Body composition and bone mineral density in breast cancer survivors and non-cancer controls: A 12- to 15-month follow-up.

While prognosis for breast cancer in women has improved, adverse side effects of treatments may negatively affect body composition and bone mineral density (BMD). This study assessed body composition and BMD changes in breast cancer survivors (BCS) (n = 10, 57.9 ± 5.7 years) and age-matched women (non-cancer, n = 10, 56.5 ± 4.3 years) over a 12- to 15-month period via dual-energy X-ray absorptiometry. No differences were observed between groups at baseline except forearm BMD values were lower in BCS (BCS: 0.462 ± 0.070 g/cm2 ; Control: 0.539 ± 0.052 g/cm2 , p = .012). Body fat increased in both groups compared to baseline (BCS: 38.3-39.6 kg, p = .013; Control: 38.2-39.5 kg, p = .023) at the follow-up. Significant decreases in BMD at the lumbar spine, femoral neck, total femur and ulna were observed in both groups. Breast cancer survivors had a greater decrease in left femoral neck BMD. While BCS demonstrated lower baseline forearm BMD values and a greater decrease in left femoral neck BMD, both groups showed an increase in body fat and decrease in forearm BMD. These findings support the implementation of interventions to improve body composition and BMD in both BCS and women without cancer.

Effect of maraviroc on non-R5 tropic HIV-1: refined analysis of subjects from the phase IIb study A4001029.

We characterized maraviroc susceptibility of dual/mixed tropic viruses from subjects enrolled onto phase IIb study A4001029. Maraviroc baseline plasma samples from 13 multidrug-experienced subjects were sequenced and the HIV-1-env gene cloned into pNL4.3Δenv to obtain recombinant viruses. The V3 region was sequenced by the Sanger method and ultradeep sequencing. By analysing subjects having a weighted optimized background therapy susceptibility (wOBT) score of <1, 3/7 subjects were characterized by good in vivo and in vitro response to maraviroc therapy. Molecular docking simulations allowed us to rationalize the maraviroc susceptibility of dual/mixed tropic viruses. A subset of subjects with dual/mixed tropic viruses responded to maraviroc. Further investigations are warranted of CCR5 antagonists in subjects carrying dual/mixed tropic virus that explore the feasible use of maraviroc in subjects that is potentially larger than those infected with a pure R5 virus.

Hepatitis C virus genetic variability and the presence of NS5B resistance-associated mutations as natural polymorphisms in selected genotypes could affect the response to NS5B inhibitors.

Because of the extreme genetic variability of hepatitis C virus (HCV), we analyzed the NS5B polymerase genetic variability in circulating HCV genotypes/subtypes and its impact on the genetic barrier for the development of resistance to clinically relevant nucleoside inhibitors (NIs)/nonnucleoside inhibitors (NNIs). The study included 1,145 NS5B polymerase sequences retrieved from the Los Alamos HCV database and GenBank. The genetic barrier was calculated for drug resistance emergence. Prevalence and genetic barrier were calculated for 1 major NI and 32 NNI resistance variants (13 major and 19 minor) at 21 total NS5B positions. Docking calculations were used to analyze sofosbuvir affinity toward the diverse HCV genotypes. Overall, NS5B polymerase was moderately conserved among all HCV genotypes, with 313/591 amino acid residues (53.0%) showing ≤1% variability and 83/591 residues (14.0%) showing high variability (≥25.1%). Nine NNI resistance variants (2 major variants, 414L and 423I; 7 minor variants, 316N, 421V, 445F, 482L, 494A, 499A, and 556G) were found as natural polymorphisms in selected genotypes. In particular, 414L and 423I were found in HCV genotype 4 (HCV-4) (n = 14/38, 36.8%) and in all HCV-5 sequences (n = 17, 100%), respectively. Regardless of HCV genotype, the 282T major NI resistance variant and 10 major NNI resistance variants (316Y, 414L, 423I/T/V, 448H, 486V, 495L, 554D, and 559G) always required a single nucleotide substitution to be generated. Conversely, the other 3 major NNI resistance variants (414T, 419S, and 422K) were associated with a different genetic barrier score development among the six HCV genotypes. Sofosbuvir docking analysis highlighted a better ligand affinity toward HCV-2 than toward HCV-3, in agreement with the experimental observations. The genetic variability among HCV genotypes, particularly with the presence of polymorphisms at NNI resistance positions, could affect their responsiveness to NS5B inhibitors. A pretherapy HCV NS5B sequencing could help to provide patients with the full efficacy of NNI-containing regimens.

Effect of extraction in the late mixed dentition on the eruption of the first premolar in Macaca nemestrina.

The effect of deciduous tooth extraction in the late mixed dentition on the eruption of succedaneous teeth was studied in ten Macaca nemestrina. Nineteen deciduous teeth were extracted: nine maxillary and ten mandibular left deciduous first molars. Regardless of sex, arch, chronologic or dental age, all first premolars on the experimental side erupted before those on the control side and this pattern was statistically significant. Extraction of deciduous molars in the late mixed dentition is seen to accelerate eruption of first premolars in Macaca nemestrina. This could be the result of eliminating the need for deciduous tooth root resorption during the normal process of eruption.