In Deaf classrooms, social studies instruction is usually conveyed via the banking approach instead the inquiry approach leaving students without opportunities to exercise their critical thinking skills. This curriculum addressed this problem by demonstrating how deaf students can be given opportunities to develop and use their critical thinking skills in social studies content using maps. Learning activities in this curriculum designed with the following four goals in mind; support students in developing their critical thinking skills, foster students' skills in reading, interpreting, and using maps, develop and use academic language associated with maps in both ASL and English, and encourage students to use the inquiry approach as a learning strategy. This curriculum was field tested at a school for the deaf in a 5th grade classroom with seven deaf and hard of hearing students. Field notes, artifacts, and lesson assessments were used to evaluate the outcomes of the curriculum to determine whether if it was a success. The evaluation indicates that the curricular goals were successfully met. Students showed an effort to use their critical thinking skills while interacting with maps and associated graphical organizers and at the same time used academic language in both ASL and English. They also showed usage of the inquiry approach in seeking knowledge in the content area addressed

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique involving administration of well-tolerated electrical current to the brain through scalp electrodes. TDCS may improve symptoms in neuropsychiatric disorders, but mixed results from recent clinical trials underscore the need to demonstrate that tDCS can modulate clinically relevant brain systems over time in patients. Here, we analyzed longitudinal structural MRI data from a randomized, double-blind, parallel-design clinical trial in depression (NCT03556124, N = 59) to investigate whether serial tDCS individually targeted to the left dorso-lateral prefrontal cortex (DLPFC) can induce neurostructural changes. Significant (FWEc p < 0.05) treatment-related gray matter changes were observed with active high-definition (HD) tDCS relative to sham tDCS within the left DLPFC stimulation target. No changes were observed with active conventional tDCS. A follow-up analysis within individual treatment groups revealed significant gray matter increases with active HD-tDCS in brain regions functionally connected with the stimulation target, including the bilateral DLPFC, bilateral posterior cingulate cortex, subgenual anterior cingulate cortex, and the right hippocampus, thalamus and left caudate brain regions. Integrity of blinding was verified, no significant differences in stimulation-related discomfort were observed between treatment groups, and tDCS treatments were not augmented by any other adjunct treatments. Overall, these results demonstrate that serial HD-tDCS leads to neurostructural changes at a predetermined brain target in depression and suggest that such plasticity effects may propagate over brain networks.

Background

Meta-analyses have reported that the effects of cognitive remediation might go beyond improvement in cognition to include unexpected benefits for schizophrenia patients such as negative symptom reduction and improvements in functioning. In addition, some evidence indicated that these potentially beneficial effects are also present in the initial course of schizophrenia, but work in this area is still developing.

Method

A RCT compared Cognitive Remediation (CR) to Healthy Behaviors Training (HBT) in 80 patients (78% male) with a mean age of 21.9years and mean education of 12.3years who had a first psychotic episode within two years of study entry. Participants were trained using CR programs or received HBT involving 50 sessions over 6months and then booster sessions over the next 6months. The SANS and BPRS were used to assess symptoms. The UCLA Social Attainment Survey assessed social functioning.

Results

Using GLMM, improvements over 12months were found favoring CR for SANS Expressive Symptoms (p<0.01), which was composed of Affective Flattening (p<0.01) and Alogia (p=0.04), and for SANS Experiential Symptoms, composed of Avolition/Apathy (p=0.04) and Anhedonia/Asociality (p<0.01). CR was associated with improvements in social functioning (p=0.05) as compared to HBT.

Conclusions

We confirmed that the beneficial effects of CR appear to extend beyond cognition to improvements in negative symptoms and social functioning in early course schizophrenia patients. These results suggest that cognitive remediation might have an impact when the reduction of risk factors for chronicity is most critical for promoting recovery.

Cryptococcus neoformans, the most common cause of fungal meningitis, is a basidiomycete haploid budding yeast with a complete sexual cycle. Genome modification by homologous recombination is feasible using biolistic transformation and long homology arms, but the method is arduous and unreliable. Recently, multiple groups have reported the use of CRISPR-Cas9 as an alternative to biolistics, but long homology arms are still necessary, limiting the utility of this method. Since the S. pyogenes Cas9 derivatives used in prior studies were not optimized for expression in C. neoformans, we designed, synthesized, and tested a fully C. neoformans-optimized (Cno) Cas9. We found that a Cas9 harboring only common C. neoformans codons and a consensus C. neoformans intron together with a TEF1 promoter and terminator and a nuclear localization signal (Cno CAS9 or "CnoCAS9") reliably enabled genome editing in the widely used KN99α C. neoformans strain. Furthermore, editing was accomplished using donors harboring short (50 bp) homology arms attached to marker DNAs produced with synthetic oligonucleotides and PCR amplification. We also demonstrated that prior stable integration of CnoCAS9 further enhances both transformation and homologous recombination efficiency; importantly, this manipulation does not impact virulence in animals. We also implemented a universal tagging module harboring a codon-optimized fluorescent protein (mNeonGreen) and a tandem Calmodulin Binding Peptide-2X FLAG Tag that allows for both localization and purification studies of proteins for which the corresponding genes are modified by short homology-directed recombination. These tools enable short-homology genome engineering in C. neoformans.

Ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depressive disorder (MDD). Yet, how single and repeated ketamine treatment induces brain systems-level neuroplasticity underlying symptom improvement is unknown. Advanced multiband imaging (MB) pseudo-continuous arterial spin labeling (pCASL) perfusion MRI data was acquired from patients with treatment resistant depression (TRD) (N = 22, mean age=35.2 ± 9.95 SD, 27% female) at baseline, and 24 h after receiving single, and four subanesthetic (0.5 mg/kg) intravenous ketamine infusions. Changes in global and regional CBF were compared across time points, and relationships with overall mood, anhedonia and apathy were examined. Comparisons between patients at baseline and controls (N = 18, mean age=36.11 ± 14.5 SD, 57% female) established normalization of treatment effects. Results showed increased regional CBF in the cingulate and primary and higher-order visual association regions after first ketamine treatment. Baseline CBF in the fusiform, and acute changes in CBF in visual areas were related to symptom improvement after single and repeated ketamine treatment, respectively. In contrast, after serial infusion therapy, decreases in regional CBF were observed in the bilateral hippocampus and right insula with ketamine treatment. Findings demonstrate that neurophysiological changes occurring with single and repeated ketamine treatment follow both a regional and temporal pattern including sensory and limbic regions. Initial changes are observed in the posterior cingulate and precuneus and primary and higher-order visual areas, which relate to clinical responses. However, repeated exposure to ketamine, though not relating to clinical outcome, appears to engage deeper limbic structures and insula. ClinicalTrials.gov: Biomarkers of Fast Acting Therapies in Major Depression, https://clinicaltrials.gov/ct2/show/NCT02165449, NCT02165449.

Cryptococcosis is an invasive infection that accounts for 15% of AIDS-related fatalities. Still, treating cryptococcosis remains a significant challenge due to the poor availability of effective antifungal therapies and emergence of drug resistance. Interestingly, protease inhibitor components of antiretroviral therapy regimens have shown some clinical benefits in these opportunistic infections. We investigated Major aspartyl peptidase 1 (May1), a secreted Cryptococcus neoformans protease, as a possible target for the development of drugs that act against both fungal and retroviral aspartyl proteases. Here, we describe the biochemical characterization of May1, present its high-resolution X-ray structure, and provide its substrate specificity analysis. Through combinatorial screening of 11,520 compounds, we identified a potent inhibitor of May1 and HIV protease. This dual-specificity inhibitor exhibits antifungal activity in yeast culture, low cytotoxicity, and low off-target activity against host proteases and could thus serve as a lead compound for further development of May1 and HIV protease inhibitors.