Peripheral nerve blocks have long been used in headache treatment. The most widely used procedure for this purpose has been greater occipital nerve (GON) block. The rationale for using GON block in ...headache treatment comes from evidence for convergence of sensory input to trigeminal nucleus caudalis neurons from both cervical and trigeminal fibers. Although there is no standardized procedure for GON blockade, the nerve is usually infiltrated with a local anesthetic (lidocaine, bupivacaine, or both). A corticosteroid is sometimes added. Several studies suggested efficacy of GON block in the treatment of migraine, cluster headache, and chronic daily headache. However, few were controlled and blinded. Despite a favorable clinical experience, little evidence exists for the efficacy of GON block in migraine treatment. Controlled studies are needed to better assess the role of GON block in the treatment of migraine and other headaches.
Despite evidence implicating microglia in the etiology and pathophysiology of major depression, there is paucity of information regarding the contribution of microglia-dependent molecular pathways to ...antidepressant procedures. In this study, we investigated the role of microglia in a mouse model of depression (chronic unpredictable stress-CUS) and its reversal by electroconvulsive stimulation (ECS), by examining the effects of microglia depletion with the colony stimulating factor-1 antagonist PLX5622. Microglia depletion did not change basal behavioral measures or the responsiveness to CUS, but it completely abrogated the therapeutic effects of ECS on depressive-like behavior and neurogenesis impairment. Treatment with the microglia inhibitor minocycline concurrently with ECS also diminished the antidepressant and pro-neurogenesis effects of ECS. Hippocampal RNA-Seq analysis revealed that ECS significantly increased the expression of genes related to neurogenesis and dopamine signaling, while reducing the expression of several immune checkpoint genes, particularly lymphocyte-activating gene-3 (Lag3), which was the only microglial transcript significantly altered by ECS. None of these molecular changes occurred in microglia-depleted mice. Immunohistochemical analyses showed that ECS reversed the CUS-induced changes in microglial morphology and elevation in microglial LAG3 receptor expression. Consistently, either acute or chronic systemic administration of a LAG3 monoclonal antibody, which readily penetrated into the brain parenchyma and was found to serve as a direct checkpoint blocker in BV2 microglia cultures, rapidly rescued the CUS-induced microglial alterations, depressive-like symptoms, and neurogenesis impairment. These findings suggest that brain microglial LAG3 represents a promising target for novel antidepressant therapeutics.
Information elicited from witnesses is critical to the fight against terrorism. We trained experienced Israeli intelligence investigators to use the Cognitive Interview (CI) technique to enhance ...witnesses’ reporting in real-world investigations of terrorism (e.g., stabbings). We examined 60 cases in which Jewish and Arab respondents (victims, witnesses, and occasional sources of intelligence information; civilians and soldiers) were interviewed initially with a standard protocol. All respondents were interviewed a second time: 30 with a standard protocol and 30 with a CI. Compared to using a standard protocol on the second interview, the CI elicited more information and also more new information (not already in the first interview), and the CI-elicited new information was rated as being more useful. The current results are compatible with other field studies and suggest that the CI should generalize to other real-world investigations and may be effective in several as-yet-untested contexts (e.g., cold cases, debriefing professionals).
BACKGROUND: Information processing speed is often impaired in neurological disorders, as well as with healthy aging. Thus, being able to accurately assess information processing speed is of high ...importance. One of the most commonly used tests to examine information processing speed is the Symbol Digit Modalities Test (SDMT), which has been shown to have good psychometric properties. OBJECTIVES: The current study aims to examine differences between two response modalities, written and oral, on the performance of an adapted version of the Symbol Digit Modalities Test. METHODS: Ninety-nine individuals completed two alternate forms of the adapted version of the SDMT (aSDMT). Participants were instructed to complete the five lines of the task as quickly and accurately as possible. On one form participants were instructed to provide their response in writing and on the other one, orally. Form and response modality (oral vs. written) were counterbalanced to control for practice effects. RESULTS: On average, there was a significant difference between response modalities, such that participants needed more time to respond when the response modality was written. For both response modalities, time to complete each line of stimuli decreased as the task progressed. While changes in response time on the first four lines of stimuli on the oral version were not found, there was a substantial improvement in response time on the fifth line. In contrast, on the written version a gradual learning effect was observed, in which response time was the slowest on the first two lines, an intermediate response time was noted on line 3, and the fastest response time was achieved on lines four and five. CONCLUSION: The current study demonstrates that response modality, oral versus written, can significantly impact performance efficiency (the length of time it takes to complete a task), but not accuracy (total correct responses), on a new adaptation of the SDMT, the aSDMT.
Drop down or flee out? Rapaport, Carmit; Ashkenazi, Isaac
International journal of disaster resilience in the built environment,
04/2019, Letnik:
10, Številka:
1
Journal Article
Recenzirano
Purpose
The official earthquake protection instructions for schools and kindergartens in Israel have recently been updated from the traditional “drop, cover and hold on” approach to the “flee outside ...to an open space” approach. This paper aims to describe the decision-making process, discuss the dilemmas behind it and suggest new insights for challenging current instructions in other countries.
Design/methodology/approach
The authors analyze human behavior patterns during earthquakes in general, and at schools in particular, while taking into consideration the environment (in terms of applying building codes and the level of earthquake risk in various zones), personal characteristics (age, gender and past experience) and earthquake characteristics (intensity and duration).
Findings
Five aspects should be taken into consideration when changing current earthquake instructions: the general official earthquake protection instructions, the structure and construction of schools and kindergartens, common behavior during emergencies, warning systems and the need to establish standardized protection instructions and guidelines for every school and kindergarten in the country.
Practical implications
Policymakers in other countries should critique current instructions to maximize citizens’ chances of survival and mitigate possible earthquake hazards, including by improving risk communication with the public.
Originality/value
The paper describes a national decision-making process which questions current official earthquake instructions at schools and kindergartens, based on evidence gained from current construction conditions, human behavior analysis and other countries’ experiences.
The multifocal 3D digital light microscope (LM) is an advanced tool which allows the high resolution tracking of surface topographies, morphologies and colours, and offers real-time measurements of ...parameters such as length and roughness, as well as in-situ field microscopic scale documentation. The use of a multifocal digital LM, equipped with powerful software, is examined in the present work as a justified tool for the study of ancient objects retrieved from shipwrecks. For that purpose, various archaeological objects were studied with an advanced multifocal LM system, which included an improved light sensitivity sensor. The results were compared to other methods, such as XRF, SEM-EDS, Raman spectroscopy and XRD. The use of a multifocal digital LM offers a unique opportunity to relate between the macroscopic and microscopic levels of the surface with colours as they appear in daylight, and correspondingly, in many cases, to expose the manufacturing process of the object.
Apoptosis ligand 2/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL)-a member of the tumor necrosis factor cytokine family-induces apoptosis by activating the extrinsic pathway ...through the proapoptotic death receptors DR4 and DR5. Recombinant human Apo2L/TRAIL (rhApo2L/TRAIL) has broad potential as a cancer therapy. To the best of our knowledge, this is the first in-human clinical trial to assess the safety, tolerability, pharmacokinetics, and antitumor activity of multiple intravenous doses of rhApo2L/TRAIL in patients with advanced cancer.
This phase I, open-label, dose-escalation study treated patients with advanced cancer with rhApo2L/TRAIL doses ranging from 0.5 to 30 mg/kg/d, with parallel dose escalation for patients without liver metastases and with normal liver function (cohort 1) and for patients with liver metastases and normal or mildly abnormal liver function (cohort 2). Doses were given daily for 5 days, with cycles repeating every 3 weeks. Assessments included adverse events (AEs), laboratory tests, pharmacokinetics, and imaging to evaluate antitumor activity.
Seventy-one patients received a mean of 18.3 doses; seven patients completed all eight treatment cycles. The AE profile of rhApo2L/TRAIL was similar in cohorts 1 and 2. The most common AEs were fatigue (38%), nausea (28%), vomiting (23%), fever (23%), anemia (18%), and constipation (18%). Liver enzyme elevations were concurrent with progressive metastatic liver disease. Two patients with sarcoma (synovial and undifferentiated) experienced serious AEs associated with rapid tumor necrosis. Two patients with chondrosarcoma experienced durable partial responses to rhApo2L/TRAIL.
At the tested schedule and dose range, rhApo2L/TRAIL was safe and well tolerated. Dose escalation achieved peak rhApo2L/TRAIL serum concentrations equivalent to those associated with preclinical antitumor efficacy.
This study examined early Hebrew verb acquisition, highlighting CDS-CS relations across inflectional and derivational verb learning. It was carried out on a corpus of longitudinal dense dyadic ...interactions of two Hebrew-speaking toddlers aged 1;8-2;2 and their parents. Findings revealed correlated patterns within and between CDS and CS corpora in terms of verbs, structural root categories, and their components (roots, binyan conjugations, and derivational verb families), and clear relations between lexical-derivational development and inflectional growth in input-output relations, measured by MSP. It also showed that both corpora had few, yet highly semantically coherent, derivational families. Lexical learning in Hebrew was shown to be morphologically oriented, with both inflectional and derivational learning supporting and being supported by the development of the verb lexicon. These findings support findings in the general literature regarding the close relationship between parental input and child speech, and the affinity between lexical and grammatical growth.
