Economic Analysis of National Program for Hepatitis C Elimination, Israel, 2023.

In 2021, the Israel Ministry of Health began a national hepatitis C elimination program. Implementing a World Health Organization goal, Israel's program involved targeted screening, barrier minimization, workup simplification, awareness campaigns, and a patient registry. We evaluated program costs for testing and treatment.

Ion channel inhibition by targeted recruitment of NEDD4-2 with divalent nanobodies.

Targeted recruitment of E3 ubiquitin ligases to degrade traditionally undruggable proteins is a disruptive paradigm for developing new therapeutics. Two salient limitations are that <2% of the ~600 E3 ligases in the human genome have been exploited to produce proteolysis targeting chimeras (PROTACs), and the efficacy of the approach has not been demonstrated for a vital class of complex multi-subunit membrane proteins- ion channels. NEDD4-1 and NEDD4-2 are physiological regulators of myriad ion channels, and belong to the 28-member HECT (homologous to E6AP C-terminus) family of E3 ligases with widespread roles in cell/developmental biology and diverse diseases including various cancers, immunological and neurological disorders, and chronic pain.

Perturbation of the host cell Ca homeostasis and ER-mitochondria contact sites by the SARS-CoV-2 structural proteins E and M.

Coronavirus disease (COVID-19) is a contagious respiratory disease caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, a global COVID-19 pandemic was declared by the World Health Organization (WHO).

Selective posttranslational inhibition of Caβ-associated voltage-dependent calcium channels with a functionalized nanobody.

Ca influx through high-voltage-activated calcium channels (HVACCs) controls diverse cellular functions. A critical feature enabling a singular signal, Ca influx, to mediate disparate functions is diversity of HVACC pore-forming α and auxiliary Caβ-Caβ subunits. Selective Caα blockers have enabled deciphering their unique physiological roles.

Targeted ubiquitination of sensory neuron calcium channels reduces the development of neuropathic pain.

Neuropathic pain caused by lesions to somatosensory neurons due to injury or disease is a widespread public health problem that is inadequately managed by small-molecule therapeutics due to incomplete pain relief and devastating side effects. Genetically encoded molecules capable of interrupting nociception have the potential to confer long-lasting analgesia with minimal off-target effects. Here, we utilize a targeted ubiquitination approach to achieve a unique posttranslational functional knockdown of high-voltage-activated calcium channels (HVACCs) that are obligatory for neurotransmission in dorsal root ganglion (DRG) neurons.

The box task - a method for assessing in-vehicle system demand.

The use of advanced in-vehicle information systems (IVIS) and other complex devices such as smartphones while driving can lead to driver distraction, which, in turn, increases safety-critical event risk. Therefore, using methods for measuring driver distraction caused by IVIS is crucial when developing new in-vehicle systems. In this paper, we present the setup and implementation of the Box Task combined with a Detection Response Task (BT+DRT) as a tool to assess visual-manual and cognitive distraction effects.

Controlling ion channel trafficking by targeted ubiquitination and deubiquitination.

Plasma membrane-localized ion channels are essential for diverse physiological processes such as neurotransmission, muscle contraction, and osmotic homeostasis. The surface density of such ion channels is a major determinant of their function, and tuning this variable is a powerful way to regulate physiology. Dysregulation of ion channel surface density due to inherited or de novo mutations underlies many serious diseases, and molecules that can correct trafficking deficits are potential therapeutics and useful research tools.

Optical and Electrical Measurements Reveal the Orientation Mechanism of Homoleptic Iridium-Carbene Complexes.

Understanding and controlling the driving forces for molecular alignment in optoelectronic thin-film devices is of crucial importance for improving their performance. In this context, the preferential orientation of organometallic iridium complexes is in the focus of research to benefit from their improved light-outcoupling efficiencies in organic light-emitting diodes (OLEDs). Although there has been great progress concerning the orientation behavior for heteroleptic Ir complexes, the mechanism behind the alignment of homoleptic complexes is still unclear yet.

Measuring driver distraction - Evaluation of the box task method as a tool for assessing in-vehicle system demand.

Several tools have been developed over the past twenty years to assess the degree of driver distraction caused by secondary task engagement. A relatively new and promising method in this area is the box task combined with a detection response task (BT + DRT). However, no evaluation regarding the BT's sensitivity currently exists.

Using European naturalistic driving data to assess secondary task engagement when stopped at a red light.

Problem: Some evidence exists that drivers choose to engage in secondary tasks when the driving demand is low (e.g., when the car is stopped).

Ribosome-associated vesicles: A dynamic subcompartment of the endoplasmic reticulum in secretory cells.

The endoplasmic reticulum (ER) is a highly dynamic network of membranes. Here, we combine live-cell microscopy with in situ cryo-electron tomography to directly visualize ER dynamics in several secretory cell types including pancreatic β-cells and neurons under near-native conditions. Using these imaging approaches, we identify a novel, mobile form of ER, ribosome-associated vesicles (RAVs), found primarily in the cell periphery, which is conserved across different cell types and species.

A potent voltage-gated calcium channel inhibitor engineered from a nanobody targeted to auxiliary Caβ subunits.

Inhibiting high-voltage-activated calcium channels (HVACCs; Ca1/Ca2) is therapeutic for myriad cardiovascular and neurological diseases. For particular applications, genetically-encoded HVACC blockers may enable channel inhibition with greater tissue-specificity and versatility than is achievable with small molecules. Here, we engineered a genetically-encoded HVACC inhibitor by first isolating an immunized llama nanobody (nb.

Manipulating the Transition Dipole Moment of CsPbBr Perovskite Nanocrystals for Superior Optical Properties.

Colloidal cesium lead halide perovskite nanocrystals exhibit unique photophysical properties including high quantum yields, tunable emission colors, and narrow photoluminescence spectra that have marked them as promising light emitters for applications in diverse photonic devices. Randomly oriented transition dipole moments have limited the light outcoupling efficiency of all isotropic light sources, including perovskites. In this report we design and synthesize deep blue emitting, quantum confined, perovskite nanoplates and analyze their optical properties by combining angular emission measurements with back focal plane imaging and correlating the results with physical characterization.

New roles for dopamine D and D receptors in pancreatic beta cell insulin secretion.

Although long-studied in the central nervous system, there is increasing evidence that dopamine (DA) has important roles in the periphery including in metabolic regulation. Insulin-secreting pancreatic β-cells express the machinery for DA synthesis and catabolism, as well as all five DA receptors. In these cells, DA functions as a negative regulator of glucose-stimulated insulin secretion (GSIS), which is mediated by DA D-like receptors including D (D2R) and D (D3R) receptors.

Correlating Optical and Electrical Dipole Moments To Pinpoint Phosphorescent Dye Alignment in Organic Light-Emitting Diodes.

Understanding the morphology of organic materials within optoelectronic thin film devices is of crucial importance for the development of state-of-the-art organic light emitting diodes (OLEDs). In this context, the preferential alignment of organometallic Ir complexes has been in the focus of research to benefit from the improved light-outcoupling efficiencies. Although the emissive dipole orientation has been identified from an optical point of view and molecular dynamic simulations give first insights into film morphologies, new experimental techniques are necessary to pinpoint the exact alignment of phosphorescent dye molecules.

Sculpting ion channel functional expression with engineered ubiquitin ligases.

The functional repertoire of surface ion channels is sustained by dynamic processes of trafficking, sorting, and degradation. Dysregulation of these processes underlies diverse ion channelopathies including cardiac arrhythmias and cystic fibrosis. Ubiquitination powerfully regulates multiple steps in the channel lifecycle, yet basic mechanistic understanding is confounded by promiscuity among E3 ligase/substrate interactions and ubiquitin code complexity.

Fluorescent false neurotransmitter reveals functionally silent dopamine vesicle clusters in the striatum.

Neurotransmission at dopaminergic synapses has been studied with techniques that provide high temporal resolution, but cannot resolve individual synapses. To elucidate the spatial dynamics and heterogeneity of individual dopamine boutons, we developed fluorescent false neurotransmitter 200 (FFN200), a vesicular monoamine transporter 2 (VMAT2) substrate that selectively traces monoamine exocytosis in both neuronal cell culture and brain tissue. By monitoring electrically evoked Ca(2+) transients with GCaMP3 and FFN200 release simultaneously, we found that only a small fraction of dopamine boutons that exhibited Ca(2+) influx engaged in exocytosis, a result confirmed with activity-dependent loading of the endocytic probe FM1-43.

Development of a Rapid Insulin Assay by Homogenous Time-Resolved Fluorescence.

Direct measurement of insulin is critical for basic and clinical studies of insulin secretion. However, current methods are expensive and time-consuming. We developed an insulin assay based on homogenous time-resolved fluorescence that is significantly more rapid and cost-effective than current commonly used approaches.

Insulinoma as rare cause of severe post-partum hypoglycemia.

Post-partum hypoglycemia in non-diabetic women is a rare condition. We report the exceptional case of a 38-year-old obese woman who experienced recurrent neuroglycopenia 3 weeks after delivery. Corresponding to severe hypoglycemia with blood glucose levels of <30 mg/dL, there was no suppression of insulin or C-peptide.

NIRS and iSPA-PLS for predicting total anthocyanin content in jaboticaba fruit.

The aim of this study was to evaluate the potential of the successive projection algorithm for interval selection in partial least squares (iSPA-PLS) together with near-infrared reflectance spectroscopy (NIRS) as a feasible method to determine the total anthocyanin content (TAC) of intact jaboticaba fruit [Myrciaria jaboticaba (Vell.) O. Berg].

Ultrasound generation with high power and coil only EMAT concepts.

Electro-magnetic acoustic transducers (EMATs) are intended as non-contact and non-destructive ultrasound transducers for metallic material. The transmitted intensities from EMATS are modest, particularly at notable lift off distances. Some time ago a concept for a "coil only EMAT" was presented, without static magnetic field.

BZL101, a phytochemical extract from the Scutellaria barbata plant, disrupts proliferation of human breast and prostate cancer cells through distinct mechanisms dependent on the cancer cell phenotype.

BZL101 is an aqueous extract from the Scutellaria barbata plant shown to have anticancer properties in a variety of human cancers. In order to determine its efficacy on human reproductive cancers, we assessed the responses of two human breast cancer cell lines, estrogen sensitive MCF7 and estrogen insensitive MDA-MB-231, and of two human prostate cancer cell lines, androgen sensitive LNCaP and androgen insensitive PC3 which are human cell lines that represent early and late stage reproductive cancers. BZL101 inhibited reproductive cancer growth in all cell lines by regulating expression levels of key cell cycle components that differ with respect to the cancer cell phenotypes.

Surreptitious hyperkalaemia and its complications.

Surreptitious hyperkalaemia is not a common problem, particularly in patients not yet dialysis dependent. We encountered a patient who baffled her physicians and their consultants, who nonetheless proposed life-saving treatments and novel explanations. However, according to the maxim that common things are common and rare things are rare, we solved the problem by focusing on the accompanying anion.

Weight and symptom diary for self-monitoring in heart failure clinic patients.

Background: For people with chronic heart failure, self-monitoring has been linked with improved body awareness and better communication with health professionals. Cognitive theory and the concept of somatic awareness help explain self-monitoring behaviors. This study compares the clinical and hospital outcomes of heart failure patients who are using and not using a diary to record weight, vital signs and, symptoms and evaluates the diary format.