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Trotman H.D.,Georgia Regents University | Trotman H.D.,Charlie Norwood Veterans Affairs Medical Center | Trotman H.D.,Emory University | Kirkpatrick B.,Georgia Regents University | Compton M.T.,Emory University
Schizophrenia Research | Year: 2011

Patients with schizophrenia who have primary, enduring negative symptoms, or the deficit syndrome, have poorer psychosocial functioning but lesser clinical distress compared with nondeficit patients. Poor awareness of impairment in patients with deficit schizophrenia may contribute to this seeming contradiction. We hypothesized that poor insight would be present early in the course of illness in deficit patients, and that those with deficit features would have greater impairment in insight than those without deficit features. One-hundred one first-episode patients with nonaffective psychotic disorders were categorized into deficit (n = 31) and nondeficit (n = 70) groups. The deficit patients had significantly poorer insight than nondeficit patients when rated using a self-report questionnaire, and nearly significantly poorer insight rated by clinical researchers. Further, this effect remained for self-rated insight and reached statistical significance for researcher-rated insight after controlling for positive, negative, and general psychopathology symptoms. These results suggest that the treatment of deficit patients may be particularly complicated by poor insight. © 2010 Elsevier B.V.


Qin H.,Georgia Regents University | Frohman M.A.,State University of New York at Stony Brook | Bollag W.B.,Georgia Regents University | Bollag W.B.,Charlie Norwood Veterans Affairs Medical Center
Endocrinology | Year: 2010

In primary bovine adrenal glomerulosa cells, the signaling enzyme phospholipase D (PLD) is suggested to mediate priming, the enhancement of aldosterone secretion after pretreatment with and removal of angiotensin II (AngII), via the formation of persistently elevated diacylglycerol (DAG). To further explore PLD's role in priming, glomerulosa cells were pretreated with an exogenous bacterial PLD. Using this approach, phosphatidic acid (PA) is generated on the outer, rather than the inner, leaflet of the plasma membrane. Although PA is not readily internalized, the PA is nonetheless rapidly hydrolyzed by cell-surface PA phosphatases to DAG, which efficiently flips to the inner leaflet and accesses the cell interior. Pretreatment with bacterial PLD resulted in priming upon subsequent AngII exposure, supporting a role of DAG in this process, because the increase in DAG persisted after exogenous PLD removal. To determine the PLD isoform mediating aldosterone secretion, and presumably priming, primary glomerulosa cells were infected with adenoviruses expressing GFP, PLD1, PLD2, or lipase-inactive mutants. Overexpressed PLD2 increased aldosterone secretion by approximately 3-fold over the GFP-infected control under basal conditions, with a significant enhancement to about 16-fold over the basal value upon AngII stimulation. PLD activity was also increased basally and upon stimulation with AngII. In contrast, PLD1 overexpression had little effect on aldosterone secretion, despite the fact that PLD activity was enhanced. In both cases, the lipase-inactive PLD mutants showed essentially no effect on PLD activity or aldosterone secretion. Our results suggest that PLD2 is the isoform that mediates aldosterone secretion and likely priming. Copyright © 2010 by The Endocrine Society.


Bhatt K.,Georgia Regents University | Mi Q.-S.,Ford Motor Company | Dong Z.,Georgia Regents University | Dong Z.,Charlie Norwood Veterans Affairs Medical Center
American Journal of Physiology - Renal Physiology | Year: 2011

MicroRNAs (miRNA) are endogenously produced, short RNAs that repress and thus regulate the expression of almost half of known protein-coding genes. miRNA-mediated gene repression is an important regulatory mechanism to modulate fundamental cellular processes such as the cell cycle, growth, proliferation, phenotype, and death, which in turn have major influences on pathophysiological outcomes. In kidneys, miRNAs are indispensable for renal development and homeostasis. Emerging evidence has further pinpointed the pathogenic roles played by miRNAs in major renal diseases, including diabetic nephropathy, acute kidney injury, renal carcinoma, polycystic kidney disease, and others. Although the field of renal miRNA research is still in its infancy and important questions remain, future investigation on miRNA regulation in kidneys has the potential to revolutionize both the diagnosis and treatment of major renal diseases. © 2011 by the American Physiological Society.


Mohamed I.N.,University of Georgia | Mohamed I.N.,Charlie Norwood Veterans Affairs Medical Center | Hafez S.S.,University of Georgia | Hafez S.S.,Charlie Norwood Veterans Affairs Medical Center | And 7 more authors.
Diabetologia | Year: 2014

Aims/hypothesis: Obesity and hypertension, known pro-inflammatory states, are identified determinants for increased retinal microvascular abnormalities. However, the molecular link between inflammation and microvascular degeneration remains elusive. Thioredoxin-interacting protein (TXNIP) is recognised as an activator of the NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome. This study aims to examine TXNIP expression and elucidate its role in endothelial inflammasome activation and retinal lesions. Methods: Spontaneously hypertensive (SHR) and control Wistar (W) rats were compared with groups fed a high-fat diet (HFD) (W+F and SHR+F) for 8-10 weeks. Results: Compared with W controls, HFD alone or in combination with hypertension significantly induced formation of acellular capillaries, a hallmark of retinal ischaemic lesions. These effects were accompanied by significant increases in lipid peroxidation, nitrotyrosine and expression of TXNIP, nuclear factor κB, TNF-α and IL-1β. HFD significantly increased interaction of TXNIP-NLRP3 and expression of cleaved caspase-1 and cleaved IL-1β. Immunolocalisation studies identified TXNIP expression within astrocytes and Müller cells surrounding retinal endothelial cells. To model HFD in vitro, human retinal endothelial (HRE) cells were stimulated with 400 μmol/l palmitate coupled to BSA (Pal-BSA). Pal-BSA triggered expression of TXNIP and its interaction with NLRP3, resulting in activation of caspase-1 and IL-1β in HRE cells. Silencing Txnip expression in HRE cells abolished Pal-BSA-mediated cleaved IL-1β release into medium and cell death, evident by decreases in cleaved caspase-3 expression and the proportion of live to dead cells. Conclusions/interpretation: These findings provide the first evidence for enhanced TXNIP expression in hypertension and HFD-induced retinal oxidative/inflammatory response and suggest that TXNIP is required for HFD-mediated activation of the NLRP3 inflammasome and the release of IL-1β in endothelial cells. © 2013 Springer-Verlag Berlin Heidelberg.


Kolhe R.,University of Georgia | Reid M.D.,Emory University | Lee J.R.,Charlie Norwood Veterans Affairs Medical Center | Cohen C.,Emory University | And 2 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2013

Background: Merkel cell carcinoma is a high-grade neuroendocrine carcinoma of skin that is characterized by immature cells which, because of its striking morphologic similarity, may be confused with other small round blue cell tumors such as pulmonary small cell carcinoma or lymphoblastic leukemia/lymphoma. Immunohistochemistry is therefore paramount to ensuring accurate diagnostic distinction between these tumors. The aim of our study was to evaluate and compare the expression of PAX5 and Terminal deoxynucleotidyl transferase (TdT), in Merkel cell carcinoma and pulmonary small cell carcinoma. Design: PAX5 and TdT immunohistochemical stains were performed on 27 Merkel cell carcinomas and 10 pulmonary small cell carcinomas. Results: PAX5 was expressed in 24/27 (89%) Merkel cell carcinomas and 0/10 (0%) pulmonary small cell carcinomas. TdT was expressed in 21/27 (78%) Merkel cell carcinomas and 9/10 (90%) pulmonary small cell carcinomas. Conclusions: Our study confirms that PAX5 and TdT expression can be expressed in a high percentage of Merkel cell carcinomas and so when positive are not diagnostic of lymphoblastic leukemia/lymphoma. When dealing with metastatic lesions, PAX5 negativity would favor a diagnosis of pulmonary small cell carcinoma over Merkel cell carcinoma. In addition, TTF-1 negative pulmonary small cell carcinoma is to be differentiated from Merkel cell carcinoma.


Phillips B.B.,University of Georgia | Phillips B.B.,Charlie Norwood Veterans Affairs Medical Center | Williams K.C.,Charlie Norwood Medical Center
American Journal of Health-System Pharmacy | Year: 2012

Purpose. The implementation of an innovative ambulatory care pharmacy residency program at a Veterans Affairs (VA) outpatient clinic is described. Summary. Community-based outpatient clinics (CBOCs) are a largely underutilized resource for pharmacy residency training. Through a collaboration of the University of Georgia College of Pharmacy in Athens and Charlie Norwood VA Medical Center in Augusta, a postgraduate year 2 (PGY2) pharmacy residency program was established at the CBOC in Athens. The program graduated its first resident in 2009; components of training included (1) disease state management at an anticoagulation clinic and a newly created disease state-focused pharmacotherapy clinic, (2) participation in the planning and implementation of a new lipid management service, (3) a variety of didactic, laboratory, and experiential teaching activities at the college of pharmacy, and (4) management experiences such as completing requests for nonformulary medications, management of drug shortages, adverse drug reaction reporting, and participation in meetings of local and regional VA pharmacy and therapeutics committees. The demonstrated value of the ongoing program led to position upgrades for two CBOC clinical pharmacists and the addition of a clinical faculty member, enabling the program to offer additional learning experiences and preceptorship opportunities. Conclusion. A PGY2 ambulatory care residency program established in a CBOC provided a novel practice setting for the resident, helped improve patient care and pharmacy student education, and assisted in the professional development of preceptors and providers at the training site.


Alhusban A.,University of Georgia | Alhusban A.,Charlie Norwood Veterans Affairs Medical Center | Fagan S.C.,University of Georgia | Fagan S.C.,Charlie Norwood Veterans Affairs Medical Center
American Journal Geriatric Pharmacotherapy | Year: 2011

Background: Stroke is a major health problem with significant impact on the affected individuals and the whole community. In light of stroke being the leading cause of disability, the ageing of the population and the high incidence of stroke among the elderly, highlight the importance of primary and secondary prevention interventions among this group. The elderly generally have been underrepresented in clinical trials, creating many uncertainties and less optimal medical care for this group of patients. Objective: This review aims to make evidence-based management recommendations for secondary stroke prevention in the elderly. Methods: Secondary preventionrelated primary literature was identified using MEDLINE and PubMed (1982 to present) with combinations of the following search terms being employed: antiplatelets, aspirin, atrial fibrillation, elderly, geriatrics, hypertension, lipids, secondary prevention, statins, stroke, and warfarin. In addition, the references of these articles were also reviewed. Results: Twenty-three clinical trials were included in this review, covering different aspects of secondary stroke prevention. Many of these trials were not specifically limited to the elderly, but conclusions related to their care can be derived from them. Although the American Heart Association/American Stroke Association guidelines suggest an equal benefit of aspirin, aspirin/dipyridamole, and clopidogrel in secondary prevention, the use of aspirin in the elderly may be preferred for reasons related to compliance and experience. Warfarin was largely avoided in the management of elderly stroke patients in the past, although available evidence demonstrates its efficacy and safety as a first choice for elderly patients with atrial fibrillation and presumed cardiac source of emboli. Lowering blood pressure among the elderly is an important aspect of secondary stroke prevention and can be achieved with the same agents used among younger age groups with a preference for a thiazide diuretic/angiotensin-converting enzyme inhibitor combination that has proven efficacy among elderly patients. Available evidence supports the use of statins among elderly patients with history of stroke or transient ischemic attack (TIA), and the derived benefit of treatment does not differ significantly from that in the younger age group. Elderly patients with 50% to 99% carotid artery stenosis and history of stroke or TIA should be considered for early carotid endarterectomy to reduce recurrent stroke. Conclusion: Age should not be considered a barrier for the provision of optimal secondary prevention interventions. The available evidence supports similar and sometimes superior derived benefit from secondary preventive stroke measures in the elderly compared with that seen in younger patients. © 2011 Elsevier HS Journals, Inc. All rights reserved.


Pyla R.,University of Georgia | Pyla R.,Charlie Norwood Veterans Affairs Medical Center | Poulose N.,University of Georgia | Poulose N.,Charlie Norwood Veterans Affairs Medical Center | And 4 more authors.
American Journal of Physiology - Cell Physiology | Year: 2013

Intimal hyperplasia is characterized by exaggerated proliferation of vascular smooth muscle cells (VSMCs). Enhanced VSMC growth is dependent on increased glucose uptake and metabolism. Facilitative glucose transporters (GLUTs) are comprised of conventional GLUT isoforms (GLUT1-5) and novel GLUT isoforms (GLUT6-14). Previous studies demonstrate that GLUT1 overexpression or GLUT10 downregulation contribute to phenotypic changes in VSMCs. To date, the expression profile of all 14 GLUT isoforms has not been fully examined in VSMCs. Using the proliferative and differentiated phenotypes of human aortic VSMCs, the present study has determined the relative abundance of GLUT1-14 mRNAs by quantitative real-time PCR analysis. Twelve GLUT mRNAs excluding GLUT7 and GLUT14 were detectable in VSMCs. In the proliferative phenotype, the relative abundance of key GLUT mRNAs was GLUT1 (~43%) > GLUT10 (~26%) > GLUT9 (~13%) > GLUT12 (~4%), whereas in the differentiated phenotype the relative abundance was GLUT10 (~28%) > GLUT1 (~25%) > GLUT12 (~20%) > GLUT9 (~14%), together constituting 86-87% of total GLUT transcripts. To confirm the expression of key GLUT proteins, immunoblot and immunocytochemical analyses were performed using GLUT isoform-specific primary antibodies. The protein bands characteristic of GLUT1, -9, -10, and-12 were detected in VSMCs in parallel with respective positive controls. In particular, GLUT1 protein expression showed different molecular forms representative of altered glycosylation. While GLUT1 protein displayed a predominant distribution in the plasma membrane, GLUT9, -10, and-12 proteins were mostly distributed in the intracellular compartments. The present study provides the first direct evidence for GLUT9 and GLUT12 expression in VSMCs in conjunction with the previously identified GLUT1 and GLUT10. © 2013 the American Physiological Society.


Xing Y.,University of Georgia | Rainey W.E.,University of Georgia | Apolzan J.W.,University of Georgia | Francone O.L.,Pfizer | And 3 more authors.
Endocrinology | Year: 2012

Very low-density lipoproteins (VLDL) are a class of large lipoprotein synthesized in the liver. The key function of VLDL, in vivo, is to carry triglyceride from the liver to adipose tissue. As a steroidogenic organ, the adrenal gland mainly uses lipoproteins as sources of cholesterol. Although VLDL receptors have been detected in the human adrenal, the function of VLDL in the adrenal gland remains unknown. Herein, we used primary cultures of human and bovine adrenal cells and the adrenocortical cell line H295R as models to determine the effects of VLDL on adrenal steroidogenesis. Our studies revealed that VLDL significantly increased aldosterone synthesis in all of the models tested. This increase was largely due to VLDL's stimulation of the expression of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2). VLDL increased CYP11B2 mRNA expression in a concentration-dependent manner. Effects of VLDL on CYP11B2 transcript levels were not additive with angiotensin II or potassium but were additive with the cAMP pathway agonists ACTH and forskolin. Nifedipine completely inhibited the effects of VLDL on CYP11B2 mRNA, suggesting that calcium is the main signal transduction pathway used by VLDL in adrenal cells. Indeed, VLDL increased cytosolic free calcium levels. An in vivo study conducted in sucrose-fed rats showed a positive correlation between elevated triglyceride (VLDL) levels in plasma and CYP11B2 expression in the adrenal. In conclusion, we have shown that VLDL can stimulate aldosterone synthesis in adrenocortical cells by increasing StAR and CYP11B2 expression, an event likely mediated by a calcium-initiated signaling cascade. Copyright © 2012 by The Endocrine Society.


DeCou C.R.,Idaho State University | Cole T.T.,Idaho State University | Rowland S.E.,Charlie Norwood Veterans Affairs Medical Center | Kaplan S.P.,Idaho State University | Lynch S.M.,Idaho State University
Sexual Abuse: Journal of Research and Treatment | Year: 2015

Female sex offenders may be implicated in up to one fifth of all sex crimes committed in the United States. Despite previous research findings that suggest unique patterns of offending among female sex offenders, limited empirical research has investigated the motivations and processes involved. The present study qualitatively examined female sex offenders’ offense-related experiences and characterized the internal and external factors that contributed to offending. Semi-structured interviews with 24 female sex offenders were analyzed by a team of coders with limited exposure to the existing literature using grounded theory analysis. A conceptual framework emerged representing distinctive processes for solo- and co-offending, contextualized within ecological layers of social and environmental influence. This model extends previous work by offering an example of nested vulnerabilities proximal to female sexual offending. Implications for future research, prevention, and treatment are discussed. © The Author(s) 2014

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