Developing a curriculum to improve cardiology fellows' training in pregnancy and cardiovascular disease.

BACKGROUND: Exposure to pregnant women with cardiovascular disease (CVD) during cardiology fellowship training is limited and without a standard curriculum in the United States. The authors sought to evaluate a dedicated curriculum to teach management of CVD in pregnancy to improve general cardiology fellowship training. METHODS: The authors developed a dedicated CVD in pregnancy curriculum for the general cardiology fellows at a large academic medical center in the fall of 2019. Fellows' knowledge was assessed via a board-style examination and exposure and attitudes related to the care of pregnant women with CVD were evaluated with a needs assessment questionnaire before and after the curriculum. RESULTS: Of the 17 fellows who participated in the curriculum, 12 completed the needs assessment pre-curriculum and 9 post-curriculum. The mean (SD) number of pregnant women with CVD cared for by each fellow in the inpatient and outpatient settings were 0.75 (1.29) and 0.56 (0.73), respectively. After the curriculum, all fellows reported awareness of available resources to treat pregnant women with CVD, while a majority disagreed that they receive regular exposure to pregnant patients with CVD in their training. The authors observed significant increases in fellows' confidence in their knowledge of normal cardiovascular physiology of pregnancy, physical exam skills, and ability to care for pregnant women with valvular disease and arrhythmias from pre to post-curriculum. A total of 15 fellows completed the board-style exam pre-curriculum and 15 post-curriculum. Fellows' performance on the board-style examination improved slightly from before to after the curriculum (64.0 to 75.3% correct, p = 0.02). CONCLUSIONS: A dedicated curriculum improved cardiology fellows' knowledge to recognize and treat CVD in pregnancy and improved confidence in caring for this unique patient population.

Proteomics based markers of clinical pain severity in juvenile idiopathic arthritis.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a cluster of autoimmune rheumatic diseases occurring in children 16 years of age or less. While it is well-known that pain may be experienced during inflammatory and non-inflammatory states, much remains ambiguous regarding the molecular mechanisms that may drive JIA pain. Thus, in this pilot study, we explored the variability of the serum proteomes in relation to pain severity in a cohort of JIA patients. METHODS: Serum samples from 15 JIA patients (male and female, 12.7 ± 2.8 years of age) were assessed using liquid chromatography/mass spectrometry (LC/MS). Correlation analyses were performed to determine the relationships among protein levels and self-reported clinical pain severity. Additionally, how the expression of pain-associated proteins related to markers of inflammation (Erythrocyte Sedimentation Rate (ESR)) or morphological properties of the central nervous system (subcortical volume and cortical thickness) implicated in JIA were also evaluated. RESULTS: 306 proteins were identified in the JIA cohort of which 14 were significantly (p < 0.05) associated with clinical pain severity. Functional properties of the identified pain-associated proteins included but were not limited to humoral immunity (IGLV3.9), inflammatory response (PRG4) and angiogenesis (ANG). Associations among pain-associated proteins and ESR (IGHV3.9, PRG4, CST3, VWF, ALB), as well as caudate nucleus volume (BTD, AGT, IGHV3.74) and insular cortex thickness (BTD, LGALS3BP) were also observed. CONCLUSIONS: The current proteomic findings suggest both inflammatory- and non-inflammatory mediated mechanisms as potential factors associated with JIA pain. Validation of these preliminary observations using larger patient cohorts and a longitudinal study design may further point to novel serologic markers of pain in JIA.

Identifying barriers, facilitators, and interventions to support healthy eating in pregnant women with or at risk for hypertensive disorders of pregnancy.

Background: Heart-healthy diets are important in the prevention and treatment of hypertension (HTN), including among pregnant women. Yet, the barriers, facilitators, and beliefs/preferences regarding healthy eating are not well described in this population. Objective: To identify barriers and facilitators to healthy diet, examine the prevalence of food insecurity, and determine interest in specific healthy diet interventions. Methods: Pregnant women, aged 18-50 years (N = 38), diagnosed with HTN, hypertensive disorders in pregnancy (HDP), or risk factors for HDP, were recruited from a large academic medical center in central Massachusetts between June 2020 and June 2022. Participants completed an electronic survey using a 5-point Likert scale (strongly disagree to strongly agree). Results: The mean age of participants was 31.6 years (SD 5.5) and 35.1% identified as Hispanic. Finances and time were major barriers to a healthy diet, reported by 42.1% and 28.9% of participants, respectively. Participants reported that their partners and families were supportive of healthy eating and preparing meals at home, though 30.0% of those with children considered their children's diet a barrier to preparing healthy meals. Additionally, 40.5% of the sample were considered food insecure. Everyone agreed that healthy diet was important for maternal and fetal health, and the most popular interventions were healthy ingredient grocery deliveries (89.4%) and meal deliveries (84.2%). Conclusion: Time and cost emerged as major challenges to healthy eating in these pregnant women. Such barriers, facilitators, and preferences can aid in intervention development and policy-level changes to mitigate obstacles to healthy eating in this vulnerable patient population.

A multidisciplinary assessment of pain in juvenile idiopathic arthritis.

INTRODUCTION: Pain is prevalent in juvenile idiopathic arthritis (JIA). Unknowns regarding the biological drivers of pain complicate therapeutic targeting. We employed neuroimaging to define pain-related neurobiological features altered in JIA. METHODS: 16 male and female JIA patients (12.7 ± 2.8 years of age) on active treatment were enrolled, together with age- and sex-matched controls. Patients were assessed using physical examination, clinical questionnaires, musculoskeletal MRI, and structural neuroimaging. In addition, functional magnetic resonance imaging (fMRI) data were collected during the resting-state, hand-motor task performance, and cold stimulation of the hand and knee. RESULTS: Patients with and without pain and with and without inflammation (joint and systemic) were evaluated.  Pain severity was associated with more physical stress and poorer cognitive function. Corrected for multiple comparisons, morphological analysis revealed decreased cortical thickness within the insula cortex and a negative correlation between caudate nucleus volume and pain severity. Functional neuroimaging findings suggested alteration within neurocircuitry structures regulating emotional pain processing (anterior insula) in addition to the default-mode and sensorimotor networks. CONCLUSIONS: Patients with JIA may exhibit changes in neurobiological circuits related to pain. These preliminary findings suggest mechanisms by which pain could potentially become dissociated from detectable joint pathology and persist independently of inflammation or treatment status.

Altered Brain Network Connectivity Underlies Persistent Post-Traumatic Headache following Mild Traumatic Brain Injury in Youth.

Post-traumatic headaches (PTHs) are associated with mild traumatic brain injuries (mTBI) and may predict the persistence of concussion symptoms. Altered brain networks implicated in brain injury and the affective components of headache-related pain may underlie the resolution of PTH. This is a hypothesis-generating investigation to evaluate the extent to which pain symptom reporting and functional brain changes are different in a cohort of young mTBI patients with resolved (PTH-R) and persistent (PTH-P) post-traumatic headache symptoms relative to healthy controls. This was a cross-sectional investigation involving 59 participants between the ages of 12-24 (PTH-P, n = 21; PTH-R, n = 18; healthy control, n = 20). Participants had no significant history of pre-existing headaches, chronic pain, or psychiatric neurological conditions. The primary outcome was resting-state functional connectivity (RS-Fc) alterations between cohorts. Secondary outcomes were self-reported pain-related symptoms. Elevated scores were reported for fear of pain in both PTH cohorts. Using a false discovery rate of p = 0.05, the PTH-P cohort showed altered connectivity relative to healthy controls in brain regions such as the frontal, temporal, and cerebellar regions, as well as sub-cortical regions including the amygdala and accumbens. The PTH-R cohort showed altered RS-Fc between cerebellar and temporal lobe sub-regions. Our results indicate that a core network of brain regions implicated in the affective pain response are functionally altered in PTH cohorts. Results should be interpreted given limitations on sample size and multiple comparisons. Despite the resolution of symptoms, persons who experience PTH may experience ongoing functional brain abnormalities, which may underlie symptom chronification.

Chaperone-like activity of the N-terminal region of a human small heat shock protein and chaperone-functionalized nanoparticles.

Small heat shock proteins (sHsps) are molecular chaperones employed to interact with a diverse range of substrates as the first line of defense against cellular protein aggregation. The N-terminal region (NTR) is implicated in defining features of sHsps; notably in their ability to form dynamic and polydisperse oligomers, and chaperone activity. The physiological relevance of oligomerization and chemical-scale mode(s) of chaperone function remain undefined. We present novel chemical tools to investigate chaperone activity and substrate specificity of human HspB1 (B1NTR), through isolation of B1NTR and development of peptide-conjugated gold nanoparticles (AuNPs). We demonstrate that B1NTR exhibits chaperone capacity for some substrates, determined by anti-aggregation assays and size-exclusion chromatography. The importance of protein dynamics and multivalency on chaperone capacity was investigated using B1NTR-conjugated AuNPs, which exhibit concentration-dependent chaperone activity for some substrates. Our results implicate sHsp NTRs in chaperone activity, and demonstrate the therapeutic potential of sHsp-AuNPs in rescuing aberrant protein aggregation.