Faculty Bibliography

RATIONALE & OBJECTIVE/OBJECTIVE:Arterial stiffness is associated with prevalent chronic kidney disease (CKD). Whether arterial stiffness is prospectively associated with incident CKD is inconclusive. STUDY DESIGN/METHODS:Longitudinal cohort study. SETTING & PARTICIPANTS/METHODS:Using data from the Atherosclerosis Risk in Communities (ARIC) Study, the primary analysis included 3,161 participants without prevalent CKD at visit 5; a secondary analysis studied 4,341 participants with any estimated glomerular filtration rate (eGFR) record across visits 5 to 7. EXPOSURE/METHODS:Carotid-femoral pulse wave velocity (cfPWV), heart-femoral PWV (hfPWV), heart-ankle PWV (haPWV), brachial-ankle PWV (baPWV), heart-carotid PWV (hcPWV), and femoral-ankle PWV (faPWV). OUTCOMES/RESULTS:accompanied by >25% decline eGFR or CKD hospitalization. Secondary analysis - eGFR slope. ANALYTICAL APPROACH/METHODS:Primary analysis - Cox regression models to calculate hazard ratio (HR). Secondary analysis - multilevel mixed effects models to estimate the eGFR slope across visits. RESULTS:/year [95% CI, -0.56 to -0.33] in Q4 versus -0.37 [95% CI, -0.48 to -0.26] in Q1). All p-value <0.05. faPWV was not associated with incident CKD or eGFR slope. LIMITATIONS/CONCLUSIONS:Residual confounding. CONCLUSIONS:Greater arterial stiffness, especially higher cfPWV, hfPWV, and haPWV, was prospectively associated with a higher risk of incident CKD and faster decline in eGFR among community-dwelling older adults, supporting a pathophysiological contribution of arterial stiffness to the development of CKD.

The activity-based anorexia (ABA) animal model captures key maladaptive behaviors of anorexia nervosa - starvation-evoked hyperactivity, voluntary food restriction, severe weight loss and elevated anxiety-like behavior. By repeating ABA induction, the model reveals an animal's gain of resilience against ABA relapses and concomitant synaptic plasticity. We review findings on the efficacy of sub-anesthetic ketamine administered during ABA in mid-adolescence in gaining resilience against ABA relapses, and the molecular changes evoked at medial prefrontal cortex (mPFC) synapses. GluN2B-containing NMDA receptors are significantly greater at excitatory synapses on dendritic spines of pyramidal cells. Drebrin, an F-actin binding protein that promotes activity-dependent trafficking of NMDA receptors to synaptic membranes, also increases at excitatory synapses on GABA-interneurons and pyramidal cells. These changes are at sites very near (<1 μm) but clearly not at the post-synaptic plasma membrane of excitatory synapses, enabling rapid strengthening of synapses through receptor trafficking to the plasma membrane without increasing steady-state excitability. We propose that these changes underlie the ketamine-evoked gain of resilience against anorexia-like behaviors >15 days post-injection, during ABA relapse in late adolescence. Ketamine treatment during ABA in late-adolescence ameliorates ABA relapse in adulthood >15 days later but to a lesser extent. A new EM analysis revealed that wheel running promotes GABAergic inhibitory synapse formation on pyramidal cells of the hippocampus and that ketamine augments GABAergic inhibition's contribution towards suppression of the most maladaptive behavior - starvation-evoked hyperactivity - while also augmenting food consumption, as reflected by weight gain at the end of food availability periods.

Given the increasingly global nature of work, the global workforce needs STEM (science, technology, engineering and math) workers who have both STEM content knowledge and intercultural competence. This study reports on findings from a 10-week bi-national virtual STEM challenge, the World Smarts STEM Challenge, that brought adolescents in the United States and Ghana together to complete a STEM learning program. There were 114 participants from Ghana (female = 56%) and 95 from the US (female = 48%); Mage = 16.21 years, SD = 1.65. In Ghana 100% of participants identified as ethnically Ghanaian and in the US participants identified as Black/African-American (50%), Latino/a/x or Hispanic (23.9%), Asian/Asian-American (7.6%), White/European-American (7.6%), bi-racial or multi-racial (7.6%), and "other" (3.3%). After the Challenge, participants increased in awareness of global issues, and engagement with others, but also showed a small but significant decrease in respect for people from other cultural backgrounds. Girls demonstrated an increase in global-mindedness in both countries and Ghanaian participants reported an increase in self-efficacy for global issues and demonstrated significant growth in both STEM ability self-concept and STEM activism orientation. Findings suggest the value of virtual STEM Challenges for building both STEM and global competence skills.

Colorectal cancer is a major cause of cancer-related deaths in Asian Americans, yet Asian Americans have the lowest colorectal cancer screening rates in New York City. The Charles B. Wang Community Health Center implemented a patient navigation program to increase colorectal cancer screening. This report describes the lessons learned from the program.

We investigated the cytoarchitecture of the anterior superior temporal area (TA2) of the postmortem cerebral cortex in 9 subjects with autism and 9 age-matched typically developing subjects between the ages of 13 and 56 years. The superior temporal gyrus is involved in auditory processing and social cognition and its pathology has been correlated with autism. We quantified the number and soma volume of pyramidal neurons in the supragranular layers and pyramidal neurons in the infragranular layers in each subject. We did not find significant differences in the number or volume of supragranular or infragranular neurons in the cerebral cortex of subjects with autism compared to typically developing subjects. This report does not support an alteration of supragranular to infragranular neurons in autism. However, further stereological analysis of the number of cells and cell volumes in specific cortical areas is needed to better establish the cellular phenotype of the autistic cerebral cortex and to understand its clinical relevance in autism.

The purposes of this study were to identify the number and types of symptom clusters using yes/no responses from the Memorial Symptom Assessment Scale, identify the number and types of symptom clusters using severity scores from the Memorial Symptom Assessment Scale, compare the identified symptom clusters derived using severity scores to those derived using occurrence ratings, and evaluate for differences in symptom cluster severity scores between patients with breast and prostate cancer at the end of radiation therapy. Separate exploratory factor analyses were performed to determine the number of symptom clusters based on symptom occurrence rates and symptom severity ratings. Although specific symptoms within each symptom cluster were not identical, 3 very similar symptom clusters (ie, "mood-cognitive" symptom cluster, "sickness-behavior" symptom cluster, "treatment-related" symptom cluster) were identified regardless of whether occurrence rates or severity ratings were used to create the symptom clusters at the end of radiation therapy. However, the factor solution derived using the severity ratings fit the data better. Significant differences in severity scores for all 3 symptom clusters were found between patients with breast and prostate cancer. For all 3 symptom clusters, the patients with breast cancer had higher symptom cluster severity scores than the patients with prostate cancer.

GOALS OF WORK: The goals of the study were to determine the occurrence rates for and the severity of symptoms at the middle, end, and 1 month after the completion of radiation therapy (RT), to determine the number and types of symptom clusters at these three time points, and to evaluate for changes over time in these symptom clusters. MATERIALS AND METHODS: Symptom occurrence and severity were evaluated using the Memorial Symptom Assessment Scale (MSAS) in a sample of patients (n = 160) who underwent RT for breast or prostate cancer. At each time point, an exploratory factor analysis was done to determine the number of symptom clusters (i.e., symptom factors) based on the MSAS symptom severity ratings. MAIN RESULTS: The majority of the patients were male and married with a mean age of 61.1 years. The five symptoms with the highest occurrence rates across all three time points were lack of energy, pain, difficulty sleeping, feeling drowsy, and sweats. Although the number of symptoms and the specific symptoms within each symptom cluster were not identical across the three time points, three relatively similar symptom clusters (i.e., "mood-cognitive" symptom cluster, "sickness-behavior" symptom cluster, "treatment-related", or "pain" symptom cluster) were identified in this sample. The internal consistency coefficients for the mood-cognitive symptom cluster and sickness-behavior symptom cluster were adequate at > or =0.68. CONCLUSIONS: Three relatively stable symptom clusters were found across RT. The majority of the symptom cluster severity scores were significantly higher in patients with breast cancer compared to patients with prostate cancer.

Evidence implicates anandamide in dopamine-related cocaine function. In the present study, we investigated the effect of methanandmide (5 mg/kg, i.p.), a stable anandamide analog, on the hyperthermia and hyperactivity induced by a fixed dose of cocaine (15 mg/kg, i.p.). Cocaine administered to rats produced hyperthermia and hyperactivity whereas methanandamide was ineffective. For combined administration, methanandamide attenuated the hyperthermia, but not hyperactivity, induced by cocaine. The effect of methanandamide was abolished by pretreatment with a cannabinoid CB1 receptor antagonist, SR141716A (5 mg/kg, i.p.), or dopamine D2 receptor antagonist, S(-)-raclopride (5 mg/kg, i.p.) but not by capsazepine (40 mg/kg, i.p.), a transient receptor potential vanilloid 1 cation channel antagonist. Methanandamide also attenuated the hyperthermia caused by a dopamine D1 receptor agonist, SKF 38393 (10 mg/kg, s.c.), indicating that it reduces hyperthermia produced by dopamine D1 receptor activation. URB597 (0.25 mg/kg, i.p.), an inhibitor of anandamide metabolism, did not alter cocaine-induced hyperthermia. Our results demonstrate that methanandamide activates cannabinoid CB1 receptors to attenuate cocaine-induced hyperthermia, and that dopamine D2 receptor activation plays a permissive role in the thermoregulatory effects of methanandamide.