Hb Amsterdam [alpha32(B13)Met--Ile (alpha2)]: a new unstable variant associated with an alpha-thalassemia phenotype and a new African polymorphism

We have characterized a new abnormal hemoglobin (Hb) at position 32 of the alpha-globin chain. The proband, a 38-year-old woman of Surinamese Black ancestry, was referred to the Academic Hospital in Amsterdam, The Netherlands, after 3 years of Prednisone treatment in Surinam. Kidney failure was diagnosed at the Nephrology Department, Free University Medical Center, Amsterdam, The Netherlands; the cortisone treatment was interrupted and dialysis was started. At this stage, a microcytic hypochromic anemia was observed with high reticulocyte (40%) and ferritin (500 microg/L) levels, and hemoglobinopathy was suspected. No abnormal bands were visible on alkaline electrophoresis and high performance liquid chromatography (HPLC). The Hb A2 level was normal (2.7%) and the erythrocyte count was low (3.59 x 10(12)/L) with a normal haptoglobin level (68 mg/100 mL). None of the common alpha-thalassemia (thal) deletion defects were present. The beta-globin gene sequence was normal but the alpha2-globin gene sequence revealed an ATG-->ATA transition at codon 32, changing the methionine into an isoleucine residue. The mutation, called Hb Amsterdam, was observed in the mother of the proband, who was also heterozygous for the--alpha3.7-thal deletion and affected by a moderate microcytic hypochromic anemia. Both Hb Amsterdam and the--alpha(-3.7) allele were found in association with a new polymorphism, IVS-I-39 (C-->T), previously observed in our laboratory in seven patients of African origin, on both the alpha1 and alpha2 genes. In addition, Hb Amsterdam was also associated with the common African alpha2 polymorphism (G-->CTCGGCCC at position 7238 and T-->G at position 7174). Hb Amsterdam is the first mutation ever described at codon alpha32, a position involved in alpha1/beta1 interaction. The possibility of a contribution of this mutation to the nephropatic state of the proband is discussed.     

ERbeta1 and the ERbeta2 splice variant (ERbetacx/beta2) are expressed in distinct cell populations in the adult human testis

Estrogens can regulate germ cell function. Estrogen action is mediated via high affinity ERs; two subtypes (ERalpha and ERbeta) have been identified. We have shown previously that ERbeta is expressed in nuclei of multiple human testicular cells. A variant isoform of human (h) ERbeta (hERbetacx/2), formed by alternative splicing, has been identified in testicular cDNA libraries by two laboratories. The present study examined the expression of wild-type (ERbeta1) and variant (ERbeta2) beta receptors in human testes by 1) RT-PCR with isoform specific primers, and 2) single and double immunohistochemistry using monoclonal antibodies raised against peptides unique to the C termini of hERbeta1 and hERbeta2. PCR products specific for ERbeta1 and ERbeta2 were amplified from cDNA pools prepared from human testes and granulosa cells. On Western blots, the anti-ERbeta1 monoclonal antibody bound to recombinant ERbeta1 and the anti-ERbeta2 monoclonal to recombinant hERbeta2. Neither bound to the other ERbeta isoform nor to recombinant ERalpha. ERbeta1 and ERbeta2 proteins were both detected in human testis. Immunoexpression of ERbeta1 was most intense in pachytene spermatocytes and round spermatids, whereas low levels of expression were detected in Sertoli cells, spermatogonia, preleptotene, leptotene, zygotene, and diplotene spermatocytes. Highest levels of expression of ERbeta2 protein were detected in Sertoli cells and spermatogonia with low/variable expression in preleptotene, pachytene, and diplotene spermatocytes. No immunostaining was detected in elongating spermatids. Most interstitial cells expressed more ERbeta2 than ERbeta1. It is speculated that the cells most susceptible to modulation by estrogenic ligands are round spermatids in which levels of expression of ERbeta1 are high. In contrast, expression of ERbeta2, an isoform that may act as a dominant negative inhibitor of ER action, in Sertoli cells and spermatogonia, could protect these cells from adverse effects of estrogens.     

No door to lock: victimization among homeless and marginally housed persons

BACKGROUND: Homeless persons experience high rates of sexual and physical assault; homeless women are thought to be at highest risk. To determine the prevalence, distribution, and factors associated with sexual and physical assault, we surveyed homeless and marginally housed adults in San Francisco, Calif. METHODS: We interviewed 2577 respondents about their history of recent sexual and physical assault, housing history, sexual practices, substance use, health status, and criminal justice history. The main outcome measures were self-reported sexual and physical assault in the previous 12 months. RESULTS: Overall, 32.3% of women, 27.1% of men, and 38.1% of transgendered persons reported a history of either sexual or physical assault in the previous year; 9.4% of women, 1.4% of men, and 11.9% of transgendered persons reported sexual assault, and 30.6% of women, 26.6% of men, and 33.3% of transgendered persons reported physical assault. In multivariate models, being homeless (as opposed to marginally housed) was associated with sexual assault for women, but not for men (adjusted odds ratio for homeless women, 3.4 [1.2-9.7]). Housing status was not associated with physical assault for women or men. Mental illness and sex work were both common and associated with high rates of assault in multivariate analyses. CONCLUSIONS: Sexual and physical assault are common experiences for homeless and marginally housed persons. Housing is associated with lower rates of sexual assault among women. Strategies to decrease sexual and physical assault and its consequences are needed in this population.     

Maternal Health Literacy Progression Among Rural Perinatal Women

This research examined changes in maternal health literacy progression among 106 low income, high risk, rural perinatal African American and White women who received home visits by Registered Nurse Case Managers through the Enterprise Community Healthy Start Program. Maternal health literacy progression would enable women to better address intermediate factors in their lives that impacted birth outcomes, and ultimately infant mortality (Lu and Halfon in Mater Child Health J 7(1):13–30, 2003; Sharma et al. in J Natl Med Assoc 86(11):857–860, 1994). The Life Skills Progression Instrument (LSP) (Wollesen and Peifer, in Life skills progression. An outcome and intervention planning instrument for use with families at risk. Paul H. Brookes Publishing Co., Baltimore, 2006) measured changes in behaviors that represented intermediate factors in birth outcomes. Maternal Health Care Literacy (LSP/M-HCL) was a woman’s use of information, critical thinking and health care services; Maternal Self Care Literacy (LSP/M-SCL) was a woman’s management of personal and child health at home (Smith and Moore in Health literacy and depression in the context of home visitation. Mater Child Health J, 2011). Adequacy was set at a score of (≥4). Among 106 women in the study initial scores were inadequate (<4) on LSP/M-HCL (83 %), and on LSP/M-SCL (30 %). Significant positive changes were noted in maternal health literacy progression from the initial prenatal assessment to the first (p < .01) postpartum assessment and to the final (p < .01) postpartum assessment using McNemar’s test of gain scores. Numeric comparison of first and last gain scores indicated women’s scores progressed (LSP/M-HCL; p < .0001) and (LSP/M-SCL; p < .0001). Elevated depression scores were most frequent among women with <4 LSP/M-HCL and/or <4 LSP/M-SCL. Visit notes indicated lack or loss of relationship with the father of the baby and intimate partner discord contributed to higher depression scores.     

Avoidance Symptom Presentation of Preschoolers Exposed to Intimate Partner Violence in a Group Therapy Setting

Post-traumatic stress disorder (PTSD) is a serious problem for children exposed to intimate partner violence (IPV). Recent changes to diagnostic criteria for PTSD include a reduction in avoidance symptom criteria from three to one and the separation of emotional numbing from avoidance symptoms, thus creating a need to better understand how avoidance symptoms of PTSD present themselves in young children. This study evaluated 56 children aged four to six as they participated in an intervention for mothers and children exposed to IPV. Therapists documented behaviours indicative of avoidance symptoms during group sessions. Data were analysed and coded into symptom categories and thematically emergent domains. Results demonstrated that avoidance symptoms fell into three separate categories: physical avoidance, emotional avoidance, and changing topics. Additionally, the data support the Diagnostic and Statistical Manual of Mental Disorders (5th edition) change to remove emotional numbing from the avoidance symptom category. These results give insight into how to develop more targeted treatments for PTSD as well as improve the assessment and diagnosis of PTSD symptoms in preschoolers.     

Prognosis of Mild Cognitive Impairment in General Practice: Results of the German AgeCoDe Study

PURPOSE

The concept of mild cognitive impairment (MCI) has recently been introduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as mild neurocognitive disorder, making it a formal diagnosis. We investigated the prognostic value of such a diagnosis and analyzed the determinants of the future course of MCI in the AgeCoDe study (German Study on Ageing, Cognition, and Dementia in Primary Care Patients).

METHODS

We recruited 357 patients with MCI aged 75 years or older from primary care practices and conducted follow-up with interviews for 3 years. Depending on the course of impairment over time, the patients were retrospectively split into 4 groups representing remittent, fluctuating, stable, and progressive courses of MCI. We performed ordinal logistic regression analysis and classification and regression tree (CART) analysis.

RESULTS

Overall, 41.5% of the patients had remission of symptoms with normal cognitive function 1.5 and 3 years later, 21.3% showed a fluctuating course, 14.8% had stable symptoms, and 22.4% had progression to dementia. Patients were at higher risk for advancing from one course to the next along this spectrum if they had symptoms of depression, impairment in more than 1 cognitive domain, or more severe cognitive impairment, or were older. The result on a test of the ability to learn and reproduce new material 10 minutes later was the best indicator at baseline for differentiating between remittent and progressive MCI. Symptoms of depression modified the prognosis.

CONCLUSIONS

In primary care, about one-quarter of patients with MCI have progression to dementia within the next 3 years. Assessments of memory function and depressive symptoms are helpful in predicting a progressive vs a remittent course. When transferring the concept of MCI into clinical diagnostic algorithms (eg, DSM-5), however, we should not forget that three-quarters of patients with MCI stayed cognitively stable or even improved within 3 years. They should not be alarmed unnecessarily by receiving such a diagnosis.