A potent, proteolysis-resistant inhibitor of kallikrein-related peptidase 6 (KLK6) for cancer therapy, developed by combinatorial engineering.

Human tissue kallikrein (KLK) proteases are hormone-like signaling molecules with important functions in cancer pathophysiology. KLK-related peptidase 6 (KLK6), specifically, is highly up-regulated in several types of cancer, where its increased activity promotes cancer invasion and metastasis. This characteristic suggests KLK6 as an attractive target for therapeutic interventions.

Impaired Organization of GABAergic Neurons Following Prenatal Hypoxia.

Several conditions related to the intrauterine environment are associated with neuropsychiatric conditions in later life. In humans, approximately 2% of infants are exposed to perinatal hypoxia-ischemia or prolonged anoxic insult, a condition to which very low birth weight preterm infants exhibit the highest susceptibility. Analyses of postmortem tissue link some presentations of these conditions to changes in GABA pathway functionality in the brains of affected subjects.

Ultrasound targeting of Q-starch/miR-197 complexes for topical treatment of psoriasis.

Psoriasis is a common, worldwide autoinflammatory, incurable skin disease. miR-197 has therapeutic potential for psoriasis since it can down-regulate the expression of both IL-22RA1 and IL-17RA, subunits of the receptors of IL-22 and IL-17, respectively, which are key cytokines in the disease. Although miR-197 has the potential to treat the disease, several inherent physical barrier properties of the skin challenge miRNA's delivery to the target skin cells.

Trapped in a Daydream: Daily Elevations in Maladaptive Daydreaming Are Associated With Daily Psychopathological Symptoms.

Maladaptive Daydreaming (MD) characterizes individuals who engage in vivid, fanciful daydreaming for hours on end, neglecting real-life relationships and responsibilities, resulting in clinical distress and functional impairment. Sufferers have embraced the term MD in cyber-communities devoted to this problem because it seemed to uniquely fit their experience and since existing diagnostic labels and their therapies seemed inadequate. However, scientific research in the field has been scarce, relying on cross-sectional or case study designs.

Quantity-based analysis of household food consumption patterns and drivers: The case of Israel.

The interest in better understanding the characteristics and drivers of food consumption by individuals and social groups has grown in recent years, because of various social, environmental, health and economic issues. Most analyses have focused either on the macro or national scale, using food balance/disappearance data, or on the micro scale, focusing on nutrition analysis in limited groups of individual consumers. While various household characteristics are expected to influence food-purchasing habits, the scope and methodology of most previous studies limited their ability to relate to multiple factors, and integrate all into specific consumption patterns.

A probabilistic approach to joint cell tracking and segmentation in high-throughput microscopy videos.

We present a novel computational framework for the analysis of high-throughput microscopy videos of living cells. The proposed framework is generally useful and can be applied to different datasets acquired in a variety of laboratory settings. This is accomplished by tying together two fundamental aspects of cell lineage construction, namely cell segmentation and tracking, via a Bayesian inference of dynamic models.

Multidimensional co-segmentation of longitudinal brain MRI ensembles in the presence of a neurodegenerative process.

MRI Segmentation of a pathological brain poses a significant challenge, as the available anatomical priors that provide top-down information to aid segmentation are inadequate in the presence of abnormalities. This problem is further complicated for longitudinal data capturing impaired brain development or neurodegenerative conditions, since the dynamic of brain atrophies has to be considered as well. For these cases, the absence of compatible annotated training examples renders the commonly used multi-atlas or machine-learning approaches impractical.

Cerebellar transcranial direct current stimulation interacts with BDNF Val66Met in motor learning.

Background: Cerebellar transcranial direct current stimulation has been reported to enhance motor associative learning and motor adaptation, holding promise for clinical application in patients with movement disorders. However, behavioral benefits from cerebellar tDCS have been inconsistent.

Objective: Identifying determinants of treatment success is necessary.

Ovarian hyperstimulation syndrome leading to ventriculoperitoneal shunt malfunction: Case report.

Ventriculoperitoneal shunt (VPS) insertion is a common neurosurgical procedure for hydrocephalus. Unfortunately, VPS malfunction is not uncommon, with an estimated cumulative rate of 32% at 5 years. As flow through the shunt is influenced by the pressure gradient between the ventricles and the peritoneal cavity, malfunction may be caused by elevated intra-abdominal pressure.

Myocardial Infarction With No Obstructive Coronary Artery Disease: Angiographic and Clinical Insights in Patients With Premature Presentation.

Background: Premature myocardial infarction (MI) is an increasingly prevalent cause of morbidity and mortality worldwide. A subset of patients, predominantly young women, present with MI with no obstructive coronary artery disease (MINOCA), a nomenclature gaining recognition. However, few data exist on presentation and prognosis according to the severity of coronary artery disease (CAD).

Foraminiferal single chamber analyses of heavy metals as a tool for monitoring permanent and short term anthropogenic footprints.

In order to establish environmentally sustainable industries there is a need for high-resolution temporal and spatial monitoring of heavy metal pollutants even at low concentrations before they become hazardous for local ecosystems. Here we present single chamber records of Cu, Zn and Pb in shells of two benthic foraminifera species with different shell types from two shallow coastal stations in Israel: An area adjacent to an electrical power plant and desalination factory (Hadera) and an industrially free nature reserve (Nachsholim). Records of both foraminifera species show elevated metal concentrations in Hadera clearly identifying the footprint of the local industrial facilities.

Hypoxic-induced truncation of voltage-dependent anion channel 1 is mediated by both asparagine endopeptidase and calpain 1 activities.

The voltage-dependent anion channel 1 (VDAC1), an outer mitochondria membrane (OMM) protein, serves as a mitochondrial gatekeeper, mediating the transport of nucleotides, Ca and other metabolites across the OMM. VDAC1 also plays a central role in mitochondria-mediated apoptosis by facilitating the release of apoptotic proteins and by association with both pro- and anti-apoptotic proteins. Tumor cells, which are constantly exposed to hypoxic conditions, affect the cell via the transcription factor hypoxia-inducible factor (HIF) that induces transcriptional activity.

Association between mental disorders, cognitive disturbances and vitamin D serum level: Current state.

Background & Aims: Vitamin D deficiency has been identified as a global problem. Approximately 14% of the world population has inadequate vitamin D levels. This vitamin has been usually associated with bone disorders such as rickets, osteomalacia, and osteoporosis.

Airsoft gun-related ocular injuries: long-term follow-up.

Purpose: To describe the long-term ocular effects of airsoft gun pellet injuries.

Methods: The present study extends by 7-10 years the results of a 2010 study on the acute ocular findings related to airsoft gun pellet injuries in 59 patients, wherein we found a variety of anterior and posterior segment injuries, including hyphema (66%), corneal edema (61%), corneal erosions (59%), and traumatic mydriasis (25%), as well as retinal edema in (22%), retinal hemorrhages and mild vitreous hemorrhage in (2.1%), and, in 1 patient, elevated intraocular pressure and traumatic cataract.

Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: a cross-sectional population-based study.

Background: The population prevalence, clinical characteristics, and associations for Rome IV functional dyspepsia are not known. Following the publication of the Rome IV criteria for functional gastrointestinal disorders, we aimed to assess the prevalence, characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults across the USA, Canada, and the UK.

Methods: We sent an internet-based cross-sectional health survey to adults in the general population of three English-speaking countries: the USA, Canada, and the UK.

Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study.

Background: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined.

Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors.

A flexible control system designed for lab-scale simulations and optimization of composting processes.

Understanding and optimization of composting processes can benefit from the use of controlled simulators of various scales. The Agricultural Research Organization Composting Simulator (ARO-CS) was recently built and it is flexibly automated by means of a programmable logic controller (PLC). Temperature, carbon dioxide, oxygen and airflow are monitored and controlled in seven 9-l reactors that are mounted into separate 80-l water baths.

Revisiting the validity of the mouse forced swim test: Systematic review and meta-analysis of the effects of prototypic antidepressants.

One problem area regarding animal models for affective disorders is unclear reproducibility, including external validity or generalizability. One way to evaluate external validity is with systematic reviews and meta-analyses. The current study presents a meta-analysis of the effects of prototypic antidepressants in the mouse forced swim test (FST).

Measurement equivalence of the BDS scale with young and older adults with bipolar disorder.

Instruments developed for mental health research are commonly devised and validated with young adults only. However, the measurement properties of these scales may differ over the lifespan. For this study, we set out to demonstrate the psychometric equivalence of the BDSx scale with an international sample of young and older adults with bipolar disorder (BD).

Dissecting disease entities out of the broad spectrum of bipolar-disorders.

The etiopathology of bipolar disorders is yet unraveled and new avenues should be pursued. One such avenue may be based on the assumption that the bipolar broad spectrum includes, among others, an array of rare medical disease entities. Towards this aim we propose a dissecting approach based on a search for rare medical diseases with known etiopathology which also exhibit bipolar disorders symptomatology.

Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

There is common agreement that many disorders of the central nervous system are 'complex', that is, there are many potential factors that influence the development of the disease, underlying mechanisms, and successful treatment. Most of these disorders, unfortunately, have no cure at the present time, and therapeutic strategies often have debilitating side effects. Interestingly, some of the 'complexities' of one disorder are found in another, and the similarities are often network defects.

A quantitative assessment of the membrane-integral sub-proteome of a bacterial magnetic organelle.

Unlabelled: Magnetotactic bacteria produce chains of complex membrane-bound organelles that direct the biomineralization of magnetic nanoparticles and serve for magnetic field navigation. These magnetosome compartments have recently emerged as a model for studying the subcellular organization of prokaryotic organelles. Previous studies indicated the presence of specific proteins with various functions in magnetosome biosynthesis.

The implications and applications of learning via instructions.

Whereas psychology knows a long tradition of studies that focused on the role of practice and training in acquiring new skills or knowledge, systematic studies into learning via instructions remain relatively scarce. This is surprising given the tremendous influence instructions have on human behavior and cognition. In recent years, however, a (re)new(ed) interest into learning via instructions resulted in new paradigms and findings that can inspire future research in this understudied domain.