Search

The methyl CpG‐binding protein‐2 (MECP2) gene is located on the Xq28 region. Loss of function mutations or increased copies of MECP2 result in Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), respectively. Individuals with both disorders exhibit overlapping autism symptoms, yet few studies have dissected the differences between these gene dosage sensitive disorders. Further, research examining sensory processing patterns in persons with RTT and MDS is largely absent. Thus, the goal of this study was to analyze and compare sensory processing patterns in persons with RTT and MDS. Towards this goal, caregivers of 50 female individuals with RTT and 122 male individuals with MDS, between 1 and 46 years of age, completed a standardized measure of sensory processing, the Sensory Experiences Questionnaire. Patterns detected in both disorders were compared against each other and against normative values. We found sensory processing abnormalities for both hyper‐ and hypo‐sensitivity in both groups. Interestingly, abnormalities in MDS were more pronounced compared with in RTT, particularly with items concerning hypersensitivity and sensory seeking, but not hyposensitivity. Individuals with MDS also exhibited greater sensory symptoms compared with RTT in the areas of tactile and vestibular sensory processing and for both social and nonsocial stimuli. This study provides a first description of sensory symptoms in individuals with RTT and individuals with MDS. Similar to other neurodevelopmental disorders, a variety of sensory processing abnormalities was found. These findings reveal a first insight into sensory processing abnormalities caused by a dosage sensitive gene and may ultimately help guide therapeutic approaches for these disorders. Lay Summary: This study evaluated sensory processing differences in individuals with disorders related to the MECP2 protein. We found both individuals with deficits in MECP2 (Rett syndrome), and those with too much MECP2 protein (MECP2 duplication syndrome, MDS) exhibited atypical sensory behaviors but that hypersensitivity was much more pronounced in MDS. [ABSTRACT FROM AUTHOR]

Objective: Nonresponsive parental feeding practices are associated with poorer appetite self‐regulation in children. It is unknown whether this relationship extends beyond childhood to be prospectively associated with the onset of eating disorder (ED) symptoms in adolescence. This exploratory study therefore investigated prospective associations between early childhood parental feeding practices and adolescent ED symptoms and disordered eating behaviors. Methods: Data were from two population‐based cohorts with harmonized measures: Generation R (Netherlands; n = 4900) and Gemini (UK; n = 2094). Parents self‐reported their pressure to eat, restriction and instrumental feeding (i.e., using food as a reward) at child age 4–5 years. Adolescents self‐reported their compensatory behaviors (e.g., fasting, purging), binge‐eating symptoms, restrained eating, uncontrolled eating, and emotional eating at 12–14 years. Associations between feeding practices and ED symptoms were examined separately in each cohort using generalized linear models. Results: In Gemini, pressure to eat in early childhood was associated with adolescents engaging in compensatory behaviors. In Generation R, parental restriction was associated with adolescents engaging in compensatory behaviors, restrained eating, uncontrolled eating, and emotional eating. Instrumental feeding was associated with uncontrolled eating and emotional eating in Generation R. Discussion: Nonresponsive parental feeding practices were associated with a greater frequency of specific ED symptoms and disordered eating in adolescence, although effect sizes were small and findings were inconsistent between cohorts. Potentially, the cultural and developmental context in which child–parent feeding interactions occur is important for ED symptoms. Further replication studies are required to better understand parents' role in the development and maintenance of ED‐related symptoms. Public Significance: Prospective research examining how early childhood parental feeding practices might contribute to adolescent ED symptoms is limited. In two population‐based cohorts, nonresponsive feeding practices (restriction, instrumental feeding, pressure to eat) predicted increased frequency of some ED symptoms and disordered eating behaviors in adolescence, although associations were small and further replication is required. Findings support the promotion of responsive feeding practices, which may benefit young children's developing relationship with food. [ABSTRACT FROM AUTHOR]

Engaging people with lived experience of mental health system encounters in the design and actualization of continuing professional development initiatives for mental health professionals can have transformative systemic impacts. Yet, despite evidence that involving people with lived experience benefits mental health professional education, far less focus has been placed on how to engage people with lived experience in continuing professional development initiatives. Tensions persist regarding the role of lived experience perspectives in continuing professional development, as well as how to establish people with lived experience as partners, educators and leaders in a thoughtful way. We propose that meaningful and equitable partnerships with people with lived experience can be realized by engaging in critical reflexivity and by systematically challenging assumptions. This paper explores three topics: (1) the current state of engagement with people with lived experience in continuing professional development initiatives; (2) barriers to meaningful engagement and (3) recommendations for using critical reflexivity to support the involvement and leadership of people with lived experience in continuing professional development for mental health professionals. Patient or Public Involvement: This viewpoint manuscript was co‐designed and co‐written by people with diverse lived and learned experiences. Each author's professional roles involve meaningfully and equitably partnering with and centring the perspectives of those with lived experience of mental health system encounters. In addition, approximately half of the authorship team identifies as having lived experience of accessing the psychiatric system and/or supporting family members who are navigating challenges related to mental health. These lived and learned experiences informed the conception and writing of this article. [ABSTRACT FROM AUTHOR]

Obesity prevention interventions have been designed to promote responsive feeding in early childhood. However, existing interventions primarily target first-time mothers without considering the complexities of feeding multiple children within a family unit. By applying principles of Constructivist Grounded Theory (CGT), this study aimed to explore how mealtimes are enacted in families with more than one child. A mixed- methods study was conducted with parent-sibling triads (n = 18 families) in South East Queensland, Australia. Data included direct mealtime observations, semistructured interviews, field notes, and memos. Data were analysed using open and focused coding, during which constant comparative analysis was applied. The sample comprised of two- parent families with children ranging in age from 12 to 70 months (median sibling age difference = 24 months). A conceptual model was developed to map sibling-related processes integral to the enactment of mealtimes in families. Notably, this model captured feeding practices used by siblings, such as pressure to eat and overt restriction, that previously had only been described in parents. It also documented feeding practices used by parents that may occur only in the presence of a sibling, such as leveraging sibling competitiveness and rewarding a child to vicariously condition their sibling's behaviour. The conceptual model demonstrates complexities in feeding that give shape to the overall family food environment. Findings from this study can inform the design of early feeding interventions that support parents to remain responsive, particularly when their perceptions and expectations of siblings differ. [ABSTRACT FROM AUTHOR]

Summary: Background: Children with Autism Spectrum Disorder (ASD) and Attention‐Deficit/Hyperactivity Disorder (ADHD) have an increased obesity risk. Although these conditions commonly co‐occur, shared factors relating to obesity risk are unknown. Objectives: To examine the shared and unique associations of ADHD and autistic traits with eating behaviours and BMI. Methods: Children (N = 4134) from the population‐based Generation R Study were categorized into subgroups based on parent‐reported ADHD and autistic traits scores at 6 years: ADHDHigh, ASDHigh, ADHD+ASDHigh and REF (reference group: ADHD+ASDLow). Multiple linear regressions examined the associations between subgroups and eating behaviours (at 10 years) and BMIz (at 14 years), relative to REF. Mediation analyses tested the indirect effect of subgroup and BMIz through eating behaviours. Results: ADHD + ASDHigh children expressed both food approach (increased food responsiveness and emotional overeating) and avoidant eating behaviours (increased emotional undereating, satiety responsiveness/ slowness in eating and picky eating, and decreased enjoyment in food). ASDHigh children were more food avoidant, while ADHDHigh children had more food approach behaviours and greater BMIz. ADHDHigh and BMIz were indirectly associated with food responsiveness and emotional overeating. Conclusions: ADHD and autistic trait phenotypes show distinct associations with potential obesity risk factors, and further research is needed to improve targeted early intervention. [ABSTRACT FROM AUTHOR]

Aim: Percutaneous endoscopic colostomy (PEC) represents an important intervention in specific patients. Limited data currently exist. We present the largest recorded study of patients undergoing PEC. Methods: Retrospective analysis of consultant logbooks highlighted all patients from 1997 to 2020. Two independent reviewers assessed records. Parameters measured were age, sex, indication, number of sites, complications, mortality and survival. Three subgroups were identified: recurrent sigmoid volvulus (RSV), pseudo‐obstruction and neurogenic. ANOVA, chi‐squared and Fischer's exact tests were utilized; Kaplan–Meier curves estimated survival and the log‐rank test was applied. A p value of <0.05 was considered statistically significant. Results: Ninety‐six PEC insertions were done on 91 patients (five reinsertions). There were 66 men (69%) and the mean age was 73.1 years (interquartile range 23). The indications were RSV n = 72, pseudo‐obstruction n = 13, neurogenic n = 11. The 30‐day complication rate was overall n = 27 (28%), RSV n = 23, pseudo‐obstruction n = 4. Nine patients leaked (9.9%) (eight RSV, one pseudo‐obstruction), of whom five died. 90‐day mortality was 14.6% (14 patients), 18.5% (13/72) for RSV, 7.7% (1/13) for pseudo‐obstruction. Overall recurrence following PEC was 10.4%. The median follow‐up was 25 months (interquartile range 4.6–62.2 months). At 3, 5 and 10 years survival was 46%, 34% and 26% for RSV, 70%, 55% and 15% for pseudo‐obstruction and 91%, 91% and 81% for neurogenic respectively. Conclusion: Recurrent sigmoid volvulus and pseudo‐obstruction patients undergoing PEC compared to neurogenic patients have poorer outcomes with higher complication rates and shorter life expectancy. We advocate that high volume specialist units undertake PEC. The significant associated risks of PEC require careful consideration when determining patient suitability. Utilizing risk stratification scores may help guide shared decision making between patients, relatives and clinicians. [ABSTRACT FROM AUTHOR]

Black women diagnosed with epithelial ovarian cancer have poorer survival compared to white women. Factors that contribute to this disparity, aside from socioeconomic status and guideline‐adherent treatment, have not yet been clearly identified. We examined data from the Ovarian Cancer in Women of African Ancestry (OCWAA) consortium which harmonized data on 1074 Black women and 3263 white women with ovarian cancer from seven US studies. We selected potential mediators and confounders by examining associations between each variable with race and survival. We then conducted a sequential mediation analysis using an imputation method to estimate total, direct, and indirect effects of race on ovarian cancer survival. Black women had worse survival than white women (HR = 1.30; 95% CI 1.16‐1.47) during study follow‐up; 67.9% of Black women and 69.8% of white women died. In our final model, mediators of this disparity include college education, nulliparity, smoking status, body mass index, diabetes, diabetes/race interaction, postmenopausal hormone (PMH) therapy duration, PMH duration/race interaction, PMH duration/age interaction, histotype, and stage. These mediators explained 48.8% (SE = 12.1%) of the overall disparity; histotype/stage and PMH duration accounted for the largest fraction. In summary, nearly half of the disparity in ovarian cancer survival between Black and white women in the OCWAA consortium is explained by education, lifestyle factors, diabetes, PMH use, and tumor characteristics. Our findings suggest that several potentially modifiable factors play a role. Further research to uncover additional mediators, incorporate data on social determinants of health, and identify potential avenues of intervention to reduce this disparity is urgently needed. [ABSTRACT FROM AUTHOR]

Background: MECP2 Duplication Syndrome (MDS), resulting from the duplication of Xq28 region, including MECP2, is a rare disorder with a nascent understanding in clinical features and severity. Studies using antisense oligonucleotides revealed a broad phenotypic rescue in transgenic mice. With human clinical trials on the horizon, there is a need to develop clinical outcome measures for MDS. Methods: We surveyed caregivers of MDS individuals to explore the frequency and severity of MDS clinical features, and identify the most meaningful symptoms/domains that need to be included in the outcome measure scales. Results: A total of 101 responses were eligible for the survey. The top six most meaningful symptoms to caregivers in descending order included epilepsy, gross motor, fine motor, communication, infection, and constipation problems. Epilepsy was present in 58.4% of the subjects and 75% were drug‐resistant, Furthermore, ~12% required intensive care unit (ICU) admission. Infections were present in 55% of the subjects, and one‐fourth of them required ICU admission. Constipation was present in ~85% of the subjects and one‐third required enemas/suppositories. Conclusion: Our study is one of the largest cohorts conducted on MDS individuals characterizing the frequency and severity of MDS symptoms. Additionally, these study results will contribute to establishing a foundation to develop parent‐reported outcomes in MDS. [ABSTRACT FROM AUTHOR]

Background: Appendicitis is a common surgical emergency that can be a challenging entity to manage. In the elderly, it is associated with significant morbidity and mortality. Risk prediction is not routinely performed prior to surgery. Methods: All patients aged >65 years undergoing appendicectomy over 5 years from one NHS Trust were included. Age, American Society of Anesthesiologists physical status classification system (ASA grade), Rockwood score, type of surgery, length of stay, morbidity and 90‐day mortality were recorded. ACS NSQIP was retrospectively calculated. Spearman's Rank correlation coefficient and linear regression analysis were conducted, assessing correlation between ASA, Age, Rockwood Score and ACS NSQIP with length of stay and post‐operative complications. Results: A total of 225 patient cases were reviewed. A complication rate of 29.3% was recorded, with a 6.7% serious complication rate. Two mortalities occurred. ASA, Age, Rockwood and NSQIP scoring systems all showed low degree positive correlation with length of stay (+0.16–+0.34). As predictors of length of stay, ASA was superior. Rockwood and age showed low degree positive correlation (+0.25–+0.33) with post‐operative complications. NSQIP and ASA demonstrated a greater degree of correlation (+0.38–+0.40). Conclusion: Both ASA and ACS NSQIP appear superior indicators for outcomes compared to age and Rockwood score. However, caution is warranted when interpreting the superiority of ASA over validated risk stratification tools. Therefore, we advocate the use of pre‐operative risk stratification for elderly patients undergoing low‐risk surgery such as appendicectomy. Validated tools are not routinely applied in many centres currently. Utilisation of scores such as ACS NSQIP may help improve consent, patient selection, outcomes and expectations. [ABSTRACT FROM AUTHOR]

Problem: Associations between immune dysfunction conditions (eg, systemic lupus erythematous, rheumatoid arthritis) and endometriosis have been observed in adult women, but not assessed among a younger population. We investigated the association between immune‐mediated conditions and endometriosis among young women. Method of Study: This cross‐sectional analysis in the Women's Health Study: From Adolescence to Adulthood included 551 participants with surgically diagnosed endometriosis (median age=19) and 652 controls without endometriosis (median age=24). Participants completed an expanded Endometriosis Phenome and Biobanking Harmonization Project questionnaire. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to investigate the associations between autoimmune/inflammatory, atopic, chronic pain/fatigue, and endocrine disorders with endometriosis, adjusting for confounders. Results: Participants with any autoimmune and/or inflammatory condition had an increased odds of co‐occurring endometriosis (OR: 1.87; CI: 0.92–3.80), as did participants with allergies (OR: 1.76; CI: 1.32–2.36), asthma (OR: 1.35; CI: 0.97–1.88), chronic fatigue syndrome and/or fibromyalgia (OR: 5.81; CI: 1.89–17.9), or previous mononucleosis (OR: 1.75; CI: 1.14–2.68). Odds of endometriosis were lower among participants with eczema (OR: 0.68; CI: 0.44–1.04). We observed a positive trend between the number of immune‐mediated conditions and the odds of endometriosis (p‐trend=0.0002). Endocrine disorders were not associated with endometriosis. Conclusions: Among this population of adolescents and adult women, endometriosis was more likely among participants with autoimmune and/or inflammatory diseases, allergies, asthma, previous mononucleosis infection, and chronic fatigue and/or fibromyalgia. We observed that an increasing number of immune‐mediated conditions were positively associated with endometriosis risk. It is important for clinicians who care for adolescents and women with these conditions to consider endometriosis as a comorbidity. [ABSTRACT FROM AUTHOR]

Family history (FH) of ovarian cancer and breast cancer are well‐established risk factors for ovarian cancer, but few studies have examined this association in African American (AA) and white women by histotype. We assessed first‐ and second‐degree FH of ovarian and breast cancer and risk of epithelial ovarian cancer in the Ovarian Cancer in Women of African Ancestry Consortium. Analyses included 1052 AA cases, 2328 AA controls, 2380 white cases and 3982 white controls. Race‐specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multilevel logistic regression with adjustment for covariates. Analyses were stratified by histotype (high‐grade serous vs others). First‐degree FH of ovarian cancer was associated with high‐grade serous carcinoma in AA (OR = 2.32, 95% CI: 1.50, 3.59) and white women (OR = 2.48, 95% CI: 1.82, 3.38). First‐degree FH of breast cancer increased risk irrespective of histotype in AAs, but with high‐grade serous carcinoma only in white women. Associations with second‐degree FH of ovarian cancer were observed for overall ovarian cancer in white women and with high‐grade serous carcinoma in both groups. First‐degree FH of ovarian cancer and of breast cancer, and second‐degree FH of ovarian cancer is strongly associated with high‐grade serous ovarian carcinoma in AA and white women. The association of FH of breast cancer with high‐grade serous ovarian carcinoma is similar in white women and AA women, but may differ for other histotypes. What's new Family history of breast or ovarian cancer are well known risk factors for ovarian cancer. Here, the authors looked at first‐ and second‐degree family history as it related to risk of epithelial ovarian cancer, stratified by serotype, among white and African American women. Having a first‐degree relative with breast cancer increased the risk in African American women regardless of histotype, but the increased risk was specific to high‐grade serous carcinoma (HGSC) in white women. First‐ or second‐degree history of ovarian cancer was associated with increased risk of high‐grade serous carcinoma in both racial groups, but less strongly associated with non‐HGSC. [ABSTRACT FROM AUTHOR]

Objective: This study examines the association between child autistic traits and constipation symptoms, and explores whether this association is mediated by food selectivity. Method: The sample included participants (N = 2,818) from the population‐based birth cohort, Generation R (Rotterdam, the Netherlands). Parents reported their child's autistic traits at 6 years (using the Social Responsiveness Scale), food selectivity at 10 years (using the Stanford Feeding Questionnaire) and the frequency and severity of constipation symptoms they experienced at 10 years (using the ROME III functional constipation diagnostic criteria). Mediation analyses tested mediation through food selectivity in the association of autistic traits and the number of constipation symptoms, adjusting for covariates. Results: There was a positive association between parent‐reported child autistic traits and constipation symptoms (r = 0.08, p <.001). We identified a significant indirect effect of autistic traits on constipation symptoms through food selectivity (β = 0.008, 95% Confidence Interval: 0.002, 0.014). Discussion: This study provides empirical support for the mediating role of food selectivity in the association between autistic traits and constipation. Behavioral interventions aimed to target food selectivity and support families of children with autistic traits may bolster conventional medical and nutritional treatments to alleviate gastrointestinal symptoms like constipation. [ABSTRACT FROM AUTHOR]

When powder is applied to the genital area, it has the potential to reach internal reproductive organs and promote carcinogenesis by irritating and inflaming exposed tissues. Although many studies have considered the association between genital powder use and ovarian cancer risk, the relationship between genital powder use and uterine cancer is less well‐studied. We pooled data from four large, prospective cohorts (the Nurses' Health Study, the Nurses' Health Study II, the Sister Study and the Women's Health Initiative ‐ Observational Study). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for prespecified confounders. In total, 209 185 women were included, with 37% reporting ever genital powder use. Over a mean 14.5 years of follow‐up, 3272 invasive uterine cancers were diagnosed. There was no overall association between ever genital powder use and uterine cancer (HR = 1.01, 95% CI: 0.94‐1.09), with little difference observed for frequent (≥1 times/week) vs never use (HR = 1.05, 95% CI: 0.95‐1.16; P‐for‐trend =.46). Long‐term use (>20 years; HR = 1.12, 95% CI: 0.96‐1.31; P‐for‐trend = 0.14) was associated with a small, but not statistically significant, increase in risk, compared to never use. There were not clear differences by uterine cancer histologic subtypes or across strata of relevant covariates, including race/ethnicity, follow‐up time, menopausal status and body mass index. The results of this large, pooled analysis do not support a relationship between the use of genital powder and uterine cancer, although the positive associations observed for long‐term use may merit further consideration. [ABSTRACT FROM AUTHOR]

SUMMARY: Background: Deliberate practice facilitates skill mastery. We aimed to create a novel resident‐as‐teacher rotation, leveraging a deliberate practice framework with repeated practice in real‐life teaching settings, with feedback from dedicated faculty member coaches. Methods: A resident‐as‐teacher rotation was designed for 35 Postgraduate Year‐2 (PGY2) paediatric residents. To facilitate deliberate practice, teaching experiences were observed by faculty member coaches and were repeated with different audiences. Participating residents received pre‐rotation, post‐rotation and follow‐up surveys on their confidence and comfort with teaching, supervision and feedback skills. All residents were also surveyed the year before and the year after implementation on their perceptions of their teaching, supervision and feedback skills, and whether the residency provided adequate training on these topics. Results: Survey response rates varied from 40 to 71%. The rotation was highly valued, and deliberate practice was a most valued aspect. Mean scores in comfort and confidence significantly increased from pre‐ to post‐rotation, with these increases sustained months later. Prior to implementation, residents' perceptions of their teaching skills and the adequacy of their training increased incrementally with each postgraduate year. After the inaugural year of the rotation, the PGY2 class rated their teaching skills and training as higher than more experienced residents. Discussion: A novel resident‐as‐teacher rotation successfully incorporated deliberate practice in real‐life settings by repeating teaching activities with feedback from dedicated coaches. The rotation led to sustained increases in residents' confidence in their teaching, supervising and feedback skills, and improved perceptions of their teaching training during residency. [ABSTRACT FROM AUTHOR]

Summary: Background: Child emotional overeating is a risk factor for obesity that is learned in the home environment. Parents' use of food to soothe child distress may contribute to the development of children's emotional overeating. Objectives: To examine the effect of a responsive parenting (RP) intervention on mother‐reported child emotional overeating, and explore whether effects are mediated by mother‐reported use of food to soothe child distress. Methods: The sample included primiparous mother‐infant dyads randomized to a RP intervention (n = 105) or home safety control group (n = 102). Nurses delivered RP guidance in four behavioral domains: sleeping, fussy, alert/calm, and drowsy. Mothers reported their use of food to soothe at age 18 months and child emotional overeating at age 30 months. Mediation was analyzed using the SAS PROCESS macro. Results: RP intervention mothers reported less frequent use of food to soothe and perceived their child's emotional overeating as lower compared to the control group. Food to soothe mediated the RP intervention effect on child emotional overeating (mediation model: R2 = 0.13, P <.0001). Conclusions: Children's emotional overeating may be modified through an early life RP intervention. Teaching parents alternative techniques to soothe child distress rather than feeding may curb emotional overeating development to reduce future obesity risk. [ABSTRACT FROM AUTHOR]

Our knowledge of epidemiologic risk factors for ovarian cancer supports a role for androgens in the pathogenesis of this disease; however, few studies have examined associations between circulating androgens and ovarian cancer risk. Using highly sensitive LC–MS/MS assays, we evaluated associations between pre‐diagnostic serum levels of 12 androgens, including novel androgen metabolites that reflect androgen activity in tissues, and ovarian cancer risk among postmenopausal women in a nested case–control study in the Women's Health Initiative (WHI) Observational Study (OS). We frequency‐matched 169 ovarian cancer cases to 410 controls from women enrolled in WHI‐OS who were not using menopausal hormones at enrollment/blood draw. We estimated associations overall and by subtype (n = 102 serous/67 non‐serous) using multivariable adjusted logistic regression. Androgen/androgen metabolite levels were not associated with overall ovarian cancer risk. In analyses by subtype, women with increased levels of androsterone‐glucuronide (ADT‐G) and total 5‐α reduced glucuronide metabolites (markers of tissue‐level androgenic activity) were at increased risk of developing non‐serous ovarian cancer: ADT‐G tertile (T)3 versus T1 odds ratio [OR] (95% confidence interval [CI]) 4.36 (1.68–11.32), p‐heterogeneity 0.002; total glucuronide metabolites 3.63 (1.47–8.95), 0.002. Risk of developing serous tumors was unrelated to these markers. ADT‐G and total glucuronide metabolites, better markers of tissue‐level androgenic activity in women than testosterone, were associated with an increased risk of developing non‐serous ovarian cancer. Our work demonstrates that sex steroid metabolism is important in the etiology of non‐serous ovarian cancers and supports a heterogeneous hormonal etiology across histologic subtypes of ovarian cancer. What's new?: Sex steroids play a role in ovarian carcinogenesis but associations between circulating androgen levels and ovarian cancer risk are inconsistent. Using mass spectrometry, the authors focused on 5α‐reduced androgen metabolites that cannot be metabolized into estrogen and therefore better reflect androgenic activity in tissues. They found androsterone‐glucuronide levels associated with increased risk of non‐serous tumors, the less frequent cancer form, pointing to unique subtype‐specific influences of androgens in ovarian malignancies. [ABSTRACT FROM AUTHOR]

Menstrual pain, a common gynecological condition, has been associated with increased risk of ovarian cancer in some, but not all studies. Furthermore, potential variations in the association between menstrual pain and ovarian cancer by histologic subtype have not been adequately evaluated due to lack of power. We assessed menstrual pain using either direct questions about having experienced menstrual pain, or indirect questions about menstrual pain as indication for use of hormones or medications. We used multivariate logistic regression to calculate the odds ratio (OR) for the association between severe menstrual pain and ovarian cancer, adjusting for potential confounders and multinomial logistic regression to calculate ORs for specific histologic subtypes. We observed no association between ovarian cancer and menstrual pain assessed by indirect questions. Among studies using direct question, severe pain was associated with a small but significant increase in overall risk of ovarian cancer (OR = 1.07, 95% CI: 1.01-1.13), after adjusting for endometriosis and other potential confounders. The association appeared to be more relevant for clear cell (OR = 1.48, 95% CI: 1.10-1.99) and serous borderline (OR = 1.31, 95% CI: 1.05-1.63) subtypes. In this large international pooled analysis of case-control studies, we observed a small increase in risk of ovarian cancer for women reporting severe menstrual pain. While we observed an increased ovarian cancer risk with severe menstrual pain, the possibility of recall bias and undiagnosed endometriosis cannot be excluded. Future validation in prospective studies with detailed information on endometriosis is needed. [ABSTRACT FROM AUTHOR]

The World Cancer Research Fund/American Association for Cancer Research (WCRF/AICR) has published eight nutrition-related recommendations for the prevention of cancer. However, few prospective studies have examined these recommendations by breast cancer hormone receptor subtype and only one case-control study has included the dietary supplements recommendation in their evaluation. We investigated whether adherence to the WCRF/AICR cancer prevention recommendations was associated with breast cancer incidence, overall and by hormone receptor subtype, in the Swedish Mammography Cohort. Among 31,514 primarily postmenopausal women diet and lifestyle factors were assessed with a self-administered food frequency questionnaire. A score was constructed based on adherence to the recommendations for body fatness, physical activity, energy density, plant foods, animal foods, alcoholic drinks and dietary supplements (score range 0-7). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow-up 1,388 cases of breast cancer were identified. Women who met six to seven recommendations had a 51% decreased risk of breast cancer compared to women meeting only zero to two recommendations (95% CI50.35-0.70). The association between each additional recommendation met and breast cancer risk was strongest for the ER-positive/PR-positive subtype (HR50.86; 95% CI50.79-0.94), while for the ER-negative/PR-negative subtype the individual recommendations regarding plant and animal foods were most strongly associated with reduced risk. Our findings support that adherence to the WCRF/AICR recommendations reduces breast cancer risk in a population of primarily postmenopausal women. Promoting these recommendations to the public could help reduce breast cancer incidence. [ABSTRACT FROM AUTHOR]

High endogenous hormone levels have been associated with breast cancer and dietary factors have the potential to influence breast cancer risk through effects on hormone levels. Dietary patterns derived from reduced rank regression provide a way to identify food groups correlated with hormones and subsequently examine food patterns that may be associated with breast cancer risk. We investigated whether a dietary pattern previously correlated with estradiol and estrone sulfate was associated with breast cancer in the prospective Swedish Mammography Cohort. Among 37,004 primarily postmenopausal women diet was assessed with a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 15 years of follow-up 1,603 cases of breast cancer were identified. A higher estrogen dietary pattern score was associated with an increased risk of breast cancer. Women in the highest quartile of estrogen pattern score had a 29% (95% CI = 1.08-1.55) increased risk of breast cancer compared to women in the lowest quartile ( ptrend = 0.006). When the association was examined by estrogen-receptor status, it was only significant for those with estrogen-receptor-positive tumors; however, in the competing risk analysis there were no significant differences in the effect estimates by receptor subtype ( pheterogeneity = 0.65). Our findings suggest that a dietary pattern associated with higher estrogen levels may increase breast cancer risk. However, whether the influence of this dietary pattern is through a direct effect on estrogen levels deserves further study. [ABSTRACT FROM AUTHOR]

Epigenetic regulation of imprinted genes enables monoallelic expression according to parental origin, and its disruption is implicated in many cancers and developmental disorders. The expression of hormone receptors is significant in breast cancer because they are indicators of cancer cell growth rate and determine response to endocrine therapies. We investigated the frequency of aberrant events and variation in DNA methylation at nine imprinted sites in invasive breast cancer and examined the association with estrogen and progesterone receptor status. Breast tissue and blood from patients with invasive breast cancer ( n = 38) and benign breast disease ( n = 30) were compared with those from healthy individuals ( n = 36), matched with the cancer patients by age at diagnosis, ethnicity, body mass index, menopausal status and familial history of cancer. DNA methylation and allele-specific expression were analyzed by pyrosequencing. Tumor-specific methylation changes at IGF2 DMR2 were observed in 59% of cancer patients, IGF2 DMR0 in 38%, DIRAS3 DMR in 36%, GRB10 ICR in 23%, PEG3 DMR in 21%, MEST ICR in 19%, H19 ICR in 18%, KvDMR in 8% and SNRPN/SNURF ICR in 4%. Variation in methylation was significantly greater in breast tissue from cancer patients compared with that in healthy individuals and benign breast disease. Aberrant methylation of three or more sites was significantly associated with negative estrogen-alpha (Fisher's exact test, p = 0.02) and progesterone-A ( p = 0.02) receptor status. Aberrant events and increased variation in imprinted gene DNA methylation, therefore, seem to be frequent in invasive breast cancer and are associated with negative estrogen and progesterone receptor status, without loss of monoallelic expression. [ABSTRACT FROM AUTHOR]

Imprinted genes are monoallelically expressed according to the parent of origin and are critical for proper placental and embryonic development. Disruption of methylation patterns at imprinted loci resulting in loss of imprinting (LOI) may lead to serious imprinting disorders (e.g., Beckwith-Wiedemann syndrome) and is described in some cancers (e.g., Wilms' tumor). As most research has focused on children with cancer or other abnormal phenotypes, the imprinting status in healthy infants at birth has not been characterized. We examined the prevalence of H19 and IGF2 LOI at birth by allele-specific expression assays analysis on 114 human individuals. Overall expression and methylation analyses were performed on a subset of samples. We found that LOI of H19 was observed for 4% of individuals in cord blood and 3.3% in placenta, and for IGF2 of 22% of individuals in the cord blood and 0% in placenta. Interestingly, LOI status did not correspond to aberrant methylation levels of the imprinted DMRs or with changes in overall gene expression for the majority of individuals. Our observations suggest that LOI is present in phenotypically healthy infants. Determining a "normal" human epigenotype range is important for discovering factors required to maintain a healthy pregnancy and embryonic development. [ABSTRACT FROM AUTHOR]

Background Numbers of street-connected children and young people run into many millions worldwide and include children and young people who live or work in street environments. Whether or not they remain connected to their families of origin, and despite many strengths and resiliencies, they are vulnerable to a range of risks and are excluded from mainstream social structures and opportunities. Objectives To summarise the effectiveness of interventions for street-connected children and young people that promote inclusion and reintegration and reduce harms. To explore the processes of successful intervention and models of change in this area, and to understand how intervention effectiveness may vary in different contexts. Search methods We searched the following bibliographic databases, from inception to 2012, and various relevant non-governmental and organisational websites: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE and PreMEDLINE; EMBASE and EMBASE Classic; CINAHL; PsycINFO; ERIC; Sociological Abstracts; Social Services Abstracts; Social Work Abstracts; Healthstar; LILACS; System for Grey literature in Europe (OpenGrey); ProQuest Dissertations and Theses; EconLit; IDEAS Economics and Finance Research; JOLIS Library Catalog of the holdings of the World Bank Group and IMF Libraries; BLDS (British Library for Development Studies); Google, Google Scholar. Selection criteria The review included data from harm reduction or reintegration promotion intervention studies that used a comparison group study design and were all randomised or quasi-randomised studies. Studies were included if they evaluated interventions aimed to benefit street-connected children and young people, aged 0 to 24 years, in all contexts. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias of included studies. Data were extracted on intervention delivery, context, process factors, equity and outcomes. Outcome measures were grouped according to whether they measured psychosocial outcomes, risky sexual behaviours or substance use. A meta-analysis was conducted for some outcomes though it was not possible for all due to differences in measurements between studies. Other outcomes were evaluated narratively. Main results We included 11 studies evaluating 12 interventions from high income countries. We did not find any sufficiently robust evaluations conducted in low and middle income countries (LMICs) despite the existence of many relevant programmes. Study quality overall was low to moderate and there was great variation in the measurement used by studies, making comparison difficult. Participants were drop-in and shelter based. We found no consistent results on a range of relevant outcomes within domains of psychosocial health, substance misuse and sexual risky behaviours despite the many measurements collected in the studies. The interventions being evaluated consisted of time limited therapeutically based programmes which did not prove more effective than standard shelter or drop-in services for most outcomes and in most studies. There were favourable changes from baseline in outcomes for most particpants in therapy interventions and also in standard services. There was considerable heterogeneity between studies and equity data were inconsistently reported. No study measured the primary outcome of reintegration or reported on adverse effects. The review discussion section included consideration of the relevance of the findings for LMIC settings. Authors' conclusions Analysis across the included studies found no consistently significant benefit for the 'new' interventions compared to standard services for street-connected children and young people. These latter interventions, however, have not been rigorously evaluated, especially in the context of LMICs. Robustly evaluating the interventions would enable better recommendations to be made for service delivery. There is a need for future research in LMICs that includes children who are on the streets due to urbanisation, war or migration and who may be vulnerable to risks such as trafficking. Plain Language Summary Interventions for reducing risks and promoting inclusion of street children and young people There are millions of children and young people estimated to be living and working on the streets around the world. Many have become resilient but continue to be vulnerable to risks. To promote their best chances in life, services are needed to reduce risks and prevent marginalisation from mainstream society. Eleven studies evaluating 12 interventions have been rigorously conducted of services to support street-connected children and youth, all in the developed world. They compared therapy-based services with usual shelter and drop-in services. The results of these studies were mixed but overall we found that participants receiving therapy or usual services benefitted to a similar level. There is a need for research which considers the benefit of usual drop-in and shelter services, most particularly in low and middle income countries, and which includes participation of street-connected children and young people. None of the studies included participants that were comparable to some street children in low income countries, who may be on the street primarily to earn a living or as a result of war, migration or urbanisation. [ABSTRACT FROM AUTHOR]

Folate, methionine, vitamin B6 and vitamin B12 may influence carcinogenesis due to their roles in the one-carbon metabolism pathway, which is critical for DNA synthesis, methylation and repair. Low intake of these nutrients has been associated with an increased risk of breast, colon and endometrial cancers. Previous studies that have examined the relation between these nutrients and ovarian cancer risk have been inconsistent and have had limited power to examine the relation by histologic subtype. We investigated the association between folate, methionine, vitamin B6, vitamin B12 and alcohol among 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008. Diet was assessed via food frequency questionnaire. Participants were asked to recall diet one-year before diagnosis or interview. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CIs). We also examined whether the associations varied by ovarian cancer histologies using polytomous logistic regression. We observed an inverse association between dietary vitamin B6 (covariate-adjusted OR = 0.76, 95% CI 0.64-0.92; ptrend = 0.002) and methionine intake (covariate-adjusted OR = 0.72, 95% CI = 0.60-0.87; ptrend < 0.001) and ovarian cancer risk comparing the highest to lowest quartile. The association with dietary vitamin B6 was strongest for serous borderline (covariate-adjusted OR = 0.49, 95% CI = 0.32-0.77; ptrend = 0.001) and serous invasive (covariate-adjusted OR = 0.74, 95% CI = 0.58-0.94; ptrend = 0.012) subtypes. Overall, we observed no significant association between folate and ovarian cancer risk. One-carbon metabolism related nutrients, especially vitamin B6 and methionine, may lower ovarian cancer risk. [ABSTRACT FROM AUTHOR]

Picrotoxin, a potent antagonist of the inhibitory central nervous system GABAA and glycine receptors, is believed to interact with residues that line the central ion pore. These pore-lining residues are in the second transmembrane domain (TM2) of each of the five constituent subunits. One of these amino acids, a threonine at the 6′ location, when mutated to phenylalanine, abolishes picrotoxin sensitivity. It has been suggested that this threonine, via hydrogen bonding, directly interacts with the picrotoxin molecule. We previously demonstrated that this mutation, in the α, β or γ subunit, can impart picrotoxin resistance to the GABA receptor. Since the functional pentameric GABA receptor contains two α subunits, two β subunits and one γ subunit, it is not clear how many α and β subunits must carry this mutation to impart the resistant phenotype. In this study, by coexpression of mutant α or β subunits with their wild-type counterparts in various defined ratios, we demonstrate that any single subunit carrying the 6′ mutation imparts picrotoxin resistance. Implications of this finding in terms of the mechanism of antagonism are considered. [ABSTRACT FROM AUTHOR]

Folate, methionine, vitamin B6, and vitamin B12 may influence carcinogenesis due to their roles in the one-carbon metabolism pathway which is critical for DNA synthesis, methylation, and repair. Low intake of these nutrients has been associated with an increased risk of breast, colon, and endometrial cancers. Previous studies that have examined the relation between these nutrients and ovarian cancer risk have been inconsistent and have had limited power to examine the relation by histologic subtype. We investigated the association between folate, methionine, vitamin B6, vitamin B12, and alcohol among 1910 women with ovarian cancer and 1989 controls from a case-control study conducted in eastern Massachusetts and New Hampshire from 1992 to 2008. Diet was assessed via food frequency questionnaire. Participants were asked to recall diet one-year before diagnosis or interview. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CIs). We also examined whether the associations varied by ovarian cancer histologies using polytomous logistic regression. We observed an inverse association between dietary vitamin B6 (covariate-adjusted OR=0.76, 95% CI 0.64–0.92; ptrend=0.002) and methionine intake (covariate-adjusted OR=0.72, 95% CI=0.60–0.87; ptrend<0.001) and ovarian cancer risk comparing the highest to lowest quartile. The association with dietary vitamin B6 was strongest for serous borderline (covariate-adjusted OR=0.49, 95% CI=0.32–0.77; ptrend=0.001) and serous invasive (covariate-adjusted OR=0.74, 95% CI=0.58–0.94; ptrend=0.012) subtypes. Overall, we observed no significant association between folate and ovarian cancer risk. One-carbon metabolism related nutrients, especially vitamin B6 and methionine, may lower ovarian cancer risk.

Reports about the workshop by the East-West Environmental Linkages entitled `Indigenous Environmental Knowledge and its Transformations' held at the University of Kent at Canterbury, from May 8-10, 1997. Background information of the East-West Environmental Linkages; Overview of some seminar papers delivered; Two main approaches grounding the discussions.