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Inorganic arsenic exposure may be associated with diabetes, but the evidence at low-moderate levels is not sufficient. Polymorphisms in diabetes-related genes have been involved in diabetes risk. We evaluated the association of inorganic arsenic exposure on diabetes in the Hortega Study, a representative sample of a general population from Valladolid, Spain. Total urine arsenic was measured in 1451 adults. Urine arsenic speciation was available in 295 randomly selected participants. To account for the confounding introduced by non-toxic seafood arsenicals, we designed a multiple imputation model to predict the missing arsenobetaine levels. The prevalence of diabetes was 8.3%. The geometric mean of total arsenic was 66.0 μg/g. The adjusted odds ratios (95% confidence interval) for diabetes comparing the highest with the lowest tertile of total arsenic were 1.76 (1.01, 3.09) and 2.14 (1.47, 3.11) before and after arsenobetaine adjustment, respectively. Polymorphisms in several genes including IL8RA, TXN, NR3C2, COX5A and GCLC showed suggestive differential associations of urine total arsenic with diabetes. The findings support the role of arsenic on diabetes and the importance of controlling for seafood arsenicals in populations with high seafood intake. Suggestive arsenic-gene interactions require confirmation in larger studies. [ABSTRACT FROM AUTHOR]

• Traditional technologies are insufficient for low-frequency mutation detection. • Multiple loci are necessary for higher sensitivity in ctDNA study. • Noise reduction have become indispensable for detection of ctDNA mutations. • Liquid biopsy needs to take a step into clinical setting through clinical trials. Cancer has become a global health issue and liquid biopsy has emerged as a non-invasive tool for various applications. In cancer, circulating tumor DNA (ctDNA) can be detected from cell-free DNA (cfDNA) obtained from plasma and has potential for early diagnosis, treatment, resistance, minimal residual disease detection, and tumoral heterogeneity identification. However, the low frequency of ctDNA requires techniques for accurate analysis. Multitarget assay such as Next Generation Sequencing (NGS) need improvement to achieve limits of detection that can identify the low frequency variants present in the cfDNA. In this review, we provide a general overview of the use of cfDNA and ctDNA in cancer, and discuss techniques developed to optimize NGS as a tool for ctDNA detection. We also summarize the results obtained using NGS strategies in both investigational and clinical contexts. [ABSTRACT FROM AUTHOR]

Establishing health effects of bioactive compounds from dry-cured meat is an active area of clinical research. The present study aims to investigate whether consuming dry-cured ham with biopeptides, among other bioactive compounds, modifies blood pressure (BP) and improves other risk factors for cardiovascular disease in humans. This two-arm, cross-over, randomised controlled trial involved 38 healthy subjects with pre-hypertension. Participants received 80 g/day dry-cured pork ham or 100 g/day cooked ham (control product). A daily intake of 80 g dry-cured ham did not impair BP or 24 h sodium excretion. Total cholesterol, LDL and basal glucose levels dropped after dry-cured ham consumption (p = 0.00019, p = 0.021 and p = 0.014, respectively). Cooked ham did not affect any of the clinical and biochemical markers. Dry-cured ham components could exert a plethora of activities over the cardiovascular system including lipid and glucose metabolism. Additional studies are needed to confirm the effects of dry-cured meat biopeptides on diverse risk factors in pathological conditions. [ABSTRACT FROM AUTHOR]

Cancer metabolic reprogramming promotes resistance to therapies. In this study, we addressed the role of the Warburg effect in the resistance to photodynamic therapy (PDT) in skin squamous cell carcinoma (sSCC). Furthermore, we assessed the effect of metformin treatment, an antidiabetic type II drug that modulates metabolism, as adjuvant to PDT. For that, we have used two human SCC cell lines: SCC13 and A431, called parental (P) and from these cell lines we have generated the corresponding PDT resistant cells (10GT). Here, we show that 10GT cells induced metabolic reprogramming to an enhanced aerobic glycolysis and reduced activity of oxidative phosphorylation, which could influence the response to PDT. This result was also confirmed in P and 10GT SCC13 tumors developed in mice. The treatment with metformin caused a reduction in aerobic glycolysis and an increase in oxidative phosphorylation in 10GT sSCC cells. Finally, the combination of metformin with PDT improved the cytotoxic effects on P and 10GT cells. The combined treatment induced an increase in the protoporphyrin IX production, in the reactive oxygen species generation and in the AMPK expression and produced the inhibition of AKT/mTOR pathway. The greater efficacy of combined treatments was also seen in vivo , in xenografts of P and 10GT SCC13 cells. Altogether, our results reveal that PDT resistance implies, at least partially, a metabolic reprogramming towards aerobic glycolysis that is prevented by metformin treatment. Therefore, metformin may constitute an excellent adjuvant for PDT in sSCC. [Display omitted] • Cell resistant to Photodynamic therapy (PDT) is due to the metabolic reprogramming. • Metformin modulates energetic metabolism in PDT-resistant cells, sensitizing to PDT. • Metformin increases protoporphyrin IX and reactive oxygen species generation. • Metformin+PDT is proposed as potential therapy against skin squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Abstract: In this article, we describe a case of bacteraemic pneumonia caused by Neisseria meningitidis serogroup Y. [Copyright &y& Elsevier]

The identification of biomarkers to drive treatment is one of the most important objectives of precision medicine. During last years, the role of PIK3CA mutations have been related to clinical benefit deriving from treatment with PI3K, and mTOR inhibitors. In breast cancer (BC), PIK3CA mutations are widely present and the use, in clinical trials, of selective inhibitors improved clinical outcomes. The aim of this study is to assess the value of a monocentric genomic screening program to select patients for trials with experimental targeted agents. We examined PIK3CA mutation in a cohort of 312 metastatic BC patients diagnosed at Hospital Clínico València-INCLIVA from Jan-13 to Apr-19. The sequencing of hotspot mutations was performed in primary (29.9%) and metastatic tissue (70.1%). We used two different technologies: MassARRAY technology (Sequenom MassARRAY, OncoCarta v1.0) and Iluminia MiSeq System (customised panel, OncoSpot v.1). Hotspots were selected according to databases already published. To be diagnosed as mutated, tumors needed to harbor at least 5% of mutant alleles. 7 clinical trials against PI3K pathway were available. PIK3CA analysis was performed in 312 paraffin embedded tumor samples, in which only 5.8% the analysis was not possible due to low quality of DNA. The distribution of BC subtypes were 77.6% Luminal, 13.9% HER2, and 8.5% triple negative (TN). PIK3CA mutations were detected in 96 patients (32.7%). In Luminal, PIK3CA mutations reached 36.8% while only 19.5% in HER2 and 16.0% in TN, respectively. A wide spectrum of PIK3CA mutations was found: H1047R (38.5%), E545K (30.2%), E542K (19.8%), R88Q (3.1%), M1043I (3.1%), N345K (2.1%), P539R (1.0%), K111E (1.0%), C420R (1.0%). One hundred and ninety (64.6%) patients were included in clinical trials, and 74 (38.9%) were treated with PI3K, AKT and mTOR inhibitors. PIK3CA mutations were widely present among luminal BC, being actually a specific target for new drugs. PIK3CA mutational analysis was easily and successfully performed in our center. The identification of PIK3CA hotspots mutations lead to the access for our patient to novel drugs into clinical trials, achieving relevant clinical benefits in most of the cases. The authors. Has not received any funding. A. Lluch: Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Eisai; Advisory / Consultancy: Celgene. A. Cervantes: Advisory / Consultancy: Merk serono; Advisory / Consultancy: Roche; Advisory / Consultancy: Beigine; Advisory / Consultancy: Bayer; Advisory / Consultancy: Servier; Advisory / Consultancy: Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Takeda; Advisory / Consultancy: Astelas; Advisory / Consultancy: Pierre Fabre; Speaker Bureau / Expert testimony: Foundation Medicine. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]