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County characteristics associated with behavioral health emergency medical services calls
No full textA substantial portion of the 20 million calls that emergency medical services (EMS) personnel respond to each year are considered preventable, including more than 1.5 million behavioral health calls. Despite goals of preventing behavioral health crises and reducing the burden on patients and EMS personnel, little is known about how demographic and community characteristics influence behavioral health calls. Using nationwide 2021 EMS call data, we identified counties with high behavioral health calls and examined their demographic and community characteristics. Low-income and racially diverse counties had a higher incidence of behavioral health EMS calls, while politically conservative counties had a lower incidence of behavioral health EMS calls. To better meet the emergency behavioral health needs of communities, policy and decision-makers should consider strategies that increase access to and awareness of alternative behavioral health crisis services (eg, 988 Suicide and Crisis Lifeline)
Chikamatsu, Mori, and the uncanny valley
No full textIn Japan, robotics projects like Geminoid, modeled after Hiroshi Ishiguro, exhibit a fascination with creating human doubles. Yet, warnings against this also thread through Japanese thought, from the Edo-period playwright Chikamatsu Monzaemon (1653-1724) to the robotics professor Mori Masahiro (1927-2025). Though centuries apart, they describe the same uncanny valley phenomenon-eerie, cold, repellent feelings that arise when confronting the imperfectly human. In an interview with Hozumi Ikan, translated here, Chikamatsu presents a theory of realism exemplified through puppet theater and kabuki. He divides realism into four zones: the unreal, conceptual realism, surface realism, and the real. The unreal lacks authenticity, surface realism lacks soul, and the real lacks expressiveness. For Chikamatsu, it is conceptual realism that captivates an audience. A play's unfolding events evoke empathy and emotion through their meaning for the characters. Similarly, Mori divides realism into four zones: industrial, humanoid, and android robots, and real people. Industrial robots evoke little affinity, and androids risk appearing eerie. Though real people evoke the most affinity, androids cannot become indistinguishable from them. For Mori, only humanoid robots evoke affinity without risking uncanniness. By exploring anthropomorphism, both Chikamatsu and Mori illuminate principles for designing robots that do not unsettle but delight
Inhibition of GABARAP or GABARAPL1 prevents aminoglycoside- induced hearing loss
No full textAminoglycosides (AGs) are highly potent, broad-spectrum antibiotics frequently used as first-line treatments for multiple life-threatening infections. Despite their severe ototoxicity, causing irreversible hearing loss in millions of people annually, no preventive therapy has been approved. We previously reported that GABARAP and several other central autophagy proteins are essential for AG-induced hearing loss. This finding opens avenues for the rational design and development of inhibitors that selectively target proteins in this pathway, thereby mitigating AG ototoxicity. In this study, we generated a mouse model with a targeted deletion of GABARAPL1, a homolog of GABARAP, and another model deficient in both GABARAP and GABARAPL1. We found that normal hearing is unaffected by the depletion of these proteins. Remarkably, both proteins are essential for AG-induced hearing loss, with GABARAP playing a more significant role. To further explore the therapeutic potential, we designed and validated short hairpin RNAs targeting the mouse and human GABARAP gene. By inhibiting GABARAP expression in inner ear hair cells using adeno-associated virus-mediated RNA interference, we successfully prevented AG-induced hair cell death and subsequent hearing loss. Our findings underscore the critical role of GABARAP in AG ototoxicity and highlight its potential as a therapeutic target for preventing AG-induced hearing loss
Indiana's 2023 Nursing Workforce Snapshot: All Actively Practicing Certified Registered Nurse Anesthetists
No full textThe certified registered nurse anesthetist workforce snapshot summarizes and contextualizes findings from the 2023 Indiana Registered Nurses Health Workforce Data Report and depicts information about primary setting, populations served, and geographic distribution
Opportunities to encourage adoption of a biomarker-enabled care pathway for Alzheimer's in primary care
No full textIdentification of early-stage Alzheimer's disease (AD) remains a challenge due to limited specialist availability, diagnostic access, disease awareness, and cultural factors. Blood-based biomarkers (BBBM) could play a critical role in the identification and referral of patients suspected of AD to specialty care. A multidisciplinary AD Biomarker Task Force was convened to evaluate current biomarker use cases, define an optimal biomarker-enabled AD diagnostic care pathway, and understand factors impacting adoption. The Task Force identified opportunities to support biomarker-enabled AD diagnostic care pathway adoption, including streamlining risk assessment and screening by leveraging digital tools, activating primary care providers through education, generating data to expand applicability to diverse populations, and advocating for aligned policies and quality measures. Adoption of BBBMs in the primary care setting will be critical to improve early AD detection. However, challenges to pathway adoption persist and will require action from clinicians, payers, policy makers, and patients to address.
Highlights: Blood-based biomarkers can streamline the identification of AD in primary care. Future biomarker-enabled diagnostic care pathways will leverage digital assessments. Education, data generation, and policy advocacy are vital to encourage BBBM use. Implementation of AD care pathways requires the activation of diverse stakeholders
The oligosaccharyltransferase complex is an essential component of multiple myeloma plasma cells
No full textMultiple myeloma (MM) is an incurable malignancy characterized by mutated plasma cell clonal expansion in the bone marrow, leading to severe clinical symptoms. Thus, identifying new therapeutic targets for MM is crucial. We identified the oligosaccharyltransferase (OST) complex as a novel vulnerability in MM cells. Elevated expression of this complex is associated with relapsed, high-risk MM, and poor prognosis. Disrupting the OST complex suppressed MM cell growth, induced cell-cycle arrest, and apoptosis. Combined inhibition with bortezomib synergistically eliminated MM cells in vitro and in vivo, via suppressing genes related to bortezomib-resistant phenotypes. Mechanistically, OST complex disruption downregulated MM pathological pathways (mTORC1 pathway, glycolysis, MYC targets, and cell cycle) and induced TRAIL-mediated apoptosis. Notably, MYC translation was robustly suppressed upon inhibiting the OST complex. Collectively, the OST complex presents a novel target for MM treatment, and combining its inhibition with bortezomib offers a promising approach for relapsed MM patients
Comorbidities and HIV-related factors associated with mental health symptoms and unhealthy substance use among older adults living with HIV in low- and middle-income countries: a cross-sectional study
No full textIntroduction: People with HIV (PWH) are vulnerable to mental health and substance use disorders (MSDs), but the extent to which these are associated with other non-communicable diseases in ageing PWH populations remains poorly documented. We assessed comorbidities associated with symptoms of MSD among PWH ≥40 years in the Sentinel Research Network (SRN) of the International epidemiology Database to Evaluate AIDS (IeDEA).
Methods: Baseline data collected between June 2020 and September 2022, from 10 HIV clinics in Asia, Latin America and Africa contributing to the SRN, were analysed. Symptoms of MSDs and comorbidities were assessed using standardized questionnaires, anthropometric and laboratory tests, including weight, height, blood pressure, glucose, lipids, chronic viral hepatitis and liver transient elastography. HIV viral load, CD4 count and additional routine clinical data were accessed from participant interview or medical records. HIV and non-HIV clinical associations of mental illness symptoms and unhealthy substance use were analysed using logistic regression. Mental illness symptoms were defined as moderate-to-severe depressive symptoms (PHQ-9 score >9), moderate-to-severe anxiety symptoms (GAD-7 >9) or probable post-traumatic stress disorder (PCL-5 >32). Unhealthy substance use was defined as ASSIST score >3, or AUDIT ≥7 for women (≥8 for men).
Results: Of 2614 participants assessed at baseline study visits, 57% were female, median age was 50 years, median CD4 was 548 cells/mm3 and 86% had HIV viral load 25 kg/m2, 38% hypertension, 15% type 2 diabetes, 35% dyslipidaemia, 34% liver disease and 23% history of tuberculosis. BMI >25 and dyslipidaemia were found in 54% and 40% of those with mental illness symptoms compared to 49% and 34% of those without. Mental illness symptoms were not significantly associated with the clinical factors assessed. Unhealthy substance use was more likely among those with dyslipidaemia (OR 1.55, CI 1.16-2.09, p = 0.003), and less likely in those with BMI >25 (OR 0.48, CI 0.30-0.77, p = 0.009).
Conclusions: Improved integration of MSD and comorbidity services in HIV clinical settings, and further research on the association between MSD and comorbidities, and care integration among older PWH in low-middle-income countries, are required