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Following strenuous exercise, skeletal muscle experiences an acute inflammatory state that initiates the repair process. Systemic hyaluronic acid (HA) is injected to horses routinely as a joint anti-inflammatory. To gain insight into the effects of HA on skeletal muscle, adult Thoroughbred geldings (n = 6) were injected with a commercial HA product weekly for 3 weeks prior to performing a submaximal exercise test. Gluteal muscle (GM) biopsies were obtained before and 1 h after exercise for gene expression analysis and HA localization. The results from RNA sequencing demonstrate differences in gene expression between non-injected controls (CON; n = 6) and HA horses. Prior to exercise, HA horses contained fewer (p < 0.05) transcripts associated with leukocyte activity and cytokine production than CON. The performance of exercise resulted in the upregulation (p < 0.05) of several cytokine genes and their signaling intermediates, indicating that HA does not suppress the normal inflammatory response to exercise. The transcript abundance for marker genes of neutrophils (NCF2) and macrophages (CD163) was greater (p < 0.05) post-exercise and was unaffected by HA injection. The anti-inflammatory effects of HA on muscle are indirect as no differences (p > 0.05) in the relative amount of the macromolecule was observed between the CON and HA fiber extracellular matrix (ECM). However, exercise tended (p = 0.10) to cause an increase in ECM size suggestive of muscle damage and remodeling. The finding was supported by the increased (p < 0.05) expression of CTGF, TGFβ1, MMP9, TIMP4 and Col4A1. Collectively, the results validate HA as an anti-inflammatory aid that does not disrupt the normal post-exercise muscle repair process.

Connection to nature (CTN) has been linked to improved health and well-being and an increase in an individual's pro-environmental behaviors. CTN is often thought to be developed in one's childhood, but some studies have refuted this claim by studying CTN development in adults. This study used mixed methods to investigate whether Western Carolina University's Parks and Recreation Management course PRM 365: Nature Rx (a liberal studies course) impacted students' CTN. The findings of the study were compared with those of Lankenau (2018), who studied CTN in related college courses, by replicating his quantitative instrument. A MANOVA test produced nonsignificant results, F(3, 28) = 2.09, p = .13, indicating that Nature Rx had no impact on students’ CTN. Qualitative results also showed minimal change pre-to-post semester as answers to prompted journal questions reflected a limited change across time. Both quantitative and qualitative results indicate that a ceiling effect may be a source of explanation for these results. However, more work must be done to decipher what about the course, or the population led to these results.

Strenuous exercise can cause tissue damage, leading to an extended recovery period. To counteract delayed post-exercise recovery, a commercial product containing L-carnitine (AID) was tested in adult horses performing consecutive exercise tests to exhaustion. Fit Thoroughbreds were administered an oral bolus of placebo (CON) or AID prior to performing an exercise test to exhaustion (D1). The heart rate (HR) and fetlock kinematics were captured throughout the exercise test. Blood was collected before, 10 min and 1, 4 and 6 h relative to exercise for the quantification of cytokine (IL1β, IL8, IL10, TNFa) gene expression and lactate concentration. Horses performed a second exercise test 48 h later (D2), with all biochemical and physiological measures repeated. The results demonstrate that the horses receiving AID retained a greater (p < 0.05) amount of flexion in the front fetlock on D2 than the horses given CON. The horses presented a reduced (p < 0.05) rate of HR decline on D2 compared to that on D1. The expression of IL1β, IL8 and IL10 increased at 1 h post-exercise on D1 and returned to baseline by 6 h; the cytokine expression pattern was not duplicated on D2. These results provide evidence of disrupted cytokine expression, HR recovery and joint mobility in response to consecutive bouts of exhaustive exercise. Importantly, AID may accelerate recovery through an undetermined mechanism.

[Background] In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity., [Objective] This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants., [Methods] We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3., [Results] Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4−CD8−) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate., [Conclusion] : STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome.

This thesis is concerned with the use of fluorophosphite ligands in rhodium-catalysed hydroformylation. Work has been carried out to synthesise two novel fluorophosphites, L6 and L7 (shown in Figure 1), via a new synthetic method, and computational work has been executed to map the free energy surfaces of the species in the hydroformylation cycle with two known fluorophosphites. This work aims to enhance the understanding of fluorophosphites in terms of their electronic and steric effects upon changing the backbone with the goal to put these fluorophosphites to the test in a catalytic run in the laboratory. The new cyclic fluorophosphites formed contained 6-membered dioxaphosphacycles and were derived from naphthalene-1,8-diol. Upon protection of the alcohol groups, lithiation reactions with n-BuLi were used for substitution at the ortho position with phenyl groups by Suzuki coupling of phenylboronic acid. Following deprotection, the fluorophosphite group was incorporated into the molecule by reaction with PCl3 and then SbF3. The resulting 31P and 13F NMR spectra of compounds L2, L6 and L7 revealed the peaks to lie close to each other, representing the similarity of the electronic properties of the compounds despite the change in steric effects. The computational work focused on modelling the catalytic cycle of a rhodium-catalysed hydroformylation reaction using fluorophosphite ligands. P(OMe)2F, L5, was chosen as a simple fluorophosphite ligand to help gain an insight into the general trends in free energy observed in a hydroformylation cycle. Then, a model fluorophosphite L2 (Fig. 1) was used to observe the differences in the trends when a dioxaphosphacyclic ligand was used. The key reflections were that the free energy barriers were closer in energy in comparison to the simpler ligand, showing that phosphite ligand exchange with CO is more likely to occur for L2. Lastly, 52 fluorophosphites were added to the Ligand Knowledge Base (

This thesis is concerned with the use of fluorophosphite ligands in rhodium-catalysed hydroformylation. Work has been carried out to synthesise two novel fluorophosphites, L6 and L7 (shown in Figure 1), via a new synthetic method, and computational work has been executed to map the free energy surfaces of the species in the hydroformylation cycle with two known fluorophosphites. This work aims to enhance the understanding of fluorophosphites in terms of their electronic and steric effects upon changing the backbone with the goal to put these fluorophosphites to the test in a catalytic run in the laboratory. The new cyclic fluorophosphites formed contained 6-membered dioxaphosphacycles and were derived from naphthalene-1,8-diol. Upon protection of the alcohol groups, lithiation reactions with n-BuLi were used for substitution at the ortho position with phenyl groups by Suzuki coupling of phenylboronic acid. Following deprotection, the fluorophosphite group was incorporated into the molecule by reaction with PCl3 and then SbF3. The resulting 31P and 13F NMR spectra of compounds L2, L6 and L7 revealed the peaks to lie close to each other, representing the similarity of the electronic properties of the compounds despite the change in steric effects. The computational work focused on modelling the catalytic cycle of a rhodium-catalysed hydroformylation reaction using fluorophosphite ligands. P(OMe)2F, L5, was chosen as a simple fluorophosphite ligand to help gain an insight into the general trends in free energy observed in a hydroformylation cycle. Then, a model fluorophosphite L2 (Fig. 1) was used to observe the differences in the trends when a dioxaphosphacyclic ligand was used. The key reflections were that the free energy barriers were closer in energy in comparison to the simpler ligand, showing that phosphite ligand exchange with CO is more likely to occur for L2. Lastly, 52 fluorophosphites were added to the Ligand Knowledge Base (

Background and objectives: This study investigates whether subjective memory decline in a racially diverse sample of older adults without cognitive impairment at baseline is associated with incident cognitive impairment during a 12-year follow-up period. Research design and methods: With panel data from a national sample (N=9,244) of cognitively-intact Black, White, and Hispanic Americans 65 years or older in 2004, we examine if subjective memory decline is associated with the loss of normal cognition by 2016. Cognitive status was assessed every two years with a modified version of the Telephone Interview for Cognitive Status to identify the transition from normal cognition to cognitive impairment. Results: Estimates from Weibull accelerated failure-time models reveal that subjective memory decline is associated with earlier incident cognitive impairment (time ratio = 0.96, p<.05). In subsequent models stratified by race-ethnicity, this association was evident among White respondents (time ratio = 0.95, p<.01) but not among Black, US-born Hispanic, or foreign-born Hispanic respondents. Discussion and implications: Given that the prognostic validity of subjective memory decline differs by race and ethnicity, caution is warranted when using it as a screening or clinical tool in diverse populations.

Claudia SP Fernandez,1 Melissa A Green,2 Cheryl C Noble,3 Kathleen Brandert,4 Katherine Donnald,5 Madison R Walker,1 Ellison Henry,1 Angela Rosenberg,5 Gaurav Dave,2 Giselle Corbie-Smith2 1Department of Maternal and Child Health, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2Center for Health Equity Research, UNC School of Medicine Department of Social Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 3Private Evaluation Consultancy, Scotts Valley, CA, USA; 4Office of Public Health Practice and Department of Health Promotion, Social and Behavioral Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA; 5Inside Out Enneagram Consulting, Pittsboro, NC, USACorrespondence: Claudia SP FernandezDepartment of Maternal and Child Health, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 426 Rosenau Hall, 134 Dauer Drive, Chapel Hill, NC, 27599, USATel +1 919-843-5560Fax +1-919-966-0458Email Claudia_Fernandez@unc.eduIntroduction: Since the inception of distance-based teaching modalities, a debate has ensued over the quality of online versus in-person instruction. Due to the COVID-19 pandemic, a number of teaching environments—including leadership development trainings for post-graduate learners—have been thrust into exploring the virtual learning environment more thoroughly. One three-year leadership development program for interdisciplinary healthcare professionals transitioned three simultaneous leadership intensives from in-person to online in the spring of 2020.Methods: Documented changes in overall training length, session length, and session format are described. Further, evaluative data were collected from participants at both retreats via post-session surveys. Ninety-three participants attended the 2019 retreat, and 92 participants attended the 2020 virtual retreat. Quantitative data

The role of medial prefrontal cortex (mPFC) in regulating nicotine taking and seeking remains largely unexplored. In this study we took advantage of the high time-resolution of optogenetic intervention by decreasing (Arch3.0) or increasing (ChR2) the activity of neurons in the dorsal and ventral mPFC during 5-s nicotine cue presentations in order to evaluate their contribution to cued nicotine seeking and taking. Wistar rats were trained to self-administer intravenous nicotine in 1 h self-administration sessions twice a day for a minimum of 10 days. Subsequently, dmPFC or vmPFC neuronal activity was modulated during or following presentation of the 5-s nicotine cue, both under extinction and self-administration conditions. We also used in vivo electrophysiology to record the activity of dmPFC neurons during nicotine self-administration and extinction tests. We show that optogenetic inhibition of dmPFC neurons during, but not following, response-contingent presentations of the nicotine cue increased nicotine seeking. We found no effect on nicotine self-administration or on food seeking in an extinction test. We also show that this effect is specific to dmPFC, because optogenetic inhibition of vmPFC had no effect on nicotine seeking and taking. In vivo recordings revealed that dmPFC network neuronal activity was modulated more strongly following nicotine cue presentation in extinction, compared to following nicotine self-administration. Our results strongly suggest that a population of neurons within the dmPFC is involved in encoding the incentive value of nicotine-associated cues.