minutes of completing the podcast, they completed a 20-question multiple-choice test. They subsequently crossed over to the other intervention and listened to a different 30-minute podcast followed by another 20-question test. Each podcast focused on emergency medicine-relevant journal articles that had not been covered in journal club or curriculum at any sites. Residents also completed a 40-question delayed recall test with separate questions on both podcasts at 30 days. RESULTS: Ninety-six residents were recruited for the study, with 95 (99.0%) completing the initial recall portion and 92 (97.0%) completing the delayed recall tests. No statistically significant differences were found between the exercise and seated cohorts on initial recall (74.4% vs 76.3%; d = -0.12; 95% CI, -0.33 to 0.08; P = .12) or delayed recall (52.3% vs 52.5%; d = -0.01; 95% CI, -0.22 to -0.19; P = .46). CONCLUSIONS: Exercising while listening to podcasts did not appear to meaningfully affect knowledge acquisition or retention at 30 days when compared with listening while seated and undistracted.

Educational Podcasts: Effect of Content Delivery Timing on Knowledge Acquisition and Retention.

PURPOSE: This study examined whether the order of podcast content influenced knowledge acquisition and retention among emergency medicine (EM) resident physicians. METHOD: This preplanned secondary analysis of 2 large, multicenter trials included a randomized, crossover trial conducted from November 2019 to June 2020 of 100 residents that compared driving and seated condition for two 30-minute podcasts and a randomized, crossover trial conducted from September 2022 to January 2023 of 95 EM residents that compared exercise with seated condition for the same two 30-minute podcasts. Each podcast contained 6 journal article reviews, with the segments recorded in forward or backward order. After completing each podcast, participants completed an initial 20-question test and a 40-question delayed recall test with separate questions. Segments were divided into 3 subgroups based on the order in which they were played (primacy group, recency group, and reference group) for assessment of recency and primacy effects. The mean scaled scores from the primacy and recency groups were compared with scores from the reference group. RESULTS: The study included 195 residents (390 podcasts), with 100 residents listening in the forward order and 95 residents the reverse order. No statistically significant difference was found in immediate recall scores between the primacy and reference groups (d = 0.094; 95% CI, -0.046 to 0.234) or the recency and reference groups (d = -0.041; 95% CI, -0.181 to 0.099) or in 30-day delayed recall score between the primacy and reference groups (d = -0.088; 95% CI, -0.232 to 0.056) or the recency and reference groups (d = -0.083; 95% CI, -0.227 to 0.060). CONCLUSIONS: The order of podcast information did not significantly affect immediate knowledge acquisition or delayed knowledge retention. This finding can inform podcast creators and listeners regarding the order of content when using podcasts for learning.