Ariel University

Klebsiella pneumoniae is an important multidrug-resistant (MDR) pathogen affecting humans and a major source for hospital infections associated with high morbidity and mortality due to limited treatment options. We summarize the wide resistome of this pathogen, which encompasses plentiful chromosomal and plasmid-encoded antibiotic resistance genes (ARGs). Under antibiotic selective pressure, K. pneumoniae continuously accumulates ARGs, by de novo mutations, and via acquisition of plasmids and transferable genetic elements, leading to extremely drug resistant (XDR) strains harboring a 'super resistome'. In the last two decades, numerous high-risk (HiR) MDR and XDR K. pneumoniae sequence types have emerged showing superior ability to cause multicontinent outbreaks, and continuous global dissemination. The data highlight the complex evolution of MDR and XDR K. pneumoniae, involving transfer and spread of ARGs, and epidemic plasmids in highly disseminating successful clones. With the worldwide catastrophe of antibiotic resistance and the urgent need to identify the main pathogens that pose a threat on the future of infectious diseases, further studies are warranted to determine the epidemic traits and plasmid acquisition in K. pneumoniae. There is a need for future genomic and translational studies to decipher specific targets in HiR clones to design targeted prevention and treatment.

We provide limits to practical quantum key distribution, taking into account channel losses, a realistic detection process, and imperfections in the "qubits" sent from the sender to the receiver. As we show, even quantum key distribution with perfect qubits might not be achievable over long distances when the other imperfections are taken into account. Furthermore, existing experimental schemes (based on weak pulses) currently do not offer unconditional security for the reported distances and signal strength. Finally we show that parametric down-conversion offers enhanced performance compared to its weak coherent pulse counterpart.

Two types of endogenous cannabinoid-receptor agonists have been identified thus far. They are the ethanolamides of polyunsaturated fatty acids--arachidonoyl ethanolamide (anandamide) is the best known compound in the amide series--and 2-arachidonoyl glycerol, the only known endocannabinoid in the ester series. We report now an example of a third, ether-type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether), isolated from porcine brain. The structure of noladin ether was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by comparison with a synthetic sample. It binds to the CB(1) cannabinoid receptor (K(i) = 21.2 +/- 0.5 nM) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. It binds weakly to the CB(2) receptor (K(i) > 3 microM).

Individuals with spinal cord injury (SCI) usually suffer from permanent neurological deficits, while spontaneous recovery and therapeutic efficacy are limited. Here, we demonstrate that when given intranasally, exosomes derived from mesenchymal stem cells (MSC-Exo) could pass the blood brain barrier and migrate to the injured spinal cord area. Furthermore, MSC-Exo loaded with phosphatase and tensin homolog small interfering RNA (ExoPTEN) could attenuate the expression of PTEN in the injured spinal cord region following intranasal administrations. In addition, the loaded MSC-Exo considerably enhanced axonal growth and neovascularization, while reducing microgliosis and astrogliosis. The intranasal ExoPTEN therapy could also partly improve structural and electrophysiological function and, most importantly, significantly elicited functional recovery in rats with complete SCI. The results imply that intranasal ExoPTEN may be used clinically to promote recovery for SCI individuals.

BACKGROUND: In protein engineering, site-directed mutagenesis methods are used to generate DNA sequences with mutated codons, insertions or deletions. In a widely used method, mutations are generated by PCR using a pair of oligonucleotide primers designed with mismatching nucleotides at the center of the primers. In this method, primer-primer annealing may prevent cloning of mutant cDNAs. To circumvent this problem we developed an alternative procedure that does not use forward-reverse primer pair in the same reaction. RESULTS: In initial studies we used a double-primer PCR mutagenesis protocol, but sequencing of products showed tandem repeats of primer in cloned DNA. We developed an alternative method that starts with two Single-Primer Reactions IN Parallel using high-fidelity Pwo DNA polymerase. Thus, we call the method with the acronym SPRINP. The SPRINP reactions are then combined, denatured at 95 degrees C, and slowly cooled, promoting random annealing of the parental DNA and the newly synthesized strands. The products are digested with DpnI that digests methylated parental strands, and then transformed into E. coli. Using this method we generated >40 mutants in cDNAs coding for human Epithelial Na+ Channel (ENaC) subunits. The method has been tested for 1-3 bp codon mutation and insertion of a 27 bp epitope tag into cDNAs. CONCLUSION: The SPRINP mutagenesis protocol yields mutants reliably and with high fidelity. The use of a single primer in each amplification reaction increases the probability of success of primers relative to previous methods employing a forward and reverse primer pair in the same reaction.

The authors performed a meta-analysis based on 169 conditions, gathered from 80 laboratory studies, to estimate the validity of the Guilty Knowledge Test (GKT) with the electrodermal measure. The overall average effect size was 1.55, but there were considerable variations among studies. In particular, mock-crime studies produced the highest average effect size (2.09). Three additional moderators were identified: Motivational instructions, deceptive ("no") verbal responses, and the use of at least 5 questions were associated with enhanced validity. Finally, a set of 10 studies that best approximated applications of the GKT under optimal conditions produced an average effect size of 3.12. The authors discuss factors that might limit the generalizability of these results and recommend further research of the GKT in realistic setups.

Cyber-attacks represent a potential threat to information security. As rates of data usage and internet consumption continue to increase, cyber awareness turned to be increasingly urgent. This study focuses on the relationships between cyber security awareness, knowledge and behavior with protection tools among individuals in general and across four countries: Israel, Slovenia, Poland and Turkey in particular. Results show that internet users possess adequate cyber threat awareness but apply only minimal protective measures usually relatively common and simple ones. The study findings also show that higher cyber knowledge is connected to the level of cyber awareness, beyond the differences in respondent country or gender. In addition, awareness is also connected to protection tools, but not to information they were willing to disclose. Lastly, findings exhibit differences between the explored countries that affect the interaction between awareness, knowledge, and behaviors. Results, implications, and recommendations for effective based cyber security training programs are presented and discussed.

Erdheim-Chester disease (ECD) is a rare histiocytosis that was recently recognized as a neoplastic disorder owing to the discovery of recurrent activating MAPK (RAS-RAF-MEK-ERK) pathway mutations. Typical findings of ECD include central diabetes insipidus, restrictive pericarditis, perinephric fibrosis, and sclerotic bone lesions. The histopathologic diagnosis of ECD is often challenging due to nonspecific inflammatory and fibrotic findings on histopathologic review of tissue specimens. Additionally, the association of ECD with unusual tissue tropism and an insidious onset often results in diagnostic errors and delays. Most patients with ECD require treatment, except for a minority of patients with minimally symptomatic single-organ disease. The first ECD consensus guidelines were published in 2014 on behalf of the physicians and researchers within the Erdheim-Chester Disease Global Alliance. With the recent molecular discoveries and the approval of the first targeted therapy (vemurafenib) for BRAF-V600-mutant ECD, there is a need for updated clinical practice guidelines to optimize the diagnosis and treatment of this disease. This document presents consensus recommendations that resulted from the International Medical Symposia on ECD in 2017 and 2019. Herein, we include the guidelines for the clinical, laboratory, histologic, and radiographic evaluation of ECD patients along with treatment recommendations based on our clinical experience and review of literature in the molecular era.

Background and Aims: This present paper will review the existing evidence on the effects of excessive smartphone use on physical and mental health. Results: Comorbidity with depression, anxiety, OCD, ADHD and alcohol use disorder. Excessive smartphone use is associated with difficulties in cognitive-emotion regulation, impulsivity, impaired cognitive function, addiction to social networking, shyness and low self-esteem. Medical problems include sleep problems, reduced physical fitness, unhealthy eating habits, pain and migraines, reduced cognitive control and changes in the brain's gray matter volume. In Conclusion: Excessive smartphone use is associated with psychiatric, cognitive, emotional, medical and brain changes that should be considered by health and education professionals.

Manipulations to slow biological aging and extend healthspan are of interest given the societal and healthcare costs of our aging population. Herein we report on a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients. The control group received no intervention. Genome-wide DNA methylation analysis was conducted on saliva samples using the Illumina Methylation Epic Array and DNAmAge was calculated using the online Horvath DNAmAge clock (2013). The diet and lifestyle treatment was associated with a 3.23 years decrease in DNAmAge compared with controls (p=0.018). DNAmAge of those in the treatment group decreased by an average 1.96 years by the end of the program compared to the same individuals at the beginning with a strong trend towards significance (p=0.066). Changes in blood biomarkers were significant for mean serum 5-methyltetrahydrofolate (+15%, p=0.004) and mean triglycerides (-25%, p=0.009). To our knowledge, this is the first randomized controlled study to suggest that specific diet and lifestyle interventions may reverse Horvath DNAmAge (2013) epigenetic aging in healthy adult males. Larger-scale and longer duration clinical trials are needed to confirm these findings, as well as investigation in other human populations.

We report the possibility to modify the wetting properties of the surfaces of a diversity of seeds including: lentils (Lens culinaris), beans (Phaseolus vulgaris) and wheat (Triticum, species C9) by cold radiofrequency air plasma treatment. Air plasma treatment leads to the dramatic decrease in the apparent contact angle. Moreover, the speed of germination and yield (germination rate) of seeds can be modified by preliminary plasma treatment. The change in the wetting properties of seeds is at least partially due to oxidation of their surface under plasma treatment. Significant growth of the peaks corresponding to the nitrogen containing groups in the mass spectra of air plasma treated seeds was registered by TOF-SIMS spectroscopy.

BACKGROUND: The 11th revision to the WHO International Classification of Diseases (ICD-11) identified complex post-traumatic stress disorder (CPTSD) as a new condition. There is a pressing need to identify effective CPTSD interventions. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological interventions for post-traumatic stress disorder (PTSD), where participants were likely to have clinically significant baseline levels of one or more CPTSD symptom clusters (affect dysregulation, negative self-concept and/or disturbed relationships). We searched MEDLINE, PsycINFO, EMBASE and PILOTS databases (January 2018), and examined study and outcome quality. RESULTS: Fifty-one RCTs met inclusion criteria. Cognitive behavioural therapy (CBT), exposure alone (EA) and eye movement desensitisation and reprocessing (EMDR) were superior to usual care for PTSD symptoms, with effects ranging from g = -0.90 (CBT; k = 27, 95% CI -1.11 to -0.68; moderate quality) to g = -1.26 (EMDR; k = 4, 95% CI -2.01 to -0.51; low quality). CBT and EA each had moderate-large or large effects on negative self-concept, but only one trial of EMDR provided useable data. CBT, EA and EMDR each had moderate or moderate-large effects on disturbed relationships. Few RCTs reported affect dysregulation data. The benefits of all interventions were smaller when compared with non-specific interventions (e.g. befriending). Multivariate meta-regression suggested childhood-onset trauma was associated with a poorer outcome. CONCLUSIONS: The development of effective interventions for CPTSD can build upon the success of PTSD interventions. Further research should assess the benefits of flexibility in intervention selection, sequencing and delivery, based on clinical need and patient preferences.

In spite of the huge progress in the treatment of diabetes mellitus, we are still in the situation that both pregestational (PGDM) and gestational diabetes (GDM) impose an additional risk to the embryo, fetus, and course of pregnancy. PGDM may increase the rate of congenital malformations, especially cardiac, nervous system, musculoskeletal system, and limbs. PGDM may interfere with fetal growth, often causing macrosomia, but in the presence of severe maternal complications, especially nephropathy, it may inhibit fetal growth. PGDM may also induce a variety of perinatal complications such as stillbirth and perinatal death, cardiomyopathy, respiratory morbidity, and perinatal asphyxia. GDM that generally develops in the second half of pregnancy induces similar but generally less severe complications. Their severity is higher with earlier onset of GDM and inversely correlated with the degree of glycemic control. Early initiation of GDM might even cause some increase in the rate of congenital malformations. Both PGDM and GDM may cause various motor and behavioral neurodevelopmental problems, including an increased incidence of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Most complications are reduced in incidence and severity with the improvement in diabetic control. Mechanisms of diabetic-induced damage in pregnancy are related to maternal and fetal hyperglycemia, enhanced oxidative stress, epigenetic changes, and other, less defined, pathogenic mechanisms.

The aim of this study was to evaluate the association of COVID-19 factors and psychological factors with psychological distress among dental staff during the COVID-19 pandemic outbreak. A cross-sectional survey was conducted among 338 Israeli dentists and dental hygienists, who provided their demographic data; answered questions about COVID-19-related factors; and were assessed by subjective overload, self-efficacy, and psychological distress scales. Data were analyzed using a multivariate logistic regression. Results revealed that elevated psychological distress was found among those who have background illness, fear of contracting COVID-19 from patient, and a higher subjective overload. Lower psychological distress was associated with being in a committed relationship and having higher scores for self-efficacy. Given these results, gathered during times of an infectious disease outbreak, exploring psychological distress among dental staff is warranted as the effects may be long-term.

Abstract The Laser Interferometer Space Antenna (LISA) has two scientific objectives of cosmological focus: to probe the expansion rate of the universe, and to understand stochastic gravitational-wave backgrounds and their implications for early universe and particle physics, from the MeV to the Planck scale. However, the range of potential cosmological applications of gravitational-wave observations extends well beyond these two objectives. This publication presents a summary of the state of the art in LISA cosmology, theory and methods, and identifies new opportunities to use gravitational-wave observations by LISA to probe the universe.

BACKGROUND: In recent years, obesity-related diseases have been on the rise globally resulting in major challenges for health systems and society as a whole. Emerging research in population health suggests that interventions targeting the built environment may help reduce the burden of obesity and type 2 diabetes. However, translation of the evidence on the built environment into effective policy and planning changes requires engagement and collaboration between multiple sectors and government agencies for designing neighborhoods that are more conducive to healthy and active living. In this study, we identified knowledge gaps and other barriers to evidence-based decision-making and policy development related to the built environment; as well as the infrastructure, processes, and mechanisms needed to drive policy changes in this area. METHODS: We conducted a qualitative thematic analysis of data collected through consultations with a broad group of stakeholders (N = 42) from Southern Ontario, Canada, within various sectors (public health, urban planning, and transportation) and levels of government (federal, provincial, and municipalities). Relevant themes were classified based on the specific phase of the knowledge-to-action cycle (research, translation, and implementation) in which they were most closely aligned. RESULTS: We identified 5 themes including: 1) the need for policy-informed and actionable research (e.g. health economic analyses and policy evaluations); 2) impactful messaging that targets all relevant sectors to create the political will necessary to drive policy change; 3) common measures and tools to increase capacity for monitoring and surveillance of built environment changes; (4) intersectoral collaboration and alignment within and between levels of government to enable collective actions and provide mechanisms for sharing of resources and expertise, (5) aligning public and private sector priorities to generate public demand and support for community action; and, (6) solution-focused implementation of research that will be tailored to meet the needs of policymakers and planners. Additional research priorities and key policy and planning actions were also noted. CONCLUSION: Our research highlights the necessity of involving stakeholders in identifying inter-sectoral solutions to develop and translate actionable research on the built environment into effective policy and planning initiatives.

Abstract The endorsement and deployment of character strengths in occupational contexts are two promising components for understanding how people create well-being. In this study, a model integrating character strengths, satisfaction with occupational activities, and meaning and well-being was proposed and tested in two samples of volunteers and a sample of working adults. The model fit the data well in all three samples. Results demonstrated that deploying strengths at work provided key links to satisfaction with voluntary and paid occupational activities and to meaning among both young and middle-aged volunteers, and adult working women. Among adult volunteers and paid workers, endorsing strengths was related to meaning, while both endorsing and deploying strengths were related to well-being. Together, these studies provide a model for understanding how strengths may play a role in how both volunteer and paid workers find meaning, well-being, and satisfaction. Keywords: character strengthsjob satisfactionlife satisfactionsubjective well-beingVIA-IS (Values in Action Inventory)meaning in lifevocational activities

Given the powerful implications of relationship quality for health and well-being, a central mission of relationship science is explaining why some romantic relationships thrive more than others. This large-scale project used machine learning (i.e., Random Forests) to 1) quantify the extent to which relationship quality is predictable and 2) identify which constructs reliably predict relationship quality. Across 43 dyadic longitudinal datasets from 29 laboratories, the top relationship-specific predictors of relationship quality were perceived-partner commitment, appreciation, sexual satisfaction, perceived-partner satisfaction, and conflict. The top individual-difference predictors were life satisfaction, negative affect, depression, attachment avoidance, and attachment anxiety. Overall, relationship-specific variables predicted up to 45% of variance at baseline, and up to 18% of variance at the end of each study. Individual differences also performed well (21% and 12%, respectively). Actor-reported variables (i.e., own relationship-specific and individual-difference variables) predicted two to four times more variance than partner-reported variables (i.e., the partner's ratings on those variables). Importantly, individual differences and partner reports had no predictive effects beyond actor-reported relationship-specific variables alone. These findings imply that the sum of all individual differences and partner experiences exert their influence on relationship quality via a person's own relationship-specific experiences, and effects due to moderation by individual differences and moderation by partner-reports may be quite small. Finally, relationship-quality change (i.e., increases or decreases in relationship quality over the course of a study) was largely unpredictable from any combination of self-report variables. This collective effort should guide future models of relationships.

The proposed introduction of gaming disorder (GD) in the 11th revision of the International Classification of Diseases (ICD-11) developed by the World Health Organization (WHO) has led to a lively debate over the past year. Besides the broad support for the decision in the academic press, a recent publication by van Rooij et al. (2018) repeated the criticism raised against the inclusion of GD in ICD-11 by Aarseth et al. (2017). We argue that this group of researchers fails to recognize the clinical and public health considerations, which support the WHO perspective. It is important to recognize a range of biases that may influence this debate; in particular, the gaming industry may wish to diminish its responsibility by claiming that GD is not a public health problem, a position which maybe supported by arguments from scholars based in media psychology, computer games research, communication science, and related disciplines. However, just as with any other disease or disorder in the ICD-11, the decision whether or not to include GD is based on clinical evidence and public health needs. Therefore, we reiterate our conclusion that including GD reflects the essence of the ICD and will facilitate treatment and prevention for those who need it.

Abstract The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas.