Hypothalamic involvement in multiple system atrophy: A structural MRI study.

OBJECTIVE: To investigate hypothalamic atrophy and its clinical correlates in multiple system atrophy (MSA) in-vivo. BACKGROUND: MSA is characterized by autonomic dysfunction and parkinsonian/cerebellar manifestations. The hypothalamus regulates autonomic and homeostatic functions and is also involved in memory and learning processes. METHODS: 11 MSA, 18 Parkinson's Disease (PD) and 18 Healthy Controls (HC) were included in this study. A validated and automated hypothalamic segmentation tool was applied to 3D-T1-weighted images acquired on a 3T MRI scanner. MSA hypothalamic volumes were compared to those of PD and HC. Furthermore, the association between hypothalamic volumes and scores of autonomic, depressive, sleep and cognitive manifestations were investigated. RESULTS: Posterior hypothalamus volume was reduced in MSA compared to controls (t = 2.105, p = 0.041) and PD (t = 2.055, p = 0.046). Total hypothalamus showed a trend towards a reduction in MSA vs controls (t = 1.676, p = 0.101). Reduced posterior hypothalamus volume correlated with worse MoCA scores in the parkinsonian (MSA + PD) group and in each group separately, but not with autonomic, sleep, or depression scores. CONCLUSIONS: In-vivo structural hypothalamic involvement may be present in MSA. Reduced posterior hypothalamus volume, which includes the mammillary bodies and lateral hypothalamus, is associated with worse cognitive functioning. Larger studies on hypothalamic involvement in MSA and its clinical correlates are needed.

The development of a clinical research educational training for community health workers using the joint task force for clinical trial competency framework.

Introduction: The NYU Clinical & Translational Science Institute, in collaboration with a number of community-engaged initiatives, developed a training for community health workers (CHWs) to enhance health literacy about clinical research. This innovative research training provides CHWs with a basic level of competency in clinical research to convey the importance of research to communities and better advocate for their health needs. CHWs are an underutilized resource to engage diverse populations in clinical research. The training also addresses the need to expand and diversify the clinical research workforce-integrating CHWs into research teams and connecting underserved populations with research opportunities to enhance quality of care. Methods: Structured individual interviews and focus group sessions were held with CHWs as well as clinical research faculty and staff to identify knowledge gaps in clinical research and identify best practices for educating community members on research. Using the Joint Task Force (JTF) for Clinical Trial Competency framework, an online course was developed consisting of 28 modules offered asynchronously for internal and external audiences. Topics include the fundamentals of clinical research, scientific concepts and research design, research ethics, study management, clinical study operations, communications, and teamwork, as well as the importance of diversity and equity in research and the barriers to participation. Results: Learning was evaluated using multiple choice questions after each module to ensure the fundamental level of knowledge was obtained. A separate survey, completed at the conclusion of the course, evaluated the quality of training. Discussion: The course aims to enhance the knowledge and skills of CHWs to help promote greater understanding of clinical research within the communities they serve, including the risks and benefits of clinical research and opportunities for participation. As members of the research team, community stakeholders can help design interventions tailored to the unique needs, culture, and context of their communities. In addition, this research training equips trainees with skills to engage the community actively, involving them in the research process and ensuring community priorities are represented in research through more community engaged processes.

Acute inhibition of acid sensing ion channel 1a after spinal cord injury selectively affects excitatory synaptic transmission, but not intrinsic membrane properties, in deep dorsal horn interneurons.

Following a spinal cord injury (SCI), secondary damage mechanisms are triggered that cause inflammation and cell death. A key component of this secondary damage is a reduction in local blood flow that initiates a well-characterised ischemic cascade. Downstream hypoxia and acidosis activate acid sensing ion channel 1a (ASIC1a) to trigger cell death. We recently showed that administration of a potent venom-derived inhibitor of ASIC1a, Hi1a, leads to tissue sparing and improved functional recovery when delivered up to 8 h after ischemic stroke. Here, we use whole-cell patch-clamp electrophysiology in a spinal cord slice preparation to assess the effect of acute ASIC1a inhibition, via a single dose of Hi1a, on intrinsic membrane properties and excitatory synaptic transmission long-term after a spinal cord hemisection injury. We focus on a population of interneurons (INs) in the deep dorsal horn (DDH) that play a key role in relaying sensory information to downstream motoneurons. DDH INs in mice treated with Hi1a 1 h after a spinal cord hemisection showed no change in active or passive intrinsic membrane properties measured 4 weeks after SCI. DDH INs, however, exhibit significant changes in the kinetics of spontaneous excitatory postsynaptic currents after a single dose of Hi1a, when compared to naive animals (unlike SCI mice). Our data suggest that acute ASIC1a inhibition exerts selective effects on excitatory synaptic transmission in DDH INs after SCI via specific ligand-gated receptor channels, and has no effect on other voltage-activated channels long-term after SCI.

Identifying opportunities for collective action around community nutrition programming through participatory systems science.

PURPOSE: To apply principles of group model building (GMB), a participatory systems science approach, to identify barriers and opportunities for collective impact around nutrition programming to reduce cancer risk for immigrant communities in an urban environment. METHODS: We convened four in-person workshops applying GMB with nine community partners to generate causal loop diagrams (CLDs)-a visual representation of hypothesized causal relationships between variables and feedback structures within a system. GMB workshops prompted participants to collaboratively identify programmatic goals and challenges related to (1) community gardening, (2) nutrition education, (3) food assistance programs, and (4) community-supported agriculture. Participants then attended a plenary session to integrate findings from all workshops and identify cross-cutting ideas for collective action. RESULTS: Several multilevel barriers to nutrition programming emerged: (1) food policies center the diets and practices of White Americans and inhibit culturally tailored food guidelines and funding for culturally appropriate nutrition education; (2) the lack of culturally tailored nutrition education in communities is a missed opportunity for fostering pride in immigrant food culture and sustainment of traditional food practices; and (3) the limited availability of traditional ethnic produce in food assistance programs serving historically marginalized immigrant communities increases food waste and worsens food insecurity. CONCLUSION: Emergent themes coalesced around the need to embed cultural tailoring into all levels of the food system, while also considering other characteristics of communities being reached (e.g., language needs). These efforts require coordinated actions related to food policy and advocacy, to better institutionalize these practices within the nutrition space.

Corrigendum: The longitudinal progression of autonomic dysfunction in Parkinson's disease: a 7-year study.

[This corrects the article DOI: 10.3389/fneur.2023.1155669.].

The longitudinal progression of autonomic dysfunction in Parkinson's disease: A 7-year study.

Background: Autonomic dysfunction, including gastrointestinal, cardiovascular, and urinary dysfunction, is often present in early Parkinson's Disease (PD). However, the knowledge of the longitudinal progression of these symptoms, and the connection between different autonomic domains, is limited. Furthermore, the relationship between the presence of autonomic symptoms in early-stage PD and olfactory dysfunction, a possible marker of central nervous system involvement, has not been fully investigated. Objectives: We aimed to investigate the occurrence and progression of autonomic dysfunction in recently diagnosed (< 2 years) untreated PD patients and determine any coexistence of symptoms in individual patients. We also investigated the relationship between autonomic symptoms, olfactory dysfunction, and motor impairment. Methods: Data were obtained from the Parkinson's Progression Markers Initiative (PPMI) database. Autonomic dysfunction was measured using the Scales for Outcomes in Parkinson's Disease (SCOPA-AUT). Symptom frequency and mean scores over 7 years were determined. The simultaneous occurrence of different autonomic symptoms was also examined. Finally, the relationships between SCOPA-AUT scores, olfactory dysfunction, and motor impairment were investigated using the University of Pennsylvania Smell Identification Test (UPSIT) and the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), respectively. Results: Follow-up data were available for 7 years for 171 PD patients and for 5 years for 136 HCs. Mean SCOPA-AUT score increased significantly from baseline to the 7-year follow-up for each autonomic domain, except for female sexual dysfunction. Most patients reported three or more autonomic symptoms. Common clusters of symptoms were composed of combinations of gastrointestinal, urinary, thermoregulatory, and sexual dysfunction. At baseline, greater SCOPA-AUT total score was associated with lower UPSIT scores (r = -0.209, p = 0.006) and with greater total MDS-UDPRS III score (r = 0.218, p = 0.004). Conclusions: Autonomic dysfunction, often with coexistence of autonomic manifestations, is common in early PD and progressively worsens over the first 7 years of disease, suggesting that these symptoms should be addressed with appropriate treatments early in the disease. The association between greater autonomic dysfunction and greater olfactory impairment, coupled with the association with more severe motor scores at baseline, indicates that patients who show more severe autonomic dysfunction could also have more severe involvement of the central nervous system at the time of diagnosis.

Genetic or Pharmacological Ablation of Acid-Sensing Ion Channel 1a (ASIC1a) Is Not Neuroprotective in a Mouse Model of Spinal Cord Injury.

Acid-sensing ion channel 1a (ASIC1a) is a proton-activated channel that is expressed ubiquitously throughout the central nervous system and in various types of immune cells. Its role in spinal cord injury (SCI) is controversial; inhibition of ASIC1a has been reported to improve SCI pathology in vivo, but conversely, gene ablation increased kainite-mediated excitotoxic cell death in vitro. Here, we re-examined the role of ASIC1a in a mouse model of SCI. First, we observed functional outcomes up to 42 days post-operation (DPO) in SCI mice with a selective genetic ablation of ASIC1a. Mice lacking ASIC1a had significantly worsened locomotor ability and increased lesion size compared with mice possessing the ASIC1a gene. Next, we explored pharmacological antagonism of this ion channel by administering the potent ASIC1a inhibitor, Hi1a. Consistent with a role for ASIC1a to attenuate excitotoxicity, accelerated neuronal cell loss was found at the lesion site in SCI mice treated with Hi1a, but there were no differences in locomotor recovery. Moreover, ASIC1a inhibition did not cause significant alterations to neutrophil migration, microglial density, or blood-spinal cord barrier integrity.

Identifying research practices toward achieving health equity principles within the Cancer Prevention and Control Research Network.

PURPOSE: Although there is national recognition for health equity-oriented research, there is limited guidance for researchers to engage partnerships that promote health equity in cancer research. The Cancer Prevention and Control Research Network's (CPCRN) Health Equity Work Group developed a toolkit to guide researchers in equitable collaborations. METHODS: The CPCRN's Health Equity Work Group collectively outlined health and racial equity principles guiding research collaborations with partners that include communities, community-based organizations, implementing partners in the clinical setting including providers and health care organizations, and policy makers. Using a network-wide survey to crowdsource information around ongoing practices, we leveraged and integrated the network's experience and collaborations. RESULTS: Data from the survey formed the preliminary basis for the toolkit, with a focus on sharing fiscal resources with partners, training and capacity building, collaborative decision-making, community-driven research agenda setting, and sustainability. The final toolkit provides reflection considerations for researchers and collated exemplary resources, supported by the contemporary research. CONCLUSIONS: The toolkit provides a guide to researchers at all experience levels wanting to engage in equitable research collaborations. Future efforts are underway to evaluate whether and how researchers within and outside CPCRN are able to incorporate these principles in research collaborations.

Exposure to war and conflict: The individual and inherited epigenetic effects on health, with a focus on post-traumatic stress disorder.

War and conflict are global phenomena, identified as stress-inducing triggers for epigenetic modifications. In this state-of-the-science narrative review based on systematic principles, we summarise existing data to explore the outcomes of these exposures especially in veterans and show that they may result in an increased likelihood of developing gastrointestinal, auditory, metabolic and circadian issues, as well as post-traumatic stress disorder (PTSD). We also note that, despite a potential "healthy soldier effect", both veterans and civilians with PTSD exhibit the altered DNA methylation status in hypothalamic-pituitary-adrenal (HPA) axis regulatory genes such as NR3C1. Genes associated with sleep (PAX8; LHX1) are seen to be differentially methylated in veterans. A limited number of studies also revealed hereditary effects of war exposure across groups: decreased cortisol levels and a heightened (sex-linked) mortality risk in offspring. Future large-scale studies further identifying the heritable risks of war, as well as any potential differences between military and civilian populations, would be valuable to inform future healthcare directives.

Assessing changes in the food retail environment during the COVID-19 pandemic: opportunities, challenges, and lessons learned.

BACKGROUND: COVID-19 mitigation strategies have had an untold effect on food retail stores and restaurants. Early evidence from New York City (NYC) indicated that these strategies, among decreased travel from China and increased fears of viral transmission and xenophobia, were leading to mass closures of businesses in Manhattan's Chinatown. The constantly evolving COVID -19 crisis has caused research design and methodology to fundamentally shift, requiring adaptable strategies to address emerging and existing public health problems such as food security that may result from closures of food outlets. OBJECTIVE: We describe innovative approaches used to evaluate changes to the food retail environment amidst the constraints of the pandemic in an urban center heavily burdened by COVID-19. Included are challenges faced, lessons learned and future opportunities. METHODS: First, we identified six diverse neighborhoods in NYC: two lower-resourced, two higher-resourced, and two Chinese ethnic enclaves. We then developed a census of food outlets in these six neighborhoods using state and local licensing databases. To ascertain the status (open vs. closed) of outlets pre-pandemic, we employed a manual web-scraping technique. We used a similar method to determine the status of outlets during the pandemic. Two independent online sources were required to confirm the status of outlets. If two sources could not confirm the status, we conducted phone call checks and/or in-person visits. RESULTS: The final baseline database included 2585 food outlets across six neighborhoods. Ascertaining the status of food outlets was more difficult in lower-resourced neighborhoods and Chinese ethnic enclaves compared to higher-resourced areas. Higher-resourced neighborhoods required fewer phone call and in-person checks for both restaurants and food retailers than other neighborhoods. CONCLUSIONS: Our multi-step data collection approach maximized safety and efficiency while minimizing cost and resources. Challenges in remote data collection varied by neighborhood and may reflect the different resources or social capital of the communities; understanding neighborhood-specific constraints prior to data collection may streamline the process.

Are recommended dietary patterns equitable?

OBJECTIVE: Dietary recommendations (DR) in the USA may be inadequate at improving diets in racial/ethnic minority communities and may require redesign of the systems driving their development over the long term. Meanwhile, cultural adaptation of evidence-based DR may be an important strategy for mitigating nutrition disparities, but less is known about the adaptability of these recommendations to meet the needs of diverse groups. We examined the content and origin of major DRs - aspects that provide context on their potential universality across populations and evaluated their potential for cultural adaptation. DESIGN: Case studies of Dietary Approaches to Stop Hypertension (DASH), the Mediterranean diet (MD), the EAT-Lancet diet (EAT) and the NOVA classification system. SETTING: United States. PARTICIPANTS: Racial/ethnic minority populations. RESULTS: Current DR differ in their origin/evolution but are similar in their reductionist emphasis on physical health. DASH has been successfully adapted for some cultures but may be challenged by the need for intensive resources; MD may be more beneficial if applied as part of a broader set of food procurement/preparation practices than as just diet alone; EAT-Lancet adaptation may not honor existing country-specific practices that are already beneficial to human and environmental health (e.g. traditional/plant-based diets); evidence for cultural adaptation is limited with NOVA, but classification of levels of food processing has potential for widespread application. CONCLUSIONS: For DR to equitably support diverse populations, they must move beyond a Eurocentric or 'general population' framing, be more inclusive of cultural differences and honour social practices to improve diet and reduce disparities.

COVID-19 Leads to Dramatic Changes in the Food Retail Environment in New York City: May-July 2020.

A systematic assessment of the effect of COVID-19 on the food retail environment-an important determinant of health-has not been conducted. Our objective was to assess the impact of COVID-19 on closures of restaurants, food retail stores, and fresh produce vendors in New York City (NYC). We conducted a cross-sectional study following the peak of COVID-19 in six neighborhoods in NYC. Two Chinese ethnic neighborhoods and four higher/lower resourced comparison neighborhoods were selected a priori based on 14 sociodemographic indicators. The primary outcome was indefinite/temporary closures or absence of food businesses. Of 2720 food businesses identified, produce vendors and restaurants were more likely to close than food retail stores. A higher proportion of food businesses closed in Chinese ethnic neighborhoods vs. comparison neighborhoods. COVID-19 impacted food businesses in six NYC neighborhoods examined in this period, with the greatest effect observed for Chinese ethnic neighborhoods.

Acid-Sensing Ion Channels: Expression and Function in Resident and Infiltrating Immune Cells in the Central Nervous System.

Peripheral and central immune cells are critical for fighting disease, but they can also play a pivotal role in the onset and/or progression of a variety of neurological conditions that affect the central nervous system (CNS). Tissue acidosis is often present in CNS pathologies such as multiple sclerosis, epileptic seizures, and depression, and local pH is also reduced during periods of ischemia following stroke, traumatic brain injury, and spinal cord injury. These pathological increases in extracellular acidity can activate a class of proton-gated channels known as acid-sensing ion channels (ASICs). ASICs have been primarily studied due to their ubiquitous expression throughout the nervous system, but it is less well recognized that they are also found in various types of immune cells. In this review, we explore what is currently known about the expression of ASICs in both peripheral and CNS-resident immune cells, and how channel activation during pathological tissue acidosis may lead to altered immune cell function that in turn modulates inflammatory pathology in the CNS. We identify gaps in the literature where ASICs and immune cell function has not been characterized, such as neurotrauma. Knowledge of the contribution of ASICs to immune cell function in neuropathology will be critical for determining whether the therapeutic benefits of ASIC inhibition might be due in part to an effect on immune cells.

Evaluating Closures of Fresh Fruit and Vegetable Vendors During the COVID-19 Pandemic: Methodology and Preliminary Results Using Omnidirectional Street View Imagery.

BACKGROUND: The COVID-19 pandemic has significantly disrupted the food retail environment. However, its impact on fresh fruit and vegetable vendors remains unclear; these are often smaller, more community centered, and may lack the financial infrastructure to withstand supply and demand changes induced by such crises. OBJECTIVE: This study documents the methodology used to assess fresh fruit and vegetable vendor closures in New York City (NYC) following the start of the COVID-19 pandemic by using Google Street View, the new Apple Look Around database, and in-person checks. METHODS: In total, 6 NYC neighborhoods (in Manhattan and Brooklyn) were selected for analysis; these included two socioeconomically advantaged neighborhoods (Upper East Side, Park Slope), two socioeconomically disadvantaged neighborhoods (East Harlem, Brownsville), and two Chinese ethnic neighborhoods (Chinatown, Sunset Park). For each neighborhood, Google Street View was used to virtually walk down each street and identify vendors (stores, storefronts, street vendors, or wholesalers) that were open and active in 2019 (ie, both produce and vendor personnel were present at a location). Past vendor surveillance (when available) was used to guide these virtual walks. Each identified vendor was geotagged as a Google Maps pinpoint that research assistants then physically visited. Using the "notes" feature of Google Maps as a data collection tool, notes were made on which of three categories best described each vendor: (1) open, (2) open with a more limited setup (eg, certain sections of the vendor unit that were open and active in 2019 were missing or closed during in-person checks), or (3) closed/absent. RESULTS: Of the 135 open vendors identified in 2019 imagery data, 35% (n=47) were absent/closed and 10% (n=13) were open with more limited setups following the beginning of the COVID-19 pandemic. When comparing boroughs, 35% (28/80) of vendors in Manhattan were absent/closed, as were 35% (19/55) of vendors in Brooklyn. Although Google Street View was able to provide 2019 street view imagery data for most neighborhoods, Apple Look Around was required for 2019 imagery data for some areas of Park Slope. Past surveillance data helped to identify 3 additional established vendors in Chinatown that had been missed in street view imagery. The Google Maps "notes" feature was used by multiple research assistants simultaneously to rapidly collect observational data on mobile devices. CONCLUSIONS: The methodology employed enabled the identification of closures in the fresh fruit and vegetable retail environment and can be used to assess closures in other contexts. The use of past baseline surveillance data to aid vendor identification was valuable for identifying vendors that may have been absent or visually obstructed in the street view imagery data. Data collection using Google Maps likewise has the potential to enhance the efficiency of fieldwork in future studies.

Identifying the physical features of marina infrastructure associated with the presence of non-native species in the UK.

Marine invasive non-native species (NNS) are one of the greatest threats to global marine biodiversity, causing significant economic and social impacts. Marinas are increasingly recognised as key reservoirs for invasive NNS. They provide submersed artificial habitat that unintentionally supports the establishment of NNS introduced from visiting recreational vessels. While ballast water and shipping vectors have been well documented, the role of recreational vessels in spreading NNS has been relatively poorly studied. Identification of the main physical features found within marinas, which relate to the presence of NNS, is important to inform the development of effective biosecurity measures and prevent further spread. Towards this aim, physical features that could influence the presence of NNS were assessed for marinas throughout the UK in July 2013. Thirty-three marine and brackish NNS have been recorded in UK marinas, and of the 88 marinas studied in detail, 83 contained between 1 and 13 NNS. Significant differences in freshwater input, marina entrance width and seawall length were associated with the presence of NNS. Additionally, questionnaires were distributed to marina managers and recreational vessel owners to understand current biosecurity practices and attitudes to recreational vessel biosecurity. The main barriers to biosecurity compliance were cited as cost and time. Further work identifying easily distinguished features of marinas could be used as a proxy to assess risk of invasion.

Evaluation of a peer mentoring program for early career gerontological nursing faculty and its potential for application to other fields in nursing and health sciences.

BACKGROUND: As the retirement rate of senior nursing faculty increases, the need to implement new models for providing mentorship to early career academics will become key to developing and maintaining an experienced faculty. PURPOSE: This evaluation of a peer mentorship program for predoctoral and postdoctoral gerontological nurses examined its efficacy, utility, and potential for improvement. METHODS: A web-based survey was developed, implemented, and completed by 22 mentees and 17 mentors (71% and 61% response rates, respectively) as part of the evaluation. DISCUSSION: The peer mentorship program was found to be valuable by both mentors (64.7%) and mentees (72.7%) in helping mentees further develop their careers and networks and providing mentors with supported mentorship experience. CONCLUSION: The peer mentorship program could serve as a model for other professional organizations, academic institutions, and consortiums to enhance and extend the formal vertical mentorship provided to early academic career individuals.

Anion homeostasis is important for non-lytic release of BK polyomavirus from infected cells.

BK polyomavirus (BKPyV) is a member of a family of potentially oncogenic viruses, whose reactivation can cause severe pathological conditions in transplant patients, leading to graft rejection. As with many non-enveloped viruses, it is assumed that virus release occurs through lysis of the host cell. We now show the first evidence for a non-lytic release pathway for BKPyV and that this pathway can be blocked by the anion channel inhibitor DIDS. Our data show a dose-dependent effect of DIDS on the release of BKPyV virions. We also observed an accumulation of viral capsids in large LAMP-1-positive acidic organelles within the cytoplasm of cells upon DIDS treatment, suggesting potential late endosome or lysosome-related compartments are involved in non-lytic BKPyV release. These data highlight a novel mechanism by which polyomaviruses can be released from infected cells in an active and non-lytic manner, and that anion homeostasis regulation is important in this pathway.

Development and implementation of a peer mentoring program for early career gerontological faculty.

PURPOSE: The Hartford Gerontological Nursing Leaders (HGNL) formerly known as the Building Academic Geriatric Nursing Capacity Initiative (BAGNC), in conjunction with the National Hartford Centers of Gerontological Nursing Excellence (NHCGNE), developed and executed a peer mentoring program beginning in 2011 to enhance both (a) the experience of newly selected scholars and fellows to the NHCGNE and (b) the ongoing professional development of HGNL members. The purpose of this article is to describe key strategies used to develop and execute the peer mentoring program and to present formative program evaluation. DESIGN: The program was launched in January 2011 with seven peer mentor and mentee matches. In June 2012, the peer mentoring committee solicited feedback on the development of the peer mentoring program and changes were made for the subsequent cohorts. FINDINGS: An additional 12 matches were made in the following 2 years (2012 and 2013), for a total of 31 matches to date. We have learned several key lessons from our three cohorts regarding how to structure, implement, and carefully evaluate a peer mentoring program. CONCLUSIONS: Informal evaluation of our peer mentoring program noted several challenges for both peer mentors and mentees. Having knowledge of and addressing those challenges may increase the overall quality and effectiveness of peer mentoring programs and, in turn, benefit academic nursing by strengthening the faculty workforce. CLINICAL RELEVANCE: Findings from development and implementation of a peer mentoring program for gerontological faculty could lead to new and adaptable programs in a variety of clinical and education settings.