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Dance Therapy (DT) is an effective treatment to promote emotional, social, cognitive and physical integration of the individual. Its benefits are of particular interest in children with Autism Spectrum Disorder (ASD), whose caretakers are burdened with the high cost and rigorous demand of treatment. This paper presents a Dance Therapy program that will attempt to encourage physical, social, and cognitive development amongst students through concepts of mirroring and Teaching Dance for Understanding. This program will require less resources than other types of therapies because children will not have to be supervised individually; routines are consistent and repetitive. Although more quantitative research needs to be conducted, it represents a positive step toward providing children with ASD with an optimal environment.

Purpose Obesity has been shown to be strongly associated with the development of breast and gynecologic cancers. PIK3CA is one of the most commonly altered genes in solid tumors, and patients who have alterations are routinely initiated on therapies that target this pathway. However, response can vary greatly between patients, and the reason for differences in response has yet to be completely understood. Obesity has been shown to alter cancer metabolism and further dysregulate the PI3K/AKT/mTOR pathway which may affect response to target therapy. L. Cantley and colleagues suggest that the state of consistent hyperinsulinemia, which is common in obesity, can compromise the clinical benefit of PI3K-pathway targeted therapy, as insulin is a known potent stimulator of this pathway. Therefore, the purpose of this study was to compare clinical outcomes between obese and non-obese patients on pathway-directed therapy. Methods A retrospective analysis was performed on 140 patients with breast, ovarian, cervical, or endometrial malignancies at Avera Cancer Institute. Female patients with a documented oncogenic PIK3CA alteration were included in the study. Overall survival (OS) and progression free survival (PFS) were the primary endpoints. BMI groups were determined by using existing clinical categories of obesity as defined by the CDC. Patients were stratified into 2 BMI groups: Group A 25 kg/m2 and Group B 25 kg/m2. The Kaplan-Meier method was used to derive time-to-event estimates and test for significance. A cox proportional-hazard model was utilized to determine the association between survival time for patients with BMI being the predictor variable. Results Of the 140 patients, 106 patients had breast cancer, 21 patients had endometrial cancer, 9 patients had ovarian cancer, 3 patients had cervical cancer, and 1 patient had vaginal melanoma. There were 52 patients in Group A and 88 patients in Group B. 25 of the 140 patients had documented PIK3CA alterations but were never initiated on targeted therapy. Group B was found to reduce the hazard by a factor of 0.63 (p=0.09). The subset of Group B with PI3K/mTOR targeted therapy was found to reduce the hazard by a factor of 0.43 (p=0.008). Among the 43 patients who were included in PFS analysis, it was found that there was no statistically significant (p=0.6) improved PFS between the two groups. Conclusion In this analysis, patients with a PIK3CA mutation and who had a higher BMI had an improved response rate from targeted therapy and overall survival than compared to patients with a lower BMI. Treatment lines prior to initiation of targeted therapy varied greatly, and differences in the multiple types of malignancies studied in this analysis was a limitation. More prospective studies that are statistically powered are warranted in order to assess the true impact of obesity on improved OS compared to patients with a BMI 25. Citation Format: Diana Kim, Bing Xu, Rachel Elsey, Tobias Meissner, Casey Williams. Clinical outcomes between obese and non-obese breast and gynecological cancer patients with alterations in the PI3K/AKT/mTOR pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1385.

Falls and balance difficulties remain a major source of morbidity in Parkinson's Disease (PD) and are stubbornly resistant to therapeutic interventions. The mechanisms of gait impairment in PD are incompletely understood but may involve changes in the Pedunculopontine Nucleus (PPN) and its associated connections. We utilized fMRI to explore the modulation of PPN connectivity by Galvanic Vestibular Stimulation (GVS) in healthy controls (n = 12) and PD subjects even without overt evidence of Freezing of Gait (FOG) while on medication (n = 23). We also investigated if the type of GVS stimuli (i.e., sinusoidal or stochastic) differentially affected connectivity. Approximate PPN regions were manually drawn on T1 weighted images and 58 other cortical and subcortical Regions of Interest (ROI) were obtained by automatic segmentation. All analyses were done in the native subject's space without spatial transformation to a common template. We first used Partial Least Squares (PLS) on a subject-by-subject basis to determine ROIs across subjects that covaried significantly with the voxels within the PPN ROI. We then performed functional connectivity analysis on the PPN-ROI connections. In control subjects, GVS did not have a significant effect on PPN connectivity. In PD subjects, baseline overall magnitude of PPN connectivity was negatively correlated with UPDRS scores (p < 0.05). Both noisy and sinusoidal GVS increased the overall magnitude of PPN connectivity (p = 6 × 10−5, 3 × 10−4, respectively) in PD, and increased connectivity with the left inferior parietal region, but had opposite effects on amygdala connectivity. Noisy stimuli selectively decreased connectivity with basal ganglia and cerebellar regions. Our results suggest that GVS can enhance deficient PPN connectivity seen in PD in a stimulus-dependent manner. This may provide a mechanism through which GVS assists balance in PD, and may provide a biomarker to develop individualized stimulus parameters.

Disrupted interhemispheric connectivity (IHC) is being increasingly recognized as a robust feature of a number of neurological diseases, including Parkinson's Disease (PD). We investigated whether or not Galvanic Vestibular Stimulation (GVS) - a proposed treatment for PD - affected IHC in 11 PD subjects (off medication). In order to avoid the confound of stimulation artifact disrupting the EEG, we investigated the immediate period (52 sec) after stimulation (72 sec) with noisy 1/f-type GVS stimuli. Partial Least Squares (PLS) regression was used to determine the subject-specific linear combination of EEG electrodes that maximized covariance between hemispheres and then computed coherence between the dominant PLS components. PD subjects had increased IHC;~10 Hz and decreased IHC13 Hz compared to 11 healthy, age-matched controls. After GVS in PD subjects, a significant increase in IHC was detected, especially above 30 Hz. We suggest that GVS may partially exert its beneficial effects in PD by "normalizing" impaired IHC.

Heart failure (HF) is a common clinical syndrome caused by a variety of cardiac diseases. The morbidity and mortality have increased in the last decades. The pathophysiology of HF is exceedingly complex. It has developed from the simplistic model of pump failure to that of a multisystemic disorder that affects not only the cardiovascular system but also the musculoskeletal, neuroendocrine and immune systems. Apart from myocardial hypertrophy, the pathogenetic mechanisms of HF also include deregulation of the neurohormonal system, with disturbance of the balance between sympathetic and parasympathetic tone, and disruption of the rennin-angiotensin-aldosterone system. Activation of neurohormones and pro-inflammatory cytokines has been recognized in HF progression after an initial cardiac injury. It is becoming increasingly apparent that inflammatory mediators play a crucial role in the development of HF. The purpose of this chapter is to give a brief overview of the role of inflammation in heart failure from animal models to clinical disease.

Tenascin-C (TNC) is highly expressed in melanoma; however, little is known about its functions. Recent studies indicate that TNC has a role within the stem cell niche. We hypothesized that TNC creates a specific environment for melanoma cells to show a stem cell-like phenotype, promoting tumor growth and evading conventional therapies. TNC expression was strongly upregulated in melanoma cells grown as 3D spheres (enriched for stem-like cells) when compared to adherent cells. Downmodulation of TNC by shRNA lentiviruses significantly decreased the growth of melanoma spheres. The incidence of pulmonary metastases after intravenous injection of TNC knockdown cells was significantly lower in NOD/SCID IL2Rγ(null) mice compared with control cells. Melanoma spheres contain an increased number of side population (SP) cells, which show stem cell characteristics, and have the potential for drug resistance due to their high efflux capacity. Knockdown of TNC dramatically decreased the SP fraction in melanoma spheres and lowered their resistance to doxorubicin treatment, likely because of the downregulation of multiple ATP-binding cassette (ABC) transporters, including ABCB5. These data suggest that TNC is critical in melanoma progression as it mediates protective signals in the therapy-resistant population of melanoma.

s / Brain Stimulation 8 (2015) 395e411 401 through direct or indirect approach has shown promising results in relieving tinnitus in both human and animal subjects. Among the structures stimulated include the cochlear nucleus, auditory cortex, basal ganglion, and prefrontal cortex. However, there remains a large variability in therapeutic effects across different brain stimulation modalities. In order to achieve effective therapy, our lab has established animalmodels of brain stimulation to suppress tinnitus. We have been searching for optimal stimulation strategies and to delineate the underlyingmechanisms of brain-stimulation-induced tinnitus suppression. In this conference, I will present the latest development on tinnitus suppression through brain stimulation and discuss the underlying mechanisms and technological development.

Hemitruncus arteriosus is a rare congenital deformity that results in early infant mortality. Persistence into adulthood is very unusual and is associated with pulmonary hypertension. We report a case in an adult male with the associated clinical issues.

Two studies examined the extent to which different cognitive assessment procedures yield similar data in pre-adolescent children. In Study 1, situationally anxious children reported their self-talk via think-aloud and verbal thought-listing procedures (N = 88). Half of the children reported their self-talk using both think-aloud and thought-listing while the remainder engaged in thought-listing only. Prior participation in think-aloud did not influence the self-talk subsequently reported by children during verbal thought-listing. Compared with thought-listing, more problem-solving (analytical) self-talk and less valenced self-talk was reported during think-aloud. In Study 2, 41 children reported their self-talk via both verbal thought-listing and video-mediated recall (own and other's perspective) procedures. Video-mediated recall generated self-talk of a similar valence to that obtained by thought-listing. More self-talk was generated when the children viewed their own perspective videotape compared with observer perspective videotape and thought-listing. While pre-adolescent children were able to respond to all three cognitive assessment methods, the self-talk produced was not identical. In choosing a cognitive assessment method, researchers and clinicians should be guided by the purpose of the assessment and the setting in which it occurs.

s / Brain Stimulation 8 (2015) 360e377 368 cognitive deficits in working memory and sustained attention are associated with worse outcomes. A single session of transcranial direct current stimulation (tDCS) when given to the left dorsolateral prefrontal cortex (LDLPFC) has been shown to enhance working memory in healthy and clinical populations. We examined whether a single session of tDCS can similarly enhance working memory or sustained attention in euthymic bipolar disorder patients. Fifteen euthymic bipolar disorder patients were randomized to receive a single session of sham tDCS, anodal tDCS to the LDLPFC with extracephalic cathode (F-EX tDCS) and anodal tDCS to the LDLPFC with cerebellar cathode (F-CE tDCS), in a counterbalanced order. Participants completed a 3-back letter working memory task and an auditory continuous performance test ‘online’ during active or sham tDCS at each session. Active tDCS was administered for 30 minutes at 2 mA. No effect of either active F-EX or F-CE tDCS on working memory or sustained attention was found for the entire group. However, exploratory cluster analyses conducted on performance outcomes for both active conditions relative to sham tDCS revealed 2-cluster solutions for both abilities, suggesting improvement in some individuals but not others. Specifically, working memory improved in 4/15 with F-EX, and 5/15 patients with F-CE tDCS, respectively. Improved sustained attention performance was also found in 4/15 patients with F-CE tDCS, however, no improvement was found with F-EX tDCS. Cognitive enhancing effects of active F-EX and F-CE tDCS were evident only in a minority of participants. The considerable interindividual variability in outcomes observed with active tDCS is consistent with known variability in the motor cortex. This study provides preliminary evidence in support of F-CE tDCS for improving working memory and sustained attention in euthymic bipolar disorder patients.