Screening and in silico characterization of prophages in Helicobacter pylori clinical strains.

The increase of antibiotic resistance calls for alternatives to control Helicobacter pylori, a Gram-negative bacterium associated with various gastric diseases. Bacteriophages (phages) can be highly effective in the treatment of pathogenic bacteria. Here, we developed a method to identify prophages in H.

Herbicide and Cytogenotoxic Activity of Inclusion Complexes of Leaf Essential Oil and -Caryophyllene on 2-Hydroxypropyl--cyclodextrin.

The present investigation aimed to develop inclusion complexes (ICs) from (GAU) essential oil (EO) and its major compound -caryophyllene (-CAR), and to evaluate their herbicidal (against and ) and cytogenotoxic (on ) activities. The ICs were obtained using 2-hydroxypropyl--cyclodextrin (HPCD) and they were prepared to avoid or reduce the volatility and degradation of GAU EO and -CAR. The ICs obtained showed a complexation efficiency of 91.

Tuberculosis among People Living on the Street and Using Alcohol, Tobacco, and Illegal Drugs: Analysis of Territories in Extreme Vulnerability and Trends in Southern Brazil.

(1) Background: Tuberculosis presents an epidemiological trend toward inequality, especially among people in social exclusion and situations of vulnerability. This study aimed to analyze territories with a concentration of people diagnosed with tuberculosis in a street situation and who partake in chronic use of alcohol, tobacco, and illicit drugs. We also analyzed trends in this health condition in southern Brazil.

The Peripheral Immune Landscape of Breast Cancer: Clinical Findings and In Vitro Models for Biomarker Discovery.

Breast cancer is the deadliest female malignancy worldwide and, while much is known about phenotype and function of infiltrating immune cells, the same attention has not been paid to the peripheral immune compartment of breast cancer patients. To obtain faster, cheaper, and more precise monitoring of patients' status, it is crucial to define and analyze circulating immune profiles. This review compiles and summarizes the disperse knowledge on the peripheral immune profile of breast cancer patients, how it departs from healthy individuals and how it changes with disease progression.

Iterative Analog-Digital Multi-User Equalizer for Wideband Millimeter Wave Massive MIMO Systems.

Most of the previous work on hybrid transmit and receive beamforming focused on narrowband channels. Because the millimeter wave channels are expected to be wideband, it is crucial to propose efficient solutions for frequency-selective channels. In this regard, this paper proposes an iterative analog-digital multi-user equalizer scheme for the uplink of wideband millimeter-wave massive multiple-input-multiple-output (MIMO) systems.

A bootstrap-aggregated hybrid semi-parametric modeling framework for bioprocess development.

Hybrid semi-parametric modeling, combining mechanistic and machine-learning methods, has proven to be a powerful method for process development. This paper proposes bootstrap aggregation to increase the predictive power of hybrid semi-parametric models when the process data are obtained by statistical design of experiments. A fed-batch Escherichia coli optimization problem is addressed, in which three factors (biomass growth setpoint, temperature, and biomass concentration at induction) were designed statistically to identify optimal cell growth and recombinant protein expression conditions.

Combined Organic Photovoltaic Cells and Ultra Low Power CMOS Circuit for Indoor Light Energy Harvesting.

This paper describes an energy harvesting system composed of an organic photovoltaic cell (OPV) connected to a DC-DC converter, designed in a 130 nm Complementary Metal-Oxide-Semiconductor (CMOS) technology, with a quasi- maximum power point tracking (MPPT) algorithm to maximize the system efficiency, for indoor applications. OPVs are an emerging technology with potential for low cost indoor light energy harvesting. The OPV current-voltage curves (I-V) under an irradiance of solar simulator Oriel Sol 3A, at room temperature, are obtained and an accurate electrical model is derived.

Relapse or reinfection after failing hepatitis C direct acting antiviral treatment: Unravelled by phylogenetic analysis.

Despite high response rates associated to hepatitis C virus (HCV) treatment, no protective immunity is acquired, allowing for reinfection and continued infectiousness. Distinguishing between relapse and reinfection is crucial for patient counselling and to choose the most appropriate retreatment. Here, refined phylogenetic analysis using multiple genes served to assess genotype and reinfection for 53 patients for whom the virus was sampled before start of therapy and at time of sustained virological response evaluation at week 12.

Transmission Networks of HCV Genotype 1a Enriched With Pre-existing Polymorphism Q80K Among HIV-Infected Patients With Acute Hepatitis C in Poland.

Background: Hepatitis C virus (HCV) resistance-associated variants (RAVs) have been shown to adversely affect treatment response of direct-acting antivirals. Identifying pre-existing RAVs and transmission networks among HIV/HCV genotype 1 (G1)-infected patients from Poland will assist in shaping surveillance strategies for HCV.

Methods: NS3 and NS5A sequences were obtained from samples of 112 direct-acting antiviral-naive G1 patients (45 G1a and 67 G1b), of which 74 were chronically infected and 38 were diagnosed with acute hepatitis C (AHC).

The impact of HIV-1 within-host evolution on transmission dynamics.

The adaptive potential of HIV-1 is a vital mechanism to evade host immune responses and antiviral treatment. However, high evolutionary rates during persistent infection can impair transmission efficiency and alter disease progression in the new host, resulting in a delicate trade-off between within-host virulence and between-host infectiousness. This trade-off is visible in the disparity in evolutionary rates at within-host and between-host levels, and preferential transmission of ancestral donor viruses.

Exploring resistance pathways for first-generation NS3/4A protease inhibitors boceprevir and telaprevir using Bayesian network learning.

Resistance-associated variants (RAVs) have been shown to influence treatment response to direct-acting antivirals (DAAs) and first generation NS3/4A protease inhibitors (PIs) in particular. Interpretation of hepatitis C virus (HCV) genotypic drug resistance remains a challenge, especially in patients who previously failed DAA therapy and need to be retreated with a second DAA based regimen. Bayesian network (BN) learning on HCV sequence data from patients treated with DAAs could provide insight in resistance pathways against PIs for HCV subtypes 1a and 1b, in a similar way as applied before for HIV.

Phylogenetic evidence for underreporting of male-to-male sex among human immunodeficiency virus-infected donors in the Netherlands and Flanders.

Background: Separate transmission networks for human immunodeficiency virus (HIV) coexist. Molecular typing of viral genomes can provide insight in HIV transmission routes in donors for whom risk behavior-based donor selection failed.

Study Design And Methods: This study includes all HIV-infected Dutch and Flemish donors in the period 2005 to 2014 (n = 55).

Implications of hepatitis C virus subtype 1a migration patterns for virus genetic sequencing policies in Italy.

Background: In-depth phylogeographic analysis can reveal migration patterns relevant for public health planning. Here, as a model, we focused on the provenance, in the current Italian HCV subtype 1a epidemic, of the NS3 resistance-associated variant (RAV) Q80K, known to interfere with the action of NS3/4A protease inhibitor simeprevir. HCV1a migration patterns were analysed using Bayesian phylodynamic tools, capitalising on newly generated and publicly available time and geo-referenced NS3 encoding virus genetic sequence data.

Mapping the genomic diversity of HCV subtypes 1a and 1b: Implications of structural and immunological constraints for vaccine and drug development.

Despite significant progress in hepatitis C (HCV) treatment, global viral eradication remains a challenge. An in-depth map of its genome diversity within the context of structural and immunological constraints could contribute to the design of pan-genotypic antivirals and preventive vaccines. For such analyses, extensive information is only available for the highly prevalent HCV genotypes (GT) 1a and 1b.

Toward intensifying design of experiments in upstream bioprocess development: An industrial Escherichia coli feasibility study.

In this study, step variations in temperature, pH, and carbon substrate feeding rate were performed within five high cell density Escherichia coli fermentations to assess whether intraexperiment step changes, can principally be used to exploit the process operation space in a design of experiment manner. A dynamic process modeling approach was adopted to determine parameter interactions. A bioreactor model was integrated with an artificial neural network that describes biomass and product formation rates as function of varied fed-batch fermentation conditions for heterologous protein production.

Detection of Natural Resistance-Associated Substitutions by Ion Semiconductor Technology in HCV1b Positive, Direct-Acting Antiviral Agents-Naïve Patients.

Naturally occurring resistance-associated substitutions (RASs) can negatively impact the response to direct-acting antivirals (DAAs) agents-based therapies for hepatitis C virus (HCV) infection. Herein, we set out to characterize the RASs in the HCV1b genome from serum samples of DAA-naïve patients in the context of the SINERGIE (South Italian Network for Rational Guidelines and International Epidemiology, 2014) project. We deep-sequenced the NS3/4A protease region of the viral population using the Ion Torrent Personal Genome Machine, and patient-specific majority rule consensus sequence summaries were constructed with a combination of freely available next generation sequencing data analysis software.

Impact of HCV genotype on treatment regimens and drug resistance: a snapshot in time.

The introduction of highly potent direct-acting antivirals (DAAs) has revolutionized hepatitis C virus treatment. Nevertheless, viral eradication worldwide remains a challenge also in the era of DAA treatment, because of the high associated costs, high numbers of undiagnosed patients, high re-infection rates in some risk groups and suboptimal drug efficacies associated with host and viral factors as well as advanced stages of liver disease. A correct determination of the HCV genotype allows administration of the most appropriate antiviral regimen.

Proteomics for Drug Resistance on the Food Chain? Multidrug-Resistant Escherichia coli Proteomes from Slaughtered Pigs.

Understanding global drug resistance demands an integrated vision, focusing on both human and veterinary medicine. Omics technologies offer new vistas to decipher mechanisms of drug resistance in the food chain. For example, Escherichia coli resistance to major antibiotics is increasing whereas multidrug resistance (MDR) strains are now commonly found in humans and animals.

A principal components method constrained by elementary flux modes: analysis of flux data sets.

Background: Non-negative linear combinations of elementary flux modes (EMs) describe all feasible reaction flux distributions for a given metabolic network under the quasi steady state assumption. However, only a small subset of EMs contribute to the physiological state of a given cell.

Results: In this paper, a method is proposed that identifies the subset of EMs that best explain the physiological state captured in reaction flux data, referred to as principal EMs (PEMs), given a pre-specified universe of EM candidates.

Hybrid modeling as a QbD/PAT tool in process development: an industrial E. coli case study.

Process understanding is emphasized in the process analytical technology initiative and the quality by design paradigm to be essential for manufacturing of biopharmaceutical products with consistent high quality. A typical approach to developing a process understanding is applying a combination of design of experiments with statistical data analysis. Hybrid semi-parametric modeling is investigated as an alternative method to pure statistical data analysis.

Iron overload in a murine model of hereditary hemochromatosis is associated with accelerated progression of osteoarthritis under mechanical stress.

Objective: Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress.

Design: OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice.

Effect of vancomycin on the proteome of the multiresistant Enterococcus faecium SU18 strain.

Unlabelled: Enterococci are not highly pathogenic bacteria, but the incidence of vancomycin resistance among clinical isolates of this microbial group is steadily increasing, posing a threat to public health. Vancomycin-resistant enterococci are currently some of the most recalcitrant hospital-associated pathogens against which new therapies are urgently needed. To understand the molecular mechanisms of bacterial resistance to glycopeptides, we obtained proteomic profiles of the vancomycin-resistant Enterococcus faecium SU18 strain treated with and without vancomycin.

Lyme borreliosis in Portugal caused by Borrelia lusitaniae? Clinical report on the first patient with a positive skin isolate.

Background: Borrelia lusitaniae was isolated from an Ixodes ricinus tick in Portugal in 1993 for the first time. Further, this borrelia genospecies has been found in ixodid ticks collected around the coasts of southern Portugal and North Africa. Its reservoir has not been defined yet.