Muscle Activation During Power-Oriented Resistance Training: Continuous vs. Cluster Set Configurations.

Morales-Artacho, AJ, García-Ramos, A, Pérez-Castilla, A, Padial, P, Gomez, AM, Peinado, AM, Pérez-Córdoba, JL, and Feriche, B. Muscle activation during power-oriented resistance training: continuous vs. cluster set configurations. J Strength Cond Res 33(7S): S95-S102, 2019-This study examined performance and electromyography (EMG) changes during a power training protocol comprising continuous or clustered set configurations. Eighteen active males completed 6 sets of 6 repetitions during the loaded (20% 1 repetition maximum) countermovement jump (CMJ) exercise, continuously (n = 9) or with a 30-second pause every 2 repetitions (cluster; n = 9). Power output, vastus lateralis (VL), vastus medialis (VM), and rectus femoris (RF) EMG were recorded during all CMJs. Relative changes from the first repetition were assessed on the EMG root mean square (RMS), median frequency (Fmed), and a low- to high-frequency ratio index of fatigue (FInsmk). Greater power output decrements were observed during the continuous set configuration (p = 0.001, (Equation is included in full-text article.)< 0.01). Greater RMS increments in VL (6.8 ± 11.3 vs. -1.7 ± 5.8%) and RF (9.3 ± 14.2 vs. 1.9 ± 6.9%), but not VM (2.0 ± 4.7 vs. 2.6 ± 7.3%), were also observed in the continuous compared with the cluster sets (p = 0.033, (Equation is included in full-text article.)= 0.06). Progressive decrements in Fmed and increments in FInsmk were observed across repetitions in both set configurations. In conclusion, although clustering sets between repetitions clearly maintained power output, mixed responses were observed on the examined EMG parameters.

Hepatitis E Virus (HEV) Infection in Anti-HEV Immunoglobulin G-Carrying Patients After Successful Hepatitis C Virus Treatment: Reactivation or Reinfection?

Although hepatitis E virus (HEV) is regarded as a self-limiting infection and anti-HEV antibodies seem to protect against reinfection, its pathogenesis is not well established. We describe 2 cases of acute symptomatic HEV infection after hepatitis C therapy in patients carrying anti-HEV immunoglobulin G antibodies, raising 2 major questions: reactivation or reinfection?

New insights into the role of the immune microenvironment in breast carcinoma.

Recently, immune edition has been recognized as a new hallmark of cancer. In this respect, some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings, especially in the neoadjuvant and metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) and myeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. In addition, the complex interaction of costimulatory and coinhibitory molecules on the immune synapse and the different signals that they may exert represent another exciting field to explore. In this review we try to summarize and elucidate these new concepts and knowledge from a translational perspective focusing on breast cancer, paying special attention to those aspects that might have more significance in clinical practice and could be useful to design successful therapeutic strategies in the future.

A new approach to prostate cancer screening.

Prostate cancer screening based on prostate-specific antigen (PSA) testing has been a matter of controversy. Although screening for prostate cancer was effective in reducing mortality, it resulted in overdiagnosis, which translated into unnecessary treatments and numerous adverse effects. As a result, recommendations from scientific societies became increasingly restrictive. In the recent years, new approaches to prostate cancer screening have been proposed. These new approaches are aimed at solving the controversy between widespread screening vs. no screening, and reconsidering PSA testing as a screening tool with a good benefit/risk balance. In this context, the European Association of Urology submitted a proposal to the European Commission for prostate cancer screening to be performed as a function of baseline PSA concentrations. The European Commission recently recommended the implementation of organized prostate cancer screening programs for men aged ≤70 years based on PSA values in combination with follow-up magnetic resonance imaging.

Genetic diagnosis of X-linked dominant Hypophosphatemic Rickets in a cohort study: tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type.

BACKGROUND: Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D3 (1,25(OH)2D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the PHEX gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies. METHODS: Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the PHEX gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test. RESULTS: Mutations in the PHEX gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)2D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013). CONCLUSIONS: PHEX gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious PHEX mutations had lower TRP and 1,25(OH)2D levels suggesting that the PHEX type of mutation might predict the XLHR phenotype severity.

Experimental demonstration of weak-light laser ranging and data communication for LISA.

Interferometric gravitational wave detectors with an unequal and time-varying arm length configuration like the Laser Interferometer Space Antenna rely on time-delay interferometry (TDI) for laser frequency noise subtraction. However, the TDI algorithm requires a laser ranging scheme with meter accuracy over a five million kilometer arm length. At the end of each arm only about 100 pW of light power will be detected for gravitational wave measurements and only 1% of this power can be used for laser ranging in order to avoid degradation in the phase stability of the science measurements. Here, we present the first experimental demonstration of such a ranging scheme at 1 pW power levels using a Direct Sequence Spread Spectrum (DS/SS) modulation. This type of modulation also enables optical communication by encoding data with ranging signals and provides significant noise reduction against spurious interfering signals for bidirectional ranging. Experimental results show ranging measurements of 42 cm at 3 Hz and the viability of highly reliable data transfer at several kilobits per second.

Improving reliability of Raman spectroscopy for mAb production by upstream processes during bioprocess development stages.

The use of Raman in Bioprocess development have shown great potential for process understanding and monitoring although there are still some challenges and limitations in performance when conditions such as clone, media or scale are changed during bioprocess development. This study proposes different strategies to balance the different information content of multiple mammalian cell cultivations produced during a bioprocess development program, when several conditions are investigated. The result is a pragmatic approach to PAT monitoring that serves both development and manufacturing stages. Combining risk-assessment techniques with two ways of developing monitoring calibrations (local or general models), we were able to obtain good predictive power from Raman spectroscopy used as PAT tool, when multiple cultivation conditions vary. As an example, the effects of process scale, base powder media and cell-line on Raman spectra are discussed and how using local models specific to some of these cultivation conditions, has a positive impact on calibration performance. It is shown how more accurate calibrations can be obtained using Clone-based local models, which requires less batches than usual approaches (up to 3-9). This study uses thirty-five cultivations of four different types of CHO cell lines, eight different clones, and four different scales - 2 L, 7 L, 15 L and 10,000 L - in two Cultivation Modes - fed-batch and perfusion. The aim is to serve as blueprint to how can PAT approaches be best developed in parallel to bioprocess development.

Cobalt oxide-carbon nanocatalysts with highly enhanced catalytic performance for the green synthesis of nitrogen heterocycles through the Friedländer condensation.

A novel series of eco-sustainable catalysts developed by supporting CoO nanoparticles on different carbon supports, highly efficient in the synthesis of quinolines and naphthyridines, through the Friedländer condensation, are reported for the first time. Textural properties, dispersion and location of the Co-phase are influenced by the nature of the carbon support, Co-precursor salt and metal loading, having a significant impact on the catalytic performance. Thus, the presence of the mesopores and macropores in carbon aerogels together with the homogeneous distribution of the active phase favours the formation of product 3a as a function of the metal loading. However, an increase in the metal content when using CNTs indicates the formation of CoO aggregates and an optimal concentration of 3 wt% CoO was observed, providing the highest conversion values. The carbon-based catalysts herein reported can be considered to be a sustainable alternative having advantages such as easy preparation, superior stability and notably enhanced catalytic performance, operating at lower temperature and under solvent-free conditions.

Monitoring mAb cultivations with in-situ raman spectroscopy: The influence of spectral selectivity on calibration models and industrial use as reliable PAT tool.

Raman spectroscopy is a suitable monitoring technique for CHO cultivations. However, a thorough discussion of peaks, bands, and region assignments to key metabolites and culture attributes, and the interpretability of produced calibrations is scarce. That understanding is vital for the long-term predictive ability of monitoring models, and to facilitate lifecycle management that comply with regulatory guidelines. Several fed-batch lab-scale mAb mammalian cultivations were carried out, with in situ Raman spectroscopy used for process state estimation and attribute monitoring. The goal was to evaluate its use as a process analytical technology (PAT) tool to detect residual glucose and lactate levels, understand their dynamics and interconversion, and eventually estimate key performance culture and product quality attributes. Glucose and lactate models were optimized up to 0.31 g L-1 with 3 Latent Variables (LVs) and 0.19 g L-1 (2 LVs) accuracy, respectively. Glutamine and product titer models, were not specific and accurate enough, even though indirect calibrations were obtained with a RMSEP of 0.12 g L-1 (4 LVs) and 0.29 g L-1 (5 LVs), respectively. A critical discussion and details about the extensive work done in calibration development and optimization are provided. Namely, considering a risk-based selection of variability sources impacting sample spectra, executing designed experiments with spiked cultivations, and using advanced chemometric procedures for variable selection and model cross validation. A strategy is presented to evaluation Raman spectroscopy as a reliable PAT technology fit-for industrial use. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:659-670, 2018.

Brief Report: Differential Timing of Cholesterol Increase During Successful HCV Therapy: Impact of Type of Drug Combination.

OBJECTIVE: To evaluate factors associated with increased serum cholesterol levels during interferon-free hepatitis C virus (HCV) therapy. DESIGN: Prospective longitudinal study. METHODS: HIV-infected patients who started and successfully completed interferon-free therapy for chronic HCV infection were included. Patients were treated using 2 different regimens, based on the clinician's opinion: sofosbuvir and ledipasvir (SOF/LDV), or paritaprevir coadministered with ombitasvir and dasabuvir (PrOD). Both total cholesterol and low-density lipoprotein cholesterol were evaluated at baseline, weeks 1, 2, 4, 8, end of treatment (EOT), weeks SVR4, SVR12, and SVR24. RESULTS: The study population therefore comprised 85 patients reaching sustained virological response, 42 (49.4%) of whom were treated with SOF/LDV, and 43 (50.6%) with PrOD. Patients using SOF/LDV was showed a higher increase on both total cholesterol and low-density lipoprotein cholesterol during treatment period than those receiving PrOD. Analyzing the overall increase from baseline to weeks 1, 2, 4, 8, and EOT, choice of HCV regimen was associated with differential increases in total cholesterol during therapy. After EOT, no differences were found between SOF/LDV and PrOD with respect to total cholesterol. CONCLUSIONS: Our study suggests that the differential timing of the restoration of cholesterol metabolism in HIV/HCV genotype 1 coinfected patients achieving sustained virological response is not mediated by HCV clearance but depends on the drug combination used.

Application of multivariate curve resolution to chemical process control of an esterification reaction monitored by near-infrared spectroscopy.

Multivariate curve resolution-alternating least squares (MCR-ALS) methodology was applied to near-infrared spectroscopy (NIR) data for the esterification reaction between glycerol and a mixture of caprylic and capric acids. Batch reaction processes were conducted either at the laboratory scale or at an industrial plant, while NIR data were obtained from samples withdrawn during the reaction processes. The process has been monitored via two typical parameters for this type of reaction, namely, the acid value (AV) and the hydroxyl value (OHV). Spectral and concentration profiles were estimated by applying soft-modeling MCR-ALS to a column-wise augmented data matrix with pure spectra of the components, and concentration values for the acid were used as a soft-equality constraint. The estimated concentration profiles have been compared with the AV and OHV values, and the estimated spectral profiles were used to predict the concentration profiles for new batches. Good results have been obtained in terms of RMSE for the prediction of AV and OHV.

A new signal characterization and signal-based Chou's PseAAC representation of protein sequences.

Most of the algorithms used for information extraction and for processing the amino acid chains that make up proteins treat them as symbolic chains. Fewer algorithms exploit signal processing techniques that require a numerical representation of amino acid chains. However, these algorithms are very powerful for extracting regularities that cannot be detected when working with a symbolic chain, which may be important for understanding the biological meaning of a sequence or in classification tasks. In this study, a new mathematical representation of amino acid chains is proposed, which is derived using a similarity measure based on the PAM250 amino acid substitution matrix and that generates 20 signals for each protein sequence. Using this representation 20 consensus spectra for a protein family are determined and the relevance of the frequency peaks is established, obtaining a group of significant frequency peaks that manifest common periodicities of the amino acid sequences that belong to a protein family. We also show that the proposed representation in 20 signals can be integrated into Chou's pseudo amino acid composition (PseAAC) and constitute a useful alternative to amino acid physicochemical properties in Chou's PseAAC.

High hepatitis E virus seroprevalence with absence of chronic infection in HIV-infected patients.

BACKGROUND & AIMS: The seroprevalence of the hepatitis E virus (HEV) and its chronicity rate in the HIV-infected population has not been well established. As a result, the magnitude of this emerging disease in this population cannot be established. METHODS: Prospective study that included HIV-infected patients followed up between September 2012 and May 2013. All included patients were tested for anti-HEV IgG/IgM. In patients with confirmed anti-HEV IgG/IgM positivity, RT-PCR was performed. In patients where HEV RNA was amplified, a second RT-PCR assay was performed 6 months later to identify transient or chronic HEV infections. RESULTS: Eight hundred and ninety-four HIV-infected patients were enrolled in the study. Of these patients, 399 (44.6%) were monoinfected with HIV; 462 (51.6%) were co-infected with HIV/HCV; 12 (1.3%) were co-infected with HIV/HBV; and 21 (2.3%) were co-infected with HIV/HCV/HBV. In 88 patients, anti-HEV IgG/IgM was detected (seroprevalence: 9.8% [95% CI: 8.02%-11.9%]). In five patients (0.5%; 95% CI: 0.2%-1.2%), HEV RNA was detected; 5.7% (95% CI: 2.1%-12.1%) of the patients were anti-HEV IgG/IgM positive. None of these patients showed detectable HEV RNA six months later. CONCLUSION: HEV infection is frequent in HIV-infected patients but developing a chronic HEV infection may be considered an uncommon liver disease in this population.

Imidazolium Sulfonates as Environmental-Friendly Catalytic Systems for the Synthesis of Biologically Active 2-Amino-4H-chromenes: Mechanistic Insights.

Ionic Liquids (ILs) are valuable reaction media extremely useful in industrial sustainable organic synthesis. We describe here the study on the multicomponent reaction (MCR) between salicylaldehyde (2) and ethyl cyanoacetate (3), catalyzed by imidazolium sulfonates, to form chromenes 1, a class of heterocyclic scaffolds exhibiting relevant biological activity. We have clarified the reaction mechanism by combining the experimental results with computational studies. The results reported herein suggest that both the imidazolium core and the sulfonate anions in the selected ILs are involved in the reaction course acting as hydrogen bond donors and acceptors, respectively. Contrarily to the most widely accepted mechanism through initial Knoevenagel condensation, the most favorable reaction pathway consists of an aldolic reaction between reagents followed by heterocyclization, subsequent dehydration, and, finally, the Michael addition of the second molecule of ethyl cyanoacetate (3) to yield the chromenes 1.

Recomendaciones preanalíticas para la obtención y análisis de ADN circulante a partir de sangre periférica. Recomendación (2018) / Preanalytical recomendations for circulating DNA extraction and analysis from peripheral blood. Recommendation (2018)

El análisis de ADN circulante a partir de sangre periférica ha demostrado ser de utilidad en campos clínicos tan diferentes como la oncología, los trasplantes y el cribado prenatal. Para su incorporación al laboratorio clínico es necesario asegurar protocolos preanalíticos adecuados, reproducibles y estandarizados. En este documento se pretenden dar unas recomendaciones preanalíticas para la obtención de ADN circulante a partir de sangre periférica. Incluyen el tipo de espécimen, el tipo de tubo de extracción, el modo de centrifugación de la muestra, la extracción del ADN circulante y cuantificación, así como su conservación

Cell-free DNA analysis in peripheral blood has been shown to be useful in oncology, organ transplantation, and prenatal screening. For its introduction into the clinical laboratory, it is necessary to ensure appropriate, reproducible and standardised pre-analytical protocols are in place. The aim of this document is to provide pre-analytical recommendations for obtaining of cell free DNA from peripheral blood. These recommendations include the type of sample and extraction tube, the method of centrifugation, the method for cell free DNA extraction, and measurement and storage conditions

Recomendaciones para la optimización del uso de marcadores tumorales de utilización frecuente. Recomendación (2018) / Recommendations for the optimization of the use of frequently used tumor markers. Recommendation 2018

Este documento describe las causas de error más frecuentes en la medición de marcadores tumorales séricos proteicos en sus diferentes fases: preanalítica, analítica y postanalítica y recomendaciones para detectar y solventar problemas, así como la interpretación de los resultados de los marcadores tumorales en la práctica clínica

This document describes the most frequent causes of error in the measurement of 13 serum protein tumour markers in their different phases: preanalytical, analytical and 14 postanalytic and recommendations to detect and solve problems, as well as the 15 interpretation of the results of the Tumor Markers in clinical practice

In-line quantification of two active ingredients in a batch blending process by near-infrared spectroscopy: influence of physical presentation of the sample.

The aim of this study was to apply near-infrared (NIR) spectroscopy to the simultaneous in-line monitoring of two active pharmaceutical ingredients (APIs) in a pharmaceutical batch blending process. The formulation under study consisted of a high load API (A1), one polymer, a second API (A2) and one lubricant. Additionally, the effects of the presentation of A1 on the spectral data were evaluated. For this purpose, the high load active was blended either as a cohesive powder or as a free flowing material. For improving the flow behavior of the high load active a melt-granulation (MG) step was performed. The NIR spectra of the high load API (A1) before and after MG showed that the polymer wavelength absorption band was the most affected, this wavelength range was also associated with the water band region. Thus, these frequencies carried information from the melt-granulation process and could be influenced by the water content. For the APIs quantification, independent partial least squares (PLS-1) models for each API were generated. Furthermore, a PLS-2 model was also developed for the simultaneous quantification of each API. The PLS models were used for the in-line blend uniformity monitoring of both APIs.

Use of near-infrared spectroscopy to quantify drug content on a continuous blending process: influence of mass flow and rotation speed variations.

The aim of this study was to develop a quantitative Near-Infrared (NIR) method which monitors the homogeneity of a pharmaceutical formulation coming out of a continuous blender. For this purpose, a NIR diode array spectrometer with fast data acquisition was selected. Additionally, the dynamic aspects of a continuous blending process were studied; the results showed a well-defined cluster for the steady state, and the paths for the start-up and emptying stages were clearly identified. The end point of the start-up phase was detected by moving block of standard deviation, relative standard deviation, and principal component analysis. A partial least square (PLS) model was generated for the quantification of the drug, with a standard error of prediction of 0.2% m/m. The PLS model was successfully applied for monitoring the drug level at the outlet of the continuous blender. Furthermore, the PLS model was tested under different flow and stirring rates. Flow and stirring rate variations caused different powder flow dynamics, which were reflected on the NIR measurements. Therefore, the PLS model was sensitive to changes in mass flow and rotation speeds.

Natural killer KIR3DS1 is closely associated with HCV viral clearance and sustained virological response in HIV/HCV patients.

AIM: To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR) 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients. METHODS: HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6). Rapid and sustained virological response (RVR and SVR) rates were also analyzed. RESULTS: Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week 1: p = 0.01; week 2: p = 0.038; week 4: p = 0.03). Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031). With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week 1: p<0.001; week 2: p = 0.01; week 4: p = 0.02), RVR (p = 0.015) and SVR (p = 0.029) than those not carrying KIR3DS1. CONCLUSION: Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.