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1.  Mental health, substance use, and intimate partner problems among pregnant and postpartum suicide victims in the National Violent Death Reporting System 
General Hospital Psychiatry  2011;34(2):139-145.
Objectives
Suicide during pregnancy and the postpartum is a tragic event for the victim and profoundly impacts the baby, the family, and the community. Prior efforts to study risks for pregnancy-associated suicide have been hampered by the lack of data sources which capture pregnancy and delivery status of victims. Introduction of the United States National Violent Death Reporting System (NVDRS) offers new insights into violent deaths by linking multiple data sources and allowing better examination of psychosocial risk factors.
Methods
The analysis used data from 17 states reporting to the NVDRS from 2003–2007 to evaluate suicide patterns among pregnant, postpartum, and non-pregnant or postpartum women. Demographic factors, mental health status, substance use, precipitating circumstances, intimate partner problems, and suicide methods were compared among groups.
Results
The 2083 female suicide victims of reproductive age demonstrated high prevalence of existing mental health diagnosis and current depressed mood with depressed mood significantly higher among postpartum women. Substance use and presence of other precipitating factors were high and similar among groups. Intimate partner problems were higher among pregnant and postpartum victims. Postpartum women were more likely die via asphyxia as cause of death compared to poisoning or firearms
Conclusions
These findings describe important mental health, substance use, and intimate partner problems seen with pregnancy-associated suicide. The study highlights mental health risk factors which could potentially be targeted for intervention in this vulnerable population.
doi:10.1016/j.genhosppsych.2011.09.017
PMCID: PMC3275697  PMID: 22055329
Pregnancy; postpartum; suicide; mental health; intimate partner violence
2.  β-Catenin is Essential for Ethanol Metabolism and Protection Against Alcohol-mediated Liver Steatosis in Mice 
Hepatology (Baltimore, Md.)  2012;55(3):931-940.
The liver plays a central role in ethanol metabolism and oxidative stress is implicated in alcohol-mediated liver injury. β-Catenin regulates hepatic metabolic zonation and adaptive response to oxidative stress. We hypothesized that β-catenin regulates the hepatic response to ethanol ingestion. Female liver-specific β-catenin knockout (KO) mice and wild type (WT) littermates were fed the Lieber-Decarli liquid diet (5% ethanol) in a pair-wise fashion. Liver histology, biochemistry, and gene expression studies were performed. Plasma alcohol and ammonia levels were measured using standard assays. Ethanol-fed KO mice exhibited systemic toxicity and early mortality. KO mice exhibited severe macrovesicular steatosis and five to six-fold higher serum ALT and AST levels. KO mice had modest increase in hepatic oxidative stress, lower expression of mitochondrial superoxide dismutase (SOD-2), and lower citrate synthase activity, the first step in the tricarboxylic acid cycle. N-Acetyl cysteine (NAC) did not prevent ethanol-induced mortality in KO mice. In WT livers, β-catenin was found to co-precipitate with FoxO3, the upstream regulator of SOD-2. Hepatic alcohol dehydrogenase and aldehyde dehydrogenase activities and expression were lower in KO mice. Hepatic cytochrome P450 2E1 protein levels were upregulated in ethanol-fed WT mice but were nearly undetectable in KO mice. These changes in ethanol-metabolizing enzymes were associated with 30-fold higher blood alcohol levels in KO mice.
Conclusion
β-catenin is essential for hepatic ethanol metabolism and plays a protective role in alcohol-mediated liver steatosis. Our results strongly suggest that integration of these functions by β-catenin is critical for adaptation to ethanol ingestion in vivo.
doi:10.1002/hep.24766
PMCID: PMC3288318  PMID: 22031168
Wnt pathway; Alcohol dehydrogenase; Cyp2E1; SOD-2; oxidative stress
3.  Linoleic acid metabolite drives severe asthma by causing airway epithelial injury 
Scientific Reports  2013;3:1349.
Airway epithelial injury is the hallmark of various respiratory diseases, but its mechanisms remain poorly understood. While 13-S-hydroxyoctadecadienoic acid (13-S-HODE) is produced in high concentration during mitochondrial degradation in reticulocytes little is known about its role in asthma pathogenesis. Here, we show that extracellular 13-S-HODE induces mitochondrial dysfunction and airway epithelial apoptosis. This is associated with features of severe airway obstruction, lung remodeling, increase in epithelial stress related proinflammatory cytokines and drastic airway neutrophilia in mouse. Further, 13-S-HODE induced features are attenuated by inhibiting Transient Receptor Potential Cation Channel, Vanilloid-type 1 (TRPV1) both in mouse model and human bronchial epithelial cells. These findings are relevant to human asthma, as 13-S-HODE levels are increased in human asthmatic airways. Blocking of 13-S-HODE activity or disruption of TRPV1 activity attenuated airway injury and asthma mimicking features in murine allergic airway inflammation. These findings indicate that 13-S-HODE induces mitochondrial dysfunction and airway epithelial injury.
doi:10.1038/srep01349
PMCID: PMC3583002  PMID: 23443229
4.  CASE REPORT Sternal Chondrosarcoma After Sternotomy for Coronary Artery Bypass Grafting 
Eplasty  2013;13:e7.
Objective: Primary bony tumors of the chest wall are usually benign and most commonly located in the ribs or sternum. Chondrosarcoma is regarded as one of the most frequent primary malignancies of the chest wall and its incidence after a sternotomy for a cardiac procedure is extremely rare. We present a case of sternal chondrosarcoma. Methods: The patient presented with a sternal mass 4 years after undergoing coronary artery bypass grafting for ischemic coronary artery disease. The mass originally emanated from the upper portion of the patients’ sternum and then rapidly enlarged to include the anterior aspects of his neck. Radiologic imaging studies were undertaken: computed tomographic scan and magnetic resonance imaging, with surgical intervention for excision. Results: Computed tomographic scan and magnetic resonance imaging established an 8.4 × 6.2 × 8.6 cm3 complex solid tissue mass within the lower neck arising from the sternal manubrium, with extensive bone destruction. Computed tomography-guided biopsy showed cells of uncertain significance. Surgical excision was performed and the mass was diagnosed as a grade II chondrosarcoma. Discussion: Primary sarcomas of the sternum though uncommon are potentially curable with wide surgical excision. Success depends on tumor histologic type and grade, which dictate recurrence.
PMCID: PMC3556636  PMID: 23372861
5.  CASE REPORT Anomalies Associated With Congenitally Corrected Transposition of Great Arteries: Expect the Unexpected 
Eplasty  2013;13:e6.
Objective: Congenitally corrected transposition of great arteries (CCTGA) is characterized by atrioventricular and ventriculoarterial discordance. Characterizations of these anomalies are important because they may influence surgical approach and management. Methods: We present a case of newly diagnosed CCTGA at the age of 50. He presented with sudden onset of shortness of breath for the first time and was diagnosed with CCTGA. Echocardiogram, magnetic resonance imaging, and cardiac catheterization were utilized to elucidate the pathology. Results: Intraoperatively, patient's CCTGA and ventricularization of the right ventricle were confirmed. The severe systemic atrioventricular valve regurgitation was replaced with a bioprosthetic valve (Medtronic Mosaic No. 29) with placement of epicardial ventricular leads for possible future placement of automatic implantable cardioverter defibrillators. Pathology report confirmed a degeneration of the systemic atrioventricular valve. Conclusions: Significant coronary artery anomalies have also been described in literature with CCTGA. The variances encountered in this case are excellent examples of the intricacies associated in diagnosis and surgical care in patients with CCTGA.
PMCID: PMC3556635  PMID: 23409204
6.  Assessment of effectiveness of percutaneous adhesiolysis and caudal epidural injections in managing post lumbar surgery syndrome: 2-year follow-up of a randomized, controlled trial 
Journal of Pain Research  2012;5:597-608.
Background
The literature is replete with evaluations of failed surgery, illustrating a 9.5%–25% reoperation rate. Speculated causes of post lumbar surgery syndrome include epidural fibrosis, acquired stenosis, recurrent disc herniation, sacroiliac joint pain, and facet joint pain among other causes.
Methods
Patients (n = 120) were randomly assigned to two groups with a 2-year follow-up. Group I (control group, n = 60) received caudal epidural injections with catheterization up to S3 with local anesthetic (lidocaine 2%, 5 mL), nonparticulate betamethasone (6 mg, 1 mL), and 6 mL of 0.9% sodium chloride solution. Group II (intervention group, n = 60) received percutaneous adhesiolysis of the targeted area, with targeted delivery of lidocaine 2% (5 mL), 10% hypertonic sodium chloride solution (6 mL), and nonparticulate betamethasone (6 mg). The multiple outcome measures included the Numeric Rating Scale, the Oswestry Disability Index 2.0, employment status, and opioid intake with assessments at 3, 6, 12, 18, and 24 months posttreatment. Primary outcome was defined as 50% improvement in pain and Oswestry Disability Index scores.
Results
Significant improvement with at least 50% relief with pain and improvement in functional status was illustrated in 82% of patients at the 2-year follow-up in the intervention group compared to 5% in the control group receiving caudal epidural injections. The average number of procedures over a period of 2 years in Group II was 6.4 ± 2.35 with overall total relief of approximately 78 weeks out of 104 weeks.
Conclusion
The results of this study show significant improvement in 82% of patients over a period of 2 years with an average of six to seven procedures of 1-day percutaneous adhesiolysis in patients with failed back surgery syndrome.
doi:10.2147/JPR.S38999
PMCID: PMC3533727  PMID: 23293536
epidural adhesions; epidural steroid injections; epidural fibrosis
7.  Tomato responds to green peach aphid infestation with the activation of trehalose metabolism and starch accumulation 
Plant Signaling & Behavior  2012;7(6):605-607.
The disaccharide trehalose and trehalose-6-phosphate that are present in trace amounts are suggested to have a signaling function in plants. Recently, it was demonstrated that trehalose metabolism contributes to Arabidopsis thaliana defense against the green peach aphid (GPA; Myzus persicae Sülzer), an important insect pest of a large variety of plants. TPS11 (TREHALOSE PHOSPHATE SYNTHASE11)-dependent trehalose metabolism was shown to curtail GPA infestation by promoting starch accumulation and expression of the PAD4 (PHYTOALEXIN-DEFICIENT4) gene, which has important roles in regulating antibiosis and antixenosis against GPA. Here we show that trehalose metabolism is similarly activated in leaves of GPA-infested tomato (Solanum lycopersicum) plants and likely contributes to tomato defense against GPA. GPA-infested leaves of tomato accumulated trehalose, which was accompanied by the transient upregulation of SlTPS11, a homolog of the Arabidopsis TPS11. GPA-infestation was also accompanied by starch accumulation and the upregulation of SlPAD4, the tomato homolog of Arabidopsis PAD4. Furthermore, trehalose application induced SlPAD4 expression and starch accumulation, and curtailed GPA infestation, suggesting that like in Arabidopsis trehalose contributes to tomato defense against GPA.
doi:10.4161/psb.20066
PMCID: PMC3442850  PMID: 22580694
Myzus persicae; SlPAD4; SlTPS11; Solanum lycopersicum; plant defense; starch; trehalose
8.  IP3 Receptor Type 2 Deficiency Is Associated with a Secretory Defect in the Pancreatic Acinar Cell and an Accumulation of Zymogen Granules 
PLoS ONE  2012;7(11):e48465.
Acute pancreatitis is a painful, life-threatening disorder of the pancreas whose etiology is often multi-factorial. It is of great importance to understand the interplay between factors that predispose patients to develop the disease. One such factor is an excessive elevation in pancreatic acinar cell Ca2+. These aberrant Ca2+ elevations are triggered by release of Ca2+ from apical Ca2+ pools that are gated by the inositol 1,4,5-trisphosphate receptor (IP3R) types 2 and 3. In this study, we examined the role of IP3R type 2 (IP3R2) using mice deficient in this Ca2+ release channel (IP3R2−/−). Using live acinar cell Ca2+ imaging we found that loss of IP3R2 reduced the amplitude of the apical Ca2+ signal and caused a delay in its initiation. This was associated with a reduction in carbachol-stimulated amylase release and an accumulation of zymogen granules (ZGs). Specifically, there was a 2-fold increase in the number of ZGs (P<0.05) and an expansion of the ZG pool area within the cell. There was also a 1.6- and 2.6-fold increase in cellular amylase and trypsinogen, respectively. However, the mice did not have evidence of pancreatic injury at baseline, other than an elevated serum amylase level. Further, pancreatitis outcomes using a mild caerulein hyperstimulation model were similar between IP3R2−/− and wild type mice. In summary, IP3R2 modulates apical acinar cell Ca2+ signals and pancreatic enzyme secretion. IP3R-deficient acinar cells accumulate ZGs, but the mice do not succumb to pancreatic damage or worse pancreatitis outcomes.
doi:10.1371/journal.pone.0048465
PMCID: PMC3504040  PMID: 23185258
9.  Metabolism of 4-chloro-2-nitrophenol in a Gram-positive bacterium, Exiguobacterium sp. PMA 
Background
Chloronitrophenols (CNPs) are widely used in the synthesis of dyes, drugs and pesticides, and constitute a major group of environmental pollutants. 4-Chloro-2-nitrophenol (4C2NP) is an isomer of CNPs that has been detected in various industrial effluents. A number of physicochemical methods have been used for treatment of wastewater containing 4C2NP. These methods are not as effective as microbial degradation, however.
Results
A 4C2NP-degrading bacterium, Exiguobacterium sp. PMA, which uses 4C2NP as the sole carbon and energy source was isolated from a chemically-contaminated site in India. Exiguobacterium sp. PMA degraded 4C2NP with the release of stoichiometeric amounts of chloride and ammonium ions. The effects of different substrate concentrations and various inoculum sizes on degradation of 4C2NP were investigated. Exiguobacterium sp. PMA degraded 4C2NP up to a concentration of 0.6 mM. High performance liquid chromatography and gas chromatography–mass spectrometry identified 4-chloro-2-aminophenol (4C2AP) and 2-aminophenol (2AP) as possible metabolites of the 4C2NP degradation pathway. The crude extract of 4C2NP-induced PMA cells contained enzymatic activity for 4C2NP reductase and 4C2AP dehalogenase, suggesting the involvement of these enzymes in the degradation of 4C2NP. Microcosm studies using sterile and non-sterile soils spiked with 4C2NP were carried out to monitor the bioremediation potential of Exiguobacterium sp. PMA. The bioremediation of 4C2NP by Exiguobacterium sp. PMA was faster in non-sterilized soil than sterilized soil.
Conclusions
Our studies indicate that Exiguobacterium sp. PMA may be useful for the bioremediation of 4C2NP-contaminated sites. This is the first report of (i) the formation of 2AP in the 4C2NP degradation pathway by any bacterium and (iii) the bioremediation of 4C2NP by any bacterium.
doi:10.1186/1475-2859-11-150
PMCID: PMC3539986  PMID: 23171039
4-Chloro-2-nitrophenol; 4-Chloro-2-aminophenol; 2-aminophenol; Biodegradation; Bioremediation; Soil microcosm
10.  Bacteriophytochrome controls carotenoid-independent response to photodynamic stress in a non-photosynthetic rhizobacterium, Azospirillum brasilense Sp7 
Scientific Reports  2012;2:872.
Ever since the discovery of the role of bacteriophytochrome (BphP) in inducing carotenoid synthesis in Deinococcus radiodurans in response to light the role of BphPs in other non-photosynthetic bacteria is not clear yet. Azospirillum brasilense, a non-photosynthetic rhizobacterium, harbours a pair of BphPs out of which AbBphP1 is a homolog of AtBphP1 of Agrobacterium tumefaciens. By overexpression, purification, biochemical and spectral characterization we have shown that AbBphP1 is a photochromic bacteriophytochrome. Phenotypic study of the ΔAbBphP1 mutant showed that it is required for the survival of A. brasilense on minimal medium under red light. The mutant also showed reduced chemotaxis towards dicarboxylates and increased sensitivity to the photooxidative stress. Unlike D. radiodurans, AbBphP1 was not involved in controlling carotenoid synthesis. Proteome analysis of the ΔAbBphP1 indicated that AbBphP1 is involved in inducing a cellular response that enables A. brasilense in regenerating proteins that might be damaged due to photodynamic stress.
doi:10.1038/srep00872
PMCID: PMC3503143  PMID: 23173079
11.  Radioprotective properties of tocopherol succinate against ionizing radiation in mice 
Journal of Radiation Research  2012;54(2):210-220.
Threats of nuclear and other radiologic exposures have been increasing but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. In prior publications we have demonstrated the efficacy of tocopherol succinate (TS) as a promising radiation countermeasure with the potential to protect against lethal doses of ionizing radiation exposure. The aim of this study was to gain further insight regarding how TS protects mice against a lethal dose of radiation. CD2F1 mice were injected subcutaneously with 400 mg/kg of TS, and 24 h later exposed to 60Co γ–radiation. Intestinal tissues or spleen/thymus were harvested after irradiation and analyzed for CD68-positive inflammatory cells and apoptotic cells by immunostaining of jejunal cross-sections. Comet assay was used to analyze DNA damage in various tissues. Phospho-histone H3(pH3) and the proliferating cell nuclear antigen (PCNA) were used as mitotic markers for immunostaining jejunal cross-sections. We observed that injecting TS significantly decreased the number of CD68-positive cells, DNA damage and apoptotic cells (BAX, caspase 3 and cleaved poly(ADP-ribose) polymerase-positive cells) as judged by various apoptotic pathway markers. TS treatment also increased proliferating cells in irradiated mice. Results of this study further support our contention that TS protects mice against lethal doses of ionizing radiation by inhibiting radiation-induced apoptosis and DNA damage while enhancing cell proliferation.
doi:10.1093/jrr/rrs088
PMCID: PMC3589926  PMID: 23038797
Apoptosis; mice; radiation; tocopherol succinate
12.  TRALI Syndrome Complicated by Retroperitoneal Bleeding 
Transfusion-related acute lung injury (TRALI) is an underdiagnosed and underreported syndrome which by itself is the third leading cause of transfusion-related mortality. The incidence of TRALI is reported to be 1 in 2000 to 5000 transfusions. When combined with uncontrollable bleeding, survival is unachievable. We report the case of a 25-year-old man, who underwent open heart surgery as an infant to correct his congenital heart disease in association with right pulmonary artery atresia. He presented with hemoptysis secondary to aspergilloma and required a pneumonectomy of the nonfunctional right lung. During pneumolysis, significant bleeding occurred from the superior vena cava. The patient required a blood transfusion and was placed on cardiopulmonary bypass to control the bleeding. Simultaneous occurrence of severe pulmonary edema and retroperitoneal bleeding were noted. Approximately 8 L of frothy edema fluid were drained from the only functional left lung starting ~15 minutes after the transfusion and lasting for several hours until the end of the case. It most likely represented TRALI syndrome. Increasing abdominal girth and poor volume return to the pump were consistent with and pathognomonic for retroperitoneal bleeding. Though primary surgical bleeding in the chest was controlled successfully and a pneumonectomy performed without further difficulty, we were unable to separate the patient from cardiopulmonary bypass due to the inability to oxygenate. As a result, we could not reverse the anti-coagulation which potentially exacerbated the retroperitoneal bleeding. After multiple unsuccessful attempts the patient succumbed. This ill-fated case demonstrates the quandary of obtaining vascular access for emergency cardiopulmonary bypass while in the right thoracotomy position. It may be beneficial to have both the femoral artery and vein cannulated before positioning a patient in a lateral decubitus position. In addition, early direct access to the right atrium may obviate a need for femoral venous cannulation. Also, adult extracorporeal membrane oxygenation may be indicated if faced with such a severe pulmonary edema without ongoing hemorrhage.
doi:10.1055/s-0031-1283219
PMCID: PMC3331656  PMID: 22942633
Transfusion; lung injury; pulmonary atresia; retroperitoneal hematoma
13.  Oral manifestations in type-2 diabetes and related complications 
Background:
Knowledge of the wide spectrum of the oral markers of diabetes is imperative as one frequently encounters individuals with undetected, untreated or poorly controlled diabetes.
Objectives:
The objective was to study the oral manifestations in type 2 diabetes mellitus (DM) and to establish an association between oral manifestations and associated microvascular and macrovascular complications.
Materials and Methods:
50 cases of DM were selected who had oral complications. The control group comprised 50 age- and sex-matched diabetic patients without any oral complications.
Results:
Oral manifestations in DM included periodontal disease in 34%, oral candidiasis in 24%, tooth loss in 24%, oral mucosal ulcers in 22%, taste impairment in 20%, xerostomia and salivary gland hypofunction in 14%, dental caries in 24%, and burning mouth sensation in 10% cases. Fasting [(FBG) (P = 0.003)] and postprandial blood glucose [(PPBG) (P = 0.0003)] levels were significantly higher among cases. The P values for neuropathy, retinopathy, nephropathy, cardiovascular disease, dyslipidemia, and sepsis were 0.0156, 0.0241, 0.68, 0.4047, 0.0278, and 0.3149, respectively, which were significant for neuropathy, retinopathy, and dyslipidemia.
Conclusions:
Several oral complications are seen among diabetics. Association of oral markers in DM and microvascular complications suggests that there is a significant association between the two.
doi:10.4103/2230-8210.100673
PMCID: PMC3475903  PMID: 23087863
Diabetes mellitus; dyslipidemia; neuropathy; oral complications; retinopathy
14.  Homicide and Suicide During the Perinatal Period: Findings from the National Violent Death Reporting System 
Obstetrics and gynecology  2011;118(5):1056-1063.
Objective
Homicide and suicide are two important and potentially preventable causes of maternal injury. We analyzed data from the National Violent Death Reporting System to estimate the rates of pregnancy-associated homicide and suicide in a multi-state sample, to compare these rates with other causes of maternal mortality, and to describe victims’ demographic characteristics.
Methods
We analyzed data from female victims of reproductive age from 2003–2007. We identified pregnancy-associated violent deaths as deaths due to homicide or suicide during pregnancy or within the first year postpartum. We calculated the rates of pregnancy-associated homicide and suicide as the number of deaths per 100,000 live births in the sample population. We used descriptive statistics to report victims’ demographic characteristics and prevalence of intimate partner violence (IPV).
Results
There were 94 counts of pregnancy-associated suicide and 139 counts of pregnancy-associated homicide, yielding pregnancy-associated suicide and homicide rates of 2.0 and 2.9 deaths/100,000 live births, respectively. Victims of pregnancy-associated suicide were significantly more likely to be older and of Caucasian or American Indian descent as compared to all live births in NVDRS states. Pregnancy-associated homicide victims were significantly more likely to be at the extremes of the age range and African American. 54.3% of pregnancy-associated suicides involved intimate partner conflict that appeared to contribute to the suicide. 45.3% of pregnancy-associated homicides were IPV-associated.
Conclusions
Our results indicate that pregnancy-associated homicide and suicide are important contributors to maternal mortality and confirm the need to evaluate the relationships between socio demographic disparities and IPV with pregnancy-associated violent death.
doi:10.1097/AOG.0b013e31823294da
PMCID: PMC3428236  PMID: 22015873
15.  The Role of Thoracic Medial Branch Blocks in Managing Chronic Mid and Upper Back Pain: A Randomized, Double-Blind, Active-Control Trial with a 2-Year Followup 
Study Design. A randomized, double-blind, active-control trial. Objective. To determine the clinical effectiveness of therapeutic thoracic facet joint nerve blocks with or without steroids in managing chronic mid back and upper back pain. Summary of Background Data. The prevalence of thoracic facet joint pain has been established as 34% to 42%. Multiple therapeutic techniques utilized in managing chronic thoracic pain of facet joint origin include medial branch blocks, radiofrequency neurotomy, and intraarticular injections. Methods. This randomized double-blind active controlled trial was performed in 100 patients with 50 patients in each group who received medial branch blocks with local anesthetic alone or local anesthetic and steroids. Outcome measures included the numeric rating scale (NRS), Oswestry Disability Index (ODI), opioid intake, and work status, at baseline, 3, 6, 12, 18, and 24 months. Results. Significant improvement with significant pain relief and functional status improvement of 50% or more were observed in 80% of the patients in Group I and 84% of the patients in Group II at 2-year followup. Conclusions. Therapeutic medial branch blocks of thoracic facets with or without steroids may provide a management option for chronic function-limiting thoracic pain of facet joint origin.
doi:10.1155/2012/585806
PMCID: PMC3407605  PMID: 22851967
16.  CASE REPORT Papillary Fibroelastomas and the Conundrum of the Benign Intracardiac Mass 
Eplasty  2012;12:e28.
Cardiac papillary fibroelastomas are a rare form of benign, primary cardiac tumor. They tend to develop from the valvular endocardium, with nonvalvular locations being uncommon. They are primarily found on either the mitral or aortic valve. They account for 7% of all primary cardiac tumors. Papillary fibroelastomas are usually identified through either transthoracic echocardiography or transesophageal echocardiography. The latter is more likely to provide a clearer diagnosis. Management remains controversial. The benign histology notwithstanding, the prevailing consensus is toward excision of left-sided cardiac lesions due to the risk of coronary and cerebral embolization. While the diagnosis of cardiac papillary fibroelastomas is relatively rare, the likelihood of encountering a right-sided lesion with rapid growth in a 6-month period is extraordinary. We highlight a case where an 84-year-old man with coronary artery disease was found to have a right atrial mass attached to the tricuspid valve. This mass grew by more than 1 cm in a 6-month period.
PMCID: PMC3377359  PMID: 22724043
17.  Lack of Wdr13 Gene in Mice Leads to Enhanced Pancreatic Beta Cell Proliferation, Hyperinsulinemia and Mild Obesity 
PLoS ONE  2012;7(6):e38685.
WD-repeat proteins are very diverse, yet these are structurally related proteins that participate in a wide range of cellular functions. WDR13, a member of this family, is conserved from fishes to humans and localizes into the nucleus. To understand the in vivo function(s) of Wdr13 gene, we have created and characterized a mutant mouse strain lacking this gene. The mutant mice had higher serum insulin levels and increased pancreatic islet mass as a result of enhanced beta cell proliferation. While a known cell cycle inhibitor, p21, was downregulated in the mutant islets, over expression of WDR13 in the pancreatic beta cell line (MIN6) resulted in upregulation of p21, accompanied by retardation of cell proliferation. We suggest that WDR13 is a novel negative regulator of the pancreatic beta cell proliferation. Given the higher insulin levels and better glucose clearance in Wdr13 gene deficient mice, we propose that this protein may be a potential candidate drug target for ameliorating impaired glucose metabolism in diabetes.
doi:10.1371/journal.pone.0038685
PMCID: PMC3371019  PMID: 22715406
18.  Arabidopsis thaliana—Aphid Interaction 
Aphids are important pests of plants that use their stylets to tap into the sieve elements to consume phloem sap. Besides the removal of photosynthates, aphid infestation also alters source-sink patterns. Most aphids also vector viral diseases. In this chapter, we will summarize on recent significant findings in plant-aphid interaction, and how studies involving Arabidopsis thaliana and Myzus persicae (Sülzer), more commonly known as the green peach aphid (GPA), are beginning to provide important insights into the molecular basis of plant defense and susceptibility to aphids. The recent demonstration that expression of dsRNA in Arabidopsis can be used to silence expression of genes in GPA has further expanded the utility of Arabidopsis for evaluating the contribution of the aphid genome-encoded proteins to this interaction.
doi:10.1199/tab.0159
PMCID: PMC3365623  PMID: 22666177
19.  Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity 
Science Translational Medicine  2011;3(107):107ra110.
Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid–mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis.
doi:10.1126/scitranslmed.3002573
PMCID: PMC3321362  PMID: 22049070
20.  Prevention and Mitigation of Acute Radiation Syndrome in Mice by Synthetic Lipopeptide Agonists of Toll-Like Receptor 2 (TLR2) 
PLoS ONE  2012;7(3):e33044.
Bacterial lipoproteins (BLP) induce innate immune responses in mammals by activating heterodimeric receptor complexes containing Toll-like receptor 2 (TLR2). TLR2 signaling results in nuclear factor-kappaB (NF-κB)-dependent upregulation of anti-apoptotic factors, anti-oxidants and cytokines, all of which have been implicated in radiation protection. Here we demonstrate that synthetic lipopeptides (sLP) that mimic the structure of naturally occurring mycoplasmal BLP significantly increase mouse survival following lethal total body irradiation (TBI) when administered between 48 hours before and 24 hours after irradiation. The TBI dose ranges against which sLP are effective indicate that sLP primarily impact the hematopoietic (HP) component of acute radiation syndrome. Indeed, sLP treatment accelerated recovery of bone marrow (BM) and spleen cellularity and ameliorated thrombocytopenia of irradiated mice. sLP did not improve survival of irradiated TLR2-knockout mice, confirming that sLP-mediated radioprotection requires TLR2. However, sLP was radioprotective in chimeric mice containing TLR2-null BM on a wild type background, indicating that radioprotection of the HP system by sLP is, at least in part, indirect and initiated in non-BM cells. sLP injection resulted in strong transient induction of multiple cytokines with known roles in hematopoiesis, including granulocyte colony-stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin-6 (IL-6). sLP-induced cytokines, particularly G-CSF, are likely mediators of the radioprotective/mitigative activity of sLP. This study illustrates the strong potential of LP-based TLR2 agonists for anti-radiation prophylaxis and therapy in defense and medical scenarios.
doi:10.1371/journal.pone.0033044
PMCID: PMC3314012  PMID: 22479357
21.  Relationship between sealing ability of Activ GP and Gutta Flow and methods of calcium hydroxide removal 
Aim:
To evaluate the effect of method of calcium hydroxide intracanal dressing removal, on sealing ability of Gutta Flow and Activ GP.
Materials and Methods:
Seventy extracted mandibular premolars were sectioned at CEJ and canals were prepared with profile 4% rotary file till #40. Canals were filled with calcium hydroxide, coronally sealed with Cavit G and stored at 37°C. After 7 days, samples were divided on the basis of calcium hydroxide removal method (Master apical file, Navi Tip FX, and F File) and obturating material (Activ GP and Gutta Flow). Three coats of nail polish were applied except 2 mm around apical foramen and samples were immersed in India ink dye, sectioned, and observed under stereomicroscope for microleakage.
Results:
The results were statistically analyzed with one way ANOVA-F with Tukey HSD test with the null hypothesis set as 5%.
Conclusions:
The seal of the canal system was adversely impacted by residual calcium hydroxide when Activ GP and Gutta Flow were used as obturating material and the sealing ability of Activ GP and Gutta Flow was better when MAF was used for removal of calcium hydroxide than F file or Navi tip FX.
doi:10.4103/0972-0707.92605
PMCID: PMC3284012  PMID: 22368334
Activ GP; calcium hydroxide; F file; Gutta Flow; Navi tip Fx; sealing ability
22.  Fluoroscopic Caudal Epidural Injections in Managing Post Lumbar Surgery Syndrome: Two-Year Results of a Randomized, Double-Blind, Active-Control Trial 
Study Design: A randomized, active control, double-blind trial. Objective: To evaluate the effectiveness of fluoroscopically directed caudal epidural injections with or without steroids in managing chronic low back and lower extremity pain secondary to post lumbar surgery syndrome. Summary of Background Data: There is a paucity of evidence concerning caudal epidural injections for managing chronic persistent low back pain with or without lower extremity pain caused by post lumbar surgery syndrome.
Methods: This active control randomized study included 140 patients with 70 patients in each group. Group I received 0.5% lidocaine, 10 mL; Group II received 9 mL of 0.5% lidocaine mixed with 1 mL of 6 mg of nonparticulate betamethasone. The multiple outcome measures included the numeric rating scale, the Oswestry Disability Index 2.0, employment status, and opioid intake with assessments at 3, 6, 12, 18, and 24 months posttreatment. Primary outcome was defined as at least 50% improvement in pain and Oswestry Disability Index scores. Patients with a positive response to the first 2 procedures with at least 3 weeks of relief were considered to be successful. All others were considered as failures.
Results: Overall in Group I, 53% and 47% of the patients and in Group II, 59% and 58% of the patients, showed significant improvement with reduction in pain scores and disability index at 12 months and 24 months. In contrast, in the successful groups, significant pain relief and improvement in function were observed in 70% and 62% of Group I at one and 2 years; in 75% and 69% of Group II at one and 2 years. The results in the successful group showed that at the end of the first year patients experienced approximately 38 weeks of relief and at the end of 2 years Group I had 62 weeks and Group II had 68 weeks of relief. Overall total relief for 2 years was 48 weeks in Group I and 54 weeks in Group II. The average procedures in the successful groups were at 4 in one year and 6 at the end of 2 years.
Conclusion: Caudal epidural injections of local anesthetic with or without steroid might be effective in patients with chronic persistent low back and/or lower extremity pain in patients with post lumbar surgery syndrome.
doi:10.7150/ijms.4672
PMCID: PMC3461763  PMID: 23028241
Chronic low back pain; post lumbar surgery syndrome; recurrent disc herniation; epidural fibrosis; spinal stenosis; caudal epidural steroid injections.
23.  Improving signal-to-noise ratio of structured light microscopy based on photon reassignment 
Biomedical Optics Express  2011;3(1):206-214.
In this paper, we report a method for 3D visualization of a biological specimen utilizing a structured light wide-field microscopic imaging system. This method improves on existing structured light imaging modalities by reassigning fluorescence photons generated from off-focal plane excitation, improving in-focus signal strength. Utilizing a maximum likelihood approach, we identify the most likely fluorophore distribution in 3D that will produce the observed image stacks under structured and uniform illumination using an iterative maximization algorithm. Our results show the optical sectioning capability of tissue specimens while mostly preserving image stack photon count, which is usually not achievable with other existing structured light imaging methods.
doi:10.1364/BOE.3.000206
PMCID: PMC3255338  PMID: 22254180
(180.6900) Three-dimensional microscopy; (180.2520) Fluorescence microscopy; (110.6880) Three-dimensional image acquisition; (100.3020) Image reconstruction-restoration
24.  Liver-Specific β-Catenin Knockout Mice Have Bile Canalicular Abnormalities, Bile Secretory Defect and Intrahepatic Cholestasis 
Hepatology (Baltimore, Md.)  2010;52(4):1410-1419.
β-Catenin plays important roles in liver physiology and hepatocarcinogenesis. While studying the role of β-catenin in diet-induced steatohepatitis, we recently found that liver-specific β-catenin knockout (KO) mice exhibit intrahepatic cholestasis. This study was undertaken to further characterize the role of β-catenin in biliary physiology. KO mice and wild type (WT) littermates were fed standard chow or 0.5% cholic acid supplemented diet for two weeks. Chow-fed KO mice had higher serum and hepatic total bile acid levels and lower bile flow rate than WT mice. Expression levels of bile acid biosynthetic genes were lower and levels of major bile acid exporters similar and, therefore, could not explain the KO phenotype. Despite loss of the tight junction protein claudin-2, KO mice had preserved functional integrity of tight junctions. KO mice had bile canalicular morphologic abnormalities as evidenced by staining for F-actin and zona occludens 1. Electron microscopy revealed dilated and tortuous bile canaliculi in KO livers along with decreased canalicular and sinusoidal microvilli. KO mice on cholic acid diet had higher hepatic and serum bile acid levels, bile ductular reaction, increased pericellular fibrosis, and dilated, misshapen bile canaliculi. Compensatory changes in expression levels of several bile acid transporters and regulatory genes were found in KO livers. In conclusion, liver-specific loss of β-catenin leads to defective bile canalicular morphology, bile secretory defect, and intrahepatic cholestasis. Thus, our results establish a critical role for β-catenin in biliary physiology.
doi:10.1002/hep.23801
PMCID: PMC2947599  PMID: 20722001
Wnt pathway; bile acids; tight junctions; claudin; bile canaliculi
25.  Asymptomatic Infection with Visceral Leishmaniasis in a Disease-Endemic Area in Bihar, India 
A prospective study was carried out in a cohort of 355 persons in a leishmaniasis-endemic village of the Patna District in Bihar, India, to determine the prevalence of asymptomatic persons and rate of progression to symptomatic visceral leishmaniasis (VL) cases. At baseline screening, 50 persons were positive for leishmaniasis by any of the three tests (rK39 strip test, direct agglutination test, and polymerase chain reaction) used. Point prevalence of asymptomatic VL was 110 per 1,000 persons and the rate of progression to symptomatic cases was 17.85 per 1,000 person-months. The incidence rate ratio of progression to symptomatic case was 3.36 (95% confidence interval [CI] = 0.75–15.01, P = 0.09) among case-contacts of VL compared with neighbors. High prevalence of asymptomatic persons and clinical VL cases and high density of Phlebotomus argentipes sand flies can lead to transmission of VL in VL-endemic areas.
doi:10.4269/ajtmh.2010.09-0345
PMCID: PMC2929041  PMID: 20810810

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