Enriched Environment Contributes to the Recovery from Neurotoxin-Induced Parkinson's Disease Pathology.

Parkinson's disease (PD) is a neurological disorder that affects dopaminergic neurons. The lack of understanding of the underlying molecular mechanisms of PD pathology makes treating it a challenge. Several pieces of evidence support the protective role of enriched environment (EE) and exercise on dopaminergic neurons. The specific aspect(s) of neuroprotection after exposure to EE have not been identified. Therefore, we have investigated the protective role of EE on dopamine dysregulation and subsequent downregulation of DJ1 protein using in vitro and in vivo models of PD. Our study for the first time demonstrated that DJ1 expression has a direct correlation with dopamine downregulation in PD models and exposure to EE has a significant impact on improving the behavioral changes in PD mice. This research provides evidence that exercise in EE has a positive effect on PD without interfering with the current line of therapy.

Differential expression of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in Alzheimer's disease and HIV-1 associated neurocognitive disorders.

The United Nations projects that one in every six people will be over the age of 65 by the year 2050. With a rapidly aging population, the risk of Alzheimer's disease (AD) becomes a major concern. AD is a multifactorial disease that involves neurodegeneration in the brain with mild dementia and deficits in memory and other cognitive domains. Additionally, it has been established that individuals with Human Immunodeficiency Virus-1 (HIV-1) experience a 5 to 10-year accelerated aging and an increased risk of developing HIV-associated neurocognitive disorders (HAND). Despite a significant amount of clinical evidence pointing towards a potential overlap between neuropathogenic processes in HAND and AD, the underlying epigenetic link between these two diseases is mostly unknown. This study is focused on identifying differentially expressed genes observed in both AD and HAND using linear regression models and a more robust significance analysis of microarray. The results established that the dysregulated type 1 and 2 interferon pathways observed in both AD and HAND contribute to the similar pathologies of these diseases within the brain. The current study identifies the important roles of interferon pathways in AD and HAND, a relationship that may be useful for earlier detection in the future.

Subclinical systolic dysfunction by speckle tracking echocardiography in patients with systemic lupus erythematosus.

BACKGROUND: We aimed to compare the prevalence of subclinical left ventricular systolic dysfunction in Hispanic systemic lupus erythematosus (SLE) patients versus healthy controls. MATERIAL AND METHODS: This cross-sectional study included 46 SLE patients who fulfilled the 2019 European League Against Rheumatism and American College of Rheumatology (EULAR/ACR) classification criteria for SLE and with age ≥ 18 years. For comparison, we included a control group with 46 non-SLE subjects matched by age (±5 years) and gender. A transthoracic echocardiogram was performed on every participant. The echocardiographic measurements evaluated were left ventricular ejection fraction (LVEF), relative wall thickness (RWT), and tricuspid annular plane systolic excursion (TAPSE). Left ventricular-Global Longitudinal Strain (GLS) was evaluated, and a value higher than -18% was classified as subclinical left ventricular systolic dysfunction. Comparisons between groups were made using the Chi-square test or Fisher's exact test for qualitative variables, and Student's t-test or the Mann-Whitney's U test for quantitative variables. A p-value <.05 was considered significant. RESULTS: We found a significant difference in the presence of subclinical left ventricular systolic dysfunction between SLE-patients and controls (37.0% vs 8.7%, p = .001). We also found that SLE patients had a lower left ventricular GLS (-18.90% vs -20.51%, p = .011), TAPSE (21.63 mm vs 23.60 mm, p = .009), and LVEF (57.17% vs 62.47%, p = <.001) than controls. Systemic lupus erythematosus diagnosis was independently associated with the presence of subclinical left ventricular systolic dysfunction with an OR of 6.068 (CI 95% 1.675-21.987) (p = .006). Subclinical systolic dysfunction was more common in men (29.4% vs 3.4%, p = .020), patients with obesity (17.6% vs 0%, p = .045), or hypertension (47.1% vs 6.9%, p = .001). CONCLUSION: Systemic lupus erythematosus Hispanic patients had a higher prevalence of subclinical left ventricular systolic dysfunction, and worse left ventricular GLS, LVEF, and TAPSE values than matched healthy controls. Additionally, we found that male gender, obesity, and hypertension are associated with the presence of subclinical left ventricular systolic dysfunction in SLE patients. The inclusion of speckle tracking echocardiography as part of the cardiovascular evaluation of SLE patients may help identify high cardiovascular risk patients.

Filgrastim-induced rhabdomyolysis in a healthy stem cells donor.

INTRODUCTION: Mobilization of peripheral blood progenitor cells with the use of granulocyte-colony stimulating factors is a mainstay in every protocol for allogenic stem cell transplants. Despite being considered safe, there are multiple adverse effects for this procedure some of which can be severe and bring serious complications to otherwise healthy donors. CASE REPORT: An otherwise healthy 17-year-old patient who underwent progenitor cell mobilization with filgrastim and developed rhabdomyolysis and acute kidney injury.Management and outcome: The urine analysis and kidney ultrasound failed to reveal abnormalities in the kidneys or collector system. We began reanimation with crystalloid solutions for 5 days with normalization of liver and muscle enzymes as well as a complete resolution of the acute kidney injury. DISCUSSION: We present the case of a potentially serious adverse drug reaction during mobilization of peripheral blood progenitor cells with filgrastim. Physicians need to be aware of every possible complication associated with the use of these agents in order to establish a good prognosis via an accurate diagnosis and a timely treatment.

The Increase of HIV-1 Infection, Neurocognitive Impairment, and Type 2 Diabetes in The Rio Grande Valley.

The Human Immunodeficiency Virus (HIV-1) infection remains a persistent predicament for the State of Texas, ranking seventh among the most documented HIV cases in the United States. In this regard, the Rio Grande Valley (RGV) in South Texas is considered as one of the least investigated areas of the state with respect to HIV infection and HIV associated comorbidities. Considering the 115% increase in average HIV incidence rates per 100,000 within the RGV from 2007-2015, it is worth characterizing this population with respect to their HIV-1 infection, HIV-1 Associated Neurocognitive Disorders (HAND), and the association of treatment with combined antiretroviral therapy (cART). Moreover, the increased rate of Type-2 Diabetes (T2D) in the RGV population is intertwined with that of HIV-1 infection facing challenges due to the lack of knowledge about prevention to inadequate access to healthcare. Hence, the role of T2D in the development of HAND among the people living with HIV (PLWH) in the RGV will be reviewed to establish a closer link between T2D and HAND in cART-treated patients of the RGV.

The Systemic Lupus Erythematosus Infection Predictive Index (LIPI): A Clinical-Immunological Tool to Predict Infections in Lupus Patients.

Among autoimmune diseases, systemic lupus erythematosus (SLE) patients have a unique predisposition to develop infections, which represents one of their main causes of morbidity and mortality. Many infections occur at disease diagnosis in the absence of immunosuppressive therapy, suggesting that the immunological abnormalities in SLE patients might be fundamental for the development of this complication. The aim of this study was to address the main clinical and immunological features associated with the development of infection and to create and validate a compound clinical-immunological infection predictive index in a cohort of SLE patients. We included 55 SLE patients with < 5 years since diagnosis. The clinical and immunological features were evaluated periodically and patients were followed-up during 1 year, searching for the development of infection. Immunophenotyping was performed by multiparametric flow cytometry and neutrophil extracellular traps (NETs) were assessed by confocal microscopy. Eighteen patients (32.7%) presented 19 infectious events, 5 (26.3%) were severe. For the construction of the index, we performed a logistic regression analysis and the cutoff points were determined with ROC curves. Increased numbers of peripheral Th17 cells, B cell lymphopenia, and lower TLR2 expression in monocytes, as well as the use of cyclophosphamide were the major risk factors for the development of infection and thus were included in the index. Besides, patients that developed infection were characterized by increased numbers of low-density granulocytes (LDGs) and higher expression of LL-37 in NETs upon infection. Finally, we validated the index retrospectively in a nested case-control study. A score >1.5 points was able to predict infection in the following year (AUC = 0.97; LR- = 0.001, specificity 100%, P = 0.0003). Our index encompasses novel immunological features able to prospectively predict the risk of infection in SLE patients.