Outcomes of 23 patients diagnosed with New Delhi metallo-beta-lactamase (NDM)-producing Klebsiella pneumoniae infection treated with ceftazidime/avibactam and aztreonam at a single center in Poland.

Purpose: Amongst all etiologic hospital-acquired infection factors, K. pneumoniae strains producing New Delhi metallo-β-lactamase (KP-NDM) belong to pathogens with the most effective antibiotic resistance mechanisms. Clinical guidelines recommend using ceftazidime/avibactam with aztreonam (CZA + AT) as the preferred option for NDM-producing Enterobacterales.

Seasonal prevalence of bacteria in the outflow of two full-scale municipal wastewater treatment plants.

Despite many modern wastewater treatment solutions, the most common is still the use of activated sludge (AS). Studies indicate that the microbial composition of AS is most often influenced by the raw sewage composition (especially influent ammonia), biological oxygen demand, the level of dissolved oxygen, technological solutions, as well as the temperature of wastewater related to seasonality. The available literature mainly refers to the relationship between AS parameters or the technology used and the composition of microorganisms in AS.

SHAFE Mapping on Social Innovation Ecosystems.

There have been several initiatives aiming to promote innovation and support stakeholders to increase investments in relevant societal areas connected to Smart Healthy Age-Friendly Environments-SHAFE. However, their impact usually runs shorter than desirable in the mid- and long-term due to the difficulty to identify, map, and connect stakeholders in the different European and world countries that are willing to work for the practical implementation of social innovation around SHAFE. This mapping and connection can contribute to increase awareness of innovation actors on social innovation concepts and, if well disseminated, may also leverage the creation of alliances and synergies between different stakeholders within ecosystems and between ecosystems.

Limitations and potential of analyses of cremation remains - Anthropological analysis of bone remains from a Lusatian culture cremation cemetery in Paszowice (Lower Silesia, Poland).

The main aim of the study was to identify which components of the skeleton are best identifiable after cremation, because only few publications pay attention to the best-preserved bone structures in cremation burials. However, such knowledge offers potential for further analysis and methodology development. One of the most frequently and best-identifiable parts of the skeleton were fragments of vertebrae and long bones epiphyses.

Promoting the health and wellbeing of children: A feasibility study of a digital tool among professionals.

The foundations of children's health and wellbeing are laid in early childhood. A gamified app (EmpowerKids tool) was designed to support professionals to have discussions with 6- to 12-year-olds from low-income families about their health and wellbeing. The aim of this feasibility study was to evaluate the usability and acceptability of the tool from the perspective of professionals in social, health and education settings.

AnthOligo: automating the design of oligonucleotides for capture/enrichment technologies.

Summary: A number of methods have been devised to address the need for targeted genomic resequencing. One of these methods, region-specific extraction (RSE) is characterized by the capture of long DNA fragments (15-20 kb) by magnetic beads, after enzymatic extension of oligonucleotides hybridized to selected genomic regions. Facilitating the selection of the most appropriate capture oligos for targeting a region of interest, satisfying the properties of temperature (Tm) and entropy (ΔG), while minimizing the formation of primer-dimers in a pooled experiment, is therefore necessary.

Preventable premature deaths (PYLL) in Northern Dimension partnership countries 2003-13.

Background: Objective was to measure preventable premature loss of life in countries from same geographical area but with considerable differences in social and economic development. By comparing inter-country differences and similarities in premature mortality, acceleration of health-in-all-policies is enhanced.

Methods: Preventable premature deaths were described by Potential Years of Life Lost (PYLL).

Fbxo4-mediated degradation of Fxr1 suppresses tumorigenesis in head and neck squamous cell carcinoma.

The Fbxo4 tumour suppressor is a component of an Skp1-Cul1-F-box E3 ligase for which two substrates are known. Here we show purification of SCF complexes results in the identification of fragile X protein family (FMRP, Fxr1 and Fxr2) as binding partners. Biochemical and functional analyses reveal that Fxr1 is a direct substrate of SCF.

Assessing a single targeted next generation sequencing for human leukocyte antigen typing protocol for interoperability, as performed by users with variable experience.

Background: A simplified protocol for HLA-typing -by NGS, developed for use with the Illumina MiSeq, was performed by technologists with varying NGS experience to assess accuracy and reproducibility.

Methods: Technologists from six laboratories typed the same 16 samples at HLA-A, B, C, DRB1, and DQB1. The protocol includes long range PCR, library preparation, and paired-end 250bp sequencing.

PERK Is a Haploinsufficient Tumor Suppressor: Gene Dose Determines Tumor-Suppressive Versus Tumor Promoting Properties of PERK in Melanoma.

The unfolded protein response (UPR) regulates cell fate following exposure of cells to endoplasmic reticulum stresses. PERK, a UPR protein kinase, regulates protein synthesis and while linked with cell survival, exhibits activities associated with both tumor progression and tumor suppression. For example, while cells lacking PERK are sensitive to UPR-dependent cell death, acute activation of PERK triggers both apoptosis and cell cycle arrest, which would be expected to contribute tumor suppressive activity.

The next generation of target capture technologies - large DNA fragment enrichment and sequencing determines regional genomic variation of high complexity.

Background: The ability to capture and sequence large contiguous DNA fragments represents a significant advancement towards the comprehensive characterization of complex genomic regions. While emerging sequencing platforms are capable of producing several kilobases-long reads, the fragment sizes generated by current DNA target enrichment technologies remain a limiting factor, producing DNA fragments generally shorter than 1 kbp. The DNA enrichment methodology described herein, Region-Specific Extraction (RSE), produces DNA segments in excess of 20 kbp in length.

Determining performance characteristics of an NGS-based HLA typing method for clinical applications.

This study presents performance specifications of an in-house developed human leukocyte antigen (HLA) typing assay using next-generation sequencing (NGS) on the Illumina MiSeq platform. A total of 253 samples, previously characterized for HLA-A, -B, -C, -DRB1 and -DQB1 were included in this study, which were typed at high-resolution using a combination of Sanger sequencing, sequence-specific primer (SSP) and sequence-specific oligonucleotide probe (SSOP) technologies and recorded at the two-field level. Samples were selected with alleles that cover a high percentage of HLA specificities in each of five different race/ethnic groups: European, African-American, Asian Pacific Islander, Hispanic and Native American.

Towards allele-level human leucocyte antigens genotyping - assessing two next-generation sequencing platforms: Ion Torrent Personal Genome Machine and Illumina MiSeq.

Human leucocyte antigens (HLA) typing has been a challenge due to extreme polymorphism of the HLA genes and limitations of the current technologies and protocols used for their characterization. Recently, next-generation sequencing techniques have been shown to be a well-suited technology for the complete characterization of the HLA genes. However, a comprehensive assessment of the different platforms for HLA typing, describing the limitations and advantages of each of them, has not been presented.

Evaluation of risk factor reduction in a European City Network.

There is a substantial and growing burden of premature mortality caused by non-communicable diseases (NCDs) globally. This paper evaluates the preventive efforts of the WHO European Healthy Cities Network during its fifth phase (2009-13), specifically for four behavioural risk factors (tobacco use, alcohol abuse, unhealthy diet and physical inactivity). Drawing on case studies, questionnaire responses and other materials, it notes which cities were involved, what worked and did not, the triggers for action, challenges met and lessons learnt.

Healthy Cities Phase V evaluation: further synthesizing realism.

In this article we reflect on the quality of a realist synthesis paradigm applied to the evaluation of Phase V of the WHO European Healthy Cities Network. The programmatic application of this approach has led to very high response rates and a wealth of important data. All articles in this Supplement report that cities in the network move from small-scale, time-limited projects predominantly focused on health lifestyles to the significant inclusion of policies and programmes on systems and values for good health governance.

Effectivity of antiseptics against some pathogens.

Introduction: The efficacy of antiseptics against bacteria and fungi is different. The choice of optimal antiseptic solution is very important in prophylaxis of hospital infections.

Material And Methods: In this study the efficacy of different antiseptics against some pathogens (Klebsiella pneumoniae ESBL (+), Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus MRSA, Candida dublinensis) was analyzed.

High-risk osteoporosis clinic (HiROC): improving osteoporosis and postfracture care with an organized, programmatic approach.

Summary: A programmatic outpatient high-risk osteoporosis clinic (outpatient HiROC) and inpatient fracture liaison service (inpatient HiROC) is described. Results document that this population is more effectively treated and followed up in this specialty pathway than with primary care follow-up.

Introduction: We describe a programmatic approach to outpatient care of high-risk osteoporosis patients (outpatient HiROC).

Etiological factors causing lower respiratory tract infections isolated from hospitalized patients.

Lower respiratory tract infections (LRTI) account for 20-30 % of all hospital-acquired contagions. They are characterized by high mortality of hospitalized patients. The most serious form of LRTI is pneumonia, and the most common etiological factors in such cases are bacteria.

Dominant form of congenital hyperinsulinism maps to HK1 region on 10q.

Background/aims: In a family with congenital hyperinsulinism (HI), first described in the 1950s by McQuarrie, we examined the genetic locus and clinical phenotype of a novel form of dominant HI.

Methods: We surveyed 25 affected individuals, 7 of whom participated in tests of insulin dysregulation (24-hour fasting, oral glucose and protein tolerance tests). To identify the disease locus and potential disease-associated mutations we performed linkage analysis, whole transcriptome sequencing, whole genome sequencing, gene capture, and next generation sequencing.

16(th) IHIW : review of HLA typing by NGS.

Human leucocyte antigen (HLA) genes play an important role in the success of organ transplantation and are associated with autoimmune and infectious diseases. Current DNA-based genotyping methods, including Sanger sequence-based typing (SSBT), have identified a high degree of polymorphism. This level of polymorphism makes high-resolution HLA genotyping challenging, resulting in ambiguous typing results due to an inability to resolve phase and/or defining polymorphisms lying outside the region amplified.

Filling the gaps - the generation of full genomic sequences for 15 common and well-documented HLA class I alleles using next-generation sequencing technology.

Many common and well-documented (CWD) HLA alleles have only been partially characterized. The DNA sequence of these incomplete alleles, as published in the IMGT/HLA database, is most often limited to exons that code for the extracellular domains of the mature protein. Here we describe the application of next-generation sequencing technology to obtain full length genomic sequence from a single long-range PCR amplicon for 15 common and well-documented HLA Class I alleles.

Microtubule actin crosslinking factor 1 regulates the Balbiani body and animal-vegetal polarity of the zebrafish oocyte.

Although of fundamental importance in developmental biology, the genetic basis for the symmetry breaking events that polarize the vertebrate oocyte and egg are largely unknown. In vertebrates, the first morphological asymmetry in the oocyte is the Balbiani body, a highly conserved, transient structure found in vertebrates and invertebrates including Drosophila, Xenopus, human, and mouse. We report the identification of the zebrafish magellan (mgn) mutant, which exhibits a novel enlarged Balbiani body phenotype and a disruption of oocyte polarity.

Next-generation sequencing: the solution for high-resolution, unambiguous human leukocyte antigen typing.

Human leukocyte antigen (HLA) typing has been a challenge for more than 50 years. Current methods (Sanger sequencing, sequence-specific primers [SSP], sequence-specific oligonucleotide probes [SSOP]) continue to generate ambiguities that are time-consuming and expensive to resolve. However, next-generation sequencing (NGS) overcomes ambiguity through the combination of clonal amplification, which provides on-phase sequence and a high level of parallelism, whereby millions of sequencing reads are produced enabling an expansion of the HLA regions sequenced.

Role of intracellular polysaccharide in persistence of Streptococcus mutans.

Intracellular polysaccharide (IPS) is accumulated by Streptococcus mutans when the bacteria are grown in excess sugar and can contribute toward the cariogenicity of S. mutans. Here we show that inactivation of the glgA gene (SMU1536), encoding a putative glycogen synthase, prevented accumulation of IPS.

Uncertainty during anticipation modulates neural responses to aversion in human insula and amygdala.

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which uncertain cues are followed by negative outcomes, an example of covariation bias. Using functional magnetic resonance imaging, we found that uncertainty-related expectations modulated neural responses to aversion.