Exposure and effective dose biomarkers for perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in infertile subjects: preliminary results of the PREVIENI project

Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) have been used as surfactants in various industry and consumer products. PFOS/PFOA are very persistent in the environment and bioaccumulate in humans. They are potential reproductive and developmental toxicants and are considered to be emerging endocrine disrupters (EDs). The Italian project PREVIENI, funded by the Italian Environment Ministry, aims to link environment and human health through the investigation of selected endocrine disrupters (EDs) exposure and associated biomarkers related to human infertility conditions. In the early PREVIENI phase, PFOS and PFOA were determined in 53 couples affected by an infertility status, enrolled in a metropolitan area, according to established inclusion criteria and informed consensus. Nuclear receptors related to chemical compounds interactions were selected as biomarkers of effect and their gene expression modulations were analyzed in human peripheral blood mononuclear cell (PBMC). Among couples, subjects not presenting infertility factors (IF--) were separated from affected subjects (IF++). Most IF-- serum samples showed PFOS and PFOA concentrations overlapping the limit of detection (LOD) of 0.5 ng/g wet weight (ww). A substantial percentage of IF++ serum samples showed PFOS concentrations >20-fold the LOD, i.e. from 3 to 50 ng/g ww. In male (50%, n=26) and from 3 to 144 ng/g ww in female (37%, n=30) samples. PFOA values were below the LOD levels in 90% of the total samples. Peroxisome proliferator-activated receptor-gamma (PPARγ) and aryl hydrocarbon receptor (AhR) showed a low level of expression in PBMC of both IF++ and IF-- groups. Whereas alpha and beta estrogen receptors (ERα and ERβ), androgen receptor (AR), and pregnane X receptor (PXR) were all upregulated in IF++ of both sexes with respect to IF-- group. Our preliminary results related to the metropolitan area indicate that subjects affected by infertility factors tend to have both higher PFOS levels and higher gene expression of specific nuclear receptors.     

Determinants of neonatal mortality: a case-control study in Fortaleza, Ceará State, Brazil

This case-control study with 132 cases and 264 controls aimed to determine predictors of neonatal mortality using hierarchical modeling. Cases were defined as newborns that died within 28 days of birth, and controls as the survivors, among infants of mothers living in Fortaleza, Ceará State, Brazil. Hierarchical logistic regression identified factors associated with neonatal death: maternal race, with brown/black race showing a protective effect (OR = 0.23; IC95%: 0.09-0.56), time spent from home to the hospital > 30 minutes (OR = 3.12; 95%CI: 1.34-7.25), time < 1h or > 10 hours between hospital admission and delivery (OR = 2.43; 95%CI: 1.24-4.76), inadequate prenatal care (OR = 2.03; 95%CI: 1.03-3.99), low birth weight (OR = 14.75; 95%CI: 5.26-41.35), prematurity (OR = 3.41; 95%CI: 1.29-8.98), and male gender (OR = 2.09; 95%CI: 1.09-4.03). In this case series, neonatal deaths were associated with the quality of prenatal care and direct care during labor.     

Antifungal activity of dental resins containing amphotericin B-conjugated nanoparticles

Objectives

To evaluate the antifungal activity, biocompatibility and mechanical properties of dental resins containing silica nanoparticles functionalized with amphotericin B (SNP-DexOxAmB) against five species of Candida.

Methods

Dental resin composites (Spectrum, Dentsply DeTrey, GmbH, Germany) having 2% (w/w) of SNP-DexOxAmB (SNPs of 5 and 80 nm, denoted as SNP5 and SNP80) were aged for 10, 20 and 30 days at 37 °C, in phosphate buffer saline buffer pH 7.4 (PBS). At different time, the antifungal activity was evaluated by a direct contact assay against 1 × 10⁴ cells of Candida. The biocompatibility of the resins was tested against human fibroblasts, endothelial cells and red blood cells.

Results

Dental resins containing SNP5-DexOxAmB have high (1 × 10⁴ cells killed in 5 h by ∼70 mg of dental resin composite containing 2% (w/w) of SNP-DexOxAmB) and durable (for at least 1 month) antifungal activity against five strains of Candida. The incorporation of the nanoparticles (NPs) had no significant change in the mechanical properties of the resin, specifically the flexural strength and modulus. Our results further show that the antifungal activity is mainly mediated by direct contact and not by leaching of NPs from the resin. Resins incorporating SNP5-DexOxAmB have longer-term antifungal activity than SNP80-DexOxAmB. The antimicrobial activity of resins with SNP5-DexOxAmB persists after 4 cycles of re-use and it is superior to the activity obtained for dental resins containing silver NPs. In addition, dental resins incorporating SNP5-DexOxAmB are non-cytotoxic against human skin fibroblasts and human umbilical vein endothelial cells, and non-hemolytic against human red blood cells.

Significance

The incorporation of SNP5-DexOxAmB in dental resins resulted in a non-cytotoxic composite with high and durable antifungal activity.     

The effectiveness of strain counterstrain in the treatment of patients with chronic ankle instability: A randomized clinical trial

Study Design:

Randomized clinical trial.

Objective:

To determine the effect of strain counterstrain (SCS) on dynamic balance and subjective sense of instability in individuals with chronic ankle instability (CAI).Although many studies have been published on CAI, the cause for this common clinical dysfunction remains inconclusive. No studies have assessed the effectiveness of SCS on CAI.

Methods:

At baseline all participants completed a demographic questionnaire, the star excursion balance test (SEBT), and the foot and ankle ability measure (FAAM). Following the baseline evaluation, participants were randomized into the SCS experimental group (EG) (n = 13) or the sham SCS group (SG) (n = 14). All participants received the assigned treatment once a week for 4 weeks and participated in a prescribed exercise program. At week 4, all participants repeated the outcome measures and completed a global rating of change (GROC) form. The primary aim was examined with a two-way analysis of variance (ANOVA).

Results:

A significant group-by-time interaction was found for seven directions in the SEBT (P<0.031). For subjective measures, no significant group-by-time interaction was found for the FAAM (P>0.548), but the GROC revealed a significant difference (P = 0.014) in the mean score for the EG (3.92±1.66) when compared to the SG (2.43±1.66).

Discussion:

Although SCS may not have an effect on subjective ankle function in individuals with CAI, preliminary evidence suggests that SCS may lead to an improvement in dynamic ankle stability and the subjective sense of ankle instability.

Level of Evidence:

Therapy, Level 1b.     

How detection of epigenetic alterations of blood-borne DNA could improve melanoma diagnosis

Detection in blood of the genetic and epigenetic changes present in metastatic cancers is opening up new possibilities in molecular diagnostics. A number of methodological and clinical issues await resolution before serum epigenetic biomarkers can be considered a routine part of the management of melanoma patients following primary excision. However, there is every possibility that blood testing for the presence of methylated DNA will become an integral part of the clinical follow-up of such patients. The ability to identify patients with subclinical (asymptomatic) metastatic melanoma, combined with new, highly active targeted and immunomodulatory agents, may lead to further improvements in outcomes for this patient population.