Tele-counseling based on motivational interviewing to change sexual behavior of women living with HIV: a randomized controlled clinical trial

AIDS and Behavior - Sexual transmission accounts for the majority of new HIV infections in Iran. More than 80% of HIV-positive persons are sexually active, and nearly 68% reported never using a...     

Global and specific transcriptional repression by the histone H3 amino terminus in yeast

The yeast CHA1 promoter is activated in the presence of serine or threonine. Activation requires the Cha4p activator, and it results in perturbation of a nucleosome that incorporates the TATA element under noninducing conditions. We show that in yeast lacking the amino terminus of histone H3, the promoter is constitutively active and the chromatin is concomitantly perturbed. This derepression occurs in the absence of elevated intracellular levels of serine or threonine and is not observed in cells lacking Rpd3p, Tup1p, or the amino terminus of histone H4. Furthermore, derepression in the absence of the H3 amino terminus requires the primary activator of this promoter, Cha4p, which we show by chromatin immunoprecipitation to be constitutively bound to the CHA1 promoter in WT yeast. Thus, the H3 amino terminus is required to prevent Cha4p from activating CHA1 in the absence of inducer. We also present results of a microarray experiment showing that the H3 amino terminus has a substantial repressive effect on a genome-wide scale.     

Prognostic impact of incomplete surgical clearance of radioiodine sensitive local lymph node metastases diagnosed by post-operative <Superscript>124</Superscript>I-NaI-PET/CT in patients with papillary thyroid cancer

Purpose

Nodal involvement is an independent risk factor of recurrence in papillary thyroid cancer (PTC). Neither the international guidelines nor the recently introduced ongoing risk adaptation concept consider the extent of initial surgical clearance of radioiodine sensitive lymph node metastases in their stratification systems. We investigated the prognostic relevance of incomplete initial surgical clearance in patients with purely lymphogeneous metastatic PTC (pN1 M0) despite successful radioiodine therapy. Accurate assessment of pre-ablative nodal status was attempted using PET/CT studies with both ¹²⁴I-NaI and ¹⁸F-FDG along with high-resolution cervical ultrasound.

Methods

Sixty-five patients with histologically diagnosed lymph node metastases (pN1 M0) were retrospectively analyzed. Patients with iodine-negative lymph node metastases diagnosed by ¹⁸F-FDG PET/CT or distant metastases were excluded from the analysis. The association of disease recurrence with the pre-ablative nodal status, as well as other baseline characteristics, were examined applying nonparametric tests for independent samples and multiple regression analysis. Patients with persistent lymph node metastases in ¹²⁴I-NaI PET/CT were further divided according to the additional presence or absence of FDG-uptake in ¹⁸F-FDG PET/CT. Survival analyses were performed using Kaplan–Meier curves and the Cox proportional hazards model for uni- and multivariate analyses to assess the influence of prognostic factors on progression free survival (PFS).

Results

Incomplete metastatic lymph node resection captured by ¹²⁴I-NaI PET/CT (n?=?33) was an independent risk factor for recurrence (61 % vs 25 %, p?=?0.006) and shorter PFS (46 months vs not reached, HR 4.0 [95 %-CI, 1.7–9.2], p?=?0.001). Ultrasound could detect lymph node metastases only in 19/33 patients (58 %). Among patients with positive nodal status, FDG-avidity of metastatic iodine positive lymph nodes worsened the outcome (16 vs 69 months, p?=?0.047). From all other investigated factors including age, N-stage (N1a vs N1b), and T-Stage (T4 vs T1-3), only large tumor size (pT4) had a significant impact on PFS (HR 2.9 [95 %-CI, 1.3–6.4], p?=?0.007).

Conclusions

Incomplete initial surgical clearance of lymph node metastases even after successful radioiodine therapy may increase the chances of recurrence and is an independent risk factor for impaired survival of patients with PTC. Pre-ablative (dual tracer PET/CT) imaging with ¹²⁴I-Na and ¹⁸F provides a prognostic tool for these patients and may considerably complement the current risk stratification systems.