Binding Modes and Selectivity of Ruthenium Complexes to Human Telomeric DNA G-Quadruplexes.

Metal complexes constitute an important class of DNA binders. In particular, a few ruthenium polyazaaromatic complexes are attractive as "light switches" because of their strong luminescence enhancement upon DNA binding. In this paper, a comprehensive study on the binding modes of several mononuclear and binuclear ruthenium complexes to human telomeric sequences, made of repeats of the d(TTAGGG) fragment is reported.

Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test.

Objective: Cannabidiol (CBD), one of the non-psychotomimetic compounds of Cannabis sativa, causes anxiolytic-like effects in animals, with typical bell-shaped dose-response curves. No study, however, has investigated whether increasing doses of this drug would also cause similar curves in humans. The objective of this study was to compare the acute effects of different doses of CBD and placebo in healthy volunteers performing a simulated public speaking test (SPST), a well-tested anxiety-inducing method.

Evaluation of the efficacy of a medium cut-off dialyser and comparison with other high-flux dialysers in conventional haemodialysis and online haemodiafiltration.

Background: Online haemodiafiltration (OL-HDF) has been shown to reduce all-cause mortality versus conventional haemodialysis (HD); however, it is not always available. In these situations, a novel class of membranes with a higher pore size, medium cut-off (MCO) dialysers, could be promising. The aim of this study is to evaluate the efficacy of an MCO dialyser in the removal of small and medium-size molecules and compare it with standard high-flux (HF) dialysers in HD and OL-HDF.

Evolution of the β-lactam-resistant Streptococcus pneumoniae PMEN3 clone over a 30 year period in Barcelona, Spain.

Objectives: To analyse the epidemiology and genetic evolution of PMEN3 (Spain9V-156), a penicillin-non-susceptible clone of Streptococcus pneumoniae, causing invasive pneumococcal disease (IPD) in Barcelona during 1987-2016.

Methods: WGS was performed on 46 representative isolates and the data were used to design additional molecular typing methods including partial MLST, PCR-RFLP and detection of surface-exposed proteins and prophages, to assign the remaining isolates to lineages. The isolates were also subjected to antimicrobial susceptibility testing.

Heat wave and the risk of intimate partner violence.

Background: A high number of women report experiencing intimate partner violence (IPV). It is of utmost importance to identify possible factors that precipitate IPV and incorporate them into police protocols for evaluating IPV risk. Scientific evidence shows that environmental temperature is associated with a risk of violent behavior.

Aerobic training reduces blood pressure and waist circumference and increases HDL-c in metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials.

The objective of this study is to estimate the effect of aerobic training (AT) on metabolic syndrome (MetS) outcomes. The Medline, EMBASE, SPORTDiscus, The Cochrane Library, and PEDro databases were searched from inception to May 2017. Two independent reviewers selected the studies and assessed their quality and data.

Any grade of relative overhydration is associated with long-term mortality in patients with Stages 4 and 5 non-dialysis chronic kidney disease.

Background: Overhydration (OH) is associated with mortality in chronic kidney disease (CKD). A relative overhydration adjusted for extracellular water (OH/ECW) measured by bioimpedance >15% has shown an increased mortality risk in haemodialysis but few studies have been developed in advanced CKD. Our objective was to evaluate the effect of OH on mortality in patients with Stage 4 or 5 non-dialysis CKD.

Cold-related mortality vs heat-related mortality in a changing climate: A case study in Vilnius (Lithuania).

Introduction: Direct health effects of extreme temperatures are a significant environmental health problem in Lithuania, and could worsen further under climate change. This paper attempts to describe the change in environmental temperature conditions that the urban population of Vilnius could experience under climate change, and the effects such change could have on excess heat-related and cold-related mortality in two future periods within the 21st century.

Methods: We modelled the urban climate of Vilnius for the summer and winter seasons during a sample period (2009-2015) and projected summertime and wintertime daily temperatures for two prospective periods, one in the near (2030-2045) and one in the far future (2085-2100), under the Representative Concentration Pathway (RCP) 8.

A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC.

Background: Despite the significant antitumor activity of pembrolizumab in NSCLC, clinical benefit has been less frequently observed in patients whose tumors harbor EGFR mutations compared to EGFR wild-type patients. Our single-center experience on the KEYNOTE-001 trial suggested that pembrolizumab-treated EGFR-mutant patients, who were tyrosine kinase inhibitor (TKI) naïve, had superior clinical outcomes to those previously treated with a TKI. As TKI naïve EGFR-mutants have generally been excluded from pembrolizumab studies, data to guide treatment decisions in this patient population is lacking, particularly in patients with programmed death ligand 1 (PD-L1) expression ≥50%.

Extreme pregnancy: maternal physical activity at Everest Base Camp.

High-altitude natives employ numerous physiological strategies to survive and reproduce. However, the concomitant influence of altitude and physical activity during pregnancy has not been studied above 3,700 m. We report a case of physical activity, sleep behavior, and physiological measurements on a 28-yr-old third-trimester pregnant native highlander (Sherpa) during ascent from 3,440 m to Everest Base Camp (~5,300 m) over 8 days in the Nepal Himalaya and again ~10 mo postpartum during a similar ascent profile.

Severity-Related Increase and Cognitive Correlates of Serum VEGF Levels in Alzheimer's Disease ApoE4 Carriers.

Vascular endothelial growth factor (VEGF) is an angioneurin involved in the regulation of vascular and neural functions relevant for the pathophysiology of Alzheimer's disease (AD), but the influence of AD severity and ApoE4 status on circulating VEGF and its relationship with cognition has not been investigated. We assessed serum VEGF levels and cognitive performance in AD, amnestic mild cognitive impairment (MCI), and control subjects. VEGF levels were higher in AD patients than in MCI cases and controls (p < 0.

Concurrent progressive multifocal leukoencephalopathy and central nervous system infiltration by multiple myeloma: A case report.

Progressive multifocal leukoencephalopathy rarely occurs in patients with multiple myeloma. Intracranial central nervous system invasion is also an uncommon event in multiple myeloma, occurring in less than 1% of cases. We describe herein an exceptional case of coexisting progressive multifocal leukoencephalopathy and intraparenchymal central nervous system myeloma infiltration.

The labile iron pool attenuates peroxynitrite-dependent damage and can no longer be considered solely a pro-oxidative cellular iron source.

The ubiquitous cellular labile iron pool (LIP) is often associated with the production of the highly reactive hydroxyl radical, which forms through a redox reaction with hydrogen peroxide. Peroxynitrite is a biologically relevant peroxide produced by the recombination of nitric oxide and superoxide. It is a strong oxidant that may be involved in multiple pathological conditions, but whether and how it interacts with the LIP are unclear.

Time trend in the impact of heat waves on daily mortality in Spain for a period of over thirty years (1983-2013).

Many of the studies that analyze the future impact of climate change on mortality assume that the temperature that constitutes a heat wave will not change over time. This is unlikely, however, given the process of adapting to heat changes, prevention plans, and improvements in social and health infrastructure. The objective of this study is to analyze whether, during the 1983-2013 period, there has been a temporal change in the maximum daily temperatures that constitute a heat wave (T) in Spain, and to investigate whether there has been variation in the attributable risk (AR) associated with mortality due to high temperatures in this period.

Characterization of radon levels in soil and groundwater in the North Maladeta Fault area (Central Pyrenees) and their effects on indoor radon concentration in a thermal spa.

Radon levels in the soil and groundwater in the North Maladeta Fault area (located in the Aran Valley sector, Central Pyrenees) are analysed from both geological and radiation protection perspectives. This area is characterized by the presence of two important normal faults: the North Maladeta fault (NMF) and the Tredós Fault (TF). Two primary aspects make this study interesting: (i) the NMF shows geomorphic evidence of neotectonic activity and (ii) the presence of a thermal spa, Banhs de Tredós, which exploits one of the several natural springs of the area and needs to be evaluated for radiation dosing from radon according to the European regulation on basic safety standards for protection against ionizing radiation.

Comparison of urea recirculation and thermodilution for monitoring of vascular access in patients undergoing hemodialysis.

Unlabelled: Introduction It is important to monitor vascular access in patients with stage 5 chronic kidney disease receiving hemodialysis. Access recirculation can help to detect a need for intervention.

Objectives: To compare urea recirculation with recirculation by thermodilution using blood temperature monitoring to predict a need for intervention of vascular access over a 6-month period.

First homology model of Plasmodium falciparum glucose-6-phosphate dehydrogenase: Discovery of selective substrate analog-based inhibitors as novel antimalarial agents.

In Plasmodium falciparum the bifunctional enzyme glucose-6-phosphate dehydrogenase‒6-phosphogluconolactonase (PfG6PD‒6PGL) is involved in the catalysis of the first reaction of the pentose phosphate pathway. Since this enzyme has a key role in parasite development, its unique structure represents a potential target for the discovery of antimalarial drugs. Here we describe the first 3D structural model of the G6PD domain of PfG6PD‒6PGL.

Argentinean recommendations on the identification of treatment failure in relapsing remitting multiple sclerosis patients.

Unlabelled: One of the biggest challenges in multiple sclerosis (MS) is the definition of treatment response/failure in order to optimize treatment decisions in affected patients. The objective of this consensus was to review how disease activity should be assessed and to propose recommendations on the identification of treatment failure in RRMS patients in Argentina.

Methods: A panel of experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2016 and 2017 to carry out a consensus recommendation on the identification of treatment failure in RRMS patients.

Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons.

An intronic GGGGCC repeat expansion in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the pathogenic mechanism of this repeat remains unclear. Using human induced motor neurons (iMNs), we found that repeat-expanded C9ORF72 was haploinsufficient in ALS. We found that C9ORF72 interacted with endosomes and was required for normal vesicle trafficking and lysosomal biogenesis in motor neurons.

Geriatric assessment may help decision-making in elderly patients with inoperable, locally advanced non-small-cell lung cancer.

Background: Although concurrent chemoradiotherapy (cCRT) increases survival in patients with inoperable, locally advanced non-small-cell lung cancer (NSCLC), there is no consensus on the treatment of elderly patients. The aim of this study was to determine the prognostic value of the comprehensive geriatric assessment (CGA) and its ability to predict toxicity in this setting.

Methods: We enrolled 85 consecutive elderly (⩾75 years) participants, who underwent CGA and the Vulnerable Elders Survey (VES-13).

Plasmodium species differentiation by non-expert on-line volunteers for remote malaria field diagnosis.

Background: Routine field diagnosis of malaria is a considerable challenge in rural and low resources endemic areas mainly due to lack of personnel, training and sample processing capacity. In addition, differential diagnosis of Plasmodium species has a high level of misdiagnosis. Real time remote microscopical diagnosis through on-line crowdsourcing platforms could be converted into an agile network to support diagnosis-based treatment and malaria control in low resources areas.

Impact of pre-drying and frying time on physical properties and sensorial acceptability of fried potato chips.

In this work the effects of pre-drying and frying time on colour, oil, texture and sensorial acceptability (overall liking) of potato chips were evaluated. Potato chips were pre-dried for 0, 10, 20 and 30 min at 60 °C and fried in soybean oil at 190 °C for 60, 70 and 80 s. The colour parameters (L*, a* and b*) increased or decreased depending on the pre-drying and frying time.

Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.

Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events.