HIV associated dementia and HIV encephalitis II: Genes on chromosome 22 expressed in individually microdissected Globus pallidus neurons (Preliminary analysis)

We analyzed RNA gene expression in neurons from 16 cases in four categories, HIV associated dementia with HIV encephalitis (HAD/HIVE), HAD alone, HIVE alone, and HIV-1-positive (HIV+)with neither HAD nor HIVE. We produced the neurons by laser capture microdissection (LCM) from cryopreserved globus pallidus. Of 55,000 gene fragments analyzed, expression of 197 genes was identified with significance (p = 0.005).We examined each gene for its position in the human genome and found a non-stochastic occurrence for only seven genes, on chromosome 22. Six of the seven genes were identified, CSNK1E (casein kinase 1 epsilon), DGCR8 (Di George syndrome critical region 8), GGA1 (Golgi associated gamma adaptin ear containing ARF binding protein 1), MAPK11 (mitogen activated protein kinase 11), SMCR7L (Smith-Magenis syndrome chromosome region candidate 7-like), andTBC1D22A (TBC1 domain family member 22A). Six genes (CSNK1E, DGCR8, GGA1, MAPK11, SMCR7L, and one unidentified gene) had similar expression profiles across HAD/HIVE, HAD, and HIVE vs. HIV+ whereas one gene (TBC1D22A) had a differing gene expression profile across these patient categories. There are several mental disease-related genes including miRNAs on chromosome 22 and two of the genes (DGCR8 and SMCR7L) identified here are mental disease-related. We speculate that dysregulation of gene expression may occur through mechanisms involving chromatin damage and remodeling. We conclude that the pathogenesis of NeuroAIDS involves dysregulation of expression of mental disease-related genes on chromosome 22 as well as additional genes on other chromosomes. The involvement of these genes as well as miRNA requires additional investigation since numerous genes appear to be involved

Molecular epigenetics, chromatin, and NeuroAIDS/HIV: Translational implications

We describe current research that applies epigenetics to a novel understanding of the immuno-neuropathogenesis of HIV-1 viral infection and NeuroAIDS. We propose the hypothesis that HIV-1 alters the structure-function relationship of chromatin, coding DNA and non-coding DNA, including RNA transcribed from these regions resulting in pathogenesis in AIDS, drug abuse, and NeuroAIDS. We discuss the general implications of molecular epigenetics with special emphasis on drug abuse, bar-codes, pyknons, and miRNAs for translational and clinical research. We discuss the application of the recent recursive algorithm of biology to this field and propose to synthesize the Genomic and Epigenomic views into a holistic approach of HoloGenomics

Influenza 2009 pandemic: Cellular immunemediated surveillance modulated by TH17 & Tregs.

Influenza A virus is a serious public health threat. Most recently the 2009/H1N1 pandemic virus had an inherent ability to evade the host's immune surveillance through genetic drift, shift, and genomic reassortment. Immune characterization of 2009/H1N1 utilized monoclonal antibodies, neutralizing sera, and proteomics. Increased age may have provided some degree of immunity, but vaccines against seasonal influenza viruses seldom yield cross-reactive immunity, exemplified by 2009/H1N1. Nonetheless, about 33% of individuals, over the age of 60, had cross-reactive neutralizing antibodies against 2009/H1N1, whereas only 6-9% young adults had these antibodies. Children characteristically had no detectable immunity against 2009/H1N1. Taken together, these observations suggest some degree of immune transference with at least certain strains of virus that have afflicted the human population in past decades. Because internal influenza proteins may exhibit less antigenic variation, it is possible that prior exposure to diverse strains of influenza virus provide some immunity to novel strains, including the recent pandemic strain (swine-avian A/H1N1). Current trends in immunological studies - specifically the modulation of cellular immune surveillance provided by TH17 and Tregs - also support the need for additional proteomic research for characterizing novel translational evidence-based treatment interventions based on cytokine function to help defeat the virus. Timely and critical research must characterize the impact of genetics and epigenetics of oral and systemic host immune surveillance responses to influenza A virus. The continued development and application of proteomics and gene expression across viral strains and human tissues increases our ability to combat the spread of influenza epidemics and pandemics

Predictors of Recurrent Infective Endocarditis in Intravenous Drug Users

Background: Caring for hospitalized patients with infective endocarditis (IE) can be challenging due to the nature of the disease and its complications, underlying medical and psychiatric problems, socioeconomic status and environmental factors.Some of these patients develop recurrent IE after the first episode treated. On-going intravenous (IV) drug use after hospital discharge is the highest predictive factor for recurrent IE. Besides IV drug use, there are limited data of other contributing factors to recurrent IE. Those factors may be modifiable during the first hospitalization to reduce the incidence of recurrent IE. Methods: A retrospective cohort study was conducted at a large tertiary acute care medical center in Tampa, Florida. All consecutive patients with IE with history of IV drug use from January, 2011 to December, 2017 were included. Basic demographic information, co-morbidities (diabetes, hypertension, chronic lung and kidney diseases, HIV, Hepatitis B and C status, coronary artery diseases), valves involved, length of stay, complications at their first IE episode such as septic shock and stroke were included. Groups were identified based on the first episode, first recurrence and second or more recurrences of IE. Results: A total of 106 patients were identified based on the inclusion criteria. The association between the type of valve infection (right side and left side) and IE recurrence was found to be statistically significant. (P = 0.003). Right side valves are prone to have recurrent IE episodes. People with recurrent IE were more likely to have septic shock (P = 0.02) and requiring intensive care unit (ICU) admissions (P \u3c 0.001) during their first episode There was no statistically significant difference between other demographic information and recurrent endocarditis as well as other parameters such as organisms or type of substance used. (Table 1) Conclusion: Right-sided IE and presence of septic shock during their first episode of IE may be the predictors for recurrent IE. Interventions including closer follow-up, more aggressive septic shock recognition and management, socioeconomic assessment in addition to substance abuse treatments after discharge should be considered to prevent recurrent IE

Predictors of Recurrent Infective Endocarditis in Intravenous Drug Users

Background: Caring for hospitalized patients with infective endocarditis (IE) can be challenging due to the nature of the disease and its complications, underlying medical and psychiatric problems, socioeconomic status and environmental factors.Some of these patients develop recurrent IE after the first episode treated. On-going intravenous (IV) drug use after hospital discharge is the highest predictive factor for recurrent IE. Besides IV drug use, there are limited data of other contributing factors to recurrent IE. Those factors may be modifiable during the first hospitalization to reduce the incidence of recurrent IE. Methods: A retrospective cohort study was conducted at a large tertiary acute care medical center in Tampa, Florida. All consecutive patients with IE with history of IV drug use from January, 2011 to December, 2017 were included. Basic demographic information, co-morbidities (diabetes, hypertension, chronic lung and kidney diseases, HIV, Hepatitis B and C status, coronary artery diseases), valves involved, length of stay, complications at their first IE episode such as septic shock and stroke were included. Groups were identified based on the first episode, first recurrence and second or more recurrences of IE. Results: A total of 106 patients were identified based on the inclusion criteria. The association between the type of valve infection (right side and left side) and IE recurrence was found to be statistically significant. (P = 0.003). Right side valves are prone to have recurrent IE episodes. People with recurrent IE were more likely to have septic shock (P = 0.02) and requiring intensive care unit (ICU) admissions (P \u3c 0.001) during their first episode There was no statistically significant difference between other demographic information and recurrent endocarditis as well as other parameters such as organisms or type of substance used. (Table 1) Conclusion: Right-sided IE and presence of septic shock during their first episode of IE may be the predictors for recurrent IE. Interventions including closer follow-up, more aggressive septic shock recognition and management, socioeconomic assessment in addition to substance abuse treatments after discharge should be considered to prevent recurrent IE