Role of HPV Genotype, Multiple Infections, and Viral Load on the Risk of High-Grade Cervical Neoplasia

Background:HPV testing provides a much more sensitive method of detection for high-grade lesions than cytology, but specificity is low. Here we explore the extent to which full HPV genotyping, viral load and multiplicity of types can be used to improve specificity. Methods:A population-based sample of 47,120 women undergoing cervical screening were tested for 13 high-risk HPV genotypes. Positive predictive values (PPV) for CIN grade 2 or worse (CIN2+; N=3449) and CIN3 or worse (CIN3+; N=1475) over three years of follow-up were estimated for HPV genotype and viral load. Weighted multivariate logistic regression models were used to estimate the odds of CIN2+ or CIN3+ according to genotype, multiplicity of types and viral load. Results:High-risk HPV was detected in 15.4% of women. A hierarchy of HPV genotypes based on sequentially maximizing PPVs for CIN3+ found HPV16>33>31 to be the most predictive, followed sequentially by HPV18>35>58>45>52>59>51>39>56>68. After adjusting for higher ranked genotypes, multiple HPV infections added little to risk prediction. High viral loads for HPV18, 35, 52 and 58 carried more risk than low viral loads for HPV16, 31 and 33. High viral load for HPV16 was significantly more associated with CIN3+ than low viral load. Conclusions:HPV genotype and viral load, but not multiplicity of HPV infections, are important predictors of CIN2+ and CIN3+. Impact:The ability to identify women at higher risk of CIN2+ and CIN3+ based on both HPV genotype and viral load could be important for individualising triage plans, particularly as HPV becomes the primary screening test

α-thalassaemia

Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia

The Impact of Prenatal Exposure to Dexamethasone on Gastrointestinal Function in Rats

Antenatal treatment with synthetic glucocorticoids is commonly used in pregnant women at risk of preterm delivery to accelerate tissue maturation. Exposure to glucocorticoids during development has been hypothesized to underlie different functional gastrointestinal (GI) and motility disorders. Herein, we investigated the impact of in utero exposure to synthetic glucocorticoids (iuGC) on GI function of adult rats. Wistar male rats, born from pregnant dams treated with dexamethasone (DEX), were studied at different ages. Length, histologic analysis, proliferation and apoptosis assays, GI transit, permeability and serotonin (5-HT) content of GI tract were measured. iuGC treatment decreased small intestine size and decreased gut transit. However, iuGC had no impact on intestinal permeability. iuGC differentially impacts the structure and function of the GI tract, which leads to long-lasting alterations in the small intestine that may predispose subjects prone to disorders of the GI tract.PortugueseFoundation for Science and Technology (FCT) forproviding a fellowship to Fátima Ramalhosa (SFRH/BD/52058/2012) and Carina Soares-Cunha (SFRH/BD/51992/201