What happened matters: Trauma type and cumulative trauma exposure in refugee youth psychopathology.

OBJECTIVE: Trauma exposure-a contributor to psychological risk for refugee youth-is typically assessed using cumulative indices; however, recent findings indicate that trauma type may better predict psychological outcomes. This study investigated the utility of two methods of classifying trauma exposure-cumulative trauma and exposure to specific types of trauma (i.e., trauma subtypes)-in predicting the severity of symptoms related to posttraumatic stress disorder (PTSD) and anxiety for refugee youth. METHOD: 96 Syrian and Iraqi youth resettled as refugees in the United States self-reported trauma exposure and psychological symptoms. Multiple regression was used to assess the variance in symptom severity explained by specific trauma subtypes (i.e., victimization, death threat, and accidental/injury) as compared to cumulative trauma scores. RESULTS: Multiple regression models predicting PTSD revealed cumulative trauma (b = 0.07; p = .004) and death threat trauma (b = 0.16; p = .001) as significant predictors of PTSD symptom severity; notably, death threat trauma was the only subtype associated with PTSD and explained more variance than cumulative trauma scores (10.3% and 8.4%, respectively). Cumulative trauma, but no specific trauma subtype, was associated with anxiety (b = .03; p = .043); however, this relation did not survive correction for multiple comparisons. CONCLUSION: Focused trauma assessment-particularly consideration of death threat trauma and cumulative trauma exposures-may be useful in evaluating the risk of PTSD symptoms in refugee youth, whereas symptoms related to anxiety may be driven by other factors. These findings can be leveraged toward focused identification of youth at highest risk for PTSD symptoms, to improve prevention and early intervention efforts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Incoming medical students' knowledge of and attitudes toward people with substance use disorders: Implications for curricular training.

Background: Medical students may be in an ideal position to identify patients with substance use disorders (SUDs) and provide them with information about harm reduction and treatment options. Specific education regarding opioid use disorder (OUD) and naloxone during undergraduate medical training may help students identify these patients and decrease their own negative attitudes toward patients with OUD. To plan for curriculum development, this study aimed to understand baseline knowledge and attitudes among students entering medical school. Methods: During orientation, all first-year medical students (Class of 2023) were asked to complete a survey that explored their previous experiences in healthcare and with SUDs as well as their attitudes toward opioid overdose and patients with SUDs. We administered the Opioid Overdose Knowledge Scale (OOKS), Opioid Overdose Attitudes Scale (OOAS), Medical Conditions Regard Scale (MCRS), and Naloxone Related Risk Compensation Beliefs (NaRRC-B). Results: 266 students (89.6% of the class) completed the survey. Generally, these students were relatively proficient in opioid overdose knowledge, but did not feel they were competent enough to respond to an overdose. Attitudes toward patients with SUDs were mixed. Approximately half of the students thought naloxone distribution should be unrestricted, but many were uncertain whether naloxone receipt would deter individuals from seeking treatment or increase opioid use. Students' previous experiences in healthcare (e.g., employment) results in significantly different knowledge and attitudes toward opioid overdose response. Conclusions: These incoming medical students have greater healthcare experience and level of opioid overdose knowledge than the general population, but still harbor significant misinformation and stigma toward patients with SUDs. These findings provide a foundation upon which to tailor didactic efforts, starting early in medical school, so that graduating physicians can be adequately prepared for clinical care.

Notch Transduction in Non-Small Cell Lung Cancer.

The evolutionarily-conserved Notch signaling pathway plays critical roles in cell communication, function and homeostasis equilibrium. The pathway serves as a cell-to-cell juxtaposed molecular transducer and is crucial in a number of cell processes including cell fate specification, asymmetric cell division and lateral inhibition. Notch also plays critical roles in organismal development, homeostasis, and regeneration, including somitogenesis, left-right asymmetry, neurogenesis, tissue repair, self-renewal and stemness, and its dysregulation has causative roles in a number of congenital and acquired pathologies, including cancer. In the lung, Notch activity is necessary for cell fate specification and expansion, and its aberrant activity is markedly linked to various defects in club cell formation, alveologenesis, and non-small cell lung cancer (NSCLC) development. In this review, we focus on the role this intercellular signaling device plays during lung development and on its functional relevance in proximo-distal cell fate specification, branching morphogenesis, and alveolar cell determination and maturation, then revise its involvement in NSCLC formation, progression and treatment refractoriness, particularly in the context of various mutational statuses associated with NSCLC, and, lastly, conclude by providing a succinct outlook of the therapeutic perspectives of Notch targeting in NSCLC therapy, including an overview on prospective synthetic lethality approaches.

Expression of Notch Receptors and Ligands in the Coccygeal Body.

BACKGROUND: The recent discovery of neural stem cells in the sacrococcygeal end of the filum terminale, the presence of remnants of the most powerful toti-potent stem cell generators and inductors, the primitive streak and node, the existence of the unique non-mutator sacrococcygeal teratomas, and the recent disclosing of neuroimmunomodulatory and hematopoietic roles of Luschka's body, indicate that the sacrococcygeal region is a distinctive anatomic environment rich in stem cells and instructive signals, and that the coccygeal body may constitute a more complex entity than a mere caudal, vascularly-derived glomic anastomosis. Ascribed as an arterial-venous shunt located at the tip of the coccyx and analog to the glomera caudalia in other vertebrates, the glomus coccygeum has recently revealed a complex organ with peculiar 3D topology, broad innervation, catecholamine-synthesizing activity, and neutrophil-formation and lymphopoietic-regulating properties. METHODS: In the present research work, we sought to start exploring the potential cell-functional roles of the glomus coccygeum by conducting a methodical assessment of the expression of Notch pathway receptors and ligands in the human Luschka's body. RESULTS: Our data indicates that Notch receptors are dynamically and distinctively expressed in the coccygeal body and that Notch ligands are markedly differentially expressed in newborn and adult coccygeal glomi. CONCLUSIONS: Our observations suggest that Notch signaling may have relevant roles in glomus coccygeum function and biology.

RUMI is a novel negative prognostic marker and therapeutic target in non-small-cell lung cancer.

Recent comprehensive next-generation genome and transcriptome analyses in lung cancer patients, several clinical observations, and compelling evidence from mouse models of lung cancer have uncovered a critical role for Notch signaling in the initiation and progression of non-small-cell lung cancer (NSCLC). Notably, Rumi is a "protein O-glucosyltransferase" that regulates Notch signaling through O-glucosylation of Notch receptors, and is the only enzymatic regulator whose activity is required for both ligand-dependent and ligand-independent activation of Notch. We have conducted a detailed study on RUMI's involvement in NSCLC development and progression, and have further explored the therapeutic potential of its targeting in NSCLC. We have determined that Rumi is highly expressed in the alveolar and bronchiolar epithelia, including club cells and alveolar type II cells. Remarkably, RUMI maps to the region of chromosome 3q that corresponds to the major signature of neoplastic transformation in NSCLC, and is markedly amplified and overexpressed in NSCLC tumors. Notably, RUMI expression levels are predictive of poor prognosis and survival in NSCLC patients. Our data indicates that RUMI modulates Notch activity in NSCLC cells, and that its silencing dramatically decreases cell proliferation, migration, and survival. RUMI downregulation causes severe cell cycle S-phase arrest, increases genome instability, and induces late apoptotic-nonapoptotic cell death. Our studies demonstrate that RUMI is a novel negative prognostic factor with significant therapeutic potential in NSCLC, which embodies particular relevance especially when considering that, while current Notch inhibitory strategies target only ligand-dependent Notch activation, a large number of NSCLCs are driven by ligand-independent Notch activity.