Dimensions of Change: A Model for Community Change Efforts

· The Dimension of Change Model (DOCM), developed by the authors, is offered as a potentially useful tool for foundations, government, bodies, consultants, coalitions, and even individual organizations that are initiating or engaged in substantive efforts to bring about community change. · The dimensions contained in the model - structure, parameters, intention, approach, and people - offer a frame for addressing key aspects that emerge from the literature as fundamental to all change efforts. The model is offered as a way to design, implement, adapt, and evaluate change initiatives. · The work of First 5 Marin Children and Families Commission in Marin County is used as an example to stimulate reflection and discussion about such initiatives. · Lessons learned through First 5 Marin’s experience as a change agent are offered and augmented by the literature on change initiatives

Diagnostic Value of Concentration Profiles of Glucocorticosteroids and Endocannabinoids in Hair

Background:Endogenous corticosteroids and endocannabinoids are both known to be involved in stress adaption and anti-inflammatory and immuneregulatory effects. The application of hair as retrospective specimen for long-term recording of corticosteroids and its association with stress-induced biochemical alterations was intensively examined.Methods:To evaluate the stability and correlation of various parameters of the endocannabinoid and corticosteroid systems, a prospective study was carried out. Hair samples were collected monthly over a pregnancy cycle (sixth week of pregnancy to 9 weeks postpartum). By comparison of hair concentrations in particular segments (ie, grown in the same time span but collected at different times), an examination of analyte stability in hair was achieved. Additionally, the comparison of proximal segments provided on biochemical information that is independent of alteration due to physical instability. The detection limits of a validated procedure using solid-phase extraction cleanup and liquid chromatography-mass spectrometry proved to be suitable to identify the endogenous levels of cortisol (limits of detection = 1.6 pg/mg), cortisone (2.1 pg/mg), anandamide (AEA, 0.3 pg/mg), and 2-arachidonoylglycerol (15 pg/mg).Results:Corticosteroid concentrations in corresponding hair segments were found to be reduced with increasing hair age; an average decline of cortisol and cortisone by 50% in 4 months was estimated. Independently, an increase of cortisol and cortisone in proximal segments collected during pregnancy was confirmed, which is assumed to be stress related. Endocannabinoids proved to be by far more stable, as demonstrated by subsequent monthly collection of corresponding segments and there was hardly any washout of AEA detectable. Elevated hair concentrations of AEA and 2-arachidonoylglycerol were detected in the first-second trimester of pregnancy, which corresponds to negative correlations between AEA, cortisol, and cortisone

Suicide assisted by right-to-die associations: a population based cohort study

Background: In Switzerland, assisted suicide is legal but there is concern that vulnerable or disadvantaged groups are more likely to die in this way than other people. We examined socio-economic factors associated with assisted suicide. Methods: We linked the suicides assisted by right-to-die associations during 2003-08 to a census-based longitudinal study of the Swiss population. We used Cox and logistic regression models to examine associations with gender, age, marital status, education, religion, type of household, urbanization, neighbourhood socio-economic position and other variables. Separate analyses were done for younger (25 to 64 years) and older (65 to 94 years) people. Results: Analyses were based on 5 004 403 Swiss residents and 1301 assisted suicides (439 in the younger and 862 in the older group). In 1093 (84.0%) assisted suicides, an underlying cause was recorded; cancer was the most common cause (508, 46.5%). In both age groups, assisted suicide was more likely in women than in men, those living alone compared with those living with others and in those with no religious affiliation compared with Protestants or Catholics. The rate was also higher in more educated people, in urban compared with rural areas and in neighbourhoods of higher socio-economic position. In older people, assisted suicide was more likely in the divorced compared with the married; in younger people, having children was associated with a lower rate. Conclusions: Assisted suicide in Switzerland was associated with female gender and situations that may indicate greater vulnerability such as living alone or being divorced, but also with higher education and higher socio-economic positio

Insulin gene polymorphisms in type I diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

Background: Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from ß-cell autoimmunity. Methods: We investigated the role of the -2221Msp(C/T) and -23HphI(A/T) polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317), Addison´s disease (AD, n = 107) or Hashimoto´s thyroiditis (HT, n = 61)], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62) as well as in healthy controls (HC, n = 275). Results: T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T) and "AA" -23HphI(A/T) polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively). The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion: We demonstrate that the allele "C" of the -2221Msp(C/T) and "A" -23HphI(A/T) insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II

The Adrenal Gland: Central Relay in Health and Disease

Diseases of the adrenal gland are as important for the general practitioner as for the endocrine specialist. The high prevalence of some adrenal endocrinopathies, such as adrenal incidentalomas (1-2% of the population) and primary aldosteronism (6% of hypertensives), which affect millions of patients, makes adrenal diseases a relevant health issue. The high morbidity and mortality of some of the rarer adrenal diseases, i. e., Addison's disease and Cushing's syndrome (Table 1), make early detection and appropriate treatment such a challenge for the health care system

Ectopic Prostate Tissue in the Uterine Cervix of a Female with Non-Classic Congenital Adrenal Hyperplasia-A Case Report

Introduction: The occurrence of ectopic prostate tissue in the female genital tract is rare and has only been described sporadically. The origin of these lesions is unclear, but their appearance seems to be associated with various forms of androgen excess, including androgen therapy for transgender treatment or disorders of sex development, such as classic congenital adrenal hyperplasia (CAH). This is the first described case of ectopic prostate tissue in the cervix uteri of a 46,XX patient with a confirmed diagnosis of non-classic CAH due to 21-OHD and a history of mild adrenal androgen excess. Case presentation: We describe a 34-year-old patient with a genetic diagnosis of non-classic CAH due to 21-hydroxylase deficiency (21-OHD) with a female karyo- and phenotype and a history of mild adrenal androgen excess. Due to dysplasia in the cervical smear, conization had to be performed, revealing ectopic prostate tissue in the cervix uteri of the patient. Conclusions: An association between androgen excess and the occurrence of prostate tissue is likely and should therefore be considered as a differential diagnosis for atypical tissue in the female genital tract

Pubertal presentation in seven patients with congenital adrenal hyperplasia due to P450 Oxidoreductase deficiency

Context: P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17α-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex development in both sexes, skeletal malformations, and glucocorticoid deficiency. \ud \ud Objective: The aim of the study was to describe the clinical and biochemical characteristics of ORD during puberty. \ud \ud Design: Clinical, biochemical, and genetic assessment of seven ORD patients (five females, two males) presenting during puberty was conducted. \ud \ud Results: Predominant findings in females were incomplete pubertal development (four of five) and large ovarian cysts (five of five) prone to spontaneous rupture, in some only resolving after combined treatment with estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development in the two boys was more mildly affected, with some spontaneous progression. Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies indicative of ORD in all patients; all but one failed to mount an appropriate cortisol response to ACTH stimulation indicative of adrenal insufficiency. Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease-causing POR mutations. \ud \ud Conclusion: Delayed and disordered puberty can be the first sign leading to a diagnosis of ORD. Appropriate testosterone production during puberty in affected boys but manifest primary hypogonadism in girls with ORD may indicate that testicular steroidogenesis is less dependent on POR than adrenal and ovarian steroidogenesis. Ovarian cysts in pubertal girls may be driven not only by high gonadotropins but possibly also by impaired CYP51A1-mediated production of meiosis-activating sterols due to mutant POR

Health status in 1040 adults with disorders of sex development (DSD): a European multicenter study

Objective: The knowledge about health status in adults with disorder of sex development (DSD) is scarce. Design and methods: A cross-sectional observational study in 14 European tertiary centers recruited 1040 participants (717 females, 311 males, 12 others) with DSD. Mean age was 32.4 +/- 13.6 year (range 16-75). The cohort was divided into: Turner (n = 301), Klinefelter (n = 224), XY-DSD (n = 222), XX-DSD (excluding congenital adrenal hyperplasia (CAH) and 46,XX males) (n = 21), 46,XX-CAH (n = 226) and 45,X/46,XY (n = 45). Perceived and objective health statuses were measured and compared to European control data. Results: In DSD, fair to very good general health was reported by 91.4% and only 8.6% reported (very) bad general health (controls 94.0% and 6.0%, P<0.0001) Longstanding health issues other than DSD and feeling limited in daily life were reported in 51.0% and 38.6%, respectively (controls 24.5% and 13.8%, P< 0.0001 both). Any disorder except DSD was present in 84.3% (controls 24.6%, P< 0.0001). Males reported worse health than females In the subgroup analysis, Klinefelter and 46,XX-DSD patients reported bad general health in 15.7% and 16.7%, respectively (Turner 3.2% and CAH 7.4%). Comorbidities were prevalent in all DSD subgroups but Klinefelter and Turner were most affected. Early diagnosis of DSD and a healthy lifestyle were associated with less comorbidities. Conclusions: Overall, general health appeared to be good but a number of medical problems were reported, especially in Klinefelter and Turner. Early diagnosis of DSD and a healthy lifestyle seemed to be important. Lifelong follow-up at specialized centers is necessary

The rs1990760 polymorphism within the IFIH1 locus is not associated with Graves' disease, Hashimoto's thyroiditis and Addison's disease

Background: Three genes have been confirmed as major joint susceptibility genes for endocrine autoimmune disease:human leukocyte antigen class II, cytotoxic T-lymphocyte antigen 4 and protein tyrosine phosphatase non-receptor type 22. Recent studies showed that a genetic variation within the interferon induced helicase domain 1 (IFIH1) locus (rs1990760 polymorphism) is an additional risk factor in type 1 diabetes and Graves' disease (GD). Methods: The aim of the present study was to investigate the role of the rs1990760 polymorphism within the IFIH1 gene in German patients with GD (n=258), Hashimoto's thyroiditis (HT,n=106), Addison's disease (AD,n=195) and healthy controls (HC,n=227) as well as in 55 GD families (165 individuals, German) and 100 HT families (300 individuals, Italian). Furthermore, the interaction between rs1990760 polymorphism with human leukocyte antigen (HLA) risk haplotype DQ2(DQA*0501-DQB*0201), the risk haplotypes DQ2/DQ8 (DQA*0301-DQB*0302) and the status of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and TSH receptor antibody (TRAb) in patients and families were analysed. Results:No significant differences were found between the allele and genotype frequencies for rs1990760 IFIH1 polymorphism in patients with GD, HT, AD and HC. Also no differences were observed when stratifying the IFIH1 rs1990760 polymorphism for gender, presence or absence of thyroid antibodies (GD:TRAb and HT:TPOAb/TgAb) and HLA risk haplotypes (DQ2:for GD and HT, DQ2/DQ8:for AD). Furthermore the transmission analysis in GD and HT families revealed no differences in alleles transmission for rs1990760 IFIH1 from parents with or without HLA risk haplotype DQ2 to the affected offspring. In contrast, by dividing the HT parents according to the presence or absence of thyroid Ab titers, mothers and fathers both positive for TPOAb/TgAb overtransmitted the allele A of IFIH1 rs1990760 to their HT affected offspring (61.8% vs 38.2%;p=0.05;corrected p [pc]=0.1). However, these associations did not remain statistically significant after correction of the p-values. Conclusion: In conclusion, our data suggest, no contribution from IFIH1 rs1990760 polymorphism to the pathogenesis of either Graves' disease, Hashimoto's thyroiditis or Addison's disease in our study populations. However, in order to exclude a possible influence of the studied polymorphism in specified subgroups within patients with autoimmune thyroid disease, further investigations in larger populations are needed

An update on the long-term outcomes of prenatal dexamethasone treatment in congenital adrenal hyperplasia

First-trimester prenatal treatment with glucocorticoid (GC) dexamethasone (DEX) in pregnancies at risk for classic congenital adrenal hyperplasia (CAH) is associated with ethical dilemmas. Though effective in reducing virilisation in g irls with CAH, it entails exposure to high doses of GC in fetuses that do not benefit from the treatment. The current paper provides an update on the literature on outcomes of prenatal DEX treatment in CAH cases and unaffected subjects. Long-term follow-up resear ch is still needed to determine treatment safety. In addition, advances in early prenatal diagnostics for CAH and sex-typing as well as studies assessing dosing effects of DE X may avoid unnecessary treatment and improve treatment safety