Chronic intermittent hypoxia (CIH) increases sympathetic tone and respiratory instability. Our previous work showed that chronic hypoxia induces the oxygen-sensing enzyme heme oxygenase-1 (HO-1) ...within the C1 sympathoexcitatory region and the pre-Bötzinger complex (pre-BötC). We therefore examined the effect of CIH on time course of induced expression of HO-1 within these regions and determined whether the induction of HO-1 correlated with changes in respiratory, sigh frequency, and sympathetic responses (spectral analysis of heart rate) to acute hypoxia (10% O
) during 10 days of exposure to CIH in chronically instrumented awake wild-type (WT) and HO-1 null mice (HO-1
). HO-1 was induced within the C1 and pre-BötC regions after 1 day of CIH. There were no significant differences in the baseline respiratory parameters between WT and HO-1
Prior to CIH, acute hypoxia increased respiratory frequency in both WT and HO-1
; however, minute diaphragm electromyogram activity increased in WT but not HO-1
The hypoxic respiratory response after 1 and 10 days of CIH was restored in HO-1
CIH resulted in an initial significant decline in 1) the hypoxic sigh frequency response, which was restored in WT but not HO-1
, and 2) the baseline sympathetic activity in WT and HO-1
, which remained stable subsequently in WT but not in HO-1
We conclude that 1) CIH induces expression of HO-1 in the C1 and pre-BötC regions within 1 day and 2) HO-1 is necessary for hypoxia respiratory response and contributes to the maintenance of the hypoxic sigh responses and baseline sympathetic activity during CIH.
Background And Objectives: Epidemiologie studies have attributed adverse health effects to air pollution; however, controversy remains regarding the relationship between ambient oxidante ozone (O₃) ...and nitrogen dioxide (NO₂) and mortality, especially in Asia. We conducted a fourcity time-series study to investigate acute effects of O₃ and NO₂ in the Pearl River Delta (PRD) of southern China, using data from 2006 through 2008. Methods: We used generalized linear models with Poisson regression incorporating natural spline functions to analyze acute mortality in association with O₃ and NO₂, with PM₁₀ (paniculate matter ≤ 10 μm in diameter) included as a major confounder. Effect estimates were determined for individual cities and for the four cities as a whole. We stratified the analysis according to high-and low-exposure periods for O₃. Results: We found consistent positive associations between ambient oxidants and daily mortality across the PRD cities. Overall, 10-μg/m³ increases in average O₃ and NO₂ concentrations over the previous 2 days were associated with 0.81% 95% confidence interval (CI): 0.63%, 1.00% and 1.95% (95% CI: 1.62%, 2.29%) increases in total mortality, respectively, with stronger estimated effects for cardiovascular and respiratory mortality. After adjusting for PM₁₀, estimated effects of O₃ on total and cardiovascular mortality were stronger for exposure during high-exposure months (September through November), whereas respiratory mortality was associated with O3 exposure during nonpeak exposure months only. Conclusions: Our findings suggest significant acute mortality effects of O₃ and NO₂ in the PRD and strengthen the rationale for further limiting the ambient pollution levels in the area.
Ambient air pollution has been linked to cardiovascular and respiratory morbidity and mortality in epidemiology studies. Frequently, oxidative and nitrosative stress are hypothesized to mediate these ...pollution effects, however precise mechanisms remain unclear. This paper describes the methodology for a major panel study to examine air pollution effects on these and other mechanistic pathways. The study took place during the drastic air pollution changes accompanying the 2008 Olympics in Beijing, China. After a general description of air pollution health effects, we provide a discussion of panel studies and describe the unique features of this study that make it likely to provide compelling results. This study should lead to a clearer and more precise definition of the role of oxidative and nitrosative stress, as well as other mechanisms, in determining acute morbidity and mortality from air pollution exposure.
To examine whether the presence of sleep-disordered breathing (SDB) is associated with an earlier age at mild cognitive impairment (MCI) or Alzheimer disease (AD)-dementia onset in participants from ...the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We also examined whether continuous positive airway pressure (CPAP) use is associated with delayed onset of cognitive decline.
From the ADNI cohort, 3 subsets with progressively stringent criteria were created in a step-wise manner. Age at MCI or AD-dementia onset was the main outcome variable. Analyses were performed separately for each subset in untreated SDB+ vs SDB- and untreated SDB+ vs CPAP+ groups. Chi-square and t tests were performed to examine between-group differences. Survival analyses were performed using the Kaplan-Meier method, compared by the log-rank test, and assessed by multivariate Cox regression adjusting for potential confounders.
SDB+ patients had a younger age at MCI onset in all subsets (MC1: 72.63 vs 83.67; MC2: 72.15 vs 83.45; MC3: 77.40 vs 89.89; p < 0.01). SDB+ patients had a younger age at AD-dementia onset only in our most conservative subset (AC3: 83.46 vs 88.13; p < 0.05). In a combined outcome analysis, SDB+ patients had a younger age at onset to MCI or AD-dementia in all subsets. In subsets 1 and 2, CPAP use delayed the age at MCI onset (CMC1: 72.63 vs 82.10; CMC2: 72.11 vs 82.10; p < 0.01).
Consistent with our hypothesis, the presence of SDB was associated with an earlier age at cognitive decline. Our findings in CPAP+ participants suggest that CPAP treatment of SDB may delay progression of cognitive impairment.
National guidelines recommend cancer genetic risk assessment (CGRA) (i.e. genetic counseling prior to genetic testing) for women at increased risk for hereditary breast and ovarian cancer (HBOC). ...Less than one-half of eligible women obtain CGRA, leaving thousands of women and their family members without access to potentially life-saving cancer prevention interventions.
The Genetic Risk Assessment for Cancer Education and Empowerment Project (GRACE) addressed this translational gap, testing the efficacy of a tailored counseling and navigation (TCN) intervention vs. a targeted print brochure vs. usual care on CGRA intentions. Selected behavioral variables were theorized to mediate CGRA intentions.
Breast and ovarian cancer survivors meeting criteria for guideline-based CGRA were recruited from three state cancer registries (N = 654), completed a baseline survey, and were randomized. TCN and targeted print arms received the brochure; TCN also participated in a tailored, telephone-based decision coaching and navigation session grounded in the Extended Parallel Process Model and Ottawa Decision Support Framework. Participants completed a one-month assessment. Logistic regression was used to compare the rate of CGRA intentions. CGRA intentions and theorized mediator scores (continuous level variables) were calculated using mixed model analysis.
CGRA intentions increased for TCN (53.2%) vs. targeted print (26.7%) (OR =
3
.129; 95% CI: 2.028, 4.827, p < .0001) and TCN vs. usual care (23.1%) (OR =
3
.778, CI: 2.422, 5.894, p < .0001). Perceived risk (p = 0.023) and self-efficacy (p = 0.035) mediated CGRA intentions in TCN.
Improvements in CGRA intentions and theorized mediators support the use of a tailored communication intervention among women at increased HBOC risk. (Clinicaltrials.gov: NCT03326713.)
Trial registration:
ClinicalTrials.gov identifier: NCT03326713
.
Limiting oxidative stress to the ovarian epithelium has been proposed as a first-line defense against ovarian cancer. Although evidence for an association between individual dietary antioxidant ...intake and ovarian cancer risk is conflicting, the combined evidence suggests a modest inverse association. Our study aimed to evaluate the association between total antioxidant capacity (TAC) and individual antioxidant intakes (vitamin C, vitamin E, beta-carotene, selenium, lutein, and lycopene) and ovarian cancer risk.
We conducted a population-based case-control study in New Jersey. Cases were women ages 21 years and older with newly diagnosed epithelial ovarian cancer who resided in six counties of New Jersey. Controls were women in the same age range who resided in the same geographic area. A total of 205 ovarian cancer cases and 390 controls were included. Dietary intake was ascertained using the Block food frequency questionnaire (FFQ), and TAC indices were constructed by linking FFQ-derived estimates to two standardized antioxidant capacity databases, the USDA Oxygen Radical Absorbance Capacity (ORAC) Database, and the University of Olso's Antioxidant Food Database. Multivariate logistic regression models were used to calculate odds ratios and 95 % confidence intervals while controlling for major ovarian cancer risk factors.
We found a strong inverse association with selenium from food sources (OR: 0.41; 95 % CI: 0.20-0.85, for the highest vs. lowest tertile of dietary selenium intake). However, there was little evidence of an association with dietary TAC or the others individual antioxidants. In contrast, compared to non-users, supplement users had significant increased risk for all micronutrients, but no statistically significant increased risk was observed for combined intake from foods and supplements of any of these antioxidants.
This study found an inverse association between selenium consumption from food sources and ovarian cancer risk, while there was little evidence of an association with TAC or any of the other individual antioxidants. Additional research is needed to confirm these findings.
Healthy eating index and ovarian cancer risk Chandran, Urmila; Bandera, Elisa V; Williams-King, Melony G ...
CCC. Cancer causes & control/CCC, Cancer causes & control,
04/2011, Letnik:
22, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The evidence for a role of diet on ovarian cancer prevention remains inconclusive. While many studies have evaluated individual foods and food groups, the evaluation of a comprehensive dietary ...quality index for predicting cancer risk has received little attention. This study investigates the association between the Healthy Eating Index (HEI), which reflects adherence to the current USDA Dietary Guidelines for Americans and ovarian cancer risk in a population-based case-control study in New Jersey. A total of 205 cases and 390 controls completed the Block 98.2 food frequency questionnaire (FFQ) in addition to reporting on potential risk factors for ovarian cancer. FFQ data were then utilized to calculate the HEI score, and cup, ounce, gram, or caloric equivalents for the 12 different food groups comprising the index. In multivariate models, the OR for the highest tertile of the HEI score compared with the lowest (reflecting a better diet compared with a worse diet) was 0.90 (95% CI: 0.55-1.47). There was limited evidence for a statistically significant association between any of the 12 individual food components and ovarian cancer risk. Based on this study's results, neither individual food groups nor dietary quality showed potential for preventing ovarian cancer.
The assay of plasma very long chain fatty acids (VLCFAs), developed in our laboratory in 1981, has become the most widely used procedure for the diagnosis of X‐linked adrenoleukodystrophy (X‐ALD) and ...other peroxisomal disorders. We present here our 17 years' experience with this assay. Three VLCFA parameters, the level of hexacosanoic acid (C26:0), the ratio of C26:0 to tetracosanoic acid (C24:0), and of C26:0 to docosanoic acid (C22:0), were measured in 1,097 males (hemizygotes) with X‐ALD, 1,282 women heterozygous for this disorder, including 379 obligate heterozygotes, 797 patients with other peroxisomal disorders, and 29,600 control subjects. All X‐ALD hemizygotes who had not previously received Lorenzo's oil or a diet with a high erucic acid content had increased VLCFA levels, but the application of a discriminant function based on all three measurements is required to avoid the serious consequences of a false‐negative result. VLCFA levels are increased at day of birth, thus providing the potential for neonatal mass screening, are identical in the childhood and adult forms, and do not change with age. Eighty‐five percent of obligate heterozygotes had abnormally high VLCFA levels, but a normal result does not exclude carrier status. VLCFA levels were increased in all patients homozygous for Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum's disease, and in patients with deficiencies of peroxisomal acyl‐coenzyme A oxidase, bifunctional enzyme, and 3‐oxoacyl‐coenzyme A thiolase. In these patients the degree of VLCFA excess correlated with clinical severity. Ann Neurol 1999;45:100–110
Methadone treatment (MT) fails to address the emotion dysregulation, pain, and reward processing deficits that often drive opioid use disorder (OUD). New interventions are needed to address these ...factors.
To evaluate the efficacy of MT as usual (usual care) vs telehealth Mindfulness-Oriented Recovery Enhancement (MORE) plus usual care among people with an OUD and pain.
This study was a randomized clinical trial conducted from August 2020 to June 2022. Participants receiving MT for OUD and experiencing chronic pain were recruited at 5 clinics in New Jersey.
In usual care, participants received MT, including medication and counseling. Participants receiving MORE plus usual care attended 8 weekly, 2-hour telehealth groups that provided training in mindfulness, reappraisal, and savoring in addition to usual care.
Primary outcomes were return to drug use and MT dropout over 16 weeks. Secondary outcomes were days of drug use, methadone adherence, pain, depression, and anxiety. Analyses were based on an intention-to-treat approach.
A total of 154 participants (mean SD age, 48.5 11.8 years; 88 female 57%) were included in the study. Participants receiving MORE plus usual care had significantly less return to drug use (hazard ratio HR, 0.58; 95% CI, 0.37-0.90; P = .02) and MT dropout (HR, 0.41; 95% CI, 0.18-0.96; P = .04) than those receiving usual care only after adjusting for a priori-specified covariates (eg, methadone dose and recent drug use, at baseline). A total of 44 participants (57.1%) in usual care and 39 participants (50.6%) in MORE plus usual care returned to drug use. A total of 17 participants (22.1%) in usual care and 10 participants (13.0%) in MORE plus usual care dropped out of MT. In zero-inflated models, participants receiving MORE plus usual care had significantly fewer days of any drug use (ratio of means = 0.58; 95% CI, 0.53-0.63; P < .001) than those receiving usual care only through 16 weeks. A significantly greater percentage of participants receiving MORE plus usual care maintained methadone adherence (64 of 67 95.5%) at the 16-week follow-up than those receiving usual care only (56 of 67 83.6%; χ2 = 4.49; P = .04). MORE reduced depression scores and ecological momentary assessments of pain through the 16-week follow-up to a significantly greater extent than usual care (group × time F2,272 = 3.13; P = .05 and group × time F16,13000 = 6.44; P < .001, respectively). Within the MORE plus usual care group, EMA pain ratings decreased from a mean (SD) of 5.79 (0.29) at baseline to 5.17 (0.30) at week 16; for usual care only, pain decreased from 5.19 (0.28) at baseline to 4.96 (0.29) at week 16. Within the MORE plus usual care group, mean (SD) depression scores were 22.52 (1.32) at baseline and 18.98 (1.38) at 16 weeks. In the usual care-only group, mean (SD) depression scores were 22.65 (1.25) at baseline and 20.03 (1.27) at 16 weeks. Although anxiety scores increased in the usual care-only group and decreased in the MORE group, this difference between groups did not reach significance (group × time unadjusted F2,272 = 2.10; P= .12; Cohen d = .44; adjusted F2,268 = 2.33; P = .09). Within the MORE plus usual care group, mean (SD) anxiety scores were 25.5 (1.60) at baseline and 23.45 (1.73) at 16 weeks. In the usual care-only group, mean (SD) anxiety scores were 23.27 (1.75) at baseline and 24.07 (1.73) at 16 weeks.
This randomized clinical trial demonstrated that telehealth MORE was a feasible adjunct to MT with significant effects on drug use, pain, depression, treatment retention, and adherence.
ClinicalTrials.gov Identifier: NCT04491968.
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