orly lazarov

Here, we provide an in-depth consideration of our current understanding of engrams, spanning from molecular to network levels, and hippocampal neurogenesis, in health and Alzheimer's disease (AD). This review highlights novel findings in these emerging research fields and future research directions for novel therapeutic avenues for memory failure in dementia. Engrams, memory in AD, and hippocampal neurogenesis have each been extensively studied. The integration of these topics, however, has been relatively less deliberated, and is the focus of this review...

BACKGROUND: Recently we showed that a brief video-based intervention can improve openness to help-seeking and decrease treatment-related stigma among essential workers, particularly for female and Black individuals viewing demographically matched protagonists. The current randomized controlled trial explored two additional factors which may enhance the efficacy of this intervention: income level, known to be associated with help-seeking, and emotional engagement, which may enhance a person's ability to engage with the intervention...

Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however few studies have investigated its role in neurodegenerative processes such as Alzheimer's Disease (AD). Here we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated variants preferentially target the MAPK pathway, including recurrent CBL ring-domain mutations...

BACKGROUND: Intrusive traumatic re-experiencing domain (ITRED) was recently introduced as a novel perspective on posttraumatic psychopathology, proposing to focus research of posttraumatic stress disorder (PTSD) on the unique symptoms of intrusive and involuntary re-experiencing of the trauma, namely, intrusive memories, nightmares, and flashbacks. The aim of the present study was to explore ITRED from a neural network connectivity perspective. METHODS: Data were collected from 9 sites taking part in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) PTSD Consortium ( n = 584) and included itemized PTSD symptom scores and resting-state functional connectivity (rsFC) data...

Alzheimer's disease (AD) is the most common form of dementia and results in neurodegeneration and cognitive impairment. White matter (WM) is affected in AD and has implications for neural circuitry and cognitive function. The trajectory of these changes across age, however, is still not well understood, especially at earlier stages in life. To address this, we used the AppNL ∼G ∼F/NL ∼G ∼F knock-in (APPKI) mouse model that harbors a single copy knock-in of the human amyloid precursor protein ( App ) gene with three familial AD mutations...

BACKGROUND: Patients evaluated in an emergency department for suspected acute coronary syndromes (ACS; e.g., myocardial infarction) often experience a lingering fear of recurrence, which may adversely affect their mental health and adherence to recommended health behaviors. Cognitive bias modification training (CBMT) is an acceptable, easy-to-use intervention that reduces fear of recurrence in cancer patients, and reduces fear and anxiety in other populations, providing an alternative to psychotherapy or counseling-based approaches...

Gaze-Contingent Music Reward Therapy (GC-MRT) is an eye-tracking-based attention bias modification protocol for social anxiety disorder (SAD) with established clinical efficacy. However, it remains unclear if improvement following GC-MRT hinges on modification of threat-related attention or on more general enhancement of attention control. Here, 50 patients with SAD were randomly allocated to GC-MRT using either threat faces or shapes. Results indicate comparable reductions in social anxiety and co-morbid depression symptoms in the two conditions...

BACKGROUND: The 'mood-congruency' hypothesis of attention allocation postulates that individuals' current emotional states affect their attention allocation, such that mood-congruent stimuli take precedence over non-congruent ones. This hypothesis has been further suggested as an underlying mechanism of biased attention allocation in depression. METHODS: The present research explored the mood-congruency hypothesis using a novel video-based mood elicitation procedure (MEP) and an established eye-tracking attention allocation assessment task, elaborating prior research in the field...

During the past decade, the carotid body (CB) has been considered an innovative therapeutic target for the treatment of certain cardiorespiratory and metabolic diseases most of which are sympathetically mediated. It has recently been revealed that CB stem cells provide new target sites for the development of promising cell-based therapies. Specifically, generation of CB progenitors in vitro which can differentiate into functionally active glomus cells may be a useful procedure to produce the cell mass required for replacement cell therapy...

Accumulating evidence suggests that the mammalian carotid body (CB) constitutes a neurogenic center that contains a functionally active germinal niche. A variety of transcription factors is required for the generation of a precursor cell pool in the developing CB. Most of them are later silenced in their progeny, thus allowing for the maturation of the differentiated neurons. In the adult CB, neurotransmitters and vascular cytokines released by glomus cells upon exposure to chronic hypoxia act as paracrine signals that induce proliferation and differentiation of pluripotent stem cells, neuronal and vascular progenitors...

Carotid body (CB) glomus cells in most mammals, including humans, contain a broad diversity of classical neurotransmitters, neuropeptides and gaseous signaling molecules as well as their cognate receptors. Among them, acetylcholine, adenosine triphosphate and dopamine have been proposed to be the main excitatory transmitters in the mammalian CB, although subsequently dopamine has been considered an inhibitory neuromodulator in almost all mammalian species except the rabbit. In addition, co-existence of biogenic amines and neuropeptides has been reported in the glomus cells, thus suggesting that they store and release more than one transmitter in response to natural stimuli...

The mammalian carotid body (CB) is a polymodal chemoreceptor, which is activated by blood-borne stimuli, most notably hypoxia, hypercapnia and acidosis, thus ensuring an appropriate cellular response to changes in physical and chemical parameters of the blood. The glomus cells are considered the CB chemosensory cells and the initial site of chemoreceptor transduction. However, the molecular mechanisms by which they detect changes in blood chemical levels and how these changes lead to transmitter release are not yet well understood...

The mammalian carotid body (CB) exhibits considerable plasticity of its structure during development and aging and as a consequence of environmental, metabolic and inflammatory stimuli. The structural changes during maturation include an enlargement of the total and vascular volume of the CB. Conversely, aging results in a reduction in the number and volume of glomus cells with progressive cellular degeneration and an apparent increase in the surrounding connective tissue. Age-related structural alterations are similar to those during chronic hypoxia...

The carotid body (CB) is the main peripheral arterial chemoreceptor that registers the levels of pO2 , pCO2 and pH in the blood and responds to their changes by regulating breathing. It is strategically located in the bifurcation of each common carotid artery. The organ consists of "glomera" composed of two cell types, glomus and sustentacular cells, interspersed by blood vessels and nerve bundles and separated by connective tissue. The neuron-like glomus or type I cells are considered as the chemosensory cells of the CB...

BACKGROUND: The hippocampus plays an important role in the pathophysiology of posttraumatic stress disorder (PTSD) and its prognosis. Accumulating findings suggest that individuals with larger pretreatment hippocampal volume are more likely to benefit from PTSD treatment, but the mechanism underlying this effect is unknown. We investigated whether further increase in hippocampal volume during treatment explains the better prognosis of individuals with greater pretreatment hippocampal volume...

The Seeking Proxies for Internal States (SPIS) model of obsessive-compulsive disorder (OCD) explains symptoms of OCD as stemming from attenuated access to internal states, which is compensated for by using proxies, which are indices of these states that are more discernible or less ambiguous. Internal states in the SPIS model are subjective states that are not accessible to others, encompassing physiological states, motivations, preferences, memories, and emotions. Compensatory proxies in OCD include fixed rules and rituals as well as seeking and relying on external information...

BACKGROUND: Argentina currently uses a pentavalent vaccine containing diphtheria, tetanus, pertussis (whole cell), Haemophilus influenza type b and hepatitis B antigens, administered concomitantly with the inactivated polio vaccine (IPV) (DTwP-Hib-HB plus IPV) in its childhood vaccination schedule. However, hexavalent vaccines containing acellular pertussis antigens (DTaP-Hib-HB-IPV) and providing protection against the same diseases are also licensed, but are only available with a private prescription or for high-risk pre-term infants in the public health program...

Thiol-reactive Michael acceptors are commonly used for the formation of chemically cross-linked hydrogels. In this paper, we address the drawbacks of many Michael acceptors by introducing pyridazinediones as new cross-linking agents. Through the use of pyridazinediones and their mono- or dibrominated analogues, we show that the mechanical strength, swelling ratio, and rate of gelation can all be controlled in a pH-sensitive manner. Moreover, we demonstrate that the degradation of pyridazinedione-gels can be induced by the addition of thiols, thus providing a route to responsive or dynamic gels, and that monobromo-pyridazinedione gels are able to support the proliferation of human cells...

The mechanisms underlying adult hippocampal neurogenesis (AHN) are not fully understood. AHN plays instrumental roles in learning and memory. Understanding the signals that regulate AHN has implications for brain function and therapy. Here we show that Caveolin-1 (Cav-1), a protein that is highly enriched in endothelial cells and the principal component of caveolae, autonomously regulates AHN. Conditional deletion of Cav-1 in adult neural progenitor cells (nestin +) led to increased neurogenesis and enhanced performance of mice in contextual discrimination...

INTRODUCTION: The purpose of this article is to describe a soft-tissue augmentation procedure for multiple tooth extraction sites during immediate placement and immediate loading (IPIL) dental implant surgery in periodontally compromised patients and to present follow-up results of its effectiveness. METHODS: A retrospective study was conducted on data from patients who underwent IPIL dental implant surgery between 2018 and 2021 at an oral implant centre in Bulgaria...