Protocol for the Support Application for Food PAntrieS trial: design, implementation, and evaluation plan for a digital application to promote healthy food access and support food pantry operations.

Introduction: Food-insecure households commonly rely on food pantries to supplement their nutritional needs, a challenge that was underscored during the COVID-19 pandemic. Food pantries, and the food banks that supply them, face common challenges in meeting variable client volume and dietary needs under normal and emergency (e.g., pandemic, natural disaster) conditions. A scalable digital strategy that has the capacity to streamline the emergency food distribution system, while promoting healthy food options, managing volunteer recruitment and training, and connecting to emergency management systems in times of need, is urgently required. To address this gap, we are developing a working mobile application (app) called the Support Application for Food PAntrieS (SAFPAS) and will evaluate its feasibility and impact on food pantry staff preparedness, stocking, and client uptake of healthful foods and beverages in two urban United States settings. Methods: This paper describes the protocol for a randomized controlled trial of the SAFPAS mobile application. We will conduct formative research in Baltimore, Maryland and Detroit, Michigan to develop and refine the SAFPAS app and increase scalability potential to other urban settings. Then we will test the app in 20 food pantries in Baltimore randomized to intervention or comparison. The impact of the app will be evaluated at several levels of the emergency food system, including food pantry clients (n = 360), food pantry staff and volunteers (n = 100), food pantry stock, and city agencies such as the local food bank and Office of Emergency Management. The primary outcome of the SAFPAS trial is to improve the healthfulness of the foods received by food pantry clients, measured using the Food Assessment Scoring Tool (FAST). Post-trial, we will conduct additional formative research in Detroit to prepare the app for scale-up. Discussion: We anticipate that SAFPAS will improve alignment in the supply and demand for healthy foods among food pantry clients, food pantries, and city agencies which supply food in Baltimore. Real-time, bidirectional communication between entities across the system allows for increased situational awareness at all levels during normal and emergency operations. By conducting formative research in Detroit, we hope to increase the scalability of the SAFPAS app to additional settings nationwide. Clinical trial registration: NCT87654321. https://classic.clinicaltrials.gov/ct2/show/NCT05880004.

Effect of a Higher-Protein Nut versus Higher-Carbohydrate Cereal Enriched Diet on the Gut Microbiomes of Chinese Participants with Overweight and Normoglycaemia or Prediabetes in the Tu Ora Study.

Global increases in metabolic disorders such as type 2 diabetes (T2D), especially within Asian populations, highlight the need for novel approaches to dietary intervention. The Tu Ora study previously evaluated the effects on metabolic health of including a nut product into the diet of a New Zealand cohort of Chinese participants with overweight and normoglycaemia or prediabetes through a 12-week randomised, parallel-group clinical trial. In this current study, we compared the impact of this higher-protein nut bar (HP-NB) versus a higher-carbohydrate cereal bar (HC-CB) on the faecal microbiome by employing both 16S rRNA gene amplicon and shotgun metagenomic sequencing of pre- and post-intervention pairs from 84 participants. Despite the higher fibre, protein, and unsaturated fat content of nuts, there was little difference between dietary groups in gut microbiome composition or functional potential, with the bacterial phylum Firmicutes dominating irrespective of diet. The lack of observed change suggests the dietary impact of the bars may have been insufficient to affect the gut microbiome. Manipulating the interplay between the diet, microbiome, and metabolic health may require a more substantial and/or prolonged dietary perturbation to generate an impactful modification of the gut ecosystem and its functional potential to aid in T2D risk reduction.

Assessing message deployment during public health emergencies through social media: An empirical test of optimizing content for effective dissemination.

BACKGROUND: During an infodemic, the need for timely, reliable, and accessible information is crucial to combat the proliferation of health misinformation. Message testing can provide vital information to make data-informed decisions, but traditional methods tend to be time and resource intensive. Recognizing this need, we developed the Rapid Message Testing at Scale (RMTS) approach to allow communicators to repurpose existing social media advertising tools and understand the full spectrum of audience engagement. OBJECTIVE: We had two main objectives: a) to demonstrate the use of the RMTS approach for message testing, especially when resources are limited and there is a need to act in a timely manner, and (b) to propose and test the efficacy of an outcome variable that measures engagement along a continuum of viewing experience. METHODS: We developed 12 versions of a single video that was created for a vaccine confidence project in India. We manipulated video length, aspect ratio, and use of subtitles. The videos were tested across four demographic groups (women/men, younger/older). We assessed user engagement along a continuum of viewing experience: getting attention, sustaining attention, conveying the message, and inspiring action. These were measured by percentage of video watched and clicks on the call-to-action link. RESULTS: The video ads were placed on Facebook over four consecutive days at the cost of $450 (U.S.) and garnered a total of 3.34 million impressions. Overall, we found that the best performing video was the shorter version presented in portrait aspect ratio and without subtitles. There was a significant but small association between the length of the video and users' level of engagement at key points along the continuum of viewing experience (N=1,032,888; 〖χ^2〗_4=48,261.97; P<.001; V=.22). We found that for the longer video, those with subtitles held viewers longer after 25% video watch time than those without subtitles (n=15,597; 〖χ^2〗_1=7.33; P<.01; V=.02). While we found some significant associations between the aspect ratio, the use of subtitles, and the number of users watching the video and clicking on the call-to-action link, the effect size for those were extremely small. CONCLUSIONS: This test served as a proof of concept for the RMTS approach. We obtained rapid feedback on formal message attributes from a very large sample in a very short timeframe. The results of this test reinforce the need for platform-specific tailoring of communications. While our data showed a general preference for the short video in portrait orientation and without subtitles among our target audiences on Facebook, that may not necessarily be the case in other social media platforms such as YouTube or TikTok, where users go primarily to watch videos. RMTS testing highlights nuances that communication professionals can address instead of being limited to a 'one size fits all' approach.

Hippocampal astrocytes induce sex-dimorphic effects on memory.

Astrocytic receptors influence cognitive function and can promote behavioral deficits in disease. These effects may vary based on variables such as biological sex, but it is not known if the effects of astrocytic receptors are dependent on sex. We leveraged in vivo gene editing and chemogenetics to examine the roles of astrocytic receptors in spatial memory and other processes. We show that reductions in metabotropic glutamate receptor 3 (mGluR3), the main astrocytic glutamate receptor in adults, impair memory in females but enhance memory in males. Similarly, increases in astrocytic mGluR3 levels have sex-dependent effects and enhance memory in females. mGluR3 manipulations also alter spatial search strategies during recall in a sex-specific manner. In addition, acute chemogenetic stimulation of Gi/o-coupled or Gs-coupled receptors in hippocampal astrocytes induces bidirectional and sex-dimorphic effects on memory. Thus, astrocytes are sex-dependent modulators of cognitive function and may promote sex differences in aging and disease.

Centering Health Equity in the Implementation of the Hospital Incident Command System: A Qualitative Case Comparison Study.

OBJECTIVE: Disasters exacerbate inequities in health care. Health systems use the Hospital Incident Command System (HICS) to plan and coordinate their disaster response. This study examines how 2 health systems prioritized equity in implementing the Hospital Incident Command System (HICS) during the coronavirus disease 2019 (COVID-19) pandemic and identifies factors that influenced implementation. METHODS: This is a qualitative case comparison study, involving semi-structured interviews with 29 individuals from 2 US academic health systems. Strategies for promoting health equity were categorized by social determinants of health. The Consolidated Framework for Implementation Research (CFIR) guided analysis using a hybrid inductive-deductive approach. RESULTS: The health systems used various strategies to incorporate health equity throughout implementation, addressing all 5 social determinants of health domains. Facilitators included HICS principles, external partnerships, community relationships, senior leadership, health equity experts and networks, champions, equity-stratified data, teaming, and a culture of health equity. Barriers encompassed clarity of the equity representative role, role ambiguity for equity representatives, tokenism, competing priorities, insufficient resource allocation, and lack of preparedness. CONCLUSIONS: These findings elucidate how health systems centered equity during HICS implementation. Health systems and regulatory bodies can use these findings as a foundation to revise the HICS and move toward a more equitable disaster response.

Cysteine induces mitochondrial reductive stress in glioblastoma through hydrogen peroxide production.

Glucose and amino acid metabolism are critical for glioblastoma (GBM) growth, but little is known about the specific metabolic alterations in GBM that are targetable with FDA-approved compounds. To investigate tumor metabolism signatures unique to GBM, we interrogated The Cancer Genome Atlas for alterations in glucose and amino acid signatures in GBM relative to other human cancers and found that GBM exhibits the highest levels of cysteine and methionine pathway gene expression of 32 human cancers. Treatment of patient-derived GBM cells with the FDA-approved single cysteine compound N-acetylcysteine (NAC) reduced GBM cell growth and mitochondrial oxygen consumption, which was worsened by glucose starvation. Normal brain cells and other cancer cells showed no response to NAC. Mechanistic experiments revealed that cysteine compounds induce rapid mitochondrial H2O2 production and reductive stress in GBM cells, an effect blocked by oxidized glutathione, thioredoxin, and redox enzyme overexpression. From analysis of the clinical proteomic tumor analysis consortium (CPTAC) database, we found that GBM cells exhibit lower expression of mitochondrial redox enzymes than four other cancers whose proteomic data are available in CPTAC. Knockdown of mitochondrial thioredoxin-2 in lung cancer cells induced NAC susceptibility, indicating the importance of mitochondrial redox enzyme expression in mitigating reductive stress. Intraperitoneal treatment of mice bearing orthotopic GBM xenografts with a two-cysteine peptide induced H2O2 in brain tumors in vivo. These findings indicate that GBM is uniquely susceptible to NAC-driven reductive stress and could synergize with glucose-lowering treatments for GBM.

Embedding Equity into the Hospital Incident Command System: A Narrative Review.

BACKGROUND: Disasters exacerbate health inequities, with historically marginalized populations experiencing unjust differences in health care access and outcomes. Health systems plan and respond to disasters using the Hospital Incident Command System (HICS), an organizational structure that centralizes communication and decision-making. The HICS does not have an equity role or considerations built into its standard structure. The authors conducted a narrative review to identify and summarize approaches to embedding equity into the HICS. METHODS: The peer-reviewed (PubMed, SCOPUS) and gray literature was searched for articles from high-income countries that referenced the HICS or Incident Command System (ICS) and equity, disparities, or populations that experience inequities in disasters. The primary focus of the search strategy was health care, but the research also included governmental and public health system articles. Two authors used inductive thematic analysis to assess commonalities and refined the themes based on feedback from all authors. RESULTS: The database search identified 479 unique abstracts; 76 articles underwent full-text review, and 11 were included in the final analysis. The authors found 5 articles through cited reference searching and 13 from the gray literature search, which included websites, organizations, and non-indexed journal articles. Three themes from the articles were identified: including equity specialists in the HICS, modifying systems to promote equity, and sensitivity to the local community. CONCLUSION: Several efforts to embed equity into the HICS and disaster preparedness and response were discovered. This review provides practical strategies health system leaders can include in their HICS and emergency preparedness plans to promote equity in their disaster response.

Assessing US Small Animal Veterinary Clinic Adaptations and Their Impacts on Workforce COVID-19 Preparedness and Response.

Veterinary personnel are an essential yet often underappreciated workforce, critical for zoonotic disease prevention and response efforts that impact human health. During the early COVID-19 pandemic, the veterinary workforce supported emergency responses by promoting zoonotic disease risk communication, sharing animal health expertise, and boosting laboratory surge capacity against SARS-CoV-2 in animals and people. However, small animal veterinary workers (SAVWs), similar to healthcare workers, faced organizational challenges in providing clinical care to family pets, including those susceptible to SARS-CoV-2. We analyzed a cross-sectional survey of 1,204 SAVWs in the United States to assess veterinary clinic adaptations and their associations with SAVWs' self-perceived readiness, willingness, and ability to respond to the COVID-19 pandemic as a workforce. SAVWs who worked fewer hours than before the pandemic (ready, OR 0.59; willing, OR 0.66; able, OR 0.52) or used personal protective equipment less frequently for protection in the clinic (ready, OR 0.69; willing, OR 0.69; able, OR 0.64) felt less ready, willing, and able to respond to COVID-19. SAVWs working remotely felt less ready (OR 0.46) but not less willing or able to respond to COVID-19. Lastly, SAVWs with dependents felt less ready (OR 0.67) and able (OR 0.49) to respond to COVID-19 than SAVWs without dependents. Our findings highlight the importance of proactively managing work schedules, having access to personal protective equipment, and addressing caregiving concerns to enhance SAVW preparedness and response outcomes. SAVWs are knowledgeable, motivated personnel who should be integrated into local public health emergency preparedness and response plans, supporting a One Health framework that unites multidisciplinary teams to respond to future zoonotic disease threats.

Astrocytes as Drivers and Disruptors of Behavior: New Advances in Basic Mechanisms and Therapeutic Targeting.

Astrocytes are emerging as key regulators of cognitive function and behavior. This review highlights some of the latest advances in the understanding of astrocyte roles in different behavioral domains across lifespan and in disease. We address specific molecular and circuit mechanisms by which astrocytes modulate behavior, discuss their functional diversity and versatility, and highlight emerging astrocyte-targeted treatment strategies that might alleviate behavioral and cognitive dysfunction in pathologic conditions. Converging evidence across different model systems and manipulations is revealing that astrocytes regulate behavioral processes in a precise and context-dependent manner. Improved understanding of these astrocytic functions may generate new therapeutic strategies for various conditions with cognitive and behavioral impairments.

Gut microbiota profiles in two New Zealand cohorts with overweight and prediabetes: a Tu Ora/PREVIEW comparative study.

Obesity-related metabolic diseases such as type 2 diabetes (T2D) are major global health issues, affecting hundreds of millions of people worldwide. The underlying factors are both diverse and complex, incorporating biological as well as cultural considerations. A role for ethnicity - a measure of self-perceived cultural affiliation which encompasses diet, lifestyle and genetic components - in susceptibility to metabolic diseases such as T2D is well established. For example, Asian populations may be disproportionally affected by the adverse 'TOFI' (Thin on the Outside, Fat on the Inside) profile, whereby outwardly lean individuals have increased susceptibility due to excess visceral and ectopic organ fat deposition. A potential link between the gut microbiota and metabolic disease has more recently come under consideration, yet our understanding of the interplay between ethnicity, the microbiota and T2D remains incomplete. We present here a 16S rRNA gene-based comparison of the fecal microbiota of European-ancestry and Chinese-ancestry cohorts with overweight and prediabetes, residing in New Zealand. The cohorts were matched for mean fasting plasma glucose (FPG: mean ± SD, European-ancestry: 6.1 ± 0.4; Chinese-ancestry: 6.0 ± 0.4 mmol/L), a consequence of which was a significantly higher mean body mass index in the European group (BMI: European-ancestry: 37.4 ± 6.8; Chinese-ancestry: 27.7 ± 4.0 kg/m2; p < 0.001). Our findings reveal significant microbiota differences between the two ethnicities, though we cannot determine the underpinning factors. In both cohorts Firmicutes was by far the dominant bacterial phylum (European-ancestry: 93.4 ± 5.5%; Chinese-ancestry: 79.6 ± 10.4% of 16S rRNA gene sequences), with Bacteroidetes and Actinobacteria the next most abundant. Among the more abundant (≥1% overall relative sequence abundance) genus-level taxa, four zero-radius operational taxonomic units (zOTUs) were significantly higher in the European-ancestry cohort, namely members of the Subdoligranulum, Blautia, Ruminoclostridium, and Dorea genera. Differential abundance analysis further identified a number of additional zOTUs to be disproportionately overrepresented across the two ethnicities, with the majority of taxa exhibiting a higher abundance in the Chinese-ancestry cohort. Our findings underscore a potential influence of ethnicity on gut microbiota composition in the context of individuals with overweight and prediabetes.

Decision-Making Prepandemic: University Curtailment of Academic Operations Closure Processes During the Novel Coronavirus Disease 2019 (COVID-19) Outbreak.

OBJECTIVE: Through in-depth interviews, this study aimed to understand perspectives of key stakeholders regarding the decision to curtail academic operations in the setting of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak before the declaration of a pandemic on March 11, 2020, and how such processes may be optimized in the future to best protect public health and safety. METHODS: Virtual interviews with key stakeholders from 4 academic institutions were conducted from September to December 2020 using a standardized interview question template. The interviews lasted approximately 30-45 minutes and each interview was recorded with permission. The interviews were then transcribed and reviewed for qualitative analysis. RESULTS: The decision to curtail academic operations involved several common themes, such as discussing how institutions would control the outbreak and the process of transitioning to virtual learning and remote work. Universities were monitoring other universities' responses as well as evaluating the prevalence of cases nationally and globally. Risks and challenges identified included housing for international students, financial implications, and loss of academic productivity. CONCLUSIONS: The decision-making process may be optimized in the future by focusing on communication within a smaller committee, prioritizing epidemiology over fiscal implications, and embracing an openness to consider new strategies. Further research regarding this topic should be pursued to best protect public health and safety.

Sociodemographic and Health Indicators of Diet Quality in Pre-Frail Older Adults in New Zealand.

This study aimed to identify sociodemographic and health indicators of diet quality in pre-frail community-dwelling older adults. Pre-frail older adults are those at risk of progression to clinical manifestations of frailty and are targets for preventative intervention. We previously reported that pre-frail older adults have reasonably good overall diet quality. However, further analyses found a low intake of energy, protein and several micronutrients. METHODS: We collected detailed dietary intake from pre-frail (FRAIL scale 1-2) older adults using NZ Intake24, an online version of 24 h multiple pass dietary recall. Diet quality was ascertained with the Diet Quality Index-International (DQI-I). We used regression generalized linear models to determine predictors of diet quality as well as classification and regression tree (CART) analysis to examine the complex relationships between predictors and identified profiles of sub-groups of older adults that predict diet quality. RESULTS: The median age in this sample (n = 468) was 80.0 years (77.0-84.0). Living with others, a high deprivation index and a higher BMI were independent predictors of poorer diet quality. With CART analysis, we found that those with a BMI > 29 kg/m2, living with others and younger than 80 years were likely to have a lower diet quality. CONCLUSIONS: We found that BMI, living arrangement and socioeconomic status were independent predictors of diet quality in pre-frail older adults, with BMI being the most important variable in this sample when the interaction of these variables was considered. Future research is needed to determine the similarities and/or differences in the profile of subgroups of older adults with poorer diet quality.

Effect of a 12-Week Polyphenol Rutin Intervention on Markers of Pancreatic ß-Cell Function and Gut Microbiota in Adults with Overweight without Diabetes.

Supplementation with prebiotic polyphenol rutin is a potential dietary therapy for type 2 diabetes prevention in adults with obesity, based on previous glycaemic improvement in transgenic mouse models. Gut microbiota are hypothesised to underpin these effects. We investigated the effect of rutin supplementation on pancreatic ß-cell function measured as C-peptide/glucose ratio, and 16S rRNA gene-based gut microbiota profiles, in a cohort of individuals with overweight plus normoglycaemia or prediabetes. Eighty-seven participants were enrolled, aged 18-65 years with BMI of 23-35 kg/m2. This was a 12-week double-blind randomised controlled trial (RCT), with 3 treatments comprising (i) placebo control, (ii) 500 mg/day encapsulated rutin, and (iii) 500 mg/day rutin-supplemented yoghurt. A 2-h oral glucose tolerance test (OGTT) was performed at baseline and at the end of the trial, with faecal samples also collected. Compliance with treatment was high (~90%), but rutin in both capsule and dietary format did not alter pancreatic ß-cell response to OGTT over 12 weeks. Gut bacterial community composition also did not significantly change, with Firmicutes dominating irrespective of treatment. Fasting plasma glucose negatively correlated with the abundance of the butyrate producer Roseburia inulinivorans, known for its anti-inflammatory capacity. This is the first RCT to investigate postprandial pancreatic ß-cell function in response to rutin supplementation.

Enhancing a Willingness to Respond to Disasters and Public Health Emergencies Among Health Care Workers, Using mHealth Intervention: A Multidisciplinary Approach.

Health care workers (HCWs) are increasingly faced with the continuous threat of confronting acute disasters, extreme weather-related events, and protracted public health emergencies. One of the major factors that determines emergency-department-based HCWs' willingness to respond during public health emergencies and disasters is self-efficacy. Despite increased public awareness of the threat of disasters and heightened possibility of future public health emergencies, the emphasis on preparing the health care workforce for such disasters is inadequate in low-and-middle-income countries (LMICs). Interventions for boosting self-efficacy and response willingness in public health emergencies and disasters have yet to be implemented or examined among emergency HCWs in LMICs. Mobile health (mHealth) technology seems to be a promising platform for such interventions, especially in a resource-constrained setting. This paper introduces an mHealth-focused project that demonstrates a model of multi-institutional and multidisciplinary collaboration for research and training to enhance disaster response willingness among emergency department workers in Pakistan.

The Role of Self-Efficacy and Risk Perception in the Willingness to Respond to Weather Disasters Among Emergency Medicine Health Care Workers in Pakistan.

OBJECTIVE: Optimizing health care workers' (HCWs) willingness to respond (WTR) is critical in low-and-middle-income countries (LMICs) for proper health system functioning during extreme weather events. Pakistan frequently experiences weather-related disasters, but limited evidence is available to examine HCW willingness. Our study examined the association between WTR and behavioral factors among emergency department HCWs. METHODS: A cross-sectional survey was conducted from August to September 2022 among HCWs from 2 hospitals in Karachi, Pakistan. Non-probability purposive sampling was used to recruit participants. A survey tool was informed by Witte's Extended Parallel Process Model (EPPM). Multivariate logistic regression analyses were performed to examine the association between WTR and attitudes/beliefs as well as EPPM profiles. RESULTS: Twenty-nine percent of HCWs indicated a low WTR. HCWs using public transportation had a higher WTR. Perceived knowledge and skills, self-efficacy, and perceived impact of one's response showed positive associations with WTR if required. Perception that one's colleagues would report to work positively predicted WTR if asked. Consistent with the EPPM, HCWs with high efficacy and perceived threat were willing to respond to weather disasters. CONCLUSIONS: Our findings highlight the need of strengthening WTR by promoting self-efficacy and enhancing accurate risk perception as a response motivator, among emergency department HCWs in Pakistan.

Social network analysis of COVID-19 vaccine YouTube videos in Odisha, India: mapping the channel network and analyzing comment sentiment.

India has reported more than 35 million confirmed cases of COVID-19 and nearly half a million cumulative deaths. Although vaccination rates for the first vaccine dose are quite high, one-third of the population has not received a second shot. Due to its widespread use and popularity, social media can play a vital role in enhancing vaccine acceptance. This study in a real-world setting utilizes YouTube videos in Odisha, India where the platform has deep penetration among the 18-35 target population, and secondarily their family and peers. Two contrasting videos were launched on the YouTube platform to examine how those videos operate within the broader recommender and subscription systems that determine the audience reach. Video analytics, algorithms for recommended videos, visual representation of connections created, centrality between the networks, and comment analysis was conducted. The results indicate that the video with a non-humorous tone and collectivistic appeal delivered by a female protagonist performed best with regard to views and time spent watching the videos. The results are of significance to health communicators who seek to better understand the platform mechanisms that determine the spread of videos and measures of viewer reactions based on viewer sentiment.

Production of vaccination videos in India: learnings from a science-art partnership.

BACKGROUND: Cross-cultural communication, often conceptualized along culture and language dimensions, is an important issue for collaborative teams that include both scientists and artists. Such teams must balance the standardization needs of rigorous scientific methods, on the one hand, with openness for artistic creativity, on the other. The scientific literature does not provide clear guidance on how to structure such collaborations. DISCUSSION: We created eight videos manipulating the type of appeal, message tone, and gender of the vaccine promoter in a 2 × 2 × 2 between-subjects experiment. The four stages of the filmmaking process were 1) conceptualizing filmmaking and script writing through a scientific lens, 2) pilot testing and finalizing the script, 3) video production and editing, and 4) dissemination. We describe the process and learnings from a collaboration that included filmmakers, researchers, and vaccine experts from India and the United States in producing, disseminating, and evaluating videos that promoted vaccine uptake in Odisha, India. CONCLUSIONS: When projects require close collaborations between scientists and artists, committing to a unified vision is essential for facilitating open, bidirectional communication and building trust between the partners. Clearly denoting research boundaries ensures that the scientific needs of the project are met while simultaneously welcoming space for the filmmakers' creativity, fostering a sense of ownership, and enhancing the final product.

PP1ß opposes classic PP1 function, inhibiting spine maturation and promoting LTP.

Protein phosphatase 1 (PP1) regulates synaptic plasticity and has been described as a molecular constraint on learning and memory. There are three neuronal isoforms, PP1α, PP1ß, and PP1γ, but little is known about their individual functions. PP1α and PP1γ are assumed to mediate the effects of PP1 on learning and memory based on their enrichment at dendritic spines and their preferential binding to neurabin and spinophilin, major PP1 synaptic scaffolding proteins. However, it was recently discovered that human de novo PP1ß mutations cause intellectual disability, suggesting an important but ill-defined role for PP1ß. In this study, we investigated the functions of each PP1 isoform in hippocampal synaptic physiology using conditional CA1-specific knockout mice. In stark contrast to classic PP1 function, we found that PP1ß promotes synaptic plasticity as well as spatial memory. These changes in synaptic plasticity and memory are accompanied by changes in GluA1 phosphorylation, GluN2A levels, and dendritic spine density and morphology, including silent synapse number. These functions of PP1ß reveal a previously unidentified signaling pathway regulating spine maturation and plasticity, broadening our understanding of the complex role of PP1 in synaptic physiology.

Differentiating radiation necrosis from tumor recurrence: a systematic review and diagnostic meta-analysis comparing imaging modalities.

PURPSOSE: Cerebral radiation necrosis (RN) is often a delayed phenomenon occurring several months to years after the completion of radiation treatment. Differentiating RN from tumor recurrence presents a diagnostic challenge on standard MRI. To date, no evidence-based guidelines exist regarding imaging modalities best suited for this purpose. We aim to review the current literature and perform a diagnostic meta-analysis comparing various imaging modalities that have been studied to differentiate tumor recurrence and RN. METHODS: A systematic search adherent to PRISMA guidelines was performed using Scopus, PubMed/MEDLINE, and Embase. Pooled sensitivities and specificities were determined using a random-effects or fixed-effects proportional meta-analysis based on heterogeneity. Using diagnostic odds ratios, a diagnostic frequentist random-effects network meta-analysis was performed, and studies were ranked using P-score hierarchical ranking. RESULTS: The analysis included 127 studies with a total of 220 imaging datasets, including the following imaging modalities: MRI (n = 10), MR Spectroscopy (MRS) (n = 28), dynamic contrast-enhanced MRI (n = 7), dynamic susceptibility contrast MRI (n = 36), MR arterial spin labeling (n = 5), diffusion-weighted imaging (n = 13), diffusion tensor imaging (DTI) (n = 2), PET (n = 89), and single photon emission computed tomography (SPECT) (n = 30). MRS had the highest pooled sensitivity (90.7%). DTI had the highest pooled specificity (90.5%). Our hierarchical ranking ranked SPECT and MRS as most preferable, and MRI was ranked as least preferable. CONCLUSION: These findings suggest SPECT and MRS carry greater utility than standard MRI in distinguishing RN from tumor recurrence.