Here, high-throughput sequencing was employed to reveal the highly diverse bacterial populations present in 62 Irish artisanal cheeses and, in some cases, associated cheese rinds. Using this approach, we revealed the presence of several genera not previously associated with cheese, including Faecalibacterium, Prevotella, and Helcococcus and, for the first time, detected the presence of Arthrobacter and Brachybacterium in goats' milk cheese. Our analysis confirmed many previously observed patterns, such as the dominance of typical cheese bacteria, the fact that the microbiota of raw and pasteurized milk cheeses differ, and that the level of cheese maturation has a significant influence on Lactobacillus populations. It was also noted that cheeses containing adjunct ingredients had lower proportions of Lactococcus species. It is thus apparent that high-throughput sequencing-based investigations can provide valuable insights into the microbial populations of artisanal foods.
Modafinil was tested for efficacy in decreasing use in methamphetamine-dependent participants, compared to placebo.
This was a randomized, double-blind, placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Eight outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, who all had a DSM-IV diagnosis of methamphetamine dependence; 68 participants to placebo, 72 to modafinil 200mg, and 70 to modafinil 400mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments, urine drug screens, and group psychotherapy. The primary outcome measure was a methamphetamine non-use week, which required all the week's qualitative urine drug screens to be negative for methamphetamine.
Regression analysis showed no significant difference between either modafinil group (200 or 400mg) and placebo in change in weekly percentage having a methamphetamine non-use week over the 12-week treatment period (p=0.53). Similarly, a number of secondary outcomes did not show significant effects of modafinil. However, an ad-hoc analysis of medication compliance, by urinalysis for modafinil and its metabolite, did find a significant difference in maximum duration of abstinence (23 days vs. 10 days, p=0.003), between those having the top quartile of compliance (>85% urines modafinil +, N=36), and the lower three quartiles of modafinil 200 and 400mg groups (N=106).
Although these data suggest that modafinil, plus group behavioral therapy, was not effective for decreasing methamphetamine use, the study is probably inconclusive because of inadequate compliance with taking medication.
Methamphetamine; Substance-Related Disorders; drug therapy [subheading]; Modafinil; Medication Adherence; Attention Deficit Hyperactivity Disorders
The daily administered dose of progestin in continuous-combined estrogen-progestin therapy is provided to counteract the proliferative effect of estrogen on the postmenopausal endometrium. However, there remains some uncertainty as to whether use of such a combined regimen, over the long-term, is associated with an altered risk of endometrial cancer. We pooled data from four population-based case-control studies of endometrial cancer in western Washington State. Cases, ages 45–74, were diagnosed between 1985 and 2005. Using logistic regression with adjustment for confounding factors, women who had exclusively used continuous-combined estrogen-progestin therapy (90 endometrial cancer cases, 227 controls) were compared to women who had never used any type of hormone therapy (774 cases, 1116 controls). Associations with duration and recency of use were evaluated overall and within strata defined by body mass index. Long-term use of continuous-combined estrogen-progestin therapy (≥10 years) was associated with a reduced risk of endometrial cancer (OR=0.37, 95% CI: 0.21–0.66). This association was most pronounced in women with a body mass index ≥30 kg/m2 (OR=0.19, 95% CI: 0.05–0.68). Associations did not differ according to recency of use. These results suggest that long duration of use of continuous-combined estrogen-progestin therapy is associated with a reduced risk of endometrial cancer risk.
endometrial cancer; hormone therapy; estrogen; progestin; body mass index
Snacking may play a role in weight control. The associations of timing and frequency of snacking with observed weight change and nutrient intake were assessed in an ancillary study to a 12-month randomized controlled trial in Seattle, WA. Overweight-to-obese postmenopausal women (n=123) enrolled in the two dietary weight loss arms from 2007–2008 with complete data at 12-months were included in these analyses. Generalized linear models were used to test the associations between snacking and weight loss (%) and nutrient intake at the 12-month time point. Participants were on average 58 years old and mainly non-Hispanic White (84%). Ninety-seven percent reported ≥ 1 snack/day. Weight loss (%) was significantly lower among mid-morning (10:30am–11:29am) snackers (7.0%, 95% CI 4.3, 9.7) compared to non-mid-morning snackers (11.4%, 95% CI 10.2, 12.6; p value: 0.004). A higher proportion of mid-morning snackers reported more than 1 snack/day (95.7%), compared to afternoon (82.8%) and evening (80.6%) snackers, though differences were not statistically significant. Women who reported ≥2 snacks/day vs. ≤ 1 snack/day had higher fiber intake (p=0.027). Afternoon snackers had higher fruit and vegetable intake compared to non-afternoon-snackers (p=0.035). These results suggest that snack meals can be a source for additional fruits, vegetables, and fiber-rich foods; however, snacking patterns might also reflect unhealthy eating habits and impede weight loss progress. Future dietary weight loss interventions should evaluate the effects of timing, frequency, and quality of snacks on weight loss.
snacking; weight loss; women; nutrient intake
Epidemiologic studies are consistent in finding that women who have had at least one birth are less likely to develop endometrial cancer. Less clear is whether timing of pregnancies during reproductive life influences risk, and the degree to which incomplete pregnancies are associated with a reduced risk.
We evaluated pregnancy history in relation to endometrial cancer risk using data from a series of four population-based endometrial cancer case-control studies of women 45–74 years of age (1,712 cases and 2,134 controls) during 1985–2005 in western Washington State. Pregnancy history and information on other potential risk factors were collected by in-person interviews.
Older age at first birth was associated with a reduced risk of endometrial cancer after adjustment for number of births and age at last birth (test for trend P = 0.004). The odds ratio comparing women at least 35 years of age at their first birth with those younger than 20 years was 0.34 (95% confidence interval = 0.14–0.84). Age at last birth was not associated with risk after adjustment for number of births and age at first birth (test for trend P = 0.830). Overall, a history of incomplete pregnancies was not associated with endometrial cancer risk to any appreciable degree.
In this study, older age at first birth was more strongly associated with endometrial cancer risk than was older age at last birth. To date, there remains some uncertainty in the literature on this issue.
To develop widely acceptable preliminary criteria of global flare for childhood-onset SLE (cSLE).
Pediatric rheumatologists (n=138) rated a total of 358 unique patient profiles (PP) with information about the cSLE flare descriptors (cSLE-FD) from two consecutive visits: patient global assessment of well-being, physician global assessment of disease activity (MD-global), health-related quality of life, anti-dsDNA antibodies, disease activity index score, protein/creatinine (P/C) ratio, complement levels and ESR. Based on 2996 rater responses about the course of cSLE (baseline vs. follow-up) the accuracy (sensitivity, specificity, area under the receiver operating characteristic curve) of candidate flare criteria was assessed. An international consensus conference was held to rank these candidate flare criteria as per the ACR-recommendations for the development and validation of criteria sets.
The highest ranked candidate criteria considered absolute changes (Δ) of the SLEDAI or BILAG, MD-global, P/C ratio, and ESR; Flare scores can be calculated [0.5 × ΔSLEDAI + 0.45 × ΔP/C ratio + 0.5 × ΔMD-global + 0.02 × ΔESR], where values ≥ 1.04 are reflective of a flare. Similarly, BILAG-based flare scores [0.4 × ΔBILAG + 0.65 × ΔP/C ratio + 0.5 × ΔMD-global + 0.02 × ΔESR] of ≥ 1.15 were diagnostic of a flare. Flare scores increase with flare severity.
Consensus has been reached on preliminary criteria for global flares in cSLE. Further validation studies are needed to confirm the usefulness of the cSLE flare criteria in research and for clinical care.
lupus; childhood-onset SLE; SLE; pediatric SLE; juvenile SLE; flare; criteria; children; cSLE
The food frequency questionnaire approach to dietary assessment is ubiquitous in nutritional epidemiology research. Food records and recalls provide approaches that may also be adaptable for use in large epidemiologic cohorts, if warranted by better measurement properties. The authors collected (2007–2009) a 4-day food record, three 24-hour dietary recalls, and a food frequency questionnaire from 450 postmenopausal women in the Women’s Health Initiative prospective cohort study (enrollment, 1994–1998), along with biomarkers of energy and protein consumption. Through comparison with biomarkers, the food record is shown to provide a stronger estimate of energy and protein than does the food frequency questionnaire, with 24-hour recalls mostly intermediate. Differences were smaller and nonsignificant for protein density. Food frequencies, records, and recalls were, respectively, able to “explain” 3.8%, 7.8%, and 2.8% of biomarker variation for energy; 8.4%, 22.6%, and 16.2% of biomarker variation for protein; and 6.5%, 11.0%, and 7.0% of biomarker variation for protein density. However, calibration equations that include body mass index, age, and ethnicity substantially improve these numbers to 41.7%, 44.7%, and 42.1% for energy; 20.3%, 32.7%, and 28.4% for protein; and 8.7%, 14.4%, and 10.4% for protein density. Calibration equations using any of the assessment procedures may yield suitable consumption estimates for epidemiologic study purposes.
bias (epidemiology); biological markers; diet; energy intake; epidemiologic methods; measurement error; nutrition assessment
To explore the association of baseline co-worker social support with follow-up measures of health care use and sickness absence.
Data were obtained on 1,240 employees from 33 worksites, through Promoting Activity and Changes in Eating, a group randomized weight maintenance trial. Co-worker social support, health care utilization, and absenteeism were assessed via a self-reported questionnaire. Generalized Estimating Equations were employed using STATA version 10.
Higher baseline co-worker social support was significantly associated with a greater number of doctors’ visits (p = 0.015). Co-worker social support was unrelated to number of hospitalizations, emergency room visits, or absenteeism.
The relationship between co-worker social support and health care utilization and absenteeism is complex and uncertain. Future studies should measure more specific outcomes, incorporate important mediating variables, and distill how social networks influence these outcomes.
Social support may be associated with improved diet and physical activity—determinants of overweight and obesity. Wellness programs increasingly target worksites. The aim was to evaluate the relationship between worksite social support and dietary behaviors, physical activity, and body mass index (BMI).
Baseline data were obtained on 2,878 employees from 2005 to 2007 from 34 worksites through Promoting Activity and Changes in Eating, a group-randomized weight reduction intervention in Greater Seattle. Worksite social support, diet, physical activity, and BMI were assessed via self-reported questionnaire. Principal components analysis was applied to workgroup questions. To adjust for design effects, random effects models were employed.
No associations were found with worksite social support and BMI, or with many obesogenic behaviors. However, individuals with higher worksite social support had 14.3% higher (95% CI: 5.6%-23.7%) mean physical activity score and 4% higher (95% CI: 1%–7%) mean fruit and vegetable intake compared to individuals with one-unit lower support.
Our findings do not support a conclusive relationship between higher worksite social support and obesogenic behaviors, with the exception of physical activity and fruit and vegetable intake. Future studies are needed to confirm these relationships and evaluate how worksite social support impacts trial outcomes.
Pediatric patients with autism spectrum disorders (ASD) and/or intellectual disabilities (ID) are at greater risk for psychiatric hospitalization compared to children with other disorders. However, general psychiatric hospital environments are not adapted for the unique learning styles, needs, and abilities of this population, and there are few specialized hospital-based psychiatric care programs in the United States. This paper compares patient outcomes from a specialized psychiatric hospital program developed for pediatric patients with an ASD and/or ID to prior outcomes of this patient population in a general psychiatric program at a children's hospital. Record review data indicate improved outcomes for patients in the specialized program of reduced recidivism rates (12% versus 33%) and decreased average lengths of inpatient stay (as short as 26 days versus 45 days). Available data from a subset of patients (n = 43) in the specialized program showed a decrease in irritability and hyperactivity behaviors from admission to discharge and that 35 previously undetected ASD diagnoses were made. Results from this preliminary study support specialized psychiatric care practices with this population to positively impact their health care outcomes.
Motivation: Shotgun sequence read data derived from xenograft material contains a mixture of reads arising from the host and reads arising from the graft. Classifying the read mixture to separate the two allows for more precise analysis to be performed.
Results: We present a technique, with an associated tool Xenome, which performs fast, accurate and specific classification of xenograft-derived sequence read data. We have evaluated it on RNA-Seq data from human, mouse and human-in-mouse xenograft datasets.
Xenome is available for non-commercial use from http://www.nicta.com.au/bioinformatics
UvrD is an SF1 family helicase involved in DNA repair that is widely conserved in bacteria. Mycobacterium tuberculosishas two annotated UvrD homologues; here we investigate the role of UvrD2. The uvrD2gene at its native locus could be knocked out only in the presence of a second copy of the gene, demonstrating that uvrD2is essential. Analysis of the putative protein domain structure of UvrD2 shows a distinctive domain architecture, with an extended C terminus containing an HRDC domain normally found in SF2 family helicases and a linking domain carrying a tetracysteine motif. Truncated constructs lacking the C-terminal domains of UvrD2 were able to compensate for the loss of the chromosomal copy, showing that these C-terminal domains are not essential. Although UvrD2 is a functional helicase, a mutant form of the protein lacking helicase activity was able to permit deletion of uvrD2at its native locus. However, a mutant protein unable to hydrolyze ATP or translocate along DNA was not able to compensate for lack of the wild-type protein. Therefore, we concluded that the essential role played by UvrD2 is unlikely to involve its DNA unwinding activity and is more likely to involve DNA translocation and, possibly, protein displacement.
To evaluate changes in the worksite environment in response to a multilevel intervention over a two year period.
Worksites were recruited in the greater Seattle area, and 34 were randomized to intervention or comparison condition. The intervention was based on the ecological model, with a framework of defined phases of intervention that included worksite wide events implemented in partnership with employee-based advisory boards. The assessment of the worksite environment used a modification of the CHEW. Subscales were developed using baseline data only. The intervention effect on different aspects of the worksite environment was estimated using logistic regression with robust estimating procedures.
Only changes in the physical activity and nutrition information environments were significantly associated with the intervention.
This paper provides one of the first attempts at using environmental assessment in the evaluation of worksite interventions.
Henoch Schonlein Purpura (HSP) is the commonest systemic vasculitis of childhood typically presenting with a palpable purpuric rash and frequently involving the renal system. We are the first group to clinically assess, critically analyse and subsequently revise a nurse led monitoring pathway for this condition.
A cohort of 102 children presenting with HSP to a secondary/tertiary level UK paediatric hospital over a five year period, were monitored using a nurse led care pathway. Using this cohort, the incidence (6.21 cases per 100,000 children per year) and natural disease course of HSP nephritis (46% initial renal inflammation; 9% subsequent renal referral; 1% renal biopsy and immunosuppression) was determined. Older patients were at higher risk of requiring a renal referral (renal referral 12.3 (8.4–13.5) years vs. normal outcome 6.0 (3.7–8.5) years; p<0.01). A normal urinalysis on day 7 had a 97% (confidence interval 90 to 99%) negative predictive value in predicting a normal renal outcome.
Using this data and existing literature base, The Alder Hey Henoch Schonlein Purpura Pathway was developed, a revised pathway for the screening of poor renal outcome in HSP. This is based on a six-month monitoring period for all patients presenting with HSP, which importantly prioritises patients according to the urine findings on day 7 and thus intensively monitors those at higher risk of developing nephritis. The pathway could be easily adapted for use in different settings and resources.
The introduction of a standardised pathway for the monitoring of HSP will facilitate the implementation of disease registries to further our understanding of the condition and permit future clinical trials.
Stress in numerous contexts may affect the risk for obesity through biobehavioral processes. Acute stress has been associated with diet and physical activity in some studies; the relationship between everyday stress and such behavior is not clear. The objective of this study was to examine associations between perceived stress, dietary behavior, physical activity, eating awareness, self-efficacy, and body mass index (BMI) among healthy working adults. Secondary objectives were to explore whether eating awareness modified the relationship between perceived stress and dietary behavior and perceived stress and BMI.
Promoting Activity and Changes in Eating (PACE) was a group-randomized worksite intervention to prevent weight gain in the Seattle metropolitan area from 2005 through 2007. A subset of 621 participants at 33 worksites provided complete information on perceived stress at baseline. Linear mixed models evaluated cross-sectional associations.
The mean (standard deviation [SD]) Perceived Stress Scale-10 score among all participants was 12.7 (6.4), and the mean (SD) BMI was 29.2 kg/m2 (6.3 kg/m2). Higher levels of perceived stress were associated with lower levels of eating awareness, physical activity, and walking. Among participants who had low levels of eating awareness, higher levels of perceived stress were associated with fewer servings of fruit and vegetables and greater consumption of fast food meals.
Dietary and physical activity behaviors of workers may be associated with average levels of perceived stress. Longitudinal studies are needed, however, to support inclusion of stress management or mindfulness techniques in workplace obesity prevention efforts.
A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive.
We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from four studies (total 3891 cases, 4490 controls): the Women’s Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case-control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene-environment interactions.
SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19; 95% CI 1.01–1.40; p-trend 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11; 95% CI 0.99–1.25; p-trend 0.07), and not associated in DALS and MinnCCS. Evaluating for gene-environment interactions yielded no consistent results across the studies. A meta-analysis of seventeen studies (including these four) gave an OR per A allele of 1.07 (95% CI 1.03–1.12; p-trend 0.001).
Our results suggest the A allele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies.
If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia.
colorectal; adenoma; cancer; 9p24; rs719725
There is rising interest in identifying precursors to bipolar disorder symptoms, including thought disorder. Thought disorder is identified in adults through self-report and in school-aged children through parent report and child story-telling. This study is an exploration to determine if preschoolers with mood dysregulation have evidence of disordered thoughts using a story-stem completion method.
Participants included two groups of 3.5–6 year-old children: 20 with mood dysregulation including manic symptoms and 11 typically-developing comparison children. Children were administered story completion narratives including one story where the child character accidentally cuts him/herself while pretending to cook. The children were asked to complete the stories and their responses were analyzed for atypical themes consistent with disordered thoughts such as violence or bizarreness outside of the story or props coming to life.
35% of symptomatic preschoolers versus 0% of typically-developing preschoolers ascribed independent actions to inanimate props (p=0.03). 80% of symptomatic preschoolers versus 9% of typically-developing preschoolers utilized props in a violent or bizarre manner outside the central story (p<0.001).
Preschool children with symptoms of dysregulated mood express themes related to the unusual use of story props which may indicate disordered thoughts. This preschool expression of dysregulated mood appears similar to and possibly continuous with school-age and adult versions of bipolar disorder.
preschool; dysregulated mood; disordered thought; mania; story completion; bipolar disorder; thought disorder
While the Chronic Care Model (CCM) has been shown to improve the care of patients with chronic illnesses, primary care physicians have been unprepared in its use, and residencies have encountered challenges in introducing it into the academic environment.
Our residency program has implemented a diabetes management program modeled on the CCM to evaluate its impact on health outcomes of diabetic patients and educational outcomes of residents.
University-affiliated, community-based family medicine residency program.
Six residents, two faculty clinicians, and clinic staff formed a diabetes management team. We redesigned the outpatient experience for diabetic patients by incorporating elements of the CCM: multidisciplinary team care through planned and group visits; creation of a diabetes registry; use of guidelines-based flow sheets; and incorporation of self-management goal-setting. Residents received extensive instruction in diabetes management, quality improvement, and patient self-management.
We achieved overall improvement in all metabolic and process measures for patients, with the percentage achieving HbA1c, LDL, and BP goals simultaneously increasing from 5.7% to 17.1%. Educational outcomes for residents, as measured by compliance with review of provider performance reports and self-management goal-setting with patients, also significantly improved.
Through a learning collaborative experience, residency programs can successfully incorporate chronic care training for residents while addressing gaps in care for patients with diabetes.
chronic care model; learning collaborative; diabetes; residency education
Glucosinolates, phytochemicals found in cruciferous vegetables, are metabolized to bioactive isothiocyanates (ITC) by certain bacteria in the human gut. Substantial individual variation in urinary ITC excretion has been observed in previous cruciferous-vegetable feeding studies. We hypothesized that individual differences in gut microbial community contribute to the observed variation in glucosinolate metabolism, i.e., gut microbiota composition between high- and low-ITC excreters differ. We recruited 23 healthy individuals and fed them a standardized meal containing 200 g cooked broccoli. 24-h urinary ITC excretion was measured after the meal. Study participants with the highest (n=5) and the lowest (n=5) ITC excretion provided fecal samples for ex vivo bacterial cultivation with 50 μM glucoraphanin, the major glucosinolate found in broccoli. When grown ex vivo, fecal bacteria from the selected high ITC excreters were able to degrade more glucoraphanin than those from the low excreters (P=0.05). However, bacterial fingerprints of fecal and ex vivo culture microbiota revealed no statistically significant differences between the high and low ITC excreters in terminal restriction fragment length polymorphism analysis of the bacterial 16S rRNA gene. In conclusion, glucosinolate degradation by fecal bacteria ex vivo may be associated with in vivo bacterial glucosinolate metabolism capacity but no direct link to specific bacterial species could be established, possibly due to the complexity and functional redundancy of the gut microbiota.
cruciferous vegetable; glucosinolate; isothiocyanate; gut bacteria