Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.     

Study protocol for a multisite randomized controlled trial of an internet and mobile‐based intervention for preventing and reducing perinatal depressive symptoms

Nearly 20% of women in the United States experience clinically significant depressive symptoms during pregnancy or the postpartum period. These women may benefit from easily accessible, nonpharmacologic, and inexpensive self‐management approaches, such as via internet and mobile‐based interventions, to prevent development of symptoms and/or intervene with current symptoms. This paper summarizes the research protocol of a nationally‐funded large‐scale randomized controlled study to evaluate “Mamma Mia,” a self‐guided program with 44 modules that women use throughout pregnancy to 6 months postpartum. The program contains a novel combination of components designed to enable women to enhance self‐efficacy, emotional self‐regulation, and perceived social support. The overall goal of this three‐arm longitudinal randomized controlled trial is to evaluate the effects and mechanisms of this self‐management approach in diverse women in the U.S. (n = 1950). Enrolled pregnant women will be randomly assigned to one of three groups: (1) “Mamma Mia” alone, which is self‐guided; (2) “Mamma Mia Plus” in which participants engage in the “Mamma Mia” modules plus receive brief guided support from a registered nurse; or (3) usual prenatal/postpartum care. The first specific aim is to evaluate effects by group on the primary outcome of interest, depressive symptoms, over time. The second aim is to evaluate effects by group on subjective well‐being, anxiety, and stress. Using a conceptual framework based upon Individual and Family Self‐Management Theory, the third aim is to evaluate possible mediators (self‐efficacy, emotion self‐regulation, perceived support) and possible moderators (e.g., race/ethnicity, type of healthcare clinician) of this self‐management approach.     

Dopamine control of LH release in the tench (Tinca tinca)

Tench (Tinca tinca) is apparently the only known member of the Cyprinidae in which ovulation is stimulated following administration of a low dose of GnRH analogue (GnRHa) without a dopamine inhibitor. This study evaluated LH release effectiveness of the most commonly used GnRHa and clarified whether LH secretion followed by ovulation is subject to inhibitory dopaminergic control in tench. Fish were intraperitoneally injected with three types of GnRHa, GnRHa with dopamine inhibitor metoclopramide (combined treatment), or the dopamine inhibitor metoclopramide alone. LH concentrations at five sampling times (0, 6, 12, 24, and 33 h) together with ovulation success and fecundity index were recorded. The combined treatment triggered an almost immediate LH release peak with a gradual decline, and resulted in a high ovulation rate. In contrast to the combined treatment, an application of GnRHa alone at 10 μg kg(-1) induced gradual increase of LH concentrations with peaks close to ovulation time, and with high ovulation success. Significant differences in LH concentrations at 6 and 12h and no differences in ovulation success were found between the combined and the GnRHa alone treatments. Metoclopramide alone induced a small increase in LH with no ovulation. The study presents clear evidence of dopaminergic control of LH release in tench, with a high ovulation rate obtained after application of GnRHa alone or in combination with dopamine inhibitor.     

Effect of IGF-I and TNF-α on intensification of steroid pathways in women with PCOS phenotypes are not identical. Enhancement of progesterone pathway in women with PCOS increases the concentration of TNF-α

Objective: The aim of this study was to determine the correlations between the concentration of tumor necrosis factor (TNF-α) and insulin-like growth factor I (IGF-I) in each woman with polycystic ovary syndrome (PCOS) phenotypes based on the levels of androgen.

Methods: Two groups of women with PCOS differing in their levels of androgens. The test group composed of 39 women with PCOS according to the Rotterdam criteria in their reproductive age. The hormonal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid stimulating hormone (TSH), prolactin (PRL), androstenedione, testosterone (T), estradiol (E₂) and sex hormone binding globulin (SHBG) were measured. Correlations analysis were performed calculating Spearman’s rank correlation coefficient of hormones with relation to TNF-α and IGF-I.

Results: There was a medium positive correlation of IGF-1 with LH levels (p?<?0.05) and negative medium correlation of TNF-α with of dehydroepiandrosterone (DHEA)-SO₄ levels (p?<?0.05) only in group of PCOS women with elevated androgens.

Conclusion: Analysis of TNF-α showed that women with high testosterone negative correlation between level of TNF-α and the concentration of DHEA-SO4. Inflammatory state involving TNF-α in women with PCOS and high concentration of androgens is caused by intensified Δ4 (progesterone) pathway and omitted or limited Δ5 (dehydroepiandrosterone) pathway of testosterone biosynthesis.     

Accuracy of three-dimensional ultrasound for thyroid volume measurement in children and adolescents.

The aim of this study was to estimate accuracy, intraobserver variability, and repeatability of thyroid volume measurement by ultrasound using conventional two-dimensional ellipsoid model (2D US) and manual planimetry of three-dimensional images (3D US). The sonographic images of 47 children with thyroid nodular pathology who were referred for thyroid surgery in Belarus were evaluated prospectively. Two-dimensional images were acquired using the ultrasound scanner with 7.5-MHz linear probe. Three-dimensional data sets were created using three-dimensional system, FreeScan. For each patient thyroid volume was measured three times using both two- and three-dimensional methods. Results of volume estimation were then compared to the volume of thyroid gland determined after surgery. Standardized difference between thyroid volume estimated by ultrasound and surgery (mean +/- standard deviation (SD), %) for 3D and 2D US methods was 1.8 +/- 5.2% and 3.2 +/- 15.3%, respectively. The 3D US has lower intraobserver variability (3.4%) and higher repeatability (96.5%) than 2D US with 14.4% variability and 84.8% repeatability (p < 0.001). In conclusion, three-dimensional sonography allows accurate measurement of thyroid volume with low intraobserver variability and high repeatability.     

Multiorgan transplantation from a deceased donor with intravascular diffuse large B‐cell lymphoma: transmission of the disease and results of treatment

This report presents the transplantation of two kidneys and the liver from a deceased donor with suspected autoimmune encephalomeningitis (ADEM). Due to an atypical post‐transplantation clinical course, the transplanted kidneys were biopsied and this disclosed diffuse large B‐cell (DLBC) lymphoma of the intravascular type in each kidney. The same malignancy was found in the postmortem donor brain examination. The renal allografts from the two recipients were removed: despite every effort, one patient died, while chemotherapy was successful in the second. No malignancy was observed in the liver transplant recipient, who received prophylactic chemotherapy. These cases highlight the occasional failure of organ donor disease screening and the consequent unforeseen complications.