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Meeting the needs of students in schools has been challenging for many years. Consequently, some schools have responded with comprehensive, multi-tiered intervention systems (e.g., MTSS) aimed at addressing students' academic, behavioral, and social-emotional needs. However, most educators have a rudimentary understanding of these systems and the impact of trauma and traumatic experiences on students' response to interventions. Currently, there is limited research on how building level-administrators integrate trauma-informedness into these tiered systems. This conceptual article outlines the importance of administrators' perception, understanding, and implementation of using a trauma-informed lens in educational decision making, specifically regarding MTSS implementation. This article presents an overview of the literature and an approach to trauma-informed approach that administrators can utilize when making educational decisions, specifically within multi-tiered systems of intervention and student supports.

A major barrier to the impact of genomic diagnosis in patients with congenital malformations is the lack of understanding regarding how sequence variants contribute to disease pathogenesis and whether this information could be used to generate patient-specific therapies. Congenital diaphragmatic hernia (CDH) is among the most common and severe of all structural malformations; however, its underlying mechanisms are unclear. We identified loss-of-function sequence variants in the epigenomic regulator gene SIN3A in two patients with complex CDH. Tissue-specific deletion of Sin3a in mice resulted in defects in diaphragm development, lung hypoplasia, and pulmonary hypertension, the cardinal features of CDH and major causes of CDH-associated mortality. Loss of SIN3A in the lung mesenchyme resulted in reduced cellular differentiation, impaired cell proliferation, and increased DNA damage. Treatment of embryonic Sin3a mutant mice with anacardic acid, an inhibitor of histone acetyltransferase, reduced DNA damage, increased cell proliferation and differentiation, improved lung and pulmonary vascular development, and reduced pulmonary hypertension. These findings demonstrate that restoring the balance of histone acetylation can improve lung development in the Sin3a mouse model of CDH.

In one university-based school leadership preparation program, aspiring school principals were asked to intern virtually with principals during the COVID-19 school closures. During this internship experience, they interviewed principals about leading during a pandemic and wrote reflective responses explaining what they learned about leading during the pandemic. This case study examines the reflections and lessons learned of leading schools during COVID-19 from 27 aspiring principals in two cohorts of a university-based school leadership preparation program. The researchers employed an abductive qualitative analysis for each aspiring principals' reflection using both deductive and inductive coding methods. Findings revealed fourth themes: (1) the need for structure and organization, (2) attending humanistic needs, (3) struggling to respond to policy changes; and (4) finding meaning and uplifting morale. This study can be used to help inform and guide educational leadership preparation and development programs on how to redirect coursework and field-based experiences to better prepare aspiring school principals to lead during school closures.

Teacher education and training vary across the world, yet research from diverse cultures supports the development of reflective teachers. Claiming that the complex dynamics of the 21st-century classroom can be managed best by reflective teachers. Through the reflective process, teachers are empowered as change agents to modify learning environments to benefit their students. Teachers hold the power to influence student learning. Therefore, it is important to understand the training processes that serve to produce reflective practitioners. In conducting rigorous cross-cultural comparative research, identifying common evaluative indicators underpinned by a theoretical framework is critical. Hence, the principles of the pre-service emerging reflective teacher training (PERTT) model were explored quantitatively and explained qualitatively to specifically focus on teachers' perceptions of their experiences of the psychosocial interpersonal process outcomes of the teacher-training environment (i.e. reflective practices, instructional scaffolding, guidance and support, modelled behaviours and reinforcement) provided during their teacher training. Such an exploration is critical because the philosophical underpinnings of the PERTT model have not been interrogated outside of Barbados. The findings demonstrate that there is merit to key theoretical principles of the PERTT model based on the lived experiences of the teachers in Antigua and Barbuda, England, and Canada during their teacher training.

IntroductionThe COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalised with severe COVID-19. The Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis (ISPY COVID-19 trial) was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation and challenges of the ISPY COVID-19 trial during the first phase of trial activity from April 2020 until December 2021.Methods and analysisThe ISPY COVID-19 Trial is a multicentre open-label phase 2 platform trial in the USA designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID-19 Trial network includes academic and community hospitals with significant geographical diversity across the country. Enrolled patients are randomised to receive one of up to four investigational agents or a control and are evaluated for a family of two primary outcomes-time to recovery and mortality. The statistical design uses a Bayesian model with 'stopping' and 'graduation' criteria designed to efficiently discard ineffective therapies and graduate promising agents for definitive efficacy trials. Each investigational agent arm enrols to a maximum of 125 patients per arm and is compared with concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrolment and adaptation of the trial design are ongoing.Ethics and disseminationISPY COVID-19 operates under a central institutional review board via Wake Forest School of Medicine IRB00066805. Data generated from this trial will be reported in peer-reviewed medical journals.Trial registration numberNCT04488081.

Botulinum neurotoxins (BoNTs), produced by the spore-forming bacterium Clostridium botulinum, cause botulism, a rare but fatal illness affecting humans and animals. Despite causing a life-threatening disease, BoNT is a multipurpose therapeutic. Nevertheless, as the most potent natural toxin, BoNT is classified as a Select Agent in the US, placing C. botulinum research under stringent governmental regulations. The extreme toxicity of BoNT, its impact on public safety, and its diverse therapeutic applications urge to devise safe solutions to expand C. botulinum research. Accordingly, we exploited CRISPR/Cas9-mediated genome editing to introduce inactivating point mutations into chromosomal bont/e gene of C. botulinum Beluga E. The resulting Beluga Ei strain displays unchanged physiology and produces inactive BoNT (BoNT/Ei) recognized in serological assays, but lacking biological activity detectable ex- and in vivo. Neither native single-chain, nor trypsinized di-chain form of BoNT/Ei show in vivo toxicity, even if isolated from Beluga Ei sub-cultured for 25 generations. Beluga Ei strain constitutes a safe alternative for the BoNT research necessary for public health risk management, the development of food preservation strategies, understanding toxinogenesis, and for structural BoNT studies. The example of Beluga Ei generation serves as template for future development of C. botulinum producing different inactive BoNT serotypes.

Aims/hypothesisHypothalamic inflammation and sympathetic nervous system hyperactivity are hallmark features of the metabolic syndrome and type 2 diabetes. Hypothalamic inflammation may aggravate metabolic and immunological pathologies due to extensive sympathetic activation of peripheral tissues. Loss of somatostatinergic (SST) neurons may contribute to enhanced hypothalamic inflammation.MethodsThe present data show that leptin receptor-deficient (db/db) mice exhibit reduced hypothalamic SST neurons, particularly in the periventricular nucleus. We model this finding, using adeno-associated virus delivery of diphtheria toxin subunit A (DTA) driven by an SST-cre system to deplete these neurons in Sstcre/gfp mice (SST-DTA).ResultsSST-DTA mice exhibit enhanced hypothalamic c-Fos expression and brain inflammation as demonstrated by microglial and astrocytic activation. Bone marrow from SST-DTA mice undergoes skewed haematopoiesis, generating excess granulocyte-monocyte progenitors and increased proinflammatory (C-C chemokine receptor type 2; CCR2hi) monocytes. SST-DTA mice exhibited a 'diabetic retinopathy-like' phenotype: reduced visual function by optokinetic response (0.4 vs 0.25 cycles/degree; SST-DTA vs control mice); delayed electroretinogram oscillatory potentials; and increased percentages of retinal monocytes. Finally, mesenteric visceral adipose tissue from SST-DTA mice was resistant to catecholamine-induced lipolysis, displaying 50% reduction in isoprenaline (isoproterenol)-induced lipolysis compared with control littermates. Importantly, hyperglycaemia was not observed in SST-DTA mice.Conclusions/interpretationThe isolated reduction in hypothalamic SST neurons was able to recapitulate several hallmark features of type 2 diabetes in disease-relevant tissues.

Classroom and behaviour management difficulties are consistently reported among the top reasons given by both novice and experienced teachers for leaving the profession. In order to successfully prepare and retain teachers, it is imperative that we understand the factors related to issues of classroom and behaviour management that may influence their decision to remain in the field. This study explored the development of preservice special education teachers' self-efficacy for classroom and behaviour management as they progressed through a four-semester professional development sequence. Findings indicated that although self-efficacy levels were variable across semesters, statistically significant changes in group self-efficacy levels were noted when compared to beginning levels. Despite noted increases in self-efficacy levels, participants continued to express a need for training in evidence-based practices and strategies for addressing extreme behaviours. Implications and limitations are discussed.