Kinetic and structural characterization of carboxyspermidine dehydrogenase of polyamine biosynthesis.

Polyamines are positively charged alkylamines ubiquitous among eukaryotes, prokaryotes, and archaea. Humans obtain polyamines through dietary intake, metabolic production, or uptake of polyamines made by gut microbes. The polyamine biosynthetic pathway used by most gut microbes differs from that used by human cells. This alternative pathway employs carboxyspermidine dehydrogenase (CASDH), an enzyme with limited characterization. Here, we solved a 1.94 Å X-ray crystal structure of Bacteroides fragilis CASDH by molecular replacement. BfCASDH is composed of three domains with a fold similar to saccharopine dehydrogenase but with a distinct active site arrangement. Using steady-state methods, we determined kcat and kcat/Km for BfCASDH and Clostridium leptum CASDH using putrescine, diaminopropane, aspartate semi-aldehyde, NADH, and NADPH as substrates. These data revealed evidence of cooperativity in BfCASDH. Putrescine is the likely polyamine substrate and NADPH is the coenzyme used to complete the reaction, forming carboxyspermidine as a product. These data provide the first kinetic characterization of CASDH-a key enzyme in the production of microbial polyamines.

Vaccinating for My Family or for My Community? The Effect of Message Framing on Parental Intention to Vaccinate during the COVID Pandemic.

BACKGROUND: Social media is one of the major platforms for disseminating essential health messages. The present study examined the effect of message framing (self-interest motive, prosocial motive) on an online platform for parental intention to vaccinate against COVID-19. It also examined how the effect may vary across participants' levels of parental identity centrality/salience and community orientation before the vaccine was officially available. METHODS: Six hundred and sixty-three Hong Kong Chinese parents were recruited, and a total of 278 valid responses were retained in the analyses. Participants were randomly assigned to one of the three conditions: self-interest motive, prosocial motive, and control. Participants in the self-interest motive condition and the prosocial motive condition read a condition-specific message about the COVID-19 vaccine. Then, they reported their levels of intention to vaccinate against COVID-19, including parent-vaccination, child-vaccination, and medical information-seeking. RESULTS: A significant group effect on child-vaccination was found. Participants in the self-interest motive condition reported a higher intention to vaccinate their children against COVID-19 compared with the other two conditions. Results of moderation analyses indicated that communal orientation moderated the effect of a self-interest-motive-emphasized message on parental intention to vaccinate against COVID-19. The effect of a self-interest-motive-emphasized message appeared to be stronger on parent-vaccination, child-vaccination, and medical information-seeking among parents who reported lower levels of communal orientation. CONCLUSION: These findings provided some initial evidence of the effectiveness of message-framing in promoting parents' intention to vaccinate their children on online platforms.

An Exploratory Content Analysis of the Use of Health Communication Strategies and Presence of Objectification in Fitness Influencer Social Media Posts.

Health and fitness content intended to inspire people to live healthy lives (e.g. "fitspiration") has been linked to negative body image among girls and young women. Fitness influencers purport wanting to motivate healthy behaviors. This study seeks to examine the presence of strategies known to positively influence health behaviors (e.g. attitudes, self-efficacy) as well as of content known to have a negative influence (e.g. objectification) among fitness influencers. We conducted a content analysis (N = 441) of a random sample of one year of posts from four Instagram fitness influencers popular with girls and young women in the United States. The main analysis consisted of codes related to objectification, health promotion strategies, health-related content, and social engagement (i.e., likes). We found that fitness influencers included content that conveyed constructs previously found to positively influence health behaviors (e.g., attitudes and self-efficacy), but objectification was frequently present, in more than half of the posts. Additionally, we found that the presence of objectification in posts was negatively associated with likes, a form of social endorsement. We suggest health communicators aim to work in tandem with fitness influencers to include content that may motivate positive health behaviors and improve media literacy and that influencers aim to reduce the amount of objectifying content included in their posts. Our findings shed light on content being conveyed and possible insights into the negative effects associated with viewing such content.

COVID-19 Vaccine Intention and Social Cognitive Theory: The Role of Individual Responsibility and Partisan Media Use in a Moderated Moderated Mediation Model.

Despite the sheer devastation caused by the COVID-19 pandemic in the United States, vaccine hesitancy is a major barrier to a successful implementation of the vaccine. We apply two moderators to examine the associations of efficacy and expectancies with COVID-19 vaccine intention. Specifically, we use national survey data collected online in 2020 (N = 1264) and a moderated moderated mediation PROCESS model to examine 1) the associations between self-efficacy about COVID-19 and vaccine intention mediated by positive outcome expectancies and 2) moderating roles of individual responsibility and partisan media use. The findings show that the path from efficacy to expectancies is moderated by individual responsibility, while the path from expectancies to vaccine intention is moderated by liberal media use. Our findings support the strategic application of SCT to emphasize the role of personal responsibility in campaigns to encourage vaccination for the COVID-19 virus.

Culture-centric narratives of influenza vaccination among high-risk groups in Hong Kong.

Despite the effectiveness of influenza vaccination, the vaccine coverage rate among high-risk groups in Hong Kong is less than optimal. Guided by the Health Belief Model (HBM) and culture-centric narrative approach, we examined the role of cultural specificities in implicit assumptions held by at-risk individuals when the individuals decided whether to receive the vaccine. Data were collected from 29 in-depth interviews with people from high-risk groups in Hong Kong. From their decision narratives, it is evident that the local socio-cultural characteristics and collectivistic ideology are useful in understanding the perceptions of influenza severity, susceptibility to infection, perceived barriers and benefits, and self-efficacy of accepting or rejecting the vaccine among the high-risk individuals. Implications of vaccination message designs are discussed.

Identification of Compounds Preventing A. fumigatus Biofilm Formation by Inhibition of the Galactosaminogalactan Deacetylase Agd3.

The opportunistic fungus Aspergillus fumigatus causes a set of diseases ranging from allergy to lethal invasive mycosis. Within the human airways, A. fumigatus is embedded in a biofilm that forms not only a barrier against the host immune defense system, but also creates a physical barrier protecting the fungi from chemicals such as antifungal drugs. Novel therapeutic strategies aim at combining drugs that inhibit biofilm synthesis or disrupt existing biofilm with classical antimicrobials. One of the major constituents of A. fumigatus biofilm is the polysaccharide galactosaminogalactan (GAG) composed of α1,4-linked N-acetylgalactosamine, galactosamine, and galactose residues. GAG is synthesized on the cytosolic face of the plasma membrane and is extruded in the extracellular space, where it is partially deacetylated. The deacetylase Agd3 that mediates this last step is essential for the biofilm formation and full virulence of the fungus. In this work, a previously described enzyme-linked lectin assay, based on the adhesion of deacetylated GAG to negatively charged plates and quantification with biotinylated soybean agglutinin was adapted to screen microbial natural compounds, as well as compounds identified in in silico screening of drug libraries. Actinomycin X2, actinomycin D, rifaximin, and imatinib were shown to inhibit Agd3 activity in vitro. At a concentration of 100 µM, actinomycin D and imatinib showed a clear reduction in the biofilm biomass without affecting the fungal growth. Finally, imatinib reduced the virulence of A. fumigatus in a Galleria mellonella infection model in an Agd3-dependent manner.

Designing dementia care activation program for Filipino American caregivers.

OBJECTIVE: This research study aims to identify the fundamental components of community adaptation for a culturally tailored care partner activation program for Filipino American family caregivers of patients with Alzheimer's Disease and related dementia (ADRD). DESIGN: The study utilized focus group interviews with community nurse leaders, stakeholders, and family caregivers of patients with ADRD. RESULTS: The research revealed that education and knowledge about the disease, community-based services and facilities, support groups and resources, spiritual and cultural values, and access to transportation are all critical components for community adaptation. CONCLUSION: The findings suggest that a culturally tailored care partner activation program that incorporates these components can enhance the quality of life for Filipino American caregivers and their loved ones with ADRD. The nursing implications of the study underscore the importance of nurses being culturally competent and sensitive to the unique challenges faced by Filipino American caregivers. Nurses can provide valuable support to caregivers by educating them, connecting them with community resources, and advocating for culturally responsive care practices.

Navigating the Complexities of Dementia Care: The Lived Experiences of Black American Family Caregivers.

Black American individuals have a higher rate of Alzheimer's disease and related dementias (ADRD) diagnoses compared to other racial/ethnic groups, and their family caregiver population is expected to increase rapidly over the next 2 decades. The current study aimed to explore Black American women's experiences caring for family members with ADRD. An interpretative phenomenology approach was used to gain a deeper understanding of the caregiving experiences of Black American women. Participants in the study were all Black American married women aged 63 to 81 years (mean = 71.3 years, SD = 6.6 years). Key themes that emerged from the study included: (a) Family Care Obligation, (b) Caregiving Journey, (c) Prioritizing Health Concerns, (d) Coping Behaviors, and (e) Support Needs and Challenges. Family caregivers require ongoing support, education, and guidance. Implications for nursing practice include focusing on family assessments, increased education and awareness, and collaboration with interdisciplinary teams to provide the best resources. [Journal of Gerontological Nursing, 49(6), 19-26.].

Integrating Advanced Lipid Testing and Biomarkers in Assessment and Treatment.

PURPOSE OF REVIEW: Our ability to assess and stratify atherosclerotic disease risk in patients is evolving. Recent advances in advanced lipid testing have created opportunities for clinical application of novel biomarkers. RECENT FINDINGS: Until recently, LDL-C has served largely as the singular biomarker of ASCVD and guide for decisions in treatment for high-risk groups. There are important evolutions in the measurement of LDL-C but even still, the pathogenesis of atherosclerosis and ASCVD is not solely driven by LDL-C. As atherosclerosis is driven by multiple complex pathways including inflammation, it is important to expand our focus beyond LDL-C and utilize multiple biomarkers in the assessment of this disease process. Non-HDL, ApoB, LDL-P, Lp(a), and hsCRP are unique tools to aid in cardiac risk evaluation, especially in higher risk patients, though not limited to this population. A multifaceted approach to advanced lipid testing with novel biomarkers will enhance comprehensive ASCVD risk assessments.

A new implantable tool for repeated assessment of supraventricular electrophysiology and atrial fibrillation susceptibility in freely moving rats.

The complex pathophysiology of atrial fibrillation (AF) is governed by multiple risk factors in ways that are still elusive. Basic electrophysiological properties, including atrial effective refractory period (AERP) and conduction velocity, are major factors determining the susceptibility of the atrial myocardium to AF. Although there is a great need for affordable animal models in this field of research, in vivo rodent studies are limited by technical challenges. Recently, we introduced an implantable system for long-term assessment of AF susceptibility in ambulatory rats. However, technical considerations did not allow us to perform concomitant supraventricular electrophysiology measurements. Here, we designed a novel quadripolar electrode specifically adapted for comprehensive atrial studies in ambulatory rats. Electrodes were fabricated from medical-grade silicone, four platinum-iridium poles, and stainless-steel fixating pins. Initial quality validation was performed ex vivo, followed by implantation in adult rats and repeated electrophysiological studies 1, 4, and 8 wk postimplantation. Capture threshold was stable. Baseline AERP values (38.1 ± 2.3 and 39.5 ± 2.0 using 70-ms and 120-ms S1-S1 cycle lengths, respectively) confirmed the expected absence of rate adaptation in the unanesthetized state and validated our prediction that markedly higher values reported under anesthesia are nonphysiological. Evaluation of AF substrate in parallel with electrophysiological parameters validated our recent finding of a gradual increase in AF susceptibility over time and demonstrated that this phenomenon is associated with an electrical remodeling process characterized by AERP shortening. Our findings indicate that the miniature quadripolar electrode is a potent new tool, which opens a window of opportunities for better utilization of rats in AF research.NEW & NOTEWORTHY Rodents are increasingly used in AF research. However, technical challenges restrict long-term supraventricular electrophysiology studies in these species. Here, we developed an implantable electrode adapted for such studies in the rat. Our findings indicate that this new tool is effective for long-term follow-up of critical parameters such as atrial refractoriness. Obtained data shed light on the normal electrophysiology and on the increased AF susceptibility that develops in rats with implanted atrial electrodes over time.

Different Food Sources of Fructose-Containing Sugars and Fasting Blood Uric Acid Levels: A Systematic Review and Meta-Analysis of Controlled Feeding Trials.

BACKGROUND: Although fructose as a source of excess calories increases uric acid, the effect of the food matrix is unclear. OBJECTIVES: To assess the effects of fructose-containing sugars by food source at different levels of energy control on uric acid, we conducted a systematic review and meta-analysis of controlled trials. METHODS: MEDLINE, Embase, and the Cochrane Library were searched (through 11 January 2021) for trials ≥ 7 days. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars in diets); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in diets) designs. Independent reviewers (≥2) extracted data and assessed the risk of bias. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the certainty of evidence. RESULTS: We included 47 trials (85 comparisons; N = 2763) assessing 9 food sources [sugar-sweetened beverages (SSBs), sweetened dairy, fruit drinks, 100% fruit juice, fruit, dried fruit, sweets and desserts, added nutritive sweetener, and mixed sources] across 4 energy control levels in predominantly healthy, mixed-weight adults. Total fructose-containing sugars increased uric acid levels in substitution trials (mean difference, 0.16 mg/dL;  95% CI:  0.06-0.27 mg/dL;  P = 0.003), with no effect across the other energy control levels. There was evidence of an interaction by food source: SSBs and sweets and desserts increased uric acid levels in the substitution design, while SSBs increased and 100% fruit juice decreased uric acid levels in addition trials. The certainty of evidence was high for the increasing effect of SSBs in substitution and addition trials and the decreasing effect of 100% fruit juice in addition trials and was moderate to very low for all other comparisons. CONCLUSIONS: Food source more than energy control appears to mediate the effects of fructose-containing sugars on uric acid. The available evidence provides reliable indications that SSBs increase and 100% fruit juice decreases uric acid levels. More high-quality trials of different food sources are needed. This trial was registered at clinicaltrials.gov as NCT02716870.

Development of an online curriculum for California early care and education providers on healthy beverages.

BACKGROUND: Children's consumption of sugar-sweetened beverages is associated with obesity, diabetes, and dental decay. California's Healthy Beverages in Child Care Act (AB 2084) requires all licensed child care centers and family child care homes to comply with healthy beverages standards, however many licensed providers in California are unaware of the law and few are fully compliant with the law's requirements. The aim of the current project is to describe the development of a self-paced online training on best practices and implementation of AB 2084 in English and Spanish for family child care home and child care center providers; and to evaluate the feasibility, defined as being accessible, acceptable, and satisfactory to providers, of this new online course. METHODS: The project was broken into two main stages: (1) development of the online course; and (2) evaluation of the final online course. The first stage was completed in five phases: (1) identify relevant course content and develop narration script; (2) conduct in-person focus groups with child care providers to review and edit the content; (3) adapt course content and translate for Spanish-speaking providers; (4) build the online course and resources; and (5) pilot online course and evaluate accessibility. The second stage, evaluation of the acceptability and satisfaction of the final course was rated on a Likert scale from 1 to 4; the evaluation was completed as part of a larger randomized control trial with 43 child care providers. The course features four key requirements of AB 2084 as the main sections of the course (milk, sweetened beverages, juice, and water), plus background information about beverages and children's health, special topics including caring for children with special needs, family engagement, written policies, and child engagement. RESULTS: The child care providers who completed the evaluation found the online training was easily understandable (median(Q1,Q3,IQR) = 4 (4,4,0)), included new information (3 (1, 3, 4)), provided useful resources (4(4,4,0)), and was rated with high overall satisfaction (3 (1, 3, 4)). CONCLUSION: Online training in English and Spanish designed for child care providers is a feasible medium to deliver important health messages to child care providers in an accessible, acceptable, and satisfactory manner.

Fact-Checking of Health Information: The Effect of Media Literacy, Metacognition and Health Information Exposure.

With the rampant circulation of health information, concerns for the information quality are growing. Thereby, scholars are calling for media literacy as an educative means to cultivate fact-checking behavior among information consumers. Focusing on the critical role of metacognition for education effectiveness, this study examined the underlying mechanism that is conducive to the success of media literacy in the context of health information consumption. Based on the survey data collected from 502 Reddit.com users, our findings showed that media literacy was positively associated with fact-checking behavior for health information. Mediation analysis indicated that metacognition mediated the positive relationship between media literacy and fact-checking behavior. In addition, moderated-mediation analysis demonstrated that the mediating effect was weaker for individuals who had higher exposure to health information. The study sheds light on the factors that are essential for the success of media literacy. Implications and future directions are discussed.

Activation of Cannabinoid Receptors Attenuates Endothelin-1-Induced Mitochondrial Dysfunction in Rat Ventricular Myocytes.

Evidence suggests that the activation of the endocannabinoid system offers cardioprotection. Aberrant energy production by impaired mitochondria purportedly contributes to various aspects of cardiovascular disease. We investigated whether cannabinoid (CB) receptor activation would attenuate mitochondrial dysfunction induced by endothelin-1 (ET1). Acute exposure to ET1 (4 hours) in the presence of palmitate as primary energy substrate induced mitochondrial membrane depolarization and decreased mitochondrial bioenergetics and expression of genes related to fatty acid oxidation (ie, peroxisome proliferator-activated receptor-gamma coactivator-1α, a driver of mitochondrial biogenesis, and carnitine palmitoyltransferase-1ß, facilitator of fatty acid uptake). A CB1/CB2 dual agonist with limited brain penetration, CB-13, corrected these parameters. AMP-activated protein kinase (AMPK), an important regulator of energy homeostasis, mediated the ability of CB-13 to rescue mitochondrial function. In fact, the ability of CB-13 to rescue fatty acid oxidation-related bioenergetics, as well as expression of proliferator-activated receptor-gamma coactivator-1α and carnitine palmitoyltransferase-1ß, was abolished by pharmacological inhibition of AMPK using compound C and shRNA knockdown of AMPKα1/α2, respectively. Interventions that target CB/AMPK signaling might represent a novel therapeutic approach to address the multifactorial problem of cardiovascular disease.

Nutrition Provided to Infants in Licensed Childcare Centers and Homes: A Descriptive Study.

BACKGROUND: Infant nutrition can influence development, eating behaviors and obesity risk. Nearly half of infants in the U.S. are in non-parental care where they consume much of their daily nutrition. Because little is known about the quality of infant nutrition in childcare, the study objective was to characterize the foods and beverages provided to infants in childcare in California. METHODS: From a randomly selected sample of 2,400 licensed childcare in California, 736 responded to a 2016 survey; a subset of 297 cared for infants. Differences in 26 foods and 7 beverages provided between centers and homes, and by CACFP participation, were assessed using logistic regression models adjusted for CACFP participation and whether the site was a center or home, respectively. RESULTS: Several differences between centers and homes were identified. One the day prior to the survey, more centers than homes ever provided cow's milk (25.1% vs 13.0%, p = 0.02) and whole grains (76.7% vs 62.9%, p = 0.03), and fewer centers than homes provided frozen treats (1.4% vs 10.3%, p = 0.003). When comparing difference by CACFP participation, fewer CACFP than non-CACFP sites usually provided breastmilk (32.6% vs 54.2%, p = 0.0004) and ever provided cow's milk (14.2% vs 37.1%, p < 0.0001). On the day prior to the survey, more CACFP than non-CACFP provided vegetables (91.0% vs 80.8%, p = 0.02), fruit (centers only) (97.2% vs 80.8%, p = 0.0003), and infant cereals (86.0% vs 61.2%, p < 0.0001). Fewer CACFP than non-CACFP provided sweetened yogurt (14.8% vs 36.7%, p < 0.0001). CONCLUSIONS FOR PRACTICE: Childcare centers and CACFP participants tended to serve nutritious foods more than childcare homes and non-CACFP participants, respectively. Additional education and policies for childcare providers on appropriate foods and beverages for infants is recommended.

A Social Networks Approach to Understanding Vaccine Conversations on Twitter: Network Clusters, Sentiment, and Certainty in HPV Social Networks.

Individuals increasingly rely on the Internet, and social media in particular, for health-related information. A recent survey reports that 80% of Internet users search for health information online. In the present study, we employ Twitter data to understand content characteristics and the patterns of content flow of the conversations about the HPV vaccine debate. Approaching the HPV vaccine conversations on Twitter as a social network, we can identify key self-formed subgroups-clusters of users who create "siloes" of interactions and information flow. Combining network analysis, computer-aided content analysis, and human-coded content analysis, we explored the communication dynamics within the groups in terms of group members' affective and cognitive characteristics. Our findings show that positive emotion is positively correlated with cluster density, an indicator of strong ties and rapid information flow. In the case of negative emotion, we found that anger is a significant negative predictor for graph density. We also found a correlation between certainty and tentativeness; both at cluster as well as at tweet level, suggesting that clusters bring together people who are sure about the HPV vaccine and people who are exploring for answers.

Status of Beverages Served to Young Children in Child Care After Implementation of California Policy, 2012-2016.

INTRODUCTION: Since 2012, licensed California child care centers and homes, per state policy, are required to serve only unflavored low-fat or nonfat milk to children aged 2 years or older, no more than one serving of 100% juice daily, and no beverages with added sweeteners, and they are required to ensure that drinking water is readily accessible throughout the day. We evaluated adherence to the policy after 4 years in comparison to the adherence evaluation conducted shortly after the policy went into effect. METHODS: Licensed California child care sites were randomly selected in 2012 and 2016 and surveyed about beverage practices and provisions to children aged 1-5 years. We used logistic regression to analyze between-year differences for all sites combined and within-year differences by site type and participation in the federal Child and Adult Care Food Program (CACFP) in self-reported policy adherence and beverage provisions. RESULTS: Respondents in 2016 (n = 680), compared with those in 2012 (n = 435), were more adherent to California's 2010 Healthy Beverages in Child Care Act overall (45.1% vs 27.2%, P < .001) and with individual provisions for milk (65.0% vs 41.4%, P < .001), 100% juice (91.2% vs 81.5%, P < .001), and sugar-sweetened beverages (97.4% vs 93.4%, P = .006). In 2016, centers compared with homes (48.5% vs 28.0%, P = .001) and CACFP sites compared with non-CACFP sites (51.6% vs 27.9%, P < .001) were more adherent to AB2084 overall. DISCUSSION: Beverage policy adherence in California child care has improved since 2012 and is higher in CACFP sites and centers. Additional policy promotion and implementation support is encouraged for non-CACFP sites and homes. Other states should consider adopting such policies.

Hypertension management in rural western Kenya: a needs-based health workforce estimation model.

BACKGROUND: Elevated blood pressure is the leading risk for mortality in the world. Task redistribution has been shown to be efficacious for hypertension management in low- and middle-income countries. However, the workforce requirements for such a task redistribution strategy are largely unknown. Therefore, we developed a needs-based workforce estimation model for hypertension management in western Kenya, using need and capacity as inputs. METHODS: Key informant interviews, focus group discussions, a Delphi exercise, and time-motion studies were conducted among administrative leadership, clinicians, patients, community leaders, and experts in hypertension management. These results were triangulated to generate the best estimates for the inputs into the health workforce model. The local hypertension clinical protocol was used to derive a schedule of encounters with different levels of clinician and health facility staff. A Microsoft Excel-based spreadsheet was developed to enter the inputs and generate the full-time equivalent workforce requirement estimates over 3 years. RESULTS: Two different scenarios were modeled: (1) "ramp-up" (increasing growth of patients each year) and (2) "steady state" (constant rate of patient enrollment each month). The ramp-up scenario estimated cumulative enrollment of 7000 patients by year 3, and an average clinical encounter time of 8.9 min, yielding nurse full-time equivalent requirements of 4.8, 13.5, and 30.2 in years 1, 2, and 3, respectively. In contrast, the steady-state scenario assumed a constant monthly enrollment of 100 patients and yielded nurse full-time equivalent requirements of 5.8, 10.5, and 14.3 over the same time period. CONCLUSIONS: A needs-based workforce estimation model yielded health worker full-time equivalent estimates required for hypertension management in western Kenya. The model is able to provide workforce projections that are useful for program planning, human resource allocation, and policy formulation. This approach can serve as a benchmark for chronic disease management programs in low-resource settings worldwide.

Ophthalmic examination findings and intraocular pressures in wild-caught African giant pouched rats (Cricetomys spp.).

PURPOSE: To report ophthalmic examination findings and intraocular pressures (IOPs) in wild-caught African giant pouched rats (Cricetomys ansorgei and gambianus) from Tanzania and Ghana. PROCEDURES: After being placed under general anesthesia for examination, slit-lamp biomicroscopy before and after pharmacologic mydriasis and indirect ophthalmoscopy was performed. Eyes were fluorescein stained and IOPs measured by rebound tonometry using the TonoVet® . RESULTS: Thirty-two sexually mature pouched rats (64 eyes) were examined, including 16 males and 16 females. The mean IOP (± standard deviation) was 7.7 (±2.9) mmHg. Fluorescein staining was negative in all eyes. One or more ocular abnormalities were detected in 21 pouched rats (35 eyes). These ocular lesions included the following: lens opacities (n = 23 eyes), persistent pupillary membranes (n = 5), chorioretinal scarring (n = 3), corneal vascularization (n = 2), palpebral margin defect with focal trichiasis (n = 2), phthisis bulbi (n = 1), and posterior synechiae (n = 1). Lens opacities included incipient anterior cortical opacities (n = 7), immature cataract (n = 6), incipient nuclear opacities (n = 5), punctate pigment on anterior lens capsule (n = 2 eyes), incipient suture tip opacities (n = 2), and hypermature cataract (n = 1). CONCLUSIONS: Ocular abnormalities were common in the evaluated population of giant pouched rats; however, most of the detected lesions were mild and believed to have minimal impact on vision. Rebound tonometry with the TonoVet® was a reliable and simple technique to measure IOPs in the anesthetized pouched rats.

Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar degenerative diseases.

Changes in climbing fiber-Purkinje cell (CF-PC) synaptic connections have been found in the essential tremor (ET) cerebellum, and these changes are correlated with tremor severity. Whether these postmortem changes are specific to ET remains to be investigated. We assessed CF-PC synaptic pathology in the postmortem cerebellum across a range of degenerative movement disorders [10 Parkinson's disease (PD) cases, 10 multiple system atrophy (MSA) cases, 10 spinocerebellar ataxia type 1 (SCA1) cases, and 20 ET cases] and 25 controls. We observed differences in terms of CF pathological features across these disorders. Specifically, PD cases and ET cases both had more CFs extending into the parallel fiber (PF) territory, but ET cases had more complex branching and increased length of CFs in the PF territory along with decreased CF synaptic density compared to PD cases. MSA cases and SCA1 cases had the most severely reduced CF synaptic density and a marked paucity of CFs extending into the PF territory. Furthermore, CFs in a subset of MSA cases formed collateral branches parallel to the PC layer, a feature not seen in other diagnostic groups. Using unsupervised cluster analysis, the cases and controls could all be categorized into four clusters based on the CF pathology and features of PC pathology, including counts of PCs and their axonal torpedoes. ET cases and PD cases co-segregated into two clusters, whereas SCA1 cases and MSA cases formed another cluster, separate from the control cluster. Interestingly, the presence of resting tremor seemed to be the clinical feature that separated the cases into the two ET-PD clusters. In conclusion, our study demonstrates that these degenerative movement disorders seem to differ with respect to the pattern of CF synaptic pathology they exhibit. It remains to be determined how these differences contribute to the clinical presentations of these diseases.