In the excavations conducted by Y. Shiloh in the City of David in Jerusalem during 1978–1985, an impressive hoard of 45 Hebrew bullae was found in the stratum destroyed by the Babylonians in 586 BCE. Two of them, stamped by the same seal, were read לאליקם̇ בן אוהל. The plene spelling with waw for the vowel o in the name אוהל was a novelty in the Hebrew epigraphy of the First Temple period, as this was the first time that such a spelling had been found in a fully preserved and provenanced inscription. In this study, it will be shown that the third letter in the second name is, in fact, a ḥet rather than a he and, hence, that the name should be read אוחל. This name is built on the root wḥl, which implies that the letter waw on the bullae is not a mater lectionis. The misreading of this letter led to a series of far-reaching conclusions concerning some aspects of the pronunciation of the Hebrew spoken by the inhabitants of Judah in the 7th–6th centuries BCE and consequently the historical development of the orthography of the Hebrew script, conclusions that should now be revised.
The COVID-19 pandemic and the measures taken to contain it have had a disproportionate impact on families with young children, especially with disabilities. This study examined factors associated with burden and growth among parents of young children in Israel, while comparing parents of children with and without disabilities. We hypothesized that the association between family functioning, informal social support, and perceived adequacy of educational services and burden and growth would be moderated by disabilities. An online questionnaire was completed by 675 parents of young children, 95 of them with disability. The moderating effect of disability on burden and growth was examined using PROCESS. Compared to parents of children without disabilities, greater burden was found among parents of children with disabilities, but levels of growth were similar. External support was lacking for both parent groups. Educational services were perceived as severely inadequate. Lower perceived adequate educational services were associated with greater burden. On the other hand, higher levels of family functioning (i.e., family cohesion and adaptability) and greater adequacy of educational services were associated with growth. The results show that while burden was greater for parents of children with disabilities, growth during the COVID-19 period was possible for parents of both groups. The findings also pointed to the importance of the family system for sustaining the wellbeing of its members in lockdown situations. Put together, the findings highlight the importance of planning for such national and global emergencies.
The COVID-19 pandemic and the measures taken to contain it have had a disproportionate impact on families with young children, especially with disabilities. This study examined factors associated with burden and growth among parents of young children in Israel, while comparing parents of children with and without disabilities. We hypothesized that the association between family functioning, informal social support, and perceived adequacy of educational services and burden and growth would be moderated by disabilities. An online questionnaire was completed by 675 parents of young children, 95 of them with disability. The moderating effect of disability on burden and growth was examined using PROCESS. Compared to parents of children without disabilities, greater burden was found among parents of children with disabilities, but levels of growth were similar. External support was lacking for both parent groups. Educational services were perceived as severely inadequate. Lower perceived adequate educational services were associated with greater burden. On the other hand, higher levels of family functioning (i.e., family cohesion and adaptability) and greater adequacy of educational services were associated with growth. The results show that while burden was greater for parents of children with disabilities, growth during the COVID-19 period was possible for parents of both groups. The findings also pointed to the importance of the family system for sustaining the wellbeing of its members in lockdown situations. Put together, the findings highlight the importance of planning for such national and global emergencies.
The focus is on the complexes with foundry equipment which were found in the necropolis of the steppe Trans-Urals, forest-steppe and taiga zones of Western Siberia. The author addresses the sites of the early phase of the Eurasian/West-Asian Metallurgical province as a part of global periodization of the Early Metal Era. The structure of the equipment and the feature of the graves structure point to various forms of emphasis of the professional foundry workers from the population of the two neighboring regions, who used different technological traditions. The masters of the Sintashta culture, who specialized in smelting of solid-cast tools based on arsenic alloys, had their own iconic attribute, which were clay tayeres and could often be ornamented. Siberian foundry workers, whose burials always contained foundry molds, performed their operation in the traditions of the Seima-Turbino technologies of thin-walled casting based on tin alloys. Similar complexes amounted maximum 1–-2 % of the burials area, they were often accompanied by abundant grave goods including the attributes of a chariot complex in the Urals and prestigious metal weapons in Siberia. Among the Siberian burials there is a big proportion of the so-called arbitrary burials, where foundry signs are represented by separate fragments of clay molds. The emergence and the decay of the practice of professional identity demonstration is considered from the perspective of universal ideological adaptations in the phase of the introduction of metal and the emergence of transformative technologies at the Bronze Age.
During the height of the COVID-19 pandemic, teachers around the globe had beenforced to move their teaching to full-time online, remote teaching. In this study, we aimedat understanding teacher burnout during COVID-19. We conducted a survey among399 teachers at the peak of a prolonged physical school closure. Teachers reportedexperiencing more burnout during (vs. before) the COVID-19 pandemic. Contributingfactors to this burnout were high family work conflict and low online teaching proficiency.Burnout was associated with lower work-related wellbeing: Lower work commitment,and higher turnover intentions. It was also associated with lower psychologicalwellbeing: More depressive and anxiety symptoms, and lower subjective wellbeing.Approach (but not avoid) coping strategies served as a protective factor against theburnout-turnover intentions association. We conclude with recommendations on howto mitigate teacher burnout, thereby contributing to teacher wellbeing.
An inscription in early Canaanite script from Lachish, incised on an ivory comb, is presented. The 17 letters, in early pictographic style, form seven words expressing a plea against lice.
Nicole Rodrigues Silva, Gomes, Francisco Isaac Fernandes , Lopes, Alexandre Hashimoto Pereira , Cortez, Isadora Lopes , dos Santos, Jéssica Cristina , Silva, Conceição Elidianne Aníbal , Raphael Mechoulam, , Gomes, Felipe Villela , Cunha, Thiago Mattar , ו Guimarães, Francisco Silveira . 2022. “The Cannabidiol Analog Pecs-101 Prevents Chemotherapy-Induced Neuropathic Pain Via Ppar$\Gamma$ Receptors.”. Neurotherapeutics : The Journal Of The American Society For Experimental Neurotherapeutics, 19, 1, Pp. 434–449. doi:10.1007/s13311-021-01164-w.
Chemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting adverse effect of chemotherapy drugs such as paclitaxel (PTX). PTX causes marked molecular and cellular damage, mainly in the peripheral nervous system, including sensory neurons in the dorsal root ganglia (DRG). Several studies have shown the therapeutic potential of cannabinoids, including cannabidiol (CBD), the major non-psychotomimetic compound found in the Cannabis plant, to treat peripheral neuropathies. Here, we investigated the efficacy of PECS-101 (former HUF-101), a CBD fluorinated analog, on PTX-induced neuropathic pain in mice. PECS-101, administered after the end of treatment with PTX, did not reverse mechanical allodynia. However, PECS-101 (1 mg/kg) administered along with PTX treatment caused a long-lasting relief of the mechanical and cold allodynia. These effects were blocked by a PPAR$\gamma$, but not CB1 and CB2 receptor antagonists. Notably, the effects of PECS-101 on the relief of PTX-induced mechanical and cold allodynia were not found in macrophage-specific PPAR$\gamma$-deficient mice. PECS-101 also decreased PTX-induced increase in Tnf, Il6, and Aif1 (Iba-1) gene expression in the DRGs and the loss of intra-epidermal nerve fibers. PECS-101 did not alter motor coordination, produce tolerance, or show abuse potential. In addition, PECS-101 did not interfere with the chemotherapeutic effects of PTX. Thus, PECS-101, a new fluorinated CBD analog, could represent a novel therapeutic alternative to prevent mechanical and cold allodynia induced by PTX potentially through the activation of PPAR$\gamma$ in macrophages.
Nicole Rodrigues Silva, Gomes, Francisco Isaac Fern, Lopes, Alexandre Hashimoto, Cortez, Isadora Lopes, Santos, Jéssica Cristina D, Silva, Conceição Elidianne Aníbal , Mechoulam, Raphael , Gomes, Felipe Villela, Cunha, Thiago Mattar, ו Guimarães, Francisco Silveira. 2022. “The Cannabidiol Analog Pecs-101 Prevents Chemotherapy-Induced Neuropathic Pain Via Pparγ Receptors”. Neurotherapeutics, 19, 1, Pp. 434-449. doi:10.1007/s13311-021-01164-w. תקציר
Chemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting adverse effect of chemotherapy drugs such as paclitaxel (PTX). PTX causes marked molecular and cellular damage, mainly in the peripheral nervous system, including sensory neurons in the dorsal root ganglia (DRG). Several studies have shown the therapeutic potential of cannabinoids, including cannabidiol (CBD), the major non-psychotomimetic compound found in the Cannabis plant, to treat peripheral neuropathies. Here, we investigated the efficacy of PECS-101 (former HUF-101), a CBD fluorinated analog, on PTX-induced neuropathic pain in mice. PECS-101, administered after the end of treatment with PTX, did not reverse mechanical allodynia. However, PECS-101 (1 mg/kg) administered along with PTX treatment caused a long-lasting relief of the mechanical and cold allodynia. These effects were blocked by a PPARγ, but not CB1 and CB2 receptor antagonists. Notably, the effects of PECS-101 on the relief of PTX-induced mechanical and cold allodynia were not found in macrophage-specific PPARγ-deficient mice. PECS-101 also decreased PTX-induced increase in Tnf, Il6, and Aif1 (Iba-1) gene expression in the DRGs and the loss of intra-epidermal nerve fibers. PECS-101 did not alter motor coordination, produce tolerance, or show abuse potential. In addition, PECS-101 did not interfere with the chemotherapeutic effects of PTX. Thus, PECS-101, a new fluorinated CBD analog, could represent a novel therapeutic alternative to prevent mechanical and cold allodynia induced by PTX potentially through the activation of PPARγ in macrophages.
Nicole Rodrigues Silva, Gomes, Francisco Isaac Fern, Lopes, Alexandre Hashimoto, Cortez, Isadora Lopes, Santos, Jéssica Cristina D, Silva, Conceição Elidianne Aníbal , Mechoulam, Raphael , Gomes, Felipe Villela, Cunha, Thiago Mattar, ו Guimarães, Francisco Silveira. 2022. “The Cannabidiol Analog Pecs-101 Prevents Chemotherapy-Induced Neuropathic Pain Via Pparγ Receptors”. Neurotherapeutics, 19, 1, Pp. 434-449. doi:10.1007/s13311-021-01164-w. תקציר
Chemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting adverse effect of chemotherapy drugs such as paclitaxel (PTX). PTX causes marked molecular and cellular damage, mainly in the peripheral nervous system, including sensory neurons in the dorsal root ganglia (DRG). Several studies have shown the therapeutic potential of cannabinoids, including cannabidiol (CBD), the major non-psychotomimetic compound found in the Cannabis plant, to treat peripheral neuropathies. Here, we investigated the efficacy of PECS-101 (former HUF-101), a CBD fluorinated analog, on PTX-induced neuropathic pain in mice. PECS-101, administered after the end of treatment with PTX, did not reverse mechanical allodynia. However, PECS-101 (1 mg/kg) administered along with PTX treatment caused a long-lasting relief of the mechanical and cold allodynia. These effects were blocked by a PPARγ, but not CB1 and CB2 receptor antagonists. Notably, the effects of PECS-101 on the relief of PTX-induced mechanical and cold allodynia were not found in macrophage-specific PPARγ-deficient mice. PECS-101 also decreased PTX-induced increase in Tnf, Il6, and Aif1 (Iba-1) gene expression in the DRGs and the loss of intra-epidermal nerve fibers. PECS-101 did not alter motor coordination, produce tolerance, or show abuse potential. In addition, PECS-101 did not interfere with the chemotherapeutic effects of PTX. Thus, PECS-101, a new fluorinated CBD analog, could represent a novel therapeutic alternative to prevent mechanical and cold allodynia induced by PTX potentially through the activation of PPARγ in macrophages.
José Alexandre S Crippa, Pacheco, Julia Cozar , Zuardi, Antonio W, Guimarães, Francisco S, Campos, Alline Cristina , de Osório, Flávia Lima , Loureiro, Sonia Regina , Dos Santos, Rafael G, Souza, José Diogo S, Ushirohira, Juliana Mayumi , Ferreira, Rafael Rinaldi , Mancini Costa, Karla Cristinne , Scomparin, Davi Silveira , Scarante, Franciele Franco , Pires-Dos-Santos, Isabela , Raphael Mechoulam, , Kapczinski, Flávio , Fonseca, Benedito AL, Esposito, Danillo LA, Passos, Afonso Dinis Costa , Fabbro, Amaury Lelis Dal , Bellissimo-Rodrigues, Fernando , Arruda, Eurico , Scarpelini, Sandro , Andraus, Maristela Haddad , Junior, Julio Cesar Nather , Wada, Danilo Tadao , Koenigkam-Santos, Marcel , Santos, Antonio Carlos , Filho, Geraldo Busatto , ו Hallak, Jaime EC. 2022. “Cannabidiol For Covid-19 Patients With Mild To Moderate Symptoms (Candidate Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.”. Cannabis And Cannabinoid Research, 7, 5, Pp. 658–669. doi:10.1089/can.2021.0093.
{Importance: Owing to its anti-inflammatory properties and antiviral "in vitro" effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cannabidiol (CBD) has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19). Objective: To investigate the safety and efficacy of CBD for treating patients with mild to moderate COVID-19. Design: Randomized, parallel-group, double-blind, placebo-controlled clinical trial conducted between July 7 and October 16, 2020, in two sites in Brazil. Setting: Patients were recruited in an emergency room. Participants: Block randomized patients (1:1 allocation ratio-by a researcher not directly involved in data collection) with mild and moderate COVID-19 living in Ribeirão Preto, Brazil, seeking medical consultation, and those who voluntarily agreed to participate in the study. Interventions: Patients received 300 mg of CBD or placebo added to standard symptomatic care during 14 days. Main Outcome and Measure: The primary outcome was reduction or prevention of the deterioration in clinical status from mild/moderate to severe/critical measured with the COVID-19 Scale or the natural course of the resolution of typical clinical symptoms. Primary study outcome was assessed on days 14, 21, and 28 after enrollment. Results: A total of 321 patients were recruited and assessed for eligibility, and 105 were randomly allocated either in CBD (n=49) or in placebo (n=42) group. Ninety-one participants were included in the analysis of efficacy. There were no baseline between-group differences regarding disease severity ($\chi$(2)=0.025
Biofilms are complex bacterial structures in which bacterial cells thrive as a community. Many bacterial species, including pathogens, form biofilms of high complexity and adaptability to a wide range of environmental conditions. One example of these is Streptococcus mutans, a gram-positive bacterium that has been associated with caries. Cannabigerol, a non-psychoactive cannabinoid, has been shown to affect S. mutans biofilms. In order to better characterize the effect of cannabigerol on biofilms of S. mutans, this paper provides a series of computational assays for biofilm analysis, applied on confocal images of S. mutans biofilms treated with cannabigerol. Confocal images are ubiquitous in biofilm analysis-they are often used to visualize the complex structure and molecular composition of biofilm macrocolonies. In this article, we demonstrate how confocal imaging data can be used to reveal more comprehensive insights into biofilm structure and measure specific anti-biofilm effects. This is accomplished by a series of computational assays, each focusing on a different aspect of biofilm structure.
Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver abnormalities and has been linked with metabolic syndrome hallmarks. Unfortunately, current treatments are limited. This work aimed to elucidate the effects of three cannabis extracts on metabolic alteration and gut microbiota composition in a mouse model of NAFLD and obesity. Male mice were fed with a high-fat diet (HFD) for 12 weeks. Following the establishment of obesity, the HFD-fed group was subdivided into HFD or HFD that was supplemented with one of three cannabis extracts (CN1, CN2, and CN6) for additional 8 weeks. Metabolic parameters together with intestinal microbiota composition were evaluated. Except for several minor changes in gene expression, no profound metabolic effect was found due to cannabis extracts addition. Nevertheless, marked changes were observed in gut microbiota diversity and composition, with CN1 and CN6 exhibiting microbial abundance patterns that are associated with more beneficial outcomes. Taken together, specific cannabis extracts' addition to an HFD results in more favorable modifications in gut microbiota. Although no marked metabolic effect was disclosed, longer treatments duration and/or higher extracts concentrations may be needed. More research is required to ascertain this conjecture and to establish the influence of various cannabis extracts on host health in general and NAFLD in particular.
We report a rare case with unilateral dysgeusia due to cerebrovascular disease. A 45-year-old man was admitted to the hospital with a sudden onset of dysesthesia in the right face and upper and lower limbs. A CT scan revealed a left pontine hemorrhage. A day after onset, the patient became aware of unilateral dysgeusia. Electrogustometry showed significantly higher thresholds in the left chorda tympani nerve and glossopharyngeal nerve compared to the right nerves. We diagnosed the hemorrhage caused unilateral dysgeusia. Although dysesthesia in the right face and upper and lower limbs disappeared, the dysgeusia in the left tongue persisted six months after symptom onset. Based on the neurological and radiological findings in this case, we discuss the central gustatory pathway with literatures.
{While there is an association between Western diets and the incidence of colorectal cancer (CRC), this dietary association has remained unexplored in Palestine. The aim of this study was to examine how fiber and fruit and vegetable (FV) intakes are associated with CRC risk among Palestinian adults. We recruited 528 Palestinians between 2014 and 2016. We identified 118 patients who received CRC treatment at Augusta Victoria Hospital, East Jerusalem. We additionally identified 410 controls who consisted of community-based Palestinians without cancer. All participants completed a survey on demographics and a validated dietary intake food screener. Multivariable logistic regression models tested associations between fiber and FV intakes (categorized into quartiles) with CRC risk. After adjusting for significant covariates (age, sex, education, physical activity, smoking status, BMI, IBD, and family history of CRC), as fibers increased across increasing quartiles, the CRC risk significantly decreased (OR = 0.36, 95% CI: 0.15–0.86
This article deals with the caves mentioned in the Old Testament, the New Testament, and the Qur’an. It highlights all the relevant occurrences of the Hebrew, Arabic, and Greek words for cave, discusses its etymologies, and provides brief details about the contexts in which it is mentioned.
Camellia vietnamensis Huang, which belongs to Camellia oleifera, is a traditional Chinese medicinal plant widely planted on Hainan Island. Tea saponin is an important functional component of C. vietnamensis, and squalene is the precursor substance that controls its formation. Squalene synthase (SQS: EC 2.5.1.21) synthesizes squalene from 2 molecules of farnesyl pyrophosphate (FPP). In this study, 1683 bp of the C. vietnamensis SQS gene, designated as CvSQS, was cloned and encoded 414 amino acids. Bioinformatics and phylogenetic tree analysis revealed the high homology of CvSQS with squalene synthases from other plants. For soluble proteins, the carboxy-terminal deleted CvSQS was obtained for expression in Escherichia coli Transetta (DE3), and the recombinant protein with a weight of 42.5 kDa was detected using SDS-PAGE and Western blot. After an enzymatic reaction, the presence of squalene in the product was analyzed using GC-MS detection, which indicated that CvSQS had catalytic activity. The tissue specificity of CvSQS and its presence in seeds at various ripening stages was detected by q-RT PCR. CvSQS had the highest transcriptional level in leaves, followed by seeds, roots, and flowers; the amount of CvSQS in the seeds was highest in September. The identification and functional characterization of CvSQS is essential for further studies on the regulation mechanism of tea saponin in C. vietnamensis.
This paper studies the impact of lobbying on policies in a centrally managed water economy. First, we develop an optimal control model in which long-run water-management policies are an outcome of negotiation between policymakers and a politically organized farming sector. We show that under equilibrium conditions in the political game, larger political power of the farmers' lobby leads to faster exhaustion of naturally replenished water resources, and expedites the investment in water-supply backstop technologies such as desalination. Then, we employ a detailed hydro-economic model of Israel's water economy to assess the validity of claims by scientists and bureaucrats that lobbying by the local agricultural sector has contributed to the depletion of the country's natural freshwater resources and thus accelerated the development of seawater desalination. Specifically, we compare observed trajectories of water-management policies in the years 2000–2020 to their simulated counterparts, and find a better fit for simulated scenarios that involve lobbying than for a socially optimal one; this result prevails under simulated conditions of extreme water shortage due to faster population growth or lower recharge of natural water sources. The best-fitted political-equilibrium scenarios indicate considerable deadweight loss. We discuss potential causes of over- and undervaluation of the lobbying effect.
