Prior research suggests disproportionate endorsement of pain among Black, Indigenous, and People of Color (BIPOC) compared to White people. Considering the high prevalence of pain in persons with MS, the present study examined potential racial-ethnic differences in pain interference among adults with MS, both before and after participation in one of two telehealth interventions aimed at improving pain, fatigue, and depressive symptoms. A national sample of adults with MS and chronic fatigue, chronic pain and/or moderate depressive symptoms (N=163) participated in a randomized controlled trial of self-management intervention focused on cognitive behavioral therapy (n=75) versus MS education (n=88), both delivered 1:1 via telephone. T-tests explored racial-ethnic differences in pain interference at baseline and posttreatment. Hierarchical multiple regression assessed race/ethnicity as a predictor of posttreatment pain interference controlling for baseline pain interference, and in subsequent blocks explored treatment condition, treatment satisfaction variables and baseline perceived social support as factors accounting for potential racial-ethnic differences and variance in pain interference. Independent sample t-tests revealed significant racial-ethnic differences in pain interference at baseline, t(159)=2.30, p=.023 and posttreatment, t(141)=2.91, p=.004. Specifically, participants who identified as (BIPOC) endorsed greater pain interference at baseline (M=4.66, SD=2.54) and posttreatment (M=4.31, SD=2.56) compared to non-Hispanic White participants (M=3.59, SD=2.32 and M=2.81, SD=2.11, respectively). Hierarchical regression analysis revealed a significant relationship between race and posttreatment pain interference, which became non-significant after controlling for baseline pain interference. Perceived social support emerged as significantly associated with posttreatment pain interference, after controlling for all variables. Ethnicity/race and perceived level of social support accounted for more variance in posttreatment pain interference than treatment type. Future investigations aimed at understanding why BIPOC report higher pain levels posttreatment are necessary to inform and adapt current treatments to address more relevant factors contributing to BIPOC’s experience of pain.

Cachexia is a debilitating condition characterized by the loss of muscle strength and mass. Affecting 50-80% of advanced cancer patients, this condition is associated with weakness, fatigue, poor tolerance to chemotherapy, and decreased quality of life. The mortality rate of patients with cancer-induced cachexia can be as high as 80%, and there is no current effective treatment. Ghrelin has recently been proposed as a therapeutic option for cancer cachexia due to its effects on preventing appetite, muscle, and fat loss. Its orexigenic effects are mediated by the growth hormone secretagogue receptor GHSR-1a, but the extent to which GHSR-1a mediates ghrelin’s effects on preventing muscle mass and function loss is unknown. This study characterizes the pathways involved in muscle mass loss and weakness in the Lewis lung carcinoma (LLC)-induced cachexia model and the effects of ghrelin in wildtype GHSR+/+ and knockout GHSR-/- mice. 5-6 month old male C57GL/6J mice were injected with LLC cells. When the tumor was palpable, tumor-bearing mice were injected with vehicle (saline solution) or ghrelin (0.8 mg/kg). We quantified body mass over 3 weeks and dissected and weighed hindlimb muscles. We analyzed mitochondrial protein concentrations via BCA and measured oxidative phosphorylation markers through Western blotting. Ghrelin attenuated LLC-induced muscle wasting in both genotypes but only prevented the decrease in grip strength in GHSR+/+. There was no significant difference in muscle mass between the two genotypes. The ubiquitin-proteasome system (UPS) and autophagy-lysosome pathways were activated by LLC in both genotypes, and these changes were more pronounced in GHSR -/-. In tumor-bearing mice, ghrelin mitigated the increased UPS markers (atrogin-1, MuRF1) independently of GHSR-1a. Ghrelin only prevented tumor-induced increases in mitophagy markers in GHSR+/+ (p62, Bnip3), and the levels of these mitophagy markers were negatively correlated with muscle strength. In conclusion, GHSR-1a is required for ghrelin’s effects on attenuating LLC-induced loss of muscle strength but not muscle mass, and this is likely due to the alterations in the autophagy-lysosome pathway and impaired mitophagy. By characterizing the preventative role of GHSR-1a in muscle wasting, we hope to improve hormonal therapy options for tumor-induced cachexia patients.

The pupillary light reflex (PLR) curve is an important point-of-care biomarker for the diagnosis of traumatic brain injury (TBI). Using PLR, first responders can determine the severity of TBI in the field and direct patients to a trauma center where staff can continually assess PLR to monitor TBI severity. Manual pupillometry, the most commonly available method for first responders and most clinicians wishing to assess PLR, is qualitative and often inaccurate. The current gold-standard device for PLR measurement is digital infrared pupillometry, but such devices are fragile and expensive. Our research team has developed a smartphone-based pupillometer (PupilScreen) with the ability to assess PLR using a standard iPhone, assisted by a cloud-based neural network. To demonstrate the feasibility of using PupilScreen in a realistic clinical setting and compare the accuracy of the device to the current clinical gold-standard, we have built an annotated dataset of the PLR in n=120 patients with TBI who are hospitalized in a neurological intensive care unit. Pupillometry is performed using the mobile device and the gold-standard digital infrared pupillometer. Pupil videos are manually annotated and used in the further training of our machine learning algorithm that generates a PLR curve for each patient. We anticipate that our technology will demonstrate accuracy in assessing the PLR that exceeds that of manual pupillometry and is at least equivalent to the gold-standard digital pupillometer. This technology has the potential to alleviate the current undertreatment of many TBI patients in the United States and abroad that results from a lack of accurate and cost-effective pupillometry equipment.

Disruptive mutations to DYRK1A, located in the Down Syndrome critical region of chromosome 21, are associated with autism spectrum disorder and medical comorbidities. Previous literature suggests facial anomalies in children with DYRK1A mutations, and studies of DYRK1A’s regulatory functions confirm its role in the expression of several morphology-affecting genes, particularly DCAF7. This study attempted to determine if quantitative differences in facial features exist between children with DYRK1A mutations and the general population, including unaffected parents. From a sample of 28 children with de novo DYRK1A mutations, analyses focused on nine white non-Hispanic children (M age = 11.33 years, 77.78% male) whose data were collected using a 3dMDhead System through an ongoing genetics-first study. Measurements between facial landmarks were later calculated using 3dMDvultus. FaceBase’s 3D Facial Norms for European Caucasians were used as a control group, and Z-scores were calculated for all complete measures. Six measures—intercanthal width, outercanthal width, palpebral fissure lengths, cranial base width, and philtrum width–were selected for analysis based on previous clinical findings. Wilcoxon sign-rank tests compared Z-scores between probands and each biological parent, assessing familial genetic influence on observed dysmorphologies. Outercanthal width in probands significantly differed from both biological parents and was significantly below population average. Additionally, palpebral fissure lengths significantly differed between probands and fathers and fell below population averages for probands. These findings bolster the link between DYRK1A and genes that code for craniofacial development and suggest the facial phenotype associated with DYRK1A mutations may be more variable and nuanced than expected, presenting challenges for clinical assessment. Additional research should examine how DYRK1A interacts with genes that code for eye regions, facial phenotypes in non-white participants, and possible differences in dysmorphology between sexes.

The nucleus accumbens (NAc) is a midbrain region associated with addiction-related behaviors. The NAc consists of medium spiny neurons (MSNs) that project to the substantia nigra (SN) or the ventral pallidum (VP) forming the direct (Go) and indirect (No-Go) pathways, respectively. The Go and No-Go pathways are mostly dichotomous in their expression of distinct receptors and neuropeptides. Dopamine receptor (D1) and adenosine receptor (A2a) expression corresponds to the Go and No-Go pathways, respectively. My goal is to investigate whether collateralization exists (i.e., single neuron projecting to both the VP and SN). This will be assessed by injecting retrograde tracers into the output regions and quantifying expression in MSNs. I used D1-iCre and A2a-iCre transgenic rats that express codon-improved Cre recombinase (iCre) in neurons expressing D1 or A2a, respectively. When the iCre expressing neurons are infected with a canine adeno-associated virus (CAV) containing a double-floxed and inverted (DIO) copy of a fluorescent protein, this anatomical marker protein is inverted and expressed specifically in these cells. I bilaterally injected four D1-iCre and four A2a-iCre males with CAV-DIO-TdTomato into the VP and CAV-DIO-ZsGreen into the SN. D1 and A2a neurons projecting to the viral injection site will uptake the virus and retrogradely label D1- or A2a-expressing MSNs in the NAc. The expression of these fluorescent proteins within the NAc will be quantified to investigate the projections’ dichotomy and collateralization. The dichotomy could be validated if the tracers expressed in exclusive populations of the NAc. Based on mouse studies, I hypothesize D1-Cre rats may have minimal colocalization in NAc MSNs but A2a-Cre rats may only express TdTomato in the NAc. Addiction continues to affect millions of individuals. We aim to elucidate anatomical differences to gain a better understanding of these midbrain pathways, which could be critical for the future of clinical treatment.

 Alzheimer’s disease (AD) is a complex and common neurodegenerative disease in humans. It is diagnosed by the presence of A beta amyloid plaques and tau tangles in the brain during autopsy, decades after neuropathology has developed. Early diagnosis is still not definitive and contributes to the inability to successfully treat the disease at an early stage. Generally, animal models are not reliable for preclinical studies since lower mammals, including laboratory rodents and nonhuman primates, pet dogs and domestic livestock do not naturally develop AD. The reason is based on conformational differences in amyloid precursor and tau proteins. We have recently observed one exception to this list of mammals- the aging pet cat. Formalin fixed paraffin embedded brain sections from ten 16 to18-year-old pet cats obtained from a regional veterinary teaching hospital were stained with antibodies 6E10 and AT8 specific for A beta and phosphorylated tau using standard immunohistochemistry procedures for diagnosing human AD. One cat showed robust tau tangles and moderate amyloid plaques, while a second cat showed moderate tau tangles and mild amyloid plaques. Brains from additional cats need to be examined for AD neuropathology but this preliminary observation suggests old pet cats develop AD. Since pet cats share the same environment as humans, clinical studies to search for ways of early diagnosis and treatment of this naturally occurring disease in cats will have a huge impact on the translational implications for early diagnosis and intervention studies in human AD.