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Abstract The hippocampus is pivotal in integrating emotional processing, learning, memory, and reward-related behaviors. The dorsal hippocampus (dHPC) is particularly crucial for episodic, spatial, and associative memory, and has been shown to be necessary for context- and cue-associated reward behaviors. The nucleus accumbens (NAc), a central structure in the mesolimbic reward pathway, integrates the salience of aversive and rewarding stimuli. Despite extensive research on dHPC→NAc direct projections, their sufficiency in driving reinforcement and reward-related behavior remains to be determined. Our study establishes that activating excitatory neurons in the dHPC is sufficient to induce reinforcing behaviors through its direct projections to the dorso-medial subregion of the NAc shell (dmNAcSh). Notably, dynorphin-containing neurons specifically contribute to dHPC-driven reinforcing behavior, even though both dmNAcSh dynorphin- and enkephalin-containing neurons are activated with dHPC stimulation. Our findings unveil a pathway governing reinforcement, advancing our understanding of the hippocampal circuity’s role in reward-seeking behaviors.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression. Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL. We aim to recruit 150 participants with diagnosed CADASIL, family history of CADASIL or suspected CADASIL symptoms, and 150 cognitively normal NOTCH3 negative individuals as controls. Participants will complete: 1) online questionnaires on medical and family history, mental health, and wellbeing; 2) neuropsychological evaluation; 3) neurological examination and brain MRI; 4) ocular examination and 5) blood sample donation. Participants will have annual follow-up for 4 years to assess their progression and will be asked to invite a study partner to corroborate their self-reported cognitive and functional abilities.Primary outcomes include cognitive function and neuroimaging abnormalities. Secondary outcomes include investigation of genetics and blood and ocular biomarkers. Data from the cohort will contribute to an international consortium, and cohort participants will be invited to access future treatment/health intervention trials. Discussion: AusCADASIL will be the first study of an Australian cohort of individuals with CADASIL. The study will identify common pathogenic variants in this cohort, and characterise the pattern of clinical presentation and longitudinal progression, including imaging features, blood and ocular biomarkers and cognitive profile.

Accumulation of α-synuclein (α-syn) into insoluble aggregates occurs in several related disorders collectively referred to as synucleinopathies. To date, studies have used neural stem cells (NSCs) to examine questions about α-syn propagation, but have overlooked the therapeutic potential of NSC transplantation to modulate cognition in disorders such as dementia with Lewy bodies or Parkinson’s disease dementia. Here, we show that striatal transplantation of NSCs into aged α-syn transgenic mice significantly improves performance in multiple cognitive and motor domains. This recovery is associated with NSC expression of brain-derived neurotrophic factor (BDNF), which restores depleted levels and modulates dopaminergic and glutamatergic systems. Most importantly, transplantation of BDNF-depleted NSCs fails to improve behavior, whereas AAV-mediated BDNF delivery mimics the benefits of NSC transplantation, supporting a critical role for this neurotrophin in functional improvement. Thus, NSC transplantation could offer a promising approach to treat the understudied yet devastating cognitive components of many synucleinopathies.

Introduction: When examining health literacy and disease specific knowledge levels across ethnicities and communities, ethnic minority groups are known to be at a higher risk of being below the average health literacy threshold which is a factor linked to poor health status and higher mortality rates. This study examined disease specific knowledge levels, perceived severity, and perceived susceptibility surrounding anal cancer and HPV-related screening behaviors. Methods: The following research questions were explored: (1) “What are the common themes and/or beliefs when asked about anal cancer, HPV, and preventive screening?” and (2) “What are the common themes and beliefs surrounding the severity and susceptibility of contracting anal cancer?”. This study utilized a cross-sectional design to survey 26 individuals regarding their knowledge level and perspectives regarding anal cancer and HPV. An 8-question survey was developed de novo based on an application of the Health Belief Model (HBM) elements. This study employed thematic analysis to explore critical themes to construct a model to understand knowledge levels, attitudes, and risk perceptions regarding anal cancer and intention to participate in preventive screenings. The fundamental attitudes and themes related to anal cancer risk and intention to participate in preventative screenings were elicited using a qualitative descriptive technique. Coded data was utilized to analyze themes based on (1) knowledge and (2) perceived risk, both severity and susceptibility. Results: Overall, the findings indicate very low levels of knowledge regarding screening, anal cancer, and HPV across all genders. The low levels of anal cancer and HPV knowledge were seen in 13 coded segments (50% of surveys) which showed no familiarity with or comprehension of HPV, and 4 coded segments indicated no familiarity with anal cancer. In addition, 15 respondents (57%) had low or no preventive or screening-related knowledge. While some respondents (46%) illustrated high perceived severity for anal cancer, only 23% indicated high perceived susceptibility for anal cancer. Conclusion: The results from this study may be used to inform practitioners, providers, and policymakers in developing interventions addressing low levels of understanding and disease specific knowledge surrounding anal cancer in support of creating a standardized health screening procedure.

Purpose: The emergence of the COVID-19 pandemic led health care systems and providers worldwide to rapidly adopt telehealth solutions to minimize risk and comply with isolation mandates. This article explores telehealth utilization trends in North Carolina (NC) free and charitable clinics?an ambulatory health care delivery setting where traditional third-party reimbursement policies are not a primary consideration. Methods: We surveyed NC free and charitable clinic administrators regarding clinic decisions to adopt an externally sponsored telehealth system, what services are provided by telehealth, clinic implementation processes, which populations used telehealth, how telehealth was incorporated into current clinic workflows, and perceptions of telehealth outcomes. Findings: Telehealth was rapidly adopted among free and charitable clinics after the COVID-19 outbreak. Reasons for implementing telehealth included the ability to continue providing services during a public health emergency and to increase access to patients. However, clinics report that telehealth utilization has dropped significantly since the initial pandemic surge. Patient and provider preferences for in-person services are a common reason cited for this drop. Free and charitable clinics report a strong interest in continuing to deliver services through telehealth. The majority reported continuing to offer telehealth services, but primarily as a supplement to in-person visits rather than as a replacement. They perceive that implementing telehealth has increased access to care but are less certain about the impact on cost of care and patient satisfaction. However, clinic administrators believe improvements in interoperability with other data systems, workflows, scheduling, and care delivery approaches are needed to achieve telehealth's fullest utilization. Conclusion: Telehealth can play a significant role in expanding access to services in the free and charitable clinic setting. However, continued refinements in the technology to facilitate integration with other systems and workflow processes are needed to reach its full potential.

Abstract Serological biomarkers of inner ear proteins are a promising new approach for studying human hearing. Here, we focus on the serological measurement of prestin, a protein integral to a human’s highly sensitive hearing, expressed in cochlear outer hair cells (OHCs). Building from recent nonhuman studies that associated noise-induced OHC trauma with reduced serum prestin levels, and studies suggesting subclinical hearing damage in humans regularly engaging in noisy activities, we investigated the relation between serum prestin levels and environmental noise levels in young adults with normal clinical audiograms. We measured prestin protein levels from circulating blood and collected noise level data multiple times over the course of the experiment using body-worn sound recorders. Results indicate that serum prestin levels have a negative relation with noise exposure: individuals with higher routine noise exposure levels tended to have lower prestin levels. Moreover, when grouping participants based on their risk for a clinically-significant noise-induced hearing loss, we found that prestin levels differed significantly between groups, even though behavioral hearing thresholds were similar. We discuss possible interpretations for our findings including whether lower serum levels may reflect subclinical levels of OHC damage, or possibly an adaptive, protective mechanism in which prestin expression is downregulated in response to loud environments.

Objective: Mindfulness-based interventions are an evidence-based approach utilized in health care. There is developing evidence for effective use with military Veterans. However, little is known about Veterans’ view of mindfulness. This study aims to understand their interests, perceptions, and use of mindfulness to enhance educational outreach and treatment engagement. Methods: A cross-sectional study was conducted across the Veterans Health Administration in Salt Lake City, UT by administering a questionnaire to military Veterans. The questionnaire included the following themes: (1) demographics and respondents’ mindfulness practice; (2) respondents’ perceptions and beliefs about mindfulness; and (3) respondents’ knowledge and interest in learning about mindfulness. Results: In all, 185 military Veterans were surveyed; 30% practiced mindfulness in the past year, mainly for stress, posttraumatic stress disorder, sleep, and depression. Over 75% who practiced reported perceived benefit. Veterans rarely reported negative beliefs about mindfulness; 56% perceived an understanding of mindfulness and 46% were aware of Veterans Health Administration mindfulness offerings. In all, 55% were interested in learning about mindfulness, 58% were interested in learning how it could help, and 43% were interested in combining mindfulness with a pleasurable activity. Conclusion: Educational engagement approaches should be directed toward the benefits of mindfulness practice with minimal need to address negative beliefs. Outreach including education, with an experiential component, about mindfulness classes, availability of evening and weekend classes, individual sessions, and virtual offerings into Veteran’s homes, may enhance engagement in mindfulness-based interventions. Mindfulness-based interventions that combine mindfulness training with an experiential pleasurable activity may be one mechanism to enhance treatment engagement.

ABSTRACT IMPACT: We aim to understand how LTCCs impact cerebellar function. OBJECTIVES/GOALS: L-type calcium channels (LTCCs) are important in activity-dependent neurite outgrowth, which comprises neurite initiation and elongation. We used cerebellar granule neurons (CGNs) to differentiate between LTCC effects on neurite initiation vs elongation. We also tested cerebellar function in mice lacking specific LTCCs with behavioral assays. METHODS/STUDY POPULATION: CGNs were cultured from 129SvEv mouse pups at P4-P6. Potassum chloride (50mM) was used to stimulate neuronal cultures for 24 hours. Isradipine (20nM) was added to culture medium to inhibit all LTCCs for 1 hour. For Cav1.2 deletion, we crossed Cav1.2 conditional knockout mice (Cav1.2-cKO) to Syn-Cre mice (for deletion in most neurons) or Atoh1-Cre mice (for deletion in CGNs). The Cav1.2-cKO line was maintained on a 129SvEv background. For constitutive Cav1.3 deletion, mice were maintained on a C57BL/6NTac. Behavioral tasks included open field, rotarod, and Erasmus Ladder. Data were analyzed with sexes combined and separated to assess for sex as a biological variable. Studies were analyzed by one-way ANOVA, two-way ANOVA, or generalized linear mixed model, where appropriate. RESULTS/ANTICIPATED RESULTS: CGNs exhibited an increase in neurite initiation but not elongation when stimulated with potassium chloride, consistent with previous reports of activity-dependent neurite outgrowth in this cell type. LTCC inhibition with isradipine blunted KCl-induced neurite initiation. We observed no change in the length of either primary or secondary neurites with isradipine treatment with or without KCl stimulation. In our behavioral experiments, we observed no deficits in open field, rotarod, or Erasmus Ladder when Cav1.2 was deleted in most neurons (driven by Syn-Cre expression) or in cerebellar granule neurons (driven by Atoh1-Cre expression). In contrast, loss of Cav1.3 was associated with impaired motor learning in the rotarod task without evidence of ataxia on Erasmus Ladder. DISCUSSION/SIGNIFICANCE OF FINDINGS: We show a specific role for LTCCs in activity-dependent CGN neurite initiation. While loss of Cav1.2 does not affect motor learning, loss of Cav1.3 does impair motor learning. Our results help expand our understanding of LTCC function in cerebellar neurodevelopment and function.

Because of escalating technological conflicts, the US-China technology war, and hegemonic competition since the late 2010s, “technonationalism,” has become a critical topic in the international political economy, and this study contributes to the ongoing discussion proposing two mediating variables, the global value chain (GVC) and the US-China competition in the 2010s. First, we propose a shift in the technonationalist paradigm, from focusing on a single-state approach with an industrial policy oriented toward development to a multistate focus approach with a geoeconomic strategy oriented toward security. It also highlights the integration of business interests into the national strategic agenda as a critical criterion. Second, the study examines investment in Japan by Elpida Memory, Kioxia, and Taiwan Semiconductor Manufacturing Company. Based on Japan as a case study, the findings show a shift to technonationalism, as the government responds to changes in international political conditions, rather than to domestic demands for supporting a specific segment of the semiconductor industry.