Evaluation of Culturally Informed and Flexible Family-Based Treatment for Adolescents (CIFFTA) implemented in community-based settings.

Effective family-based interventions are needed for youth who are experiencing emotional and behavioral difficulties and who are impacted by powerful environmental stressors. Culturally Informed and Flexible Family-Based Treatment for Adolescents (CIFFTA) is a manualized and evidence-based, multicomponent family-based treatment that has been shown to be efficacious in research settings. The purpose of this paper is to report on the effectiveness of implementing CIFFTA for the treatment of Latino and Black youth and families in community settings. Utilization of services offered and changes in youth presenting problems and family functioning were used to evaluate the program. Two hundred thirty-two youth (11-18 years of age) and their caregivers were recruited over 2 years and CIFFTA was delivered by experienced masters-level family therapists over a 12-16-week period. Seventy-six percent met the 8-session criteria for retention in treatment and 71% completed treatment. Results showed significant improvements in youth behavioral and emotional presenting problems, reduction in family conflict and improvement in family cohesion and communication. Caregiver well-being such as reductions in parental stress, relational frustration, and improvement in parental confidence also showed significant improvement. Analyses of reliable change indices showed a substantial improvement in youth who entered the program in the clinical range of presenting problems. The findings point to CIFFTA's ability to retain youth and families who tend to underutilize needed services, to significant reductions in presenting problems, and to improvements in family functioning when implemented in a community setting.

In utero ultrafine particulate matter exposure causes offspring pulmonary immunosuppression.

Early life exposure to fine particulate matter (PM) in air is associated with infant respiratory disease and childhood asthma, but limited epidemiological data exist concerning the impacts of ultrafine particles (UFPs) on the etiology of childhood respiratory disease. Specifically, the role of UFPs in amplifying Th2- and/or Th17-driven inflammation (asthma promotion) or suppressing effector T cells (increased susceptibility to respiratory infection) remains unclear. Using a mouse model of in utero UFP exposure, we determined early immunological responses to house dust mite (HDM) allergen in offspring challenged from 0 to 4 wk of age. Two mice strains were exposed throughout gestation: C57BL/6 (sensitive to oxidative stress) and BALB/C (sensitive to allergen exposure). Offspring exposed to UFPs in utero exhibited reduced inflammatory response to HDM. Compared with filtered air (FA)-exposed/HDM-challenged mice, UFP-exposed offspring had lower white blood cell counts in bronchoalveolar lavage fluid and less pronounced peribronchiolar inflammation in both strains, albeit more apparent in C57BL/6 mice. In the C57BL/6 strain, offspring exposed in utero to FA and challenged with HDM exhibited a robust response in inflammatory cytokines IL-13 and Il-17. In contrast, this response was lost in offspring exposed in utero to UFPs. Circulating IL-10 was significantly up-regulated in C57BL/6 offspring exposed to UFPs, suggesting increased regulatory T cell expression and suppressed Th2/Th17 response. Our results reveal that in utero UFP exposure at a level close to the WHO recommended PM guideline suppresses an early immune response to HDM allergen, likely predisposing neonates to respiratory infection and altering long-term pulmonary health.

Neonatal Thyroid Function and Disorders.

Thyroid hormone is essential for normal fetal brain development in utero and for the first 2 years of life. The developing fetus is initially reliant upon maternal thyroid hormones that cross the placenta, until the fetal thyroid begins to supply thyroid hormone for the fetus. Maternal thyroid status affects fetal thyroid function and maternal thyroid dysfunction can have a significant impact on the fetus and neonate. There are also several neonatal factors that can influence thyroid function. Here, we describe thyroid function in the fetus and neonate and discuss the most common thyroid disorders seen in neonates.

Peroxisome Proliferator-Activated Receptor γ and microRNA 98 in Hypoxia-Induced Endothelin-1 Signaling.

Endothelin-1 (ET-1) plays a critical role in endothelial dysfunction and contributes to the pathogenesis of pulmonary hypertension (PH). We hypothesized that peroxisome proliferator-activated receptor γ (PPARγ) stimulates microRNAs that inhibit ET-1 and pulmonary artery endothelial cell (PAEC) proliferation. The objective of this study was to clarify molecular mechanisms by which PPARγ regulates ET-1 expression in vitro and in vivo. In PAECs isolated from patients with pulmonary arterial hypertension, microRNA (miR)-98 expression was reduced, and ET-1 protein levels and proliferation were increased. Similarly, hypoxia reduced miR-98 and increased ET-1 levels and PAEC proliferation in vitro. In vivo, hypoxia reduced miR-98 expression and increased ET-1 and proliferating cell nuclear antigen (PCNA) levels in mouse lung, derangements that were aggravated by treatment with the vascular endothelial growth factor receptor antagonist Sugen5416. Reporter assays confirmed that miR-98 binds directly to the ET-1 3'-untranslated region. Compared with littermate control mice, miR-98 levels were reduced and ET-1 and PCNA expression were increased in lungs from endothelial-targeted PPARγ knockout mice, whereas miR-98 levels were increased and ET-1 and PCNA expression was reduced in lungs from endothelial-targeted PPARγ-overexpression mice. Gain or loss of PPARγ function in PAECs in vitro confirmed that alterations in PPARγ were sufficient to regulate miR-98, ET-1, and PCNA expression. Finally, PPARγ activation with rosiglitazone regimens that attenuated hypoxia-induced PH in vivo and human PAEC proliferation in vitro restored miR-98 levels. The results of this study show that PPARγ regulates miR-98 to modulate ET-1 expression and PAEC proliferation. These results further clarify molecular mechanisms by which PPARγ participates in PH pathogenesis and therapy.

Mitigation of colitis with NovaSil clay therapy.

BACKGROUND/AIMS: Five million people currently live with Crohn's disease (CD) or ulcerative colitis, the two major forms of inflammatory bowel disease. Available treatments frequently result in side effects that compromise the immune health of the patient. Consequently, alternative therapies that cause fewer systemic effects are needed. Dioctahedral smectite clays have been utilized to treat medical conditions, including diarrheal and enteric disease. Herein, we report the ability of a refined dioctahedral smectite (NovaSil, NS) to sorb inflammatory proteins and reduce inflammation in a TNBS (2,4,6-trinitrobenzenesulfonic acid) mouse model of CD. We also investigated whether NS could rescue gut microbial diversity in TNBS-induced mice. METHODS: ELISA, X-ray diffraction, and transmission electron microscopy were employed to characterize the NS-cytokine interaction in vitro. A TNBS mouse colitis model was utilized to study the efficacy of NS supplementation for 4 weeks. The three treatment groups included control, TNBS, and TNBS + NS. DNA was extracted from feces and sorted for bacterial phylogenetic analysis. RESULTS: Results suggest that NS binds TNFα in vitro. In TNBS-treated mice, supplementation with NS significantly reduced weight loss, and serum proinflammatory cytokine levels (IL-2, IL-6, and IL-12, TNFα, IFNγ) compared with the TNBS group. TNBS-treated mice demonstrated a significant reduction in gut microbiota species richness when compared with the TNBS + NS group and control group. CONCLUSIONS: NovaSil mitigated the effects of TNBS-induced colitis based on reduction in systemic markers of inflammation, significant improvement in weight gain, and intestinal microbial profile.

Calcium montmorillonite clay reduces AFB1 and FB1 biomarkers in rats exposed to single and co-exposures of aflatoxin and fumonisin.

Aflatoxins (AFs) and fumonisins (FBs) can co-contaminate foodstuffs and have been associated with hepatocellular and esophageal carcinomas in humans at high risk for exposure. One strategy to reduce exposure (and toxicity) from contaminated foodstuffs is the dietary inclusion of a montmorillonite clay (UPSN) that binds AFs and FBs in the gastrointestinal tract. In this study, the binding capacity of UPSN was evaluated for AFB1, FB1 and a combination thereof in Fischer 344 rats. Rats were pre-treated with different dietary levels of UPSN (0.25% or 2%) for 1 week. Rats were gavaged with a single dose of either 0.125 mg AFB1 or 25 mg FB1 per kg body weight and a combination thereof in the presence and absence of an aqueous solution of UPSN. The kinetics of mycotoxin excretion were monitored by analyzing serum AFB1 -albumin, urinary AF (AFM1) and FB1 biomarkers over a period of 72 h. UPSN decreased AFM1 excretion by 88-97%, indicating highly effective binding. FB1 excretion was reduced, to a lesser extent, ranging from 45% to 85%. When in combination, both AFB1 and FB1 binding occurred, but capacity was decreased by almost half. In the absence of UPSN, the combined AFB1 and FB1 treatment decreased the urinary biomarkers by 67% and 45% respectively, but increased levels of AFB1 -albumin, presumably by modulating its cytochrome metabolism. UPSN significantly reduced bioavailability of both AFB1 and FB1 when in combination; suggesting that it can be utilized to reduce levels below their respective thresholds for affecting adverse biological effects.

Society for birth defects research and prevention's multidisciplinary research needs workshop 2022: A call to action.

The Society for Birth Defects Research and Prevention (BDRP) strives to understand and protect against potential hazards to developing embryos, fetuses, children, and adults by bringing together scientific knowledge from diverse fields. The theme of 62nd Annual Meeting of BDRP, "From Bench to Bedside and Back Again", represented the cutting-edge research areas of high relevance to public health and significance in the fields of birth defects research and surveillance. The multidisciplinary Research Needs Workshop (RNW) convened at the Annual Meeting continues to identify pressing knowledge gaps and encourage interdisciplinary research initiatives. The multidisciplinary RNW was first introduced at the 2018 annual meeting to provide an opportunity for annual meeting attendees to participate in breakout discussions on emerging topics in birth defects research and to foster collaboration between basic researchers, clinicians, epidemiologists, drug developers, industry partners, funding agencies, and regulators to discuss state-of-the-art methods and innovative projects. Initially, a list of workshop topics was compiled by the RNW planning committee and circulated among the members of BDRP to obtain the most popular topics for the Workshop discussions. Based on the pre-meeting survey results, the top three discussion topics selected were, A) Inclusion of pregnant and lactating women in clinical trials. When, why, and how? B) Building multidisciplinary teams across disciplines: What cross-training is needed? And C) Challenges in applications of Artificial Intelligence (AI) and machine learning for risk factor analysis in birth defects research. This report summarizes the key highlights of the RNW workshop and specific topic discussions.

Long-term effects of prenatal arsenic exposure from gestational day 9 to birth on lung, heart, and immune outcomes in the C57BL/6 mouse model.

Prenatal arsenic exposure is a major public health concern, associated with altered birth outcomes and increased respiratory disease risk. However, characterization of the long-term effects of mid-pregnancy (second trimester) arsenic exposure on multiple organ systems is scant. This study aimed to characterize the long-term impact of mid-pregnancy inorganic arsenic exposure on the lung, heart, and immune system, including infectious disease response using the C57BL/6 mouse model. Mice were exposed from gestational day 9 till birth to either 0 or 1000 µg/L sodium (meta)arsenite in drinking water. Male and female offspring assessed at adulthood (10-12 weeks of age) did not show significant effects on recovery outcomes after ischemia reperfusion injury but did exhibit increased airway hyperresponsiveness compared to controls. Flow cytometric analysis revealed significantly greater total numbers of cells in arsenic-exposed lungs, lower MHCII expression in natural killer cells, and increased percentages of dendritic cell populations. Activated interstitial (IMs) and alveolar macrophages (AMs) isolated from arsenic-exposed male mice produced significantly less IFN-γ than controls. Conversely, activated AMs from arsenic-exposed females produced significantly more IFN-γ than controls. Although systemic cytokine levels were higher upon Mycobacterium tuberculosis (Mtb) infection in prenatally arsenic-exposed offspring there was no difference in lung Mtb burden compared to controls. This study highlights significant long-term impacts of prenatal arsenic exposure on lung and immune cell function. These effects may contribute to the elevated risk of respiratory diseases associated with prenatal arsenic exposure in epidemiology studies and point to the need for more research into mechanisms driving these maintained responses.

Association of depression and COVID-induced PTSD with cognitive symptoms after COVID-19 illness.

OBJECTIVE: Many patients recovering from COVID-19 report persistent psychological and cognitive symptoms months after viral clearance. We examined the association of depression and COVID-induced PTSD with cognitive symptoms following COVID-19 illness. METHODS: Patients treated for COVID-19 between March 26 and May 27, 2020 were surveyed three months later. Cognitive symptoms were assessed by asking "Since your COVID-19 illness, do you now have more difficulty: 1) Remembering conversations a few days later? 2) Remembering where you placed familiar objects? 3) Finding the right words while speaking?" Patients endorsing at least one such complaint were coded positive for cognitive symptoms. Logistic regression was used to estimate the association of depression (PHQ-8 ≥ 10) and COVID-induced PTSD (PCL-5 ≥ 30) with cognitive symptoms, adjusting for demographic and clinical factors. RESULTS: Among 153 participants, 44.4% reported at least one cognitive symptom, 18.3% were depressed, and 23.5% had COVID-induced PTSD. Adjusting for covariates, depression (OR 5.15, 95% CI 1.30-20.35, p = 0.02) and COVID-induced PTSD (OR 3.67, 95% CI 1.13-11.89, p = 0.03) were significantly associated with cognitive symptoms; self-reported history of mental illness was also associated (OR 4.90, 95% CI 1.24-19.41, p = 0.02). CONCLUSIONS: Depression, COVID-induced PTSD, and prior mental illness were strongly associated with cognitive symptoms three months after acute COVID-19 illness.

Maternal exposure to polycyclic aromatic hydrocarbons in South Texas, evaluation of silicone wristbands as personal passive samplers.

BACKGROUND: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health effects in children. Valid exposure assessment methods with accurate spatial and temporal resolution across pregnancy is a critical need for advancing environmental health studies. OBJECTIVE: The objective of this study was to quantify maternal PAH exposure in pregnant women residing in McAllen, Texas where the prematurity rate and childhood asthma prevalence rates are high. A secondary objective was to compare PAH levels in silicone wristbands deployed as passive samplers with concentrations measured using standardized active air-sampling techniques. METHODS: Participants carried a backpack that contained air-sampling equipment (i.e., filter and XAD sorbent) and a silicone wristband (i.e., passive sampler) for three nonconsecutive 24-h periods. Filters, XAD tubes, and wristbands were analyzed for PAHs. RESULTS: The median level of exposure for the sum of 16 PAHs measured via active sampling over 24 h was 5.54 ng/m3 (filters) and 43.82 ng/m3 (XADs). The median level measured in wristbands (WB) was 586.82 ng/band. Concentrations of the PAH compounds varied across sampling matrix type. Phenanthrene and fluorene were consistently measured for all participants and in all matrix types. Eight additional volatile PAHs were measured in XADs and WBs; the median level of exposure for the sum of these eight PAHs was 342.98 ng/m3 (XADs) and 632.27 ng/band. The silicone wristbands (WB) and XAD sorbents bound 1-methynaphthalyne, 2-methylnaphthalene, biphenyl following similar patterns of detection. SIGNIFICANCE: Since prior studies indicate linkages between PAH exposure and adverse health outcomes in children at the PAH levels detected in our study, further investigation on the associated health effects is needed. Data reflect the ability of silicone wristbands to bind smaller molecular weight, semivolatile PAHs similar to XAD resin. Application of wristbands as passive samplers may be useful in studies evaluating semivolatile PAHs.

Detrimental effects of carotenoid pigments: the dark side of bright coloration.

Carotenoid pigments produce yellow, orange, and red integumentary color displays that can serve as reliable signals of health and condition. In many birds and fish, individuals gain competitive or mating advantages by ingesting and utilizing large quantities of carotenoid pigments. Carotenoid pigments serve as antioxidants, performing important functions as free-radical scavengers. The beneficial effects of carotenoid pigments are well documented, but rarely have researchers considered potential detrimental effects of high-level accumulation of carotenoids. We maintained American goldfinches (Carduelis tristis) on high- or low-carotenoid diets through molt and tested for damage to the liver and skeletal muscle. High intake of carotenoids had no measurable effect on liver enzymes but caused an increase in creatine kinase, an indicator of skeletal muscle breakdown, and a reduction in vertical flight performance, a measure of skeletal muscle integrity. The detrimental effects of high-level carotenoid accumulation were approximately equivalent to the negative effects of removing carotenoids from the diet. The adverse effects observed in this study have important implications for theories of the function and evolution of colorful plumage.

Interventions to reduce short-wavelength ("blue") light exposure at night and their effects on sleep: A systematic review and meta-analysis.

The sleep-wake and circadian cycles are influenced by light, particularly in the short-wavelength portion of the visible spectrum. Most personal light-emitting electronic devices are enriched in this so-called "blue" light. Exposure to these devices in the evening can disturb sleep. Interventions to reduce short-wavelength light exposure before bedtime may reduce adverse effects on sleep. We conducted a systematic review and meta-analysis to examine the effect of wearing color-tinted lenses (e.g. orange or amber) in frames to filter short-wavelength light exposure to the eye before nocturnal sleep. Outcomes were self-reported or objective measures of nocturnal sleep. Relatively few (k = 12) studies have been done. Study findings were inconsistent, with some showing benefit and others showing no effect of intervention. Meta-analyses yielded a small-to-medium magnitude combined effect size for sleep efficiency (Hedge's g = 0.31; 95% CI: -0.05, 0.66; I2 = 38.16%; k = 7), and a small-to-medium combined effect size for total sleep time (Hedge's g = 0.32; 95% CI: 0.01, 0.63; I2 = 12.07%; k = 6). For self-report measures, meta-analysis yielded a large magnitude combined effects size for Pittsburgh Sleep Quality Index ratings (Hedge's g = -1.25; 95% CI: -2.39, -0.11; I2 = 36.35%; k = 3) and a medium combined effect size for total sleep time (Hedge's g = 0.51; 95% CI: 0.18, 0.84; I2 = 0%; k = 3), Overall, there is some, albeit mixed, evidence that this approach can improve sleep, particularly in individuals with insomnia, bipolar disorder, delayed sleep phase syndrome, or attention-deficit hyperactive disorder. Considering the ubiquitousness of short-wavelength-enriched light sources, future controlled studies to examine the efficacy of this approach to improve sleep are warranted. Systematic review registration: PROSPERO 2018 CRD42018105854.

Environmental exposures during pregnancy: Mechanistic effects on immunity.

In human studies, it is well established that exposures during embryonic and fetal development periods can influence immune health. Coupled with genetic predisposition, these exposures can alter lifetime chronic and infectious disease trajectory, and, ultimately, life expectancy. Fortunately, as research advances, mechanisms governing long-term effects of prenatal exposures are coming to light and providing the opportunity for intervention and risk reduction. For instance, human association studies have provided a foundation for the association of prenatal exposure to particulate matter with early immunosuppression and later allergic disease in the offspring. Only recently, the mechanisms mediating this response have been revealed and there is much we have yet to discover. Although cellular immune response is understood for many exposure scenarios, molecular pathways are still unidentified. This review will provide commentary and synthesis of the current literature regarding environmental exposures during pregnancy and mechanisms determining immune outcomes. Shared mechanistic features and current gaps in the state of the science are identified and discussed. To such purpose, we address exposures by their immune effect type: immunosuppression, autoimmunity, inflammation and tissue damage, hypersensitivity, and general immunomodulation.

Internal mechanical conditions in the soft tissues of a residual limb of a trans-tibial amputee.

Most trans-tibial amputation (TTA) patients use a prosthesis to retain upright mobility capabilities. Unfortunately, interaction between the residual limb and the prosthetic socket causes elevated internal strains and stresses in the muscle and fat tissues in the residual limb, which may lead to deep tissue injury (DTI) and other complications. Presently, there is paucity of information on the mechanical conditions in the TTA residual limb during load-bearing. Accordingly, our aim was to characterize the mechanical conditions in the muscle flap of the residual limb of a TTA patient after donning the prosthetic socket and during load-bearing. Knowledge of internal mechanical conditions in the muscle flap can be used to identify the risk for DTI and improve the fitting of the prosthesis. We used a patient-specific modelling approach which involved an MRI scan, interface pressure measurements between the residual limb and the socket of the prosthesis and three-dimensional non-linear large-deformation finite-element (FE) modelling to quantify internal soft tissue strains and stresses in a female TTA patient during static load-bearing. Movement of the truncated tibia and fibula during load-bearing was measured by means of MRI and used as displacement boundary conditions for the FE model. Subsequently, we calculated the internal strains, strain energy density (SED) and stresses in the muscle flap under the truncated bones. Internal strains under the tibia peaked at 85%, 129% and 106% for compression, tension and shear strains, respectively. Internal strains under the fibula peaked at substantially lower values, that is, 19%, 22% and 19% for compression, tension and shear strains, respectively. Strain energy density peaked at the tibial end (104kJ/m(3)). The von Mises stresses peaked at 215kPa around the distal end of the tibia. Stresses under the fibula were at least one order of magnitude lower than the stresses under the tibia. We surmise that our present patient-specific modelling method is an important tool in understanding the etiology of DTI in the residual limbs of TTA patients.

PPARγ attenuates hypoxia-induced hypertrophic transcriptional pathways in the heart.

Chronic hypoxia-induced pulmonary hypertension (PH) is characterized by increased pressure and resistance in the pulmonary vasculature and hypertrophy of the right ventricle (RV). The transcription factors, nuclear factor activated T-cells (NFAT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB/p65) contribute to RV hypertrophy (RVH). Because peroxisome proliferator-activated receptor gamma (PPARγ) activation attenuates hypoxia-induced PH and RVH, we hypothesized that PPARγ inhibits activation of RV hypertrophic transcriptional signaling mechanisms. C57BL/6J mice were exposed to normoxia (21% O2) or hypoxia (10% O2) for 21 days. During the final 10 days of exposure, selected mice were treated with the PPARγ ligand, pioglitazone. RV systolic pressure (RVSP) and RVH were measured, and NFATc2 and NF-kB/p65 protein levels were measured in RV and LV nuclear and cytosolic fractions. Cardiomyocyte hypertrophy was assessed with wheatgerm agglutinin staining. NFAT activation was also examined with luciferase reporter mice and analysis of protein levels of selected transcriptional targets. Chronic-hypoxia increased: (1) RVH, RVSP, and RV cardiomyocyte hypertrophy; (2) NFATc2 and NF-κB activation in RV nuclear homogenates; (3) RV and LV NFAT luciferase activity; and (4) RV protein levels of brain natriuretic peptide (BNP) and ß-myosin heavy chain (ß-MyHC). Treatment with pioglitazone attenuated hypoxia-induced increases in both RV and LV NFAT luciferase activity. Chronic hypoxia caused sustained RV NFATc2 and NF-κB activation. Pioglitazone attenuated PH, RVH, cardiomyocyte hypertrophy, and activation of RV hypertrophic signaling and also attenuated LV NFAT activation. PPARγ favorably modulates signaling derangements in the heart as well as in the pulmonary vascular wall.

Fruit and vegetable intakes and prostate cancer risk.

BACKGROUND: There is extensive and consistent evidence that high fruit and vegetable intakes are associated with decreased risks of many cancers, but results for prostate cancer risk have been inconsistent. We studied the associations of fruit and vegetable intakes with prostate cancer risk in a population-based, case-control study of men under 65 years of age. METHODS: Case participants were 628 men from King County (Seattle area), WA, who were newly diagnosed with prostate cancer. Control participants were 602 men recruited from the same underlying population and frequency matched to case participants by age. Self-administered food-frequency questionnaires were used to assess diet over the 3- to 5-year period before diagnosis or recruitment. Daily nutrient intakes were calculated by use of a nutrient database with recently updated analytic values for carotenoids. Odds ratios for prostate cancer risk associated with foods and nutrients were calculated by use of unconditional logistic regression. RESULTS: No associations were found between fruit intake and prostate cancer risk. The adjusted odds ratio (ORs) for the comparison of 28 or more servings of vegetables per week with fewer than 14 servings per week was 0.65 (95% confidence interval [CI] = 0.45-0.94), with a two-sided P for trend =.01. For cruciferous vegetable consumption, adjusted for covariates and total vegetable intake, the OR for comparison of three or more servings per week with less than one serving per week was 0.59 (95% CI = 0.39-0.90), with a two-sided P for trend =.02. The OR for daily intake of 2000 microg or more lutein plus zeaxanthin compared with an intake of less than 800 microg was 0.68 (95% CI = 0.45-1.00). CONCLUSION: These results suggest that high consumption of vegetables, particularly cruciferous vegetables, is associated with a reduced risk of prostate cancer.

Evaluation of the increase in breast cancer incidence in relation to mammography use.

The breast cancer incidence rate (i.e., the detected number of new cases per 100,000 women) increased by 31% in western Washington State between the time periods 1974-1978 and 1986-1987. If this increase is largely due to earlier detection of cases through mammography, it is encouraging; otherwise (if it cannot be attributed to mammography alone), investigation of other factors may be needed. The observed increase, based on 18,559 documented breast cancer cases from the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) registry, was compared with the predicted increase based on mammography utilization by year from a survey of 1,212 women in western Washington and on data from published studies regarding the impact of mammography on the detection rate for new breast cancer cases. Among women aged 45-64, all of the increase was associated with local stage disease and with tumors detected at a smaller size. Further, the 15% observed increase in incidence in this age group was less than the 20% increase predicted due to the utilization of mammography. However, the observed increase was approximately twice the predicted increase for women aged 65-74 (observed 57%, predicted 26%) and for women aged 25-44 (observed 29%, predicted 12%). Thus, all of the increase in detected breast cancer among 45-64 year old women appears to be explained by the increased use of mammography, while among older women and younger women there may be other contributing factors. The limitations and implications of this analysis are discussed.

Changes in diet, weight, and serum lipid levels associated with olestra consumption.

BACKGROUND: Specially manufactured low-fat and nonfat foods have become increasingly available over the past 2 decades and controversy has surrounded the issue of whether these products have beneficial or adverse effects on the health and nutritional status of Americans. METHODS: This study examines the association of olestra consumption with changes in dietary intakes of energy, fat, and cholesterol and changes in weight and serum lipid concentrations. Data are from a cohort of 335 participants in the Olestra Post-Marketing Surveillance Study sentinel site in Marion County (Indianapolis, Ind). Diet, weight, and serum lipid levels were assessed before the market release of olestra and 1 year later, after olestra-containing foods were widely available. Olestra intake at the 1-year follow-up was categorized as none, low (>0 to 0.4 g/d), moderate (0.4 to 2.0 g/d), and heavy (>2.0 g/d). RESULTS: Participants in the heavy olestra consumption category significantly reduced dietary intake of percentage of energy from fat (2.7 percentage points, P for trend,.003) and saturated fat (1.1 percentage points, P for trend,.02). Consumers in the highest category of olestra consumption had statistically significantly reduced total serum cholesterol levels of -0.54 mmol/L (-21 mg/dL)compared with -0.14 mmol/L (-5 mg/dL) among olestra nonconsumers (P for trend,.03). CONCLUSIONS: These results indicate that introduction of a new fat substitute (olestra) in the US market was associated with healthful changes in dietary fat intake and serum cholesterol concentrations among consumers who chose to consume olestra-containing foods.

Weight loss in women participating in a randomized trial of low-fat diets.

We examined weight changes over 1 and 2 y in 303 women enrolled in a low-fat dietary-intervention trial. Participants were randomly assigned to an intervention group that received intensive instruction in maintaining a low-fat diet or to a control group. After 1 y intervention-group women had decreased fat intake by 45.3 g (from 39.2% to 21.6% energy from fat) and weight by 3.1 kg (all P less than 0.0001); control-group women decreased fat intake by 8.8 g (from 38.9% to 37.3% energy from fat) and weight by 0.4 kg. In both univariate analyses and multivariate models, weight loss was more strongly associated with change in percent energy from fat than with change in total energy intake. These data, which are consistent with both epidemiologic and clinical studies, suggest that body adiposity is a function both of energy balance and the proportion of energy derived from fat.

Assessing change in diet-intervention research.

In nutrition-intervention research, it is important to consider the sensitivity of dietary assessment instruments to the changes in nutrient intake or dietary behavior under study. This presentation describes a measure called "responsiveness," an index of an instrument's sensitivity to change. Illustrations of this measure are from two randomized dietary-intervention trials that targeted reductions in fat intake: the Women's Health Trial (WHT), a trial to test whether fat reduction would reduce the risk of breast cancer, and the Eating Patterns Study (EPS), a trial to evaluate a self-help booklet to promote dietary change. In the WHT, a 4-d diet record (FDDR) was only slightly more responsive to dietary change than was a food-frequency questionnaire (FFQ). In the EPS, a fat-related diet-habits questionnaire was most responsive, followed by an FDDR and an FFQ. These data suggest that short, inexpensive measures such as FFQs or questionnaires that assess dietary habits can be as responsive as multiple-day diet records. More research is needed on the relative responsiveness of dietary assessment tools. Intervention studies should include at least two types of dietary assessment tools and the relative validity, reliability, and responsiveness of these tools should be reported as part of the study outcome.