2021
Shirli Werner, Gumpel, Thomas P. , Koller, Judah , Wiesenthal, Vered , ו Weintraub, Naomi . 2021.
“Can Self-Efficacy Mediate Between Knowledge Of Policy, School Support And Teacher Attitudes Towards Inclusive Education?”. Plos One, 16, 9, Pp. e0257657. doi:10.1371/journal.pone.0257657.
Publisher's Version תקציר Background While research has focused on understanding teachers’ attitudes towards the inclusion of children with special educational needs into general education classrooms, there are lacunae that have yet to be addressed. This study examined the association between perceived self-efficacy and attitudes towards inclusion among elementary school teachers. The study also examined the role of teachers’ self-efficacy as a mediating variable between knowledge of inclusion policy, perception of school support and teachers’ attitudes towards inclusion. Methods Teachers (N = 352) working in general or special education schools completed questionnaires assessing attitudes towards inclusion, sense of self-efficacy, knowledge of current policy, and perception of support for inclusive practices. Results Higher perceived knowledge of inclusion policy and higher perceived school support of inclusion were both related to higher self-efficacy regarding inclusion, which, in turn, was related to more positive attitudes about inclusion. Conclusion Our results suggest that point to being knowledgeable regarding local and national policy is important in order to increase feelings of self-efficacy regarding the implementation of effective educational practice. To enhance inclusion, local and national policy must be clearly communicated to teachers. Furthermore, leadership and a supportive school environment are conducive to successful inclusive education.
Yosef Garfinkel, Hasel, Michael G. , Klingbeil, Martin G. , Kreimerman, Igor , Pytlik, Michael , Carroll, Jon W. , Waybright, Jonathan W.B. , Kang, Hoo-Goo , Choi, Gwanghyun , Chang, SangYeup , Hong, Soonhwa , David, Arlette , Weissbein, Itamar , ו Silverberg, Noam . 2021.
“The Canaanite And Judean Cities Of Lachish, Israel: Preliminary Report Of The Fourth Expedition, 2013–2017”. American Journal Of Archaeology, 125, 3, Pp. 419–459. doi:10.3764/aja.125.3.0419.
Publisher's Version Nicole Rodrigues Silva, Gomes, Francisco Isaac Fernandes , Lopes, Alexandre Hashimoto Pereira , Cortez, Isadora Lopes , dos Santos, Jéssica Cristina , Silva, Conceição Elidianne An\'ıbal , Raphael Mechoulam, , Gomes, Felipe Villela , Cunha, Thiago Mattar , ו Guimarães, Francisco Silveira . 2021.
“The Cannabidiol Analog Pecs-101 Prevents Chemotherapy-Induced Neuropathic Pain Via Ppar$\Upgamma$ Receptors”. Neurotherapeutics. doi:10.1007/s13311-021-01164-w.
Publisher's Version 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 A.L. , Esposito, Danillo L.A. , 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 and, Jaime E.C. Hallak . 2021.
“Cannabidiol For Covid-19 Patients With Mild To Moderate Symptoms (Candidate Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial”. Cannabis And Cannabinoid Research. doi:10.1089/can.2021.0093.
Publisher's Version The therapeutic potential of cannabidiol (CBD) in seizure disorders has been known for many years, but it is only in the last decade that major progress has been made in characterizing its preclinical and clinical properties as an antiseizure medication. The mechanisms responsible for protection against seizures are not fully understood, but they are likely to be multifactorial and to include, among others, antagonism of G protein-coupled receptor, desensitization of transient receptor potential vanilloid type 1 channels, potentiation of adenosine-mediated signaling, and enhancement of GABAergic transmission. CBD has a low and highly variable oral bioavailability, and can be a victim and perpetrator of many drug-drug interactions. A pharmaceutical-grade formulation of purified CBD derived from Cannabis sativa has been evaluated in several randomized placebo-controlled adjunctive-therapy trials, which resulted in its regulatory approval for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. Interpretation of results of these trials, however, has been complicated by the occurrence of an interaction with clobazam, which leads to a prominent increase in the plasma concentration of the active metabolite N-desmethylclobazam in CBD-treated patients. Despite impressive advances, significant gaps in knowledge still remain. Areas that require further investigation include the mechanisms underlying the antiseizure activity of CBD in different syndromes, its pharmacokinetic profile in infants and children, potential relationships between plasma drug concentration and clinical response, interactions with other co-administered medications, potential efficacy in other epilepsy syndromes, and magnitude of antiseizure effects independent from interactions with clobazam. This article is part of the special issue on 'Cannabinoids'.
The therapeutic potential of cannabidiol (CBD) in seizure disorders has been known for many years, but it is only in the last decade that major progress has been made in characterizing its preclinical and clinical properties as an antiseizure medication. The mechanisms responsible for protection against seizures are not fully understood, but they are likely to be multifactorial and to include, among others, antagonism of G protein-coupled receptor, desensitization of transient receptor potential vanilloid type 1 channels, potentiation of adenosine-mediated signaling, and enhancement of GABAergic transmission. CBD has a low and highly variable oral bioavailability, and can be a victim and perpetrator of many drug-drug interactions. A pharmaceutical-grade formulation of purified CBD derived from Cannabis sativa has been evaluated in several randomized placebo-controlled adjunctive-therapy trials, which resulted in its regulatory approval for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. Interpretation of results of these trials, however, has been complicated by the occurrence of an interaction with clobazam, which leads to a prominent increase in the plasma concentration of the active metabolite N-desmethylclobazam in CBD-treated patients. Despite impressive advances, significant gaps in knowledge still remain. Areas that require further investigation include the mechanisms underlying the antiseizure activity of CBD in different syndromes, its pharmacokinetic profile in infants and children, potential relationships between plasma drug concentration and clinical response, interactions with other co-administered medications, potential efficacy in other epilepsy syndromes, and magnitude of antiseizure effects independent from interactions with clobazam. This article is part of the special issue on 'Cannabinoids'.
A cannabinoid anticancer para-quinone, HU-331, which was synthesized by our group five decades ago, was shown to have very high efficacy against human cancer cell lines in-vitro and against in-vivo grafts of human tumors in nude mice. The main mechanism was topoisomerase II$\alpha$ catalytic inhibition. Later, several groups synthesized related compounds. In the present presentation, we review the publications on compounds synthesized on the basis of HU-331, summarize their published activities and mechanisms of action and report the synthesis and action of novel quinones, thus expanding the structure-activity relationship in these series.
A cannabinoid anticancer para-quinone, HU-331, which was synthesized by our group five decades ago, was shown to have very high efficacy against human cancer cell lines in-vitro and against in-vivo grafts of human tumors in nude mice. The main mechanism was topoisomerase II$\alpha$ catalytic inhibition. Later, several groups synthesized related compounds. In the present presentation, we review the publications on compounds synthesized on the basis of HU-331, summarize their published activities and mechanisms of action and report the synthesis and action of novel quinones, thus expanding the structure-activity relationship in these series.
A cannabinoid anticancer para-quinone, HU-331, which was synthesized by our group five decades ago, was shown to have very high efficacy against human cancer cell lines in-vitro and against in-vivo grafts of human tumors in nude mice. The main mechanism was topoisomerase IIα catalytic inhibition. Later, several groups synthesized related compounds. In the present presentation, we review the publications on compounds synthesized on the basis of HU-331, summarize their published activities and mechanisms of action and report the synthesis and action of novel quinones, thus expanding the structure-activity relationship in these series.
Adi Aran, Harel, Moria , Cassuto, Hanoch , Polyansky, Lola , Schnapp, Aviad , Wattad, Nadia , Shmueli, Dorit , Golan, Daphna , ו Castellanos, Xavier F. 2021.
“Cannabinoid Treatment For Autism: A Proof-Of-Concept Randomized Trial.”. Molecular Autism, 12, 1, Pp. 6. doi:10.1186/s13229-021-00420-2.
תקציר BACKGROUND: Endocannabinoid dysfunction in animal models of autism spectrum disorder (ASD) and accumulating, albeit anecdotal, evidence for efficacy in humans motivated this placebo-controlled double-blind comparison of two oral cannabinoid solutions in 150 participants (age 5-21 years) with ASD. METHODS: We tested (1) BOL-DP-O-01-W, a whole-plant cannabis extract containing cannabidiol and $Δ$9-tetrahydrocannabinol at a 20:1 ratio and (2) BOL-DP-O-01, purified cannabidiol and $Δ$9-tetrahydrocannabinol at the same ratio. Participants (N = 150) received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout and predetermined cross-over for another 12 weeks to further assess tolerability. Registered primary efficacy outcome measures were improvement in behavioral problems (differences between whole-plant extract and placebo) on the Home Situation Questionnaire-ASD (HSQ-ASD) and the Clinical Global Impression-Improvement scale with disruptive behavior anchor points (CGI-I). Secondary measures were Social Responsiveness Scale (SRS-2) and Autism Parenting Stress Index (APSI). RESULTS: Changes in Total Scores of HSQ-ASD (primary-outcome) and APSI (secondary-outcome) did not differ among groups. Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (n = 45) versus 21% on placebo (n = 47; p = 0.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (n = 34) versus 3.6 points after placebo (n = 36); p = 0.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (n = 95); 23% and 21% on pure-cannabinoids (n = 93), and 8% and 15% on placebo (n = 94). Limitations Lack of pharmacokinetic data and a wide range of ages and functional levels among participants warrant caution when interpreting the results. CONCLUSIONS: This interventional study provides evidence that BOL-DP-O-01-W and BOL-DP-O-01, administrated for 3 months, are well tolerated. Evidence for efficacy of these interventions are mixed and insufficient. Further testing of cannabinoids in ASD is recommended. Trial registration ClinicalTrials.gov: NCT02956226. Registered 06 November 2016,
https://clinicaltrials.gov/ct2/show/NCT02956226.
Adi Aran, Harel, Moria , Cassuto, Hanoch , Polyansky, Lola , Schnapp, Aviad , Wattad, Nadia , Shmueli, Dorit , Golan, Daphna , ו Castellanos, Xavier F. 2021.
“Cannabinoid Treatment For Autism: A Proof-Of-Concept Randomized Trial.”. Molecular Autism, 12, 1, Pp. 6. doi:10.1186/s13229-021-00420-2.
תקציר BACKGROUND: Endocannabinoid dysfunction in animal models of autism spectrum disorder (ASD) and accumulating, albeit anecdotal, evidence for efficacy in humans motivated this placebo-controlled double-blind comparison of two oral cannabinoid solutions in 150 participants (age 5-21 years) with ASD. METHODS: We tested (1) BOL-DP-O-01-W, a whole-plant cannabis extract containing cannabidiol and $Δ$9-tetrahydrocannabinol at a 20:1 ratio and (2) BOL-DP-O-01, purified cannabidiol and $Δ$9-tetrahydrocannabinol at the same ratio. Participants (N = 150) received either placebo or cannabinoids for 12-weeks (testing efficacy) followed by a 4-week washout and predetermined cross-over for another 12 weeks to further assess tolerability. Registered primary efficacy outcome measures were improvement in behavioral problems (differences between whole-plant extract and placebo) on the Home Situation Questionnaire-ASD (HSQ-ASD) and the Clinical Global Impression-Improvement scale with disruptive behavior anchor points (CGI-I). Secondary measures were Social Responsiveness Scale (SRS-2) and Autism Parenting Stress Index (APSI). RESULTS: Changes in Total Scores of HSQ-ASD (primary-outcome) and APSI (secondary-outcome) did not differ among groups. Disruptive behavior on the CGI-I (co-primary outcome) was either much or very much improved in 49% on whole-plant extract (n = 45) versus 21% on placebo (n = 47; p = 0.005). Median SRS Total Score (secondary-outcome) improved by 14.9 on whole-plant extract (n = 34) versus 3.6 points after placebo (n = 36); p = 0.009). There were no treatment-related serious adverse events. Common adverse events included somnolence and decreased appetite, reported for 28% and 25% on whole-plant extract, respectively (n = 95); 23% and 21% on pure-cannabinoids (n = 93), and 8% and 15% on placebo (n = 94). Limitations Lack of pharmacokinetic data and a wide range of ages and functional levels among participants warrant caution when interpreting the results. CONCLUSIONS: This interventional study provides evidence that BOL-DP-O-01-W and BOL-DP-O-01, administrated for 3 months, are well tolerated. Evidence for efficacy of these interventions are mixed and insufficient. Further testing of cannabinoids in ASD is recommended. Trial registration ClinicalTrials.gov: NCT02956226. Registered 06 November 2016,
https://clinicaltrials.gov/ct2/show/NCT02956226.
Claudinéia P. Costa, Fisher, Kaleigh , Guillén, Blanca M. , Yamanaka, Naoki , Bloch, Guy , ו Woodard, S. Hollis . 2021.
“Care-Giver Identity Impacts Offspring Development And Performance In An Annually Social Bumble Bee”, 21, Pp. 20. .
Publisher's Version תקציר The developmental fates of offspring have the potential to be influenced by the identity of their care-givers and by the nature of the care that they receive. In animals that exhibit both parental and alloparental care, such as the annually eusocial insects, the influence of care-giver identity can be directly assessed to yield mechanistic and evolutionary insights into the origins and elaboration of brood care. Here, we performed a comparative investigation of maternal and worker brood care in bumble bees, a pollinator group where mothers (queens) rear the first offspring in the nest, and then daughters (workers) assume this role upon their emergence. Specifically, we compared the effects of queen and worker brood care on offspring development and also offspring performance, for a set of traits related to sensory biology, learning, and stress resistance.
Ragda Abdalla-Aslan, Findler, Mordechai , Zini, Avraham , ו Almoznino, Galit . 2021.
“Caries Experience, Periodontal Status, And Metabolic Morbidity In Patients With Psychiatric Disorders”. Quintessence Int, 52, 6, Pp. 516-526. doi:10.3290/j.qi.b1044091.
תקציר OBJECTIVES: To investigate the association of psychiatric disorders with (1) caries experience, (2) periodontal status, and (3) metabolic syndrome (MetS) components.
METHOD AND MATERIALS: This 7-year cross-sectional study retrospectively analyzed the medical records of 504 individuals aged 18 to 90 years who attended the student dental clinic. Collected data included: demographics, smoking habits, systolic and diastolic blood pressures, pulse, waist circumference, full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), maximal pocket probing depth (PPD), average and maximal radiographic bone loss (RBL), the sum of the number of decayed (D), missing (M), and filled (F) teeth (DMFT score), and presence of MetS components, consequences and related conditions including diabetes, hypertension, hyperlipidemia, ischemic heart disease, heart failure, s/p stroke, and cancer.
RESULTS: 68 (13.5%) had psychiatric disorders with an average age of 53.42 ± 15.71 years. Psychiatric disorders were positively associated with smoking (P = .008), smoking pack-years (P = .004), DMFT score (P = .005), and negatively associated with hypertension (P = .046). Psychiatric disorders had no statistically significant associations with all periodontal indices studied and with other components of MetS. Following multivariate analysis, psychiatric disorders retained a statistically significant positive association with smoking (odds ratio [OR] and 95% confidence interval [CI] = 2.24 [1.28 to 3.92]) and with DMFT (OR and 95% CI = 1.08 [1.02 to 1.14]), and a statistically significant negative association with hypertension (OR and 95% CI = 0.46 [0.25 to 0.84]).
CONCLUSIONS: Psychiatric disorders were positively associated with smoking and caries experience but not with periodontal status and metabolic morbidity. Communication between dental and medical professionals is needed to address the higher smoking consumption and caries morbidity in psychiatric patients. (Quintessence Int 2021;52:516-526; doi: 10.3290/j.qi.b1044091).
Ragda Abdalla-Aslan, Findler, Mordechai , Zini, Avraham , ו Almoznino, Galit . 2021.
“Caries Experience, Periodontal Status, And Metabolic Morbidity In Patients With Psychiatric Disorders”. Quintessence International, 52, Pp. 516 – 526. doi:10.3290/j.qi.b1044091.
Publisher's Version Atrazine (ATZ) is an extensively used herbicide and ubiquitous environmental contaminant. ATZ and its metabolite, diaminochlorotriazine (DACT), cause several cellular and functional alterations in spermatozoa. We aimed to examine the effect of ATZ/DACT on spermatozoon DNA integrity, fertilization competence, embryonic development, and transcriptome profile of in vitro-produced embryos derived from fertilization with pre-exposed sperm. Bovine spermatozoa exposed to ATZ (0.1 or 1 mu M) or DACT (1 or 10 mu M) during in vitro capacitation were used for in vitro fertilization of untreated oocytes. Cleavage and blastocyst-formation rates were evaluated 42 h and 7 days postfertilization, respectively. The association between DNA fragmentation and apoptosis (annexin V kit) was determined. Fertilization competence of annexin-positive (AV+) and annexin-negative (AV-) spermatozoa was examined. Microarray analysis was performed for 7-day blastocysts. Intracytoplasmic sperm injection was performed with control (AV+, AV-) and DACT (AV+, AV-) spermatozoa. Cleavage rates did not differ between groups and blastocyst formation tended to be higher for AV- vs. AV+ in both control and DACT groups, suggesting that acrosome reaction, rather than DNA fragmentation, underlies the reduced cleavage. Transcriptomic analysis revealed 139 and 230 differentially expressed genes in blastocysts derived from ATZ- and DACT-exposed spermatozoa, respectively, relative to controls. Proteomic analysis shown differential expression of proteins in ATZ- or DACT-treated spermatozoa, in particular proteins related to cellular processes and biological pathways. Therefore, we assume that factors delivered by the spermatozoa, regardless of DNA fragmentation, are also involved. Overall, the current study reveals a deleterious carryover effect of ATZ/DACT from the spermatozoa to the developing embryo. Summary sentence Summary sentence: Atrazine and its metabolite, diaminochlorotriazine, induce multifactorial damage in sperm, which is carried over to the embryo's transcriptome.
Titinunt Kitrungrotsakul, Han, Xian-Hau , Iwamoto, Yutaro , Takemoto, Satoko , Yokota, Hideo , Ipponjima, Sari , Nemoto, Tomomi , Xiong, Wei , ו Chen, Yen-Wei . 2021.
“A Cascade Of 2.5D Cnn And Bidirectional Clstm Network For Mitotic Cell Detection In 4D Microscopy Image”. Ieee/Acm Trans. Comput. Biol. Bioinform., 18, 2, Pp. 396–404.
תקציר Mitosis detection is one of the challenging steps in biomedical imaging research, which can be used to observe the cell behavior. Most of the already existing methods that are applied in detecting mitosis usually contain many nonmitotic events (normal cell and background) in the result (false positives, FPs). In order to address such a problem, in this study, we propose to apply 2.5-dimensional (2.5D) networks called CasDetNet\_CLSTM, which can accurately detect mitotic events in 4D microscopic images. This CasDetNet\_CLSTM involves a 2.5D faster region-based convolutional neural network (Faster R-CNN) as the first network, and a convolutional long short-term memory (CLSTM) network as the second network. The first network is used to select candidate cells using the information from nearby slices, whereas the second network uses temporal information to eliminate FPs and refine the result of the first network. Our experiment shows that the precision and recall of our networks yield better results than those of other state-of-the-art methods.
