Association between cervical lesion grade and micronucleus frequency in the Papanicolaou test

The aim of this study was to evaluate the association between the frequency of micronuclei (MN) and the cellular changes detected in the conventional Papanicolaou test. One hundred and seventy-four Papanicolaou test smears with cellular changes were examined. MN screening was done in cytopathological smears by counting 1,000 cervical cells in a light microscope. MN frequencies were significantly higher in the group with cellular changes compared to the control group (p < 0.001). The mean MN frequencies were 0.95 ± 1.12 (mean ± SD) in the control group (n = 223), 2.98 ± 1.20 in individuals with atypical squamous cells of undetermined significance (ASC-US) (n = 50), 4.04 ± 1.45 in cervical intraepithelial neoplasia (CIN) I (n = 52), 5.97 ± 1.83 in CIN II (n = 30), 7.29 ± 1.55 in CIN III (n = 17) and 8.64 ± 1.55 in invasive cancer (n = 25). These findings suggest that MN monitoring should be included as an additional criterion for the early detection of cytogenetic damage in routine examinations. This monitoring should be done in the same smear as used for cytopathological examination. More specific and systematic studies are necessary to confirm this proposal.     

Trop-2 Is a Determinant of Breast Cancer Survival

Trop-2 is a calcium signal transducer that drives tumor growth. Anti-Trop-2 antibodies with selective reactivity versus Trop-2 maturation stages allowed to identify two different pools of Trop-2, one localized in the cell membrane and one in the cytoplasm. Of note, membrane-localized/functional Trop-2 was found to be differentially associated with determinants of tumor aggressiveness and distinct breast cancer subgroups. These findings candidated Trop-2 states to having an impact on cancer progression. We tested this model in breast cancer. A large, consecutive human breast cancer case series (702 cases; 8 years median follow-up) was analyzed by immunohistochemistry with anti-Trop-2 antibodies with selective reactivity for cytoplasmic-retained versus functional, membrane-associated Trop-2. We show that membrane localization of Trop-2 is an unfavorable prognostic factor for overall survival (1+ versus 0 for all deaths: hazard ratio, 1.63; P = 0.04), whereas intracellular Trop-2 has a favorable impact on prognosis, with an adjusted hazard ratio for all deaths of 0.48 (high versus low; P = 0.003). A corresponding impact of intracellular Trop-2 was found on disease relapse (high versus low: hazard ratio, 0.51; P = 0.004). Altogether, we demonstrate that the Trop-2 activation states are critical determinants of tumor progression and are powerful indicators of breast cancer patients survival.     

Trends in First-Line Antiretroviral Therapy in Asia: Results from the TREAT Asia HIV Observational Database

Background

Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes.

Methods

Patients in the TREAT Asia HIV Observational Database receiving first-line ART for ≥6 months were included. Predictors of treatment failure and treatment modification were assessed.

Results

Data from 4662 eligible patients was analysed. Patients started ART in 2003–2006 (n = 1419), 2007–2010 (n = 2690) and 2011–2013 (n = 553). During the observation period, tenofovir, zidovudine and abacavir use largely replaced stavudine. Stavudine was prescribed to 5.8% of ART starters in 2012/13. Efavirenz use increased at the expense of nevirapine, although both continue to be used extensively (47.5% and 34.5% of patients in 2012/13, respectively). Protease inhibitor use dropped after 2004. The rate of treatment failure or modification declined over time (22.1 [95%CI 20.7–23.5] events per 100 patient/years in 2003–2006, 15.8 [14.9–16.8] in 2007–2010, and 11.6 [9.4–14.2] in 2011–2013). Adjustment for ART regimen had little impact on the temporal decline in treatment failure rates but substantially attenuated the temporal decline in rates of modification due to adverse event. In the final multivariate model, treatment modification due to adverse event was significantly predicted by earlier period of ART initiation (hazard ratio 0.52 [95%CI 0.33–0.81], p = 0.004 for 2011–2013 versus 2003–2006), older age (1.56 [1.19–2.04], p = 0.001 for ≥50 years versus <30years), female sex (1.29 [1.11–1.50], p = 0.001 versus male), positive hepatitis C status (1.33 [1.06–1.66], p = 0.013 versus negative), and ART regimen (11.36 [6.28–20.54], p<0.001 for stavudine-based regimens versus tenofovir-based).

Conclusions

The observed trends in first-line ART use in Asia reflect changes in drug availability, global treatment recommendations and prescriber preferences over the past decade. These changes have contributed to a declining rate of treatment modification due to adverse event, but not to reductions in treatment failure.     

New Insights into the Relationship between mIGF-1-Induced Hypertrophy and Ca2+ Handling in Differentiated Satellite Cells

Muscle regeneration involves the activation of satellite cells, is regulated at the genetic and epigenetic levels, and is strongly influenced by gene activation and environmental conditions. The aim of this study was to determine whether the overexpression of mIGF-1 can modify functional features of satellite cells during the differentiation process, particularly in relation to modifications of intracellular Ca²⁺ handling.Satellite cells were isolated from wild-type and MLC/mIGF-1 transgenic mice. The cells were differentiated in vitro, and morphological analyses, intracellular Ca²⁺ measurements, and ionic current recordings were performed.mIGF-1 overexpression accelerates satellite cell differentiation and promotes myotube hypertrophy. In addition, mIGF-1 overexpression-induced potentiation of myogenesis triggers both quantitative and qualitative changes to the control of intracellular Ca²⁺ handling. In particular, the differentiated MLC/mIGF-1 transgenic myotubes have reduced velocity and amplitude of intracellular Ca²⁺ increases after stimulation with caffeine, KCl and acetylcholine. This appears to be due, at least in part, to changes in the physico-chemical state of the sarcolemma (increased membrane lipid oxidation, increased output currents) and to increased expression of dihydropyridine voltage-operated Ca²⁺ channels. Interestingly, extracellular ATP and GTP evoke intracellular Ca²⁺ mobilization to greater extents in the MLC/mIGF-1 transgenic satellite cells, compared to the wild-type cells.These data suggest that these MLC/mIGF-1 transgenic satellite cells are more sensitive to trophic stimuli, which can potentiate the effects of mIGF-1 on the myogenic programme.     

Phytoplankton assemblage structure and dynamics as indicator [-2pt] of the recent trophic and biological evolution of the western basin of Lake Como (N. Italy)

We studied the phytoplankton assemblage of the western basin of Lake Como (Northern Italy) during 1997. The phytoplankton assemblage was composed of 65 taxa, belonging to six taxonomic groups. Chlorophyta were represented by the highest number of taxa (28) followed by Bacillariophyceae (17), Cyanoprokaryota (9), Dinophyceae (6), Chrysophyceae (3) and Cryptophyta (2). The total assemblage density and biomass ranged from 902 ind ml^–1 and 134.5 mm³ m^–3 in February to 58 766 ind ml^–1 and 9360 mm³ m^–3 in October. The density and biomass variation at three stations showed a common pattern, with higher values in the southern part of the basin where TP concentrations were always greater. The phytoplankton succession was analysed by cluster analysis (average linkage clustering) and non-metric multidimensional scaling (NMDS) ordination, both applied to a dissimilarity matrix obtained from a calculation of the Bray–Curtis index. In general, the seasonal succession followed a simple pattern, with a clear spring phase. These results are discussed considering the trophic evolution of the lake and its recent colonization by Dreissena polymorpha.     

Menarche delay and menstrual irregularities persist in adolescents with type 1 diabetes

Background  

Menarche delay has been reported in adolescent females with type 1 diabetes (T1DM), perhaps due to poor glycemic control. We sought to compare age at menarche between adolescent females with T1DM and national data, and to identify factors associated with delayed menarche and menstrual irregularity in T1DM.     

Trigeminocardiac Reflex by Mandibular Extension on Rat Pial Microcirculation: Role of Nitric Oxide

In the present study we have extended our previous findings about the effects of 10 minutes of passive mandibular extension in anesthetized Wistar rats. By prolonging the observation time to 3 hours, we showed that 10 minutes mandibular extension caused a significant reduction of the mean arterial blood pressure and heart rate respect to baseline values, which persisted up to 160 minutes after mandibular extension. These effects were accompanied by a characteristic biphasic response of pial arterioles: during mandibular extension, pial arterioles constricted and after mandibular extension dilated for the whole observation period. Interestingly, the administration of the opioid receptor antagonist naloxone abolished the vasoconstriction observed during mandibular extension, while the administration of N_ω-Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, abolished the vasodilation observed after mandibular extension. Either drug did not affect the reduction of mean arterial blood pressure and heart rate induced by mandibular extension. By qRT-PCR, we also showed that neuronal nitric oxide synthase gene expression was significantly increased compared with baseline conditions during and after mandibular extension and endothelial nitric oxide synthase gene expression markedly increased at 2 hours after mandibular extension. Finally, western blotting detected a significant increase in neuronal and endothelial nitric oxide synthase protein expression. In conclusion mandibular extension caused complex effects on pial microcirculation involving opioid receptor activation and nitric oxide release by both neurons and endothelial vascular cells at different times.     

The distribution of benthic invertebrates along a natural turbidity gradient in Lake Temiskaming,Ontario-Quebec

Lake Temiskaming, a rift valley lake on the Ontario-Quebec border, exhibits a permanent gradient of turbidity due to tributary streams which cut through clay deposits to the north of the lake. Concentrations of total phosphorus (TP) also decreased from north to south, with values suggesting mesotrophic conditions. Concentrations of chlorophyll a were characteristic of oligotrophic lakes and showed little relationship to either turbidity or TP. Large numbers of Tubificidae were found at our northernmost sampling station at a depth of 50 m, probably reflecting the localized impact of allochthonous organic matter introduced by a tributary stream. Numerical abundance of the benthic fauna was much lower and did not vary significantly among the six more southerly 50 m stations, but biomass declined from north to south as Heterotrissocladius oliveri relaced Pontoporeia hoyi. Numerical abundance did not differ significantly among stations at depths of 10 m, but biomass decreased from north to south reflecting the distributions of the largest species, Hexagenia sp. and P. hoyi. Intensive sampling on two transects showed that maximum numbers of invertebrates occurred in the profundal zone. While these results are consistent with the correlation between TP and zoobenthic biomass reported by other investigators, size selective predation by fish may also be important in controlling the distribution of benthic invertebrates in Lake Temiskaming.