The median life expectancy of people with Down syndrome has increased substantially over the past several decades, from 4 years in 1970 to 53 2010. Despite recent improvement survival, there is little data about prevalence age-related diseases, including malignancies, and impact standard cancer treatments on cardiovascular health. We retrospectively reviewed medical records for age- sex-matched patients >/= 15 old without using TriNetX platform identify malignancies explore outcomes after...

The mitochondria play a vital role in controlling cell metabolism and regulating crucial cellular outcomes. We previously demonstrated that chronic inhibition of the mitochondrial complex III rats by Antimycin A (AA) induced sustained pulmonary vasoconstriction. On metabolic level, AA-induced dysfunction resulted glycolytic shift was reported as primary contributor to hypertension pathogenesis. However, regulatory proteins driving this with are yet be explored. Therefore, delineate...

OBJECTIVES/GOALS: Electronic cigarettes have become increasingly popular, with various combustion products generated in the process. Dihydroxyacetone (DHA), a carbohydrate made during heating Exposures may reach high micromolar to low millimolar doses of DHA per day and no studies been done understand effects heart. METHODS/STUDY POPULATION: Here, we examine if contributes these using rat cardiomyocytes, H9c2 cells, cardiac tissues evaluating metabolic mitochondrial effects. Using will...

Cytotoxic CD8 + cells are critical in anticancer immune response and have become prevalent immunotherapies over the past decade. Anti-LAG3/anti-PD1 combined increase number of cells. Moderate to severe sleep apnea increases risk cancer-related mortality. Chronic intermittent hypoxia, a feature apnea, decreases percentage perforin-expressing cells, impairing cytotoxicity. Our objective is determine distribution Prf1(perforin), LAG3(lymphocyte-activation gene 3), PDCD1(programmed cell death 1)...

The NSD2 gene is overexpressed in multiple cancers and associated with cancer cell proliferation, invasion, metastasis. universally present myeloma (MM) patients t(4;14) (p16;q32) translocation, a high-risk subtype. characterized by different breakpoints. NSD2Δ3 breakpoint shorter survival than other contains non-coding RNA ACA11 within intron 18. Additionally, 80% of MM lack the retinoblastoma tumor suppressor (RB1). We hypothesize that cooperates RB1 loss pathogenesis. Also, we increases...

Anthracycline treatment for leukemia is effective but has toxic side effects on the cardiovascular system. Few studies regarding impact of anthracyclines heart in individuals with Down syndrome have been addressed although they are at a higher risk developing leukemia. It unknown if established mechanisms apply to syndrome. We hypothesize that anthracycline cardiotoxicity will lead enhanced impairment cardiac function and initiate pronounced vascular dysfunction mouse model used Ts65Dn...

Urethane is widely used for its ability to induce prolonged anesthesia. Variability in previously reported cardiovascular parameters murine models makes it challenging definitively evaluate the effects of urethane We aimed address these challenges, thereby advancing our understanding urethane's on function mice. In this study, we investigated how anesthesia, with and without supplemental oxygen, impacts heart rate, arterial oxygen saturation (SpO 2 ), blood pressure, rate variability First,...

Background. A new strategy of breast cancer management is required for effective disease prevention and control. Immunotherapy one promising options. Objective: to evaluate the effect immunoadjuvant polyoxidonium on pathmorphological changes in tumors. Materials methods. The study was performed 75 patients with cancer: 50 received a neoadjuvant regimen (main group), 25 did not receive (control group). Polyoxidonium at dose 12 mg administered intramuscularly 1 time per day days 1, 2, 3, 5 7...

Chamber exposures are commonly used to evaluate the physiological and pathophysiological consequences of intermittent hypoxia in animal models. Researchers this field use both commercial custom-built chambers their experiments. The purpose Cores Reproducibility Physiology paper is demonstrate potential sources variability these systems that researchers should consider. Evaluating relationship between arterial oxygen saturation inspired concentration, we found there important sex-dependent...

Over the last couple of decades, median survival individuals with Down syndrome (Ds) increased from 30 to 60 years. The Ts65Dn mouse model recapitulates most cognitive and neural phenotypes described in Ds its use continues expand into other fields. population is at risk for cardiovascular comorbidities. We hypothesized that contractility mice will be lower compared controls, differences between strains become exacerbated age. aim this study was comprehensively access cardiac function across...

Children with Down syndrome have a high risk of leukemia and are at higher for delayed early onset heart failure after treatment. Cardiac toxicity is more severe in female patients. Traditional factors cardiovascular diseases the general population may not be predictive chemotherapy-induced Syndrome population. We used Ts65Dn mouse model to investigate impact chemotherapy agent daunorubicin on survival arterial stiffness, predictor risk. hypothesized that stiffness will increased mice...

Multiple myeloma (MM), a terminal cancer of bone marrow plasma cells, affects about 35,000 people yearly, and kills 13,000. The KaLwRij mouse model spontaneously develops pre-malignant disease (MGUS) is receptive to development. In the C57BL/6 model, chronic intermittent hypoxia allows lethal engraftment malignant cells. Our central hypothesis that susceptibility in both models modulated by sympathetic nervous system beta-adrenergic receptor activation. 8 - week old female mice were exposed...

Urethane is used in rats and dogs recognized to minimally suppress cardiorespiratory function, but little known about its impact mouse models. The overall purpose of this study was comprehensively compare function mice anesthetized with urethane, compared conscious state. 16-week old C57BL6/J (n=30,15 males, 15 females), underwent measurements while urethane-anesthetized. Hemodynamic parameters including heart rate variability (HRV), blood pressure (BP), (HR), oxygen saturation (SpO 2 ) were...

Sleep apnea is highly prevalent in patients with multiple myeloma, a rare and incurable cancer of malignant plasma cells, associated poor outcomes. Chronic intermittent hypoxia (CIH), feature sleep apnea, facilitates myeloma development mice. However, the mechanism by which CIH contributes to progression remains unknown. Our objective was test hypothesis that provides fertile environment for cell engraftment via polarization bone marrow macrophages. We exposed mice chronic (12 cycles/hr,10...

Pulmonary arterial hypertension (PAH) is a progressive fatal disease with complex pathogenic mechanism. Recent studies report that nearly 60% of patients PAH have metabolic syndrome (MS). Unrecognized glucose intolerance and insulin resistance were also shown to be common in PAH, raising the possibility predisposes PAH. Nevertheless, mechanistic link between disorders remains unexplored. Mitochondrial dysfunction (MD) one primary events tightly associated MS/ type 2 diabetes pathobiology...