A Cord of Many Strands: A Case Study of Inclusive Practice within the Archdiocese of Los Angeles

The foundational philosophy of Catholic schools impels them toward inclusive practice. Scholars have repeatedly established that a moral mandate exists in Catholic Social Teaching for Catholic schools to include all students. However, students with disabilities have traditionally been excluded from Catholic school settings due perceived resource constraints, lack of practitioner skill, and the disposition that students with disabilities are better served in public schools. Many Catholic schools have made tremendous progress in inclusive practice, and stand at the forefront of this work, but these efforts have not been replicated at scale. The purpose of this study was to explore how communities of practice support inclusion in the Archdiocese of Los Angeles. A convergent mixed methods approach to social network analysis was used to describe the state of inclusive practice in Catholic schools and the relationships that facilitate diffusion of information and resources across these organizations. The findings of this study indicated that Catholic educators strongly support inclusion and associate it with the mission of Catholic education but lack capacity in their knowledge and resources to create inclusive environments, despite the presence of skilled teachers and other internal resources. The study found that Catholic schools are resourceful and build effective partnerships with parents, students, and outside organizations to support students with disabilities, but that networks across school sites are fragmented

Synchrotron emission from double-peaked radio light curves of the symbiotic recurrent nova V3890 Sagitarii

We present radio observations of the symbiotic recurrent nova V3890 Sagitarii following the 2019 August eruption obtained with the MeerKAT radio telescope at 1.28 GHz and Karl G. Janksy Very Large Array (VLA) at 1.26 to 5 GHz. The radio light curves span from day 1 to 540 days after eruption and are dominated by synchrotron emission produced by the expanding nova ejecta interacting with the dense wind from an evolved companion in the binary system. The radio emission is detected early on (day 6) and increases rapidly to a peak on day 15. The radio luminosity increases due to a decrease in the opacity of the circumstellar material in front of the shocked material and fades as the density of the surrounding medium decreases and the velocity of the shock decelerates. Modelling the light curve provides an estimated mass-loss rate of $M_{\textrm {wind}} \approx 10^{-8} {\textrm {M}}_\odot~{\textrm {yr}}^{-1}$ from the red giant star and ejecta mass in the range of $M_{\textrm {ej}}=10^{-5}-10^{-6}~{\textrm {M}}_\odot$from the surface of the white dwarf. V3890 Sgr likely hosts a massive white dwarf similar to other symbiotic recurrent novae, thus considered a candidate for supernovae type Ia (SNe Ia) progenitor. However, its radio flux densities compared to upper limits for SNe Ia have ruled it out as a progenitor for SN 2011fe

Paliperidone to treat psychotic disorders

Purpose of Review: This is a comprehensive review of the literature regarding the use of paliperidone in the treatment of schizophrenia and schizoaffective disorder. It covers the background and presentation of schizophrenia and schizoaffective disorder, as well as the mechanism of action and drug information for paliperidone. It covers the existing evidence of the use of paliperidone for the treatment of schizophrenia and schizoaffective disorder. Recent Findings: Schizophrenia and schizoaffective disorder lead to significant cognitive impairment. It is thought that dopamine dysreg-ulation is the culprit for the positive symptoms of schizophrenia and schizoaffective disorder. Similar to other second-generation antipsychotics, paliperidone has affinity for dopamine D2 and serotonin 5-HT2A receptors. Paliperidone was granted approval in the United States in 2006 to be used in the treatment of schizophrenia and in 2009 for schizoaffective disorder. Summary: Schizophrenia and schizoaffective disorder have a large impact on cognitive impairment, positive symptoms and negative symptoms. Patients with either of these mental illnesses suffer from impairments in everyday life. Paliperidone has been shown to reduce symptoms of schizophrenia and schizoaffective disorder

Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, GLS1 mRNA expression did not show a statistically significant difference in disease-free survival (DFS) but did show a small significant difference in overall survival (OS). In the TMA cohort, there was no correlation between GLS1 expression and stage, Gleason score, DFS and OS. GLS1 expression did not significantly correlate with the clinical outcomes measured; however, GLS1 expression was higher in PCa cells compared to benign epithelium. Future studies are warranted to evaluate expression levels in greater numbers of high-grade and advanced PCa samples to investigate whether there is a rational basis for GLS1 targeted therapy in a subset of patients with prostate cancer

Large-scale functional inference for skin-expressing lncRNAs using expression and sequence information

Long noncoding RNAs (lncRNAs) regulate the expression of protein-coding genes and have been shown to play important roles in inflammatory skin diseases. However, we still have limited understanding of the functional impact of lncRNAs in skin, partly due to their tissue specificity and lower expression levels compared with protein-coding genes. We compiled a comprehensive list of 18,517 lncRNAs from different sources and studied their expression profiles in 834 RNA-Seq samples from multiple inflammatory skin conditions and cytokine-stimulated keratinocytes. Applying a balanced random forest to predict involvement in biological functions, we achieved a median AUROC of 0.79 in 10-fold cross-validation, identifying significant DNA binding domains (DBDs) for 39 lncRNAs. G18244, a skin-expressing lncRNA predicted for IL-4/IL-13 signaling in keratinocytes, was highly correlated in expression with F13A1, a protein-coding gene involved in macrophage regulation, and we further identified a significant DBD in F13A1 for G18244. Reflecting clinical implications, AC090198.1 (predicted for IL-17 pathway) and AC005332.6 (predicted for IFN-γ pathway) had significant negative correlation with the SCORAD metric for atopic dermatitis. We also utilized single-cell RNA and spatial sequencing data to validate cell type specificity. Our research demonstrates lncRNAs have important immunological roles and can help prioritize their impact on inflammatory skin diseases.</p

A Parkinson's disease gene regulatory network identifies the signaling protein RGS2 as a modulator of LRRK2 activity and neuronal toxicity

Mutations in LRRK2 are one of the primary genetic causes of Parkinson's disease (PD). LRRK2 contains a kinase and a GTPase domain, and familial PD mutations affect both enzymatic activities. However, the signaling mechanisms regulating LRRK2 and the pathogenic effects of familial mutations remain unknown. Identifying the signaling proteins that regulate LRRK2 function and toxicity remains a critical goal for the development of effective therapeutic strategies. In this study, we apply systems biology tools to human PD brain and blood transcriptomes to reverse-engineer a LRRK2-centered gene regulatory network. This network identifies several putative master regulators of LRRK2 function. In particular, the signaling gene RGS2, which encodes for a GTPase-activating protein (GAP), is a key regulatory hub connecting the familial PD-associated genes DJ-1 and PINK1 with LRRK2 in the network. RGS2 expression levels are reduced in the striata of LRRK2 and sporadic PD patients. We identify RGS2 as a novel interacting partner of LRRK2 in vivo. RGS2 regulates both the GTPase and kinase activities of LRRK2. We show in mammalian neurons that RGS2 regulates LRRK2 function in the control of neuronal process length. RGS2 is also protective against neuronal toxicity of the most prevalent mutation in LRRK2, G2019S. We find that RGS2 regulates LRRK2 function and neuronal toxicity through its effects on kinase activity and independently of GTPase activity, which reveals a novel mode of action for GAP proteins. This work identifies RGS2 as a promising target for interfering with neurodegeneration due to LRRK2 mutations in PD patient

Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome

PURPOSE: Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS: To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS: We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS: Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer

Real-Time Fluorescence Loop Mediated Isothermal Amplification for the Diagnosis of Malaria

BACKGROUND: Molecular diagnostic methods can complement existing tools to improve the diagnosis of malaria. However, they require good laboratory infrastructure thereby restricting their use to reference laboratories and research studies. Therefore, adopting molecular tools for routine use in malaria endemic countries will require simpler molecular platforms. The recently developed loop-mediated isothermal amplification (LAMP) method is relatively simple and can be improved for better use in endemic countries. In this study, we attempted to improve this method for malaria diagnosis by using a simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in one platform. We refer to this as the RealAmp method. METHODOLOGY AND SIGNIFICANT FINDINGS: Published genus-specific primers were used to test the utility of this method. DNA derived from different species of malaria parasites was used for the initial characterization. Clinical samples of P. falciparum were used to determine the sensitivity and specificity of this system compared to microscopy and a nested PCR method. Additionally, directly boiled parasite preparations were compared with a conventional DNA isolation method. The RealAmp method was found to be simple and allowed real-time detection of DNA amplification. The time to amplification varied but was generally less than 60 minutes. All human-infecting Plasmodium species were detected. The sensitivity and specificity of RealAmp in detecting P. falciparum was 96.7% and 91.7% respectively, compared to microscopy and 98.9% and 100% respectively, compared to a standard nested PCR method. In addition, this method consistently detected P. falciparum from directly boiled blood samples. CONCLUSION: This RealAmp method has great potential as a field usable molecular tool for diagnosis of malaria. This tool can provide an alternative to conventional PCR based diagnostic methods for field use in clinical and operational programs