Indirect and direct contributions of executive functions to reading comprehension.

In the current study, we investigated the role of executive functions in explaining how word recognition and language comprehension jointly predict reading comprehension in multilingual and monolingual students (Grades 1 and 2). Specifically, mediation and moderation models were tested and compared to offer a more nuanced understanding of the role of executive functions in reading comprehension. The results provided support for the mediation model in which executive functions indirectly contribute to reading comprehension via word recognition and language comprehension in both language groups. In addition, executive functions directly predicted reading comprehension (i.e., partial mediation). These findings suggest that executive functions serve as general cognitive processes that support word recognition, language comprehension, and reading comprehension (i.e., direct contribution) as well as facilitate connecting word recognition and language comprehension in support for reading comprehension (i.e., indirect contribution). These findings are consistent with prominent models of reading comprehension.

Implementation Drivers of Data-Based Instruction for Students With Intensive Learning Needs: A Systematic Review.

Despite decades of research efforts, data-based instruction (DBI) for students with intensive intervention needs are not being widely used in practice as anticipated, and many educators have difficulties in implementing it. This systematic review aimed to examine what kinds of implementation drivers and strategies have been used to support educators implementing DBI and what kinds of implementation outcomes researchers have measured. Eighteen studies were synthesized using the Implementation Drivers framework and Implementation Outcomes taxonomy and were quality appraised. We found that the majority of studies primarily used competency drivers to increase teachers' DBI expertise, while a limited number of studies focused on organizational and leadership drivers. Acceptability and fidelity were frequently assessed as implementation outcomes. We discussed the implications of the findings, including the need for researchers to incorporate implementation drivers and outcomes at diverse levels to best support educators' implementation of DBI, as well as the limitations of this review, such as the limited generalizability of the findings.

Teacher Predictors of Student Progress in Data-Based Writing Instruction: Knowledge, Skills, Beliefs, and Instructional Fidelity.

Teacher-level factors are theoretically linked to student outcomes in data-based instruction (DBI; Lembke et al., 2018). Professional development and ongoing support can increase teachers' knowledge, skills, and beliefs related to DBI, as well as their instructional fidelity (McMaster et al., 2020). However, less is known about how each of these teacher-level factors influences student progress during an intervention. The purpose of this study was to examine the association between several important teacher-level factors-teachers' writing instruction fidelity, knowledge and skills related to DBI, explicit writing orientation, and writing instruction self-efficacy-and students' writing growth. Participants were 49 U.S. elementary teachers and their 118 students struggling with early writing skills. Using hierarchical linear modeling, we found a significant positive relation between DBI knowledge and skills and student writing growth, but no relation was found between writing instruction fidelity, writing orientation, or self-efficacy and student writing growth. Implications for writing instruction fidelity measurement in DBI and professional development related to teachers' DBI knowledge and skills are discussed.

The Effects of Data-based Instruction (DBI) for Students with Learning Difficulties in Korea: A Single-subject Meta-analysis.

Data-based instruction (DBI) is an ongoing process to utilize students' data for determining when and how to intensify intervention. It is an educational approach that is suggested as effective to enhance achievements of struggling learners, particularly for those who did not respond to intensive intervention in usual ways. In Korea, DBI was introduced and applied for students with learning difficulties especially since 2000 when the first Korea curriculum-based measurement (CBM) was developed as the name of Basic Academic Skills Assessment. Despite a number of studies accumulated since then, there has been a lack of research that examined the level of evidence-based practice (EBP) of DBI research. Thus, the present study sought to synthesize the DBI research so far in Korea by analyzing the effectiveness of DBI for school-aged students with learning difficulties via meta-analysis and evaluating the quality of the research. In this study, a total of 32 single-subject design studies were used. Multilevel meta-analysis revealed that the mean effect size of DBI was statistically significant (B = 1.34) and there was significant variance across participants in effect sizes. The results from the conditional model showed that exceptionality type, the number of sessions, and the length of each session were significantly accountable for the variability of effect sizes. In addition, the results of the qualitative analysis revealed the acceptable quality of the overall DBI research with some limitations. Based on these findings, implications and study limitations were discussed.

Low-dose Quetiapine-induced Syndrome of Inappropriate Antidiuretic Hormone in a Patient with Traumatic Brain Syndrome.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by hyponatremia, low serum osmolality, and clinical euvolemia in the absence of diuretic medication. And the causes of SIADH are various, antipsychotic agents and traumatic brain injury (TBI) are well known. Quetiapine is often chosen to manage the maladaptive behavior of patients with post-TBI. Although a previous study reported that quetiapine doses ranging from 25 to 300 mg were effective and tolerable, the symptoms of the patient might be aggravated. The symptoms of TBI such as nausea, malaise, headache, lethargy, and mild cognitive deficits are similar to those of SIADH. So the differentiation between SIADH and TBI may be difficult. This paper reports a case of SIADH in a patient with a TBI after using a small dose of 25 to 50 mg quetiapine.

TRPC6-Mediated ERK1/2 Activation Increases Dentate Granule Cell Resistance to Status Epilepticus Via Regulating Lon Protease-1 Expression and Mitochondrial Dynamics.

Transient receptor potential canonical channel-6 (TRPC6) is one of the Ca2+-permeable non-selective cation channels. TRPC6 is mainly expressed in dentate granule cell (DGC), which is one of the most resistant neuronal populations to various harmful stresses. Although TRPC6 knockdown evokes the massive DGC degeneration induced by status epilepticus (a prolonged seizure activity, SE), the molecular mechanisms underlying the role of TRPC6 in DGC viability in response to SE are still unclear. In the present study, hyperforin (a TRPC6 activator) facilitated mitochondrial fission in DGC concomitant with increases in Lon protease-1 (LONP1, a mitochondrial protease) expression and extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation under physiological conditions, which were abrogated by U0126 (an ERK1/2 inhibitor) co-treatment. TRPC6 knockdown showed the opposite effects on LONP1 expression, ERK1/2 activity, and mitochondrial dynamics. In addition, TRPC6 siRNA and U0126 evoked the massive DGC degeneration accompanied by mitochondrial elongation following SE, independent of seizure severity. However, LONP1 siRNA exacerbated SE-induced DGC death without affecting mitochondrial length. These findings indicate that TRPC6-ERK1/2 activation may increase DGC invulnerability to SE by regulating LONP1 expression as well as mitochondrial dynamics. Therefore, TRPC6-ERK1/2-LONP1 signaling pathway will be an interesting and important therapeutic target for neuroprotection from various neurological diseases.

CDDO-Me Attenuates Vasogenic Edema and Astroglial Death by Regulating NF-κB p65 Phosphorylations and Nrf2 Expression Following Status Epilepticus.

2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid that has anti-inflammatory, antioxidant, and neuroprotective activities. In the present study, we evaluate the effects of CDDO-Me on serum extravasation and astroglial death in the rat piriform cortex (PC) induced by status epilepticus (a prolonged seizure activity, SE) in order to propose an underlying pharmacological mechanism of CDDO-Me and its availability for treatment of vasogenic edema. CDDO-Me effectively mitigated serum extravasation and a massive astroglial loss in the PC following SE. CDDO-Me abrogated tumor necrosis factor-α (TNF-α) synthesis in activated microglia by inhibiting nuclear factor-κB (NF-κB) p65 serine 276 phosphorylation. CDDO-Me also abolished NF-κB threonine 435 phosphorylation in endothelial cells and TNF-α-mediated-phosphatidylinositol-3-kinase (PI3K)/AKT/endothelial nitric oxide synthase (eNOS) signaling cascades, which trigger vasogenic edema following SE. Furthermore, CDDO-Me increased astroglial viability via the up-regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) expression. Therefore, our findings suggest that CDDO-Me may ameliorate SE-induced vasogenic edema formation by regulating NF-κB p65 phosphorylations in microglia as well as endothelial cells and enhancing Nrf2 expression in astrocytes, respectively.

CDDO-Me Selectively Attenuates CA1 Neuronal Death Induced by Status Epilepticus via Facilitating Mitochondrial Fission Independent of LONP1.

2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid that exhibits promising anti-cancer, anti-inflammatory, antioxidant and neuroprotective activities. In addition, CDDO-Me affects cellular differentiation and cell cycle arrest, and irreversibly inhibits Lon protease-1 (LONP1). In the present study, we evaluate the effects of CDDO-Me on mitochondrial dynamics and its downstream effectors in order to understand the underlying mechanism of the neuronal death following status epilepticus (SE, a prolonged seizure activity). CDDO-Me increased dynamin-related proteins 1 (DRP1)-serine 616 phosphorylation via activating extracellular-signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK), but not protein kinase A (PKA) or protein phosphatases (PPs). In addition, CDDO-Me facilitated DRP1-mediated mitochondrial fissions, which selectively attenuated SE-induced CA1 neuronal death. Unlike CDDO-Me, LONP1 knockdown led to SE-induced massive degeneration of dentate granule cells, CA1 neurons and hilus interneurons without altering the expression and phosphorylation of DRP1, ERK1/2, JNK and PP2B. LONP1 knockdown could not inhibit SE-induced mitochondrial elongation in CA1 neurons. Co-treatment of CDDO-Me with LONP1 siRNA ameliorated only CA1 neuronal death, concomitant with abrogation of mitochondrial elongation induced by SE. Thus, our findings suggest that CDDO-Me may selectively attenuate SE-induced CA1 neuronal death by rescuing the abnormal mitochondrial machinery, independent of LONP1 activity.

Roscovitine Attenuates Microglia Activation and Monocyte Infiltration via p38 MAPK Inhibition in the Rat Frontoparietal Cortex Following Status Epilepticus.

Under physiological conditions, microglia are unique immune cells resident in the brain that is isolated from the systemic immune system by brain-blood barrier. Following status epilepticus (SE, a prolonged seizure activity), microglia are rapidly activated and blood-derived monocytes that infiltrate the brain; therefore, the regulations of microglia activation and monocyte infiltration are one of the primary therapeutic strategies for inhibition of undesirable consequences from SE. Roscovitine, a potent (but not selective) cyclin-dependent kinase 5 (CDK5) inhibitor, has been found to exert anti-inflammatory and microglia-inhibiting actions in several in vivo models, although the underlying mechanisms have not been clarified. In the present study, roscovitine attenuated SE-induces monocyte infiltration without vasogenic edema formation in the frontoparietal cortex (FPC), accompanied by reducing expressions of monocyte chemotactic protein-1 (MCP-1) and lysosome-associated membrane protein 1 (LAMP1) in resident microglia, while it did not affect microglia transformation to amoeboid form. Furthermore, roscovitine ameliorated the up-regulation of p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation, but not nuclear factor-κB-S276 phosphorylation. Similar to roscovitine, SB202190, a p38 MAPK inhibitor, mitigated monocyte infiltration and microglial expressions of MCP-1 and LAMP1 in the FPC following SE. Therefore, these findings suggest for the first time that roscovitine may inhibit SE-induced neuroinflammation via regulating p38 MAPK-mediated microglial responses.

Dysfunction of 67-kDa Laminin Receptor Disrupts BBB Integrity via Impaired Dystrophin/AQP4 Complex and p38 MAPK/VEGF Activation Following Status Epilepticus.

Status epilepticus (SE, a prolonged seizure activity) impairs brain-blood barrier (BBB) integrity, which results in secondary complications following SE. The non-integrin 67-kDa laminin receptor (67-kDa LR) plays a role in cell adherence to laminin (a major glycoprotein component in basement membrane), and participates laminin-mediated signaling pathways including p38 mitogen-activated protein kinase (p38 MAPK). Thus, we investigated the role of 67-kDa LR in SE-induced vasogenic edema formation in the rat piriform cortex (PC). SE diminished 67-kDa LR expression, but increased laminin expression, in endothelial cells accompanied by the reduced SMI-71 (a rat BBB barrier marker) expression. Astroglial 67-kDa LR expression was also reduced in the PC due to massive astroglial loss. 67-kDa LR neutralization led to serum extravasation in the PC concomitant with the reduced SMI-71 expression. 67-kDa LR neutralization also decreased expressions of dystrophin and aquaporin-4 (AQP4). In addition, it increased p38 MAPK phosphorylation and expressions of vascular endothelial growth factor (VEGF), laminin and endothelial nitric oxide synthase (eNOS), which were abrogated by SB202190, a p38 MAPK inhibitor. Therefore, our findings indicate that 67-kDa LR dysfunction may disrupt dystrophin-AQP4 complex, which would evoke vasogenic edema formation and subsequent laminin over-expression via activating p38 MAPK/VEGF axis.