Orlando VA Medical Center

Literature describing the phenomenology of the stress of combat suggests that war-zone experiences may lead to adverse psychological outcomes such as post-traumatic stress disorder not only because they expose persons to life threat and loss but also because they may contradict deeply held moral and ethical beliefs and expectations. We sought to develop and validate a measure of potentially morally injurious events as a necessary step toward studying moral injury as a possible adverse consequence of combat. We administered an 11-item, self-report Moral Injury Events Scale to active duty Marines 1 week and 3 months following war-zone deployment. Two items were eliminated because of low item-total correlations. The remaining 9 items were subjected to an exploratory factor analysis, which revealed two latent factors that we labeled perceived transgressions and perceived betrayals; these were confirmed via confirmatory factor analysis on an independent sample. The overall Moral Injury Events Scale and its two subscales had favorable internal validity, and comparisons between the 1-week and 3-month data suggested good temporal stability. Initial discriminant and concurrent validity were also established. Future research directions were discussed.

The Zika virus (ZIKV), first discovered in 1947, has emerged as a global public health threat over the last decade, with the accelerated geographic spread of the virus noted during the last 5 years. The World Health Organization (WHO) predicts that millions of cases of ZIKV are likely to occur in the Americas during the next 12 months. These projections, in conjunction with suspected Zika-associated increase in newborn microcephaly cases, prompted WHO to declare public health emergency of international concern. ZIKV-associated illness is characterized by an incubation period of 3-12 days. Most patients remain asymptomatic (i.e., ~80%) after contracting the virus. When symptomatic, clinical presentation is usually mild and consists of a self-limiting febrile illness that lasts approximately 2-7 days. Among common clinical manifestations are fever, arthralgia, conjunctivitis, myalgia, headache, and maculopapular rash. Hospitalization and complication rates are low, with fatalities being extremely rare. Newborn microcephaly, the most devastating and insidious complication associated with the ZIKV, has been described in the offspring of women who became infected while pregnant. Much remains to be elucidated about the timing of ZIKV infection in the context of the temporal progression of pregnancy, the corresponding in utero fetal development stage(s), and the risk of microcephaly. Without further knowledge of the pathophysiology involved, the true risk of ZIKV to the unborn remains difficult to quantify and remediate. Accurate, portable, and inexpensive point-of-care testing is required to better identify cases and manage the current and future outbreaks of ZIKV, including optimization of preventive approaches and the identification of more effective risk reduction strategies. In addition, much more work needs to be done to produce an effective vaccine. Given the rapid geographic spread of ZIKV in recent years, a coordinated local, regional, and global effort is needed to generate sufficient resources and political traction to effectively halt and contain further expansion of the current outbreak.

BACKGROUND: Current literature does not identify the significance of underlying cognitive impairment and delirium in older adults during and 30 days following acute care hospitalization. OBJECTIVE: Describe the incidence, risk factors, and outcomes associated with incident delirium superimposed on dementia. DESIGN: A 24-month prospective cohort study. SETTING: Community hospital. PATIENTS: A total of 139 older adults (>65 years) with dementia. METHODS: This prospective study followed patients daily during hospitalization and 1 month posthospital. Main measures included dementia (Modified Blessed Dementia Rating score, Informant Questionnaire on Cognitive Decline in the Elderly), daily mental status change, dementia stage/severity (Clinical Dementia Rating, Global Deterioration Scale), delirium (Confusion Assessment Method), and delirium severity (Delirium Rating Scale-Revised-98). All statistical analysis was performed using SAS 9.3, and significance was an α level of 0.05. Logistic regression, analysis of covariance, or linear regression was performed controlling for age, gender, and dementia stage. RESULTS: The overall incidence of new delirium was 32% (44/139). Those with delirium had a 25% short-term mortality rate, increased length of stay, and poorer function at discharge. At 1 month follow-up, subjects with delirium had greater functional decline. Males were more likely to develop delirium, and for every 1 unit increase in dementia severity (Global Deterioration Scale), subjects were 1.5 times more likely to develop delirium. CONCLUSIONS: Delirium prolongs hospitalization for persons with dementia. Thus, interventions to increase early detection of delirium have the potential to decrease the severity and duration of delirium and to prevent unnecessary suffering and costs from the complications of delirium and unnecessary readmissions to the hospital.

Gallstone disease is one of the most common public health problems in the United States. Approximately 10%-20% of the national adult populations currently carry gallstones, and gallstone prevalence is rising. In addition, nearly 750,000 cholecystectomies are performed annually in the United States; direct and indirect costs of gallbladder surgery are estimated to be $6.5 billion. Cholelithiasis is also strongly associated with gallbladder, pancreatic, and colorectal cancer occurrence. Moreover, the National Institutes of Health estimates that almost 3,000 deaths (0.12% of all deaths) per year are attributed to complications of cholelithiasis and gallbladder disease. Although extensive research has tried to identify risk factors for cholelithiasis, several studies indicate that definitive findings still remain elusive. In this review, predisposing factors for cholelithiasis are identified, the pathophysiology of gallstone disease is described, and nonsurgical preventive options are discussed. Understanding the risk factors for cholelithiasis may not only be useful in assisting nurses to provide resources and education for patients who are diagnosed with gallstones, but also in developing novel preventive measures for the disease.

Uric acid has been implicated in the pathophysiology of renal disease; however renal clearance makes a causal relationship difficult to prove. We examine the current literature to support a potential role of uric acid in the development of kidney disease and to determine the potential to use uric acid as a marker for future renal decline. After review, we conclude that uric acid is definitively linked to the development of chronic kidney disease and can be a poor prognostic factor for the development of acute renal failure, as well. However, further human research is needed before predictive models utilizing uric acid can be developed and used in the clinical setting.

OBJECTIVES: To explore agreement between the Family Confusion Assessment Method (FAM-CAM) for delirium identification and interviewer-rated CAM delirium ratings. DESIGN: Exploratory analysis of agreement. SETTING: Community. PARTICIPANTS: Fifty-two family caregivers and 52 elderly adults with preexisting impairment according to standardized cognitive testing. MEASUREMENTS: The interviewer-rating for delirium was determined by fulfillment of the CAM algorithm RESULTS: The total sample included 52 paired CAM:FAM-CAM assessments completed across 52 dyads of elderly adults with preexisting cognitive impairment and family caregivers. The point prevalence of delirium was 13% (7/52). Characteristics did not differ significantly between the groups with and without delirium. The FAM-CAM questions that mapped directly to the original four-item CAM algorithm had the best overall agreement with the interviewer-rated CAM (kappa = 0.85, 95% confidence interval (CI) = 0.65-1.0), sensitivity of 88% (95% CI = 47-99%), and specificity of 98% (95% CI = 86-100%). CONCLUSION: The FAM-CAM is a sensitive screening tool for detection of delirium in elderly adults with cognitive impairment using family caregivers, with relevance for research and clinical practice.

OBJECTIVES: Work related stress is a major occupational health problem that is associated with adverse effects on physical and mental health. Healthcare workers are particularly vulnerable in the era of COVID-19. Physical methods of stress relief such as yoga and massage therapy may reduce occupational stress. The objective of this systematic review and network meta-analysis is to determine the effects of yoga, massage therapy, progressive muscle relaxation, and stretching on alleviating stress and improving physical and mental health in healthcare workers. METHODS: Databases were searched for randomized controlled trials on the use of physical relaxation methods for occupational stress in healthcare workers with any duration of follow-up. Meta-analysis was performed for standard mean differences in stress measures from baseline between subjects undergoing relaxation vs non-intervention controls. Network meta-analysis was conducted to determine the best relaxation method. RESULTS: Fifteen trials representing 688 healthcare workers were identified. Random-effects meta-analysis shows that physical relaxation methods overall reduced measures of occupational stress at the longest duration of follow-up vs baseline compared to non-intervention controls (SMD -0.53; 95% CI [-0.74 to -0.33]; p < .00001). On network meta-analysis, only yoga alone (SMD -0.71; 95% CI [-1.01 to -0.41]) and massage therapy alone (SMD -0.43; 95% CI [-0.72 to -0.14]) were more effective than control, with yoga identified as the best method (p-score = .89). CONCLUSION: Physical relaxation may help reduce occupational stress in healthcare workers. Yoga is particularly effective and offers the convenience of online delivery. Employers should consider implementing these methods into workplace wellness programs.

Objective: To review the safety and efficacy of brexanolone for the treatment of moderate to severe postpartum depression (PPD). Data Sources: A literature search through PubMed was conducted (January 2012 to July 2019) using the keyword brexanolone for clinical trials published in the English language. Study Selection and Data Extraction: Articles were selected if they were related to the Food and Drug Administration (FDA) approval of brexanolone or provided novel clinical information regarding this drug entity. Data Synthesis: The findings of the review show that brexanolone administered via IV infusion is both an effective and a fairly safe option for the treatment of PPD. Relevance to Patient Care and Clinical Practice: There are several antidepressants currently used to treat PPD; however, this is the first with FDA approval for this indication. The rapid onset of action of brexanolone may offer a quicker relief of these symptoms and may possibly lead to improved quality of life for both the mother and the child. Conclusion and Relevance: The recent FDA approval of brexanolone may offer an effective treatment of moderate to severe PPD and has been shown to rapidly decrease depression symptoms.

BACKGROUND: Levodopa-carbidopa intestinal gel (designated as carbidopa-levodopa enteral suspension in the United States) provides stable plasma levodopa concentrations and reduces motor fluctuations in advanced Parkinson's disease patients through continuous delivery of levodopa via percutaneous endoscopic gastrojejunostomy. We report long-term safety and efficacy outcomes from an open-label phase 3 treatment program. METHODS: PD patients (n = 262) who completed a 12-week double-blind study and its 52-week open-label extension or a separate 54-week open-label study were enrolled in this ongoing phase 3 open-label, multinational study (NCT00660673). Safety and efficacy assessments were collected every 6 months. RESULTS: Mean total duration of exposure to levodopa-carbidopa intestinal gel was 4.1 years (range, 1.2 to 6.9 years). The overall discontinuation rate was 34% (average annual discontinuation rate, 10%). Although most patients (94%) reported an adverse event, the rate of adverse events decreased over time; 53% experienced a serious adverse event. Of patients in this extension study, 54% required jejunal tube replacement during the study, and 37% required percutaneous endoscopic gastrostomy tube replacement. Most patients were on levodopa monotherapy. Patients maintained reductions in "off" time and increases in mean "on" time without dyskinesia from initial levodopa-carbidopa intestinal gel infusion to he study end point (P < 0.001; n = 81). Activities of daily living and quality-of-life assessments demonstrated significant improvements that persisted through the study. CONCLUSIONS: This long-term study demonstrates sustained and clinically meaningful benefits from levodopa-carbidopa intestinal gel in advanced PD patients. Although adverse event rates decreased over time, vigilance is required for device-related complications and adverse events. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

The pulmonary veins (PVs) are the most proximal source of arterial thromboembolism. Pulmonary vein thrombosis (PVT) is a rare but potentially lethal disease; its incidence is unclear, as most of the literature includes case reports. It most commonly occurs as a complica-tion of malignancy, post lung surgery, or atrial fibrillation and can be idiopathic in some cases. Most patients with PVT are commonly asymptomatic or have nonspecific symptoms such as cough, hemoptysis, and dyspnea from pulmonary edema or infarction. The thrombi are typically detected using a variety of imaging modalities including transesophageal echocardiogram (TEE), computed tomography (CT) scanning, magnetic resonance imaging (MRI), or pulmonary angiog-raphy. Treatment should be determined by the obstructing pathological finding and can include antibiotic therapy, anticoagulation, thrombectomy, and/or pulmonary resection. The delay in diagnosing this medical entity can lead to complications including pulmonary infarction, pulmonary edema, right ventricular failure, allograft failure, and peripheral embolism resulting in limb ischemia, stroke, and renal infarction (RI).

RATIONALE: Because of increased levels of airborne particulate matter in Southwest Asia, deployed military personnel are at risk for developing acute and chronic lung diseases. Increased respiratory symptoms are reported, but limited data exist on reported lung diseases. OBJECTIVES: To evaluate new respiratory complaints in military personnel returning from Southwest Asia to determine potential etiologies for symptoms. METHODS: Returning military personnel underwent a prospective standardized evaluation for deployment-related respiratory symptoms within 6 months of returning to their duty station. MEASUREMENTS AND MAIN RESULTS: Prospective standardized evaluation included full pulmonary function testing, high-resolution chest tomography, methacholine challenge testing, and fiberoptic bronchoscopy with bronchoalveolar lavage. Other procedures including lung biopsy were performed if clinically indicated. Fifty patients completed the study procedures. A large percentage (42%) remained undiagnosed, including 12% with normal testing and an isolated increase in lavage neutrophils or lymphocytes. Twenty (40%) patients demonstrated some evidence of airway hyperreactivity to include eight who met asthma criteria and two with findings secondary to gastroesophageal reflux. Four (8%) additional patients had isolated reduced diffusing capacity and the remaining six had other miscellaneous airway disorders. No patients were identified with diffuse parenchymal disease on the basis of computed tomography imaging. A significant number (66%) of this cohort had underlying mental health and sleep disorders. CONCLUSIONS: Evaluation of new respiratory symptoms in military personnel after service in Southwest Asia should focus on airway hyperreactivity from exposures to higher levels of ambient particulate matter. These patients may be difficult to diagnose and require close follow-up.

Herein, we report the use of a theranostic nanocarrier (Folate-HBPE(CT20p)) to deliver a therapeutic peptide to prostate cancer tumors that express PSMA (folate hydrolase 1). The therapeutic peptide (CT20p) targets and inhibits the chaperonin-containing TCP-1 (CCT) protein-folding complex, is selectively cytotoxic to cancer cells, and is non-toxic to normal tissue. With the delivery of CT20p to prostate cancer cells via PSMA, a dual level of cancer specificity is achieved: (1) selective targeting to PSMA-expressing prostate tumors, and (2) specific cytotoxicity to cancer cells with minimal toxicity to normal cells. The PSMA-targeting theranostic nanocarrier can image PSMA-expressing cells and tumors when a near infrared dye is used as cargo. Meanwhile, it can be used to treat PSMA-expressing tumors when a therapeutic, such as the CT20p peptide, is encapsulated within the nanocarrier. Even when these PSMA-targeting nanocarriers are taken up by macrophages, minimal cell death is observed in these cells, in contrast with doxorubicin-based therapeutics that result in significant macrophage death. Incubation of PSMA-expressing prostate cancer cells with the Folate-HBPE(CT20p) nanocarriers induces considerable changes in cell morphology, reduction in the levels of integrin 1, and lower cell adhesion, eventually resulting in cell death. These results are relevant as integrin 1 plays a key role in prostate cancer invasion and metastatic potential. In addition, the use of the developed PSMA-targeting nanocarrier facilitates the selective in vivo delivery of CT20p to PSMA-positive tumor, inducing significant reduction in tumor size.

Kidneys can maintain acid-base homeostasis, despite reduced renal mass, through adaptive changes in net acid excretion, of which ammonia excretion is the predominant component. The present study examines whether these adaptations are associated with changes in the ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). We used normal Sprague-Dawley rats and a 5/6 ablation-infarction model of reduced renal mass; control rats underwent sham operation. After 1 wk, glomerular filtration rate, assessed as creatinine clearance, was decreased, serum bicarbonate was slightly increased, and Na + and K + were unchanged. Total urinary ammonia excretion was unchanged, but urinary ammonia adjusted for creatinine clearance, an index of per nephron ammonia metabolism, increased significantly. Although reduced renal mass did not alter total Rhcg protein expression, both light microscopy and immunohistochemistry with quantitative morphometric analysis demonstrated hypertrophy of both intercalated cells and principal cells in the cortical and outer medullary collecting duct that was associated with increased apical and basolateral Rhcg polarization. Rhbg expression, analyzed using immunoblot analysis, immunohistochemistry, and measurement of cell-specific expression, was unchanged. We conclude that altered subcellular localization of Rhcg contributes to adaptive changes in single-nephron ammonia metabolism and maintenance of acid-base homeostasis in response to reduced renal mass.

Destination selection criteria for meetings, conventions, trade shows, and other events have been explored by a variety of researchers. Most research in this area, however, has not evaluated how planners of different events rate the destination selection variables. The current study identified three international associations for different types of event professionals and compared members' ratings of 13 destination selection criteria. Findings show that there are differences in the most important criteria used by each of the associations, with the International Association of Exhibitions and Events (IAEE) rating exhibit space, Meeting Professionals International (MPI) rating perceived value for the money, and Professional Convention Management Association (PCMA) rating support services for events as the highest criteria. Choice of restaurant and variety of nightlife are the lowest rated criteria by all groups. This information will help destination marketing organizations and event venues in specific destinations market themselves more effectively by positioning themselves appropriately in the marketplace. © 2008 by The Haworth Press.

Dyspareunia and vulvodynia are genital pain disorders that have devastating effects on women's quality of life. These disorders occur with high prevalence and place a significant financial burden on women and the health care system. Many women do not report genital pain, and most providers do not inquire about this type of pain. As a result, women also experience social isolation. Numerous treatments are thought to improve quality of life and decrease pain; however, more studies are needed. This review aims to provide an overview of clinical evaluation methods and to summarize treatment options for women suffering from dyspareunia and vulvodynia.

// Ana C. Carr 1 , Amr S. Khaled 2 , Rania Bassiouni 1 , Orielyz Flores 1 , Daniel Nierenberg 1 , Hammad Bhatti 2 , Priya Vishnubhotla 2 , J. Manuel Perez 3 , Santimukul Santra 4 and Annette R. Khaled 1 1 Burnett School of Biomedical Science, College of Medicine, University of Central Florida, Orlando, FL 32827, USA 2 Department of Pathology and Laboratory Medicine, Department of Internal Medicine, Orlando VA Medical Center, Orlando, FL 32803, USA 3 Biomedical Imaging Research Institute, &amp; Samuel Oschin Comprehensive Cancer Institute, Department of Biomedical Sciences and Department of Neurosurgery, Cedar Sinai Medical Center, Los Angeles, CA 90048, USA 4 Department of Chemistry, Pittsburg State University, Pittsburg, KS 66762, USA Correspondence to: Annette R. Khaled, email: annette.khaled@ucf.edu Keywords: chaperone; lung cancer; peptide; STAT3; nanoparticles Received: August 16, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: November 05, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: November 25, 2017 ABSTRACT Identifying new druggable targets is desired to meet the needs for effective cancer treatments. To this end, we previously reported the efficacy of a therapeutic peptide called CT20p that displays selective cytotoxicity through inhibition of a multi-subunit, protein-folding complex called Chaperonin-Containing TCP-1 (CCT). To investigate the role of CCT in cancer progression, we examined protein levels of CCT subunits in liver, prostate, and lung cancer using human tissue microarrays. We found that these cancers expressed higher levels of CCT2 as compared to normal tissues. Small cell lung cancer (SCLC) stood out as having statistically significant difference in CCT2. Higher levels of CCT2 in tumors from lung cancer patients were also associated with decreased survival. Using SCLC cell lines, we observed detectable amounts of CCT subunits and cells were susceptible to killing by CT20p. Treatment with CT20p, delivered to cells using polymeric nanoparticles, was cytotoxic to all SCLC cell lines, decreasing the levels of CCT client proteins like STAT3. In contrast, treatment with a STAT3 inhibitor was effective in one of the SCLC cell lines. While we found that CCT levels could vary in cell lines, normal tissues had low levels of CCT and minimal toxicity to liver or kidney function was observed in mice treated with CT20p. These results indicate that in SCLC, changes in CCT levels could be used as a biomarker for diagnosis and that targeting CCT for inhibition with CT20p is a promising treatment approach for those cancers such as SCLC that currently lack targeted therapeutics.

INTRODUCTION: The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). METHODS: Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. RESULTS: Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3 months to 21 years. DISCUSSION: Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes.

PURPOSE: Metastatic disease is a leading cause of death for patients with breast cancer, driving the need for new therapies. CT20p is a peptide previously discovered by our group that displays cancer-specific cytotoxicity. To design the optimal therapeutic use of the peptide, we identified the intracellular target of CT20p in breast cancer cells, correlating expression patterns of the target with susceptibility to CT20p. EXPERIMENTAL DESIGN: Using polymeric nanoparticles to deliver CT20p, we assessed cytoskeletal changes, cell migration, adhesion, and viability in cells treated with the peptide. Protein pull-down experiments, coupled to mass spectrometry, enabled identification of the peptide's intracellular target. Biochemical and histologic techniques validated target identity in human cell lines and breast cancer tissue microarrays and revealed susceptibility patterns to CT20p. RESULTS: Chaperonin containing TCP-1 (CCT) was identified as the intracellular target of CT20p. Cancer cells susceptible to CT20p had increased CCT, and overexpression of CCTβ, a subunit of the CCT complex, enhanced susceptibility to CT20p. Susceptible cells displayed reduced tubulin, a substrate of CCT, and inhibition of migration upon CT20p treatment. CCTβ levels were higher in invasive ductal carcinomas than in cancer adjacent tissues and increased with breast cancer stage. Decreased breast cancer patient survival correlated with genomic alternations in CCTβ and higher levels of the chaperone. CONCLUSIONS: Increased CCT protein in breast cancer cells underlies the cytotoxicity of CT20p. CCT is thus a potential target for therapeutic intervention and serves as a companion diagnostic to personalize the therapeutic use of CT20p for breast cancer treatment. Clin Cancer Res; 22(17); 4366-79. ©2016 AACR.

BACKGROUND: Comorbidity in psychological disorders is common following exposure to a traumatic event. Relatively little is known about the manner in which changes in the symptoms of a given type of psychological disorder in the acute period following a trauma impact changes in symptoms of another disorder. This study investigated the relationship between changes in posttraumatic stress disorder (PTSD), depression, and anxiety symptoms in the first 12 weeks following sexual assault. METHODS: Participants were 126 women who had been sexually assaulted in the previous 4 weeks. RESULTS: Lower level mediation analyses revealed that changes in PTSD symptoms had a greater impact on changes in depression and anxiety than vice versa. CONCLUSIONS: The finding highlights the role of PTSD symptoms in influencing subsequent change in other psychological symptoms. These findings are discussed in the context of models detailing the trajectory of psychological disorders following trauma, and clinical implications are considered.

BACKGROUND: Orbital exenteration is a disfiguring procedure reserved for life-threatening malignancies. This study examines the clinical course and outcomes of a large series of patients who underwent orbital exenteration for malignant periocular neoplasms. METHODS: This is a retrospective review of patients who underwent orbital exenteration from 1 July 2005 to 30 June 2015 at four tertiary referral centres in the USA, Australia and Canada. Demographics, indication for surgery, pathology, surgical technique, reconstruction type and outcomes were reviewed. RESULTS: Orbital exenteration was performed on 102 patients. The mean age at surgery was 67.5 years. The most common malignant tumours encountered were squamous cell carcinoma, melanoma and basal cell carcinoma. Seventy-six patients (75%) underwent reconstruction with a local myocutaneous flap, twelve with partial-thickness skin grafts (PTSG), or split skin graft, two had a free flap, and one had a dermis fat graft. Sixteen patients had combined procedures of two of the above. Complete removal of the tumour was achieved with clear margins in 81 cases. Of all patients, 72% were alive at 48 months or more. CONCLUSION: The majority of orbital exenterations performed in this series were secondary to periocular malignancies with unsuccessful/insufficient previous treatments. Regional myocutaneous flaps, PTSG, full-thickness skin grafts and dermis fat grafts were all highly effective and durable reconstructive options, and were able to withstand radiation therapy without complications.