A mouse model of AChR deficiency syndrome with a phenotype reflecting the human condition

The two subtypes of mammalian muscle nicotinic acetylcholine receptors (AChR) are generated by the substitution of the epsilon (adult) subunit for the gamma (fetal) subunit within the AChR pentamer. Null mutations of the adult AChR epsilon-subunit gene are the most common cause of the AChR deficiency syndrome. This is a disorder of neuromuscular transmission characterized by non-progressive fatigable muscle weakness present throughout life. In contrast with the human disorder, mice with AChR epsilon-subunit null mutations die between 10 and 14 weeks of age. We generated transgenic mice that constitutively express the human AChR gamma-subunit in an AChR epsilon-subunit 'knock-out' background. These mice, in which neuromuscular transmission is mediated by fetal AChR, live well into adult life but show striking similarities to human AChR deficiency syndrome. They display fatigable muscle weakness, reduced miniature endplate potentials and endplate potentials, reduced motor endplate AChR number and altered endplate morphology. Our results illustrate how species differences in the control of ion-channel gene expression may affect disease phenotype, demonstrate that expression of adult AChR subtype is not essential for long-term survival, and suggest that in patients with AChR deficiency syndrome, up-regulation of the gamma-subunit could be a beneficial therapeutic strategy.     

Development of the Short Form Endometriosis Health Profile Questionnaire: The EHP-5

OBJECTIVE: To develop and validate a short form version of the Endometriosis Health Profile-30 questionnaire which consists of a 30-item core questionnaire and a 23 item modular questionnaire. METHODS: Three studies were carried out to develop the Endometriosis Health Profile-5. Study 1: a short form version of the Endometriosis Health Profile-30 core questionnaire was developed. Study 2: the results were verified in a new data set. Study 3: a short form version of the 23 item modular questionnaire was produced. The modular questionnaire contains six dimensions which may not be applicable to every woman with endometriosis and is used to supplement the five scales on the core questionnaire when required. RESULTS: The final instrument contained 11 items: five items from the core questionnaire and six items from the modular questionnaire. The 95% confidence intervals for Study 1 indicated that the scale scores overlapped with each item score and were confirmed in the second analysis (study 2). Each item was most highly correlated to its parent scale and less with the remaining four core questionnaire scales which was verified in study 2. In both studies all correlations were significant at the 0.01 level (two tailed test). CONCLUSION: The Endometriosis Health Profile-5 is a reliable and valid short form questionnaire which can also be supplemented with a short form version of the modular questionnaire when required. It will be especially useful in clinical settings where a short and economical endometriosis health status measure is required.     

Baseline CD4 T Cell Level Predicts Recovery Rate after Initiation of ART in HIV Infected Nigerians

The most characteristic immunologic disorder in HIV infection is the progressive loss of CD4 T lymphocytes, thus, it remains the most important and commonly used marker for monitoring of immune status of HIV-infected individuals. This study monitored CD4 T lymphocyte cell dynamics among HIV patients on ART, and consequently defined an optimal baseline level required for enhanced ARV treatment. Ninety-eight (M = 33; F = 65) out of 106 consenting HIV-infected ARV-naïve patients enrolled and monitored for 24 months were considered in the analysis. The patients were classified into four groups based on baseline CD4 T lymphocyte cell levels, and specific parameters were evaluated at interval. Median CD4 T lymphocyte increased from 114 (Range: 6–330) at baseline to highest 357 (Range: 15–1036) cells/μL at 18 months of therapy. Fifty (51.0%), 58(59.2%), 75(76.5%), 69(70.4%), 63(64.3%), and 69(70.4%) doubled their preceding CD4 levels during the 3^rd, 6^th, 9^th, 12^th, 18^th, and 24^th months of ART, respectively. Maximum 337, 302, 360, and 475 cells/μL of blood were attained by groups commenced on ART with baseline CD4 ≤ 50, 51–100, 101–200, and 201–350 cells/μL of blood, respectively. The results show that higher baseline CD4 T lymphocyte cell level correlates with enhanced restoration and plateau after commencement of ART.     

Incidence and Persistence of Depression Among Women Living with and Without HIV in South Africa: A Longitudinal Study

Depression and trauma are common among women living with HIV. This is the first study to track the longitudinal course of depression and examine the relationship between depression and trauma over time among women in South Africa. HIV-infected and uninfected women (N = 148) were assessed at baseline and one year later. Results of a path analysis show the multi-directional and entwined influence of early life stress, other life-threatening traumas across the lifespan, depression and PTSD over the course of HIV. We also observed higher rates of depressive symptomatology and more persistent cases among infected women compared to uninfected women, as well as a more consistent and enduring relationship between childhood trauma and depression among women living with HIV. The present study is unique in documenting the course of untreated depression and PTSD in women with and without HIV infection with a high prevalence of early childhood trauma.     

Evaluation of Amigas Latinas Motivando el Alma (ALMA): A Pilot Promotora Intervention Focused on Stress and Coping Among Immigrant Latinas

Recent immigrant Latinas are at increased risk of poor mental health due to stressors associated with adapting to life in the United States. This study evaluated Amigas Latinas Motivando el Alma, a promotora intervention to reduce stress and promote health and coping among recent immigrant Latinas. Using a pre- and post-test design, we evaluated mental health outcomes, specifically, in promotoras. Promotoras’ knowledge levels related to role of promotora and stress management increased, depressive symptoms and stress levels decreased, and coping responses and perceived social support increased as well. Results suggest that promotora programs may be an effective way to improve mental health in recent immigrant Latinas.