Cell-free DNA analysis in current cancer clinical trials: a review.

Cell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility and usefulness has been demonstrated, several issues related to standardisation and technical validation must be addressed for its routine clinical application in cancer. In this regard, most cfDNA clinical applications are still limited to clinical trials, proving its value in several settings. In this paper, we review the current clinical trials involving cfDNA/ctDNA analysis and highlight those where it has been useful for patient stratification, treatment follow-up or development of novel approaches for early diagnosis. Our query included clinical trials, including the terms 'cfDNA', 'ctDNA', 'liquid biopsy' AND 'cancer OR neoplasm' in the FDA and EMA public databases. We identified 1370 clinical trials (FDA = 1129, EMA = 241) involving liquid-biopsy analysis in cancer. These clinical trials show promising results for the early detection of cancer and confirm cfDNA as a tool for real-time monitoring of acquired therapy resistance, accurate disease-progression surveillance and improvement of treatment, situations that result in a better quality of life and extended overall survival for cancer patients.

Thin healthy women have a similar low bone mass to women with anorexia nervosa.

An association between anorexia nerviosa (AN) and low bone mass has been demonstrated. Bone loss associated with AN involves hormonal and nutritional impairments, though their exact contribution is not clearly established. We compared bone mass in AN patients with women of similar weight with no criteria for AN, and a third group of healthy, normal-weight, age-matched women. The study included forty-eight patients with AN, twenty-two healthy eumenorrhoeic women with low weight (LW group; BMI < 18.5 kg/m2) and twenty healthy women with BMI >18.5 kg/m2 (control group), all of similar age. We measured lean body mass, percentage fat mass, total bone mineral content (BMC) and bone mineral density in lumbar spine (BMD LS) and in total (tBMD). We measured anthropometric parameters, leptin and growth hormone. The control group had greater tBMD and BMD LS than the other groups, with no differences between the AN and LW groups. No differences were found in tBMD, BMD LS and total BMC between the restrictive (n 25) and binge-purge type (n 23) in AN patients. In AN, minimum weight (P = 0.002) and percentage fat mass (P = 0.02) explained BMD LS variation (r2 0.48) and minimum weight (r2 0.42; P = 0.002) for tBMD in stepwise regression analyses. In the LW group, BMI explained BMD LS (r2 0.72; P = 0.01) and tBMD (r2 0.57; P = 0.04). We concluded that patients with AN had similar BMD to healthy thin women. Anthropometric parameters could contribute more significantly than oestrogen deficiency in the achievement of peak bone mass in AN patients.

Anaphylactic shock versus Kounis syndrome in cardiac surgery: Differential diagnosis. / Shock anafiláctico versus síndrome de Kounis durante el intraoperatorio de cirugía cardiaca: diagnóstico diferencial.

Although Kounis syndrome was described almost 3 decades ago, there has been a notable increase in the reports of cases of acute coronary syndromes developed in the context of allergic reactions, also known as Kounis syndrome. This article discusses the diagnostic possibility in the face of an acute biventricular failure in the course of an anaphylactic reaction during the intra-operative period of a cardiac valve surgery.

Effects of raloxifene therapy on circulating osteoprotegerin and RANK ligand levels in post-menopausal osteoporosis.

Previous in vitro studies suggest that the anti-resorptive effect of raloxifene might be mediated by changes in several cytokines involved in the bone remodeling process. In this context, the osteoprotegerin (OPG)- receptor activator of NF kappa B ligand (RANKL) system is considered a key component in the osteoclastogenesis regulation. The aim of this study was to determine the effects of raloxifene treatment on serum concentrations of OPG, receptor RANKL and its relationship with biochemical markers of bone turnover and bone mineral density (BMD) in previously untreated women with post-menopausal osteoporosis. We selected 47 post-menopausal women (mean age 63+/-7 yr) with densitometric criteria of osteoporosis. We determined at baseline, 3, 6, and 12 months anthropometric parameters, biochemical markers of bone turnover, serum levels of 25(OH) D, serum levels of OPG and RANKL. BMD (dual-energy x-ray absorptiometry) in lumbar spine (LS) femoral neck and total hip was measured at baseline and 12 months after raloxifene (60 mg/day) treatment. Serum levels of OPG decreased in the 3rd and 6th month of treatment (p<0.001) and returned to basal levels in the 12th month. There was a significant decrease of RANKL levels and OPG/RANKL ratio after 1 yr of raloxifene treatment. In addition, BMD in LS increased significantly (2.5%) in the 12th month of treatment (p=0.031). Finally, the biochemical markers of bone turnover (total alkaline phosphatase, bone alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine cross-linked carboxi-terminal telopeptide of type I collagen) decreased significantly from the 3rd month of treatment. In conclusion, our results support the hypothesis that raloxifene may inhibit osteoclast activity, at least partly modulating the OPG-RANKL system.

Social exclusion of the adolescent with overweight: study of sociocentric social networks in the classroom.

BACKGROUND: Multiple studies have shown the social consequences of suffering overweight, with social exclusion or isolation as some of the most important. In order to study the social patterns among adolescents, we have set as objectives to analyse the position of the individual within their network from a sociocentric perspective, comparing the relational pattern of the adolescents suffering from overweight with those who are normal weight. METHOD: This was a cross-sectional descriptive study using logistic regression and social network analysis. We analysed the contact patterns of 235 adolescents in 11 social networks, classifying contact into three levels of intensity: minimum, intermediate and maximum (friendship). The WHO reference was used for the variable of overweight. RESULTS: The prevalence of overweight was 30.2% (25.5% overweight and 4.7% obesity). An analysis of the relational patterns of individuals with overweight showed that at the minimum contact level, they established fewer relationships and less closeness (odds ratio [OR]: 2.32; confidence interval [CI] 95%: 1.17-4.66; p-value: 0.016). This effect was more marked in female adolescents. At intermediate contact level, they had few relationships and low prestige (OR: 3.29; CI: 95%; 1.03-10.51; p-value: 0.045, OR: 3.18; CI: 95%; 1.00-10.04; p-value: 0.049, respectively). At maximum contact level (friendship), female adolescents related little with other adolescents (OR: 3.78; CI: 95%; 1.07-13.32; p-value: 0.038). CONCLUSIONS: Adolescents with overweight take up peripheral positions within their social network, choosing by themselves not to establish contact with others. Social network analysis is crucial to detect adolescents with overweight at risk of exclusion and help alleviate psychological and social deficits.

The effects of sediment depth and oxygen concentration on the use of organic matter: An experimental study using an infiltration sediment tank.

Water flowing through hyporheic river sediments or artificial recharge facilities promotes the development of microbial communities with sediment depth. We performed an 83-day mesocosm infiltration experiment, to study how microbial functions (e.g., extracellular enzyme activities and carbon substrate utilization) are affected by sediment depth (up to 50 cm) and different oxygen concentrations. Results indicated that surface sediment layers were mainly colonized by microorganisms capable of using a wide range of substrates (although they preferred to degrade carbon polymeric compounds, as indicated by the higher ß-glucosidase activity). In contrast, at a depth of 50 cm, the microbial community became specialized in using fewer carbon substrates, showing decreased functional richness and diversity. At this depth, microorganisms picked nitrogenous compounds, including amino acids and carboxyl acids. After the 83-day experiment, the sediment at the bottom of the tank became anoxic, inhibiting phosphatase activity. Coexistence of aerobic and anaerobic communities, promoted by greater physicochemical heterogeneity, was also observed in deeper sediments. The presence of specific metabolic fingerprints under oxic and anoxic conditions indicated that the microbial community was adapted to use organic matter under different oxygen conditions. Overall the heterogeneity of oxygen concentrations with depth and in time would influence organic matter metabolism in the sediment tank.

Optimal reconstruction of concentrations, gradients and reaction rates from particle distributions.

Random walk particle tracking methodologies to simulate solute transport of conservative species constitute an attractive alternative for their computational efficiency and absence of numerical dispersion. Yet, problems stemming from the reconstruction of concentrations from particle distributions have typically prevented its use in reactive transport problems. The numerical problem mainly arises from the need to first reconstruct the concentrations of species/components from a discrete number of particles, which is an error prone process, and then computing a spatial functional of the concentrations and/or its derivatives (either spatial or temporal). Errors are then propagated, so that common strategies to reconstruct this functional require an unfeasible amount of particles when dealing with nonlinear reactive transport problems. In this context, this article presents a methodology to directly reconstruct this functional based on kernel density estimators. The methodology mitigates the error propagation in the evaluation of the functional by avoiding the prior estimation of the actual concentrations of species. The multivariate kernel associated with the corresponding functional depends on the size of the support volume, which defines the area over which a given particle can influence the functional. The shape of the kernel functions and the size of the support volume determines the degree of smoothing, which is optimized to obtain the best unbiased predictor of the functional using an iterative plug-in support volume selector. We applied the methodology to directly reconstruct the reaction rates of a precipitation/dissolution problem involving the mixing of two different waters carrying two aqueous species in chemical equilibrium and moving through a randomly heterogeneous porous medium.