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1.  Flavonoids in modulation of cell survival signalling pathways 
Genes & Nutrition  2014;9(3):400.
Flavonoids, a family of polyphenols, generally found in various fruits and vegetables, as well as in many plant beverages such as tea, pomegranate juice, raspberry, blueberries, and red wine. Recently, studies on flavonoids have attracted scientific attention as a potential nutritional strategy to prevent a broad range of chronic disorders. Many studies suggest that consumption of these flavonoids in sufficient amount plays neuroprotective, cardioprotective, anti-inflammatory, and chemopreventive roles. While there has been a major focus on the antioxidant properties, there is an emerging view that flavonoids and their in vivo metabolites do not act only as conventional antioxidants but may also exert modulatory actions on cellular system through direct action on various signalling pathways. These pathways include phosphoinositide 3-kinase, Akt/protein kinase B, mitogen-activated protein kinase, tyrosine kinases, and protein kinase C. Various inhibitory or stimulatory actions of flavonoids on these pathways greatly affect cellular functions by altering the phosphorylation state of targeted molecules. In addition, flavonoids also modulate various gene expressions through activation of various transcription factors. Thus, the present review will bestow a breathing overview regarding the prime role of flavonoids in modulation of survival signalling pathways at cellular system.
PMCID: PMC4026439  PMID: 24682883
Plant polyphenols; Phosphoinositide 3-kinase; Akt/protein kinase B; Mitogen-activated protein kinase; Protein kinase C; Cell survival
2.  12(S)-Hydroperoxyeicosatetraenoic acid (12-HETE) increases mitochondrial nitric oxide by increasing intramitochondrial calcium 
12(S)-Hydroxyeicosatetraenoic acid (12-HETE) is one of the metabolites of arachidonic acid involved in pathological conditions associated with mitochondria and oxidative stress. The present study tested effects of 12-HETE on mitochondrial functions. In isolated rat heart mitochondria, 12-HETE increases intramitochondrial ionized calcium concentration that stimulates mitochondrial nitric oxide (NO) synthase (mtNOS) activity. mtNOS-derived NO causes mitochondrial dysfunctions by decreasing mitochondrial respiration and transmembrane potential. mtNOS-derived NO also produces peroxynitrite that induces release of cytochrome c and stimulates aggregation of mitochondria. Similarly, in HL-1 cardiac myocytes, 12-HETE increases intramitochondrial calcium and mitochondrial NO, and induces apoptosis. The present study suggests a novel mechanism for 12-HETE toxicity.
PMCID: PMC2210014  PMID: 17963719
12-HETE; intramitochondrial ionized calcium; mtNOS; mitochondrial respiration; mitochondrial transmembrane potential; peroxynitrite; cytochrome c release; apoptosis
3.  An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome 
Leukemia  2013;28(5):1015-1021.
Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL.
PMCID: PMC4283797  PMID: 24166298
iAMP21; genetics; outcome; poor prognosis; BCP-ALL; chromosomal abnormalities
4.  A Capstone Course with a Comprehensive and Integrated Review of the Pharmacy Curriculum and Student Assessment as a Preparation for Advanced Pharmacy Practice Experiences 
Objective. To create a capstone course that provides a comprehensive and integrated review of the pharmacy curriculum with a broad range of assessment tools to evaluate student knowledge and skills as a final preparation prior to beginning fourth-year advanced pharmacy practice experiences (APPEs).
Design. The capstone course was a 4 credit-hour, case-based course. Eight comprehensive cases were assigned to students over the course of the term. The cases were designed to mimic complex clinical scenarios that students were likely to encounter during an APPE. Students were required to prepare a written and oral presentation for each case and were assessed on material covered during the cases. Faculty members presented weekly reviews on selected topics such as calculations, pharmacokinetics, and pharmaceutical compounding. At the end of the course, students took an observed structured clinical examination (OSCE), which simulated the Georgia Board of Pharmacy Practical Examination, and a comprehensive examination designed to mimic the NAPLEX (North American Pharmacy Licensure Examination).
Assessment. Evaluation of student outcomes was based on written and verbal presentations of the cases, multiple-choice examinations, a short-answer calculations examination, an “Errors and Omissions” examination, a standardized patient encounter, and pharmaceutical compounding examinations. Ninety-five percent of students successfully passed the course on their first attempt. Student feedback indicated satisfaction with the depth, breadth, and organization of material covered and felt that the course helped prepare them for APPEs.
Conclusion. The culminating experience of the capstone course gave students a thorough review of practical, clinical, and communication skills and provided faculty members with feedback regarding the curriculum through robust assessment.
PMCID: PMC4315214  PMID: 25657379
Capstone; case-based learning; integrated curriculum; communication; advanced pharmacy practice experience
5.  Mood and Memory Deficits in a Model of Gulf War Illness Are Linked with Reduced Neurogenesis, Partial Neuron Loss, and Mild Inflammation in the Hippocampus 
Neuropsychopharmacology  2013;38(12):2348-2362.
Impairments in mood and cognitive function are the key brain abnormalities observed in Gulf war illness (GWI), a chronic multisymptom health problem afflicting ∼25% of veterans who served in the Persian Gulf War-1. Although the precise cause of GWI is still unknown, combined exposure to a nerve gas prophylaxis drug pyridostigmine bromide (PB) and pesticides DEET and permethrin during the war has been proposed as one of the foremost causes of GWI. We investigated the effect of 4 weeks of exposure to Gulf war illness-related (GWIR) chemicals in the absence or presence of mild stress on mood and cognitive function, dentate gyrus neurogenesis, and neurons, microglia, and astrocytes in the hippocampus. Combined exposure to low doses of GWIR chemicals PB, DEET, and permethrin induced depressive- and anxiety-like behavior and spatial learning and memory dysfunction. Application of mild stress in the period of exposure to chemicals exacerbated the extent of mood and cognitive dysfunction. Furthermore, these behavioral impairments were associated with reduced hippocampal volume and multiple cellular alterations such as chronic reductions in neural stem cell activity and neurogenesis, partial loss of principal neurons, and mild inflammation comprising sporadic occurrence of activated microglia and significant hypertrophy of astrocytes. The results show the first evidence of an association between mood and cognitive dysfunction and hippocampal pathology epitomized by decreased neurogenesis, partial loss of principal neurons, and mild inflammation in a model of GWI. Hence, treatment strategies that are efficacious for enhancing neurogenesis and suppressing inflammation may be helpful for alleviation of mood and cognitive dysfunction observed in GWI.
PMCID: PMC3799073  PMID: 23807240
adult neurogenesis; animal models; Behavioral science; cognition; depression; gulf war illness; hippocampus; learning and memory; Neuroanatomy; adult neurogenesis; anxiety; depression; learning and memory; mood; neuroinflammation
6.  Role of Splenic Artery Embolization in Management of Traumatic Splenic Injuries: A Prospective Study 
The Indian Journal of Surgery  2012;75(5):361-367.
The objective of our study was to evaluate the role of splenic artery embolization (SAE) in the management of traumatic splenic injuries. From September 2008 to September 2010, a total of 67 patients underwent nonoperative management (NOM) for blunt splenic injuries. Twenty-two patients were excluded from the study because of associated significant other organ injuries. Twenty-five patients underwent SAE followed by NOM (group A) and 20 patients underwent standard NOM (group B). Improvement in clinical and laboratory parameters during hospital stay were compared between two groups using Chi-square test and Mann–Whitney test. SAE was always technically feasible. The mean length of the total hospital stay was lower in the group A patients (5.4 vs. 6.6 day, [P = 0.050]). There was significant increase in hemoglobin and hematocrit levels and systolic blood pressure (SBP) in group A patients after SAE, whereas in group B patients there was decrease in hemoglobin and hematocrit levels and only slight increase in SBP (pre- and early posttreatment relative change in hemoglobin [P = 0.002], hematocrit [P = 0.001], and SBP [P = 0.017]). Secondary splenectomy rate was lower in group A (4 % [1/25] vs. 15 % [3/20] [P = 0.309]). No procedure-related complications were encountered during the hospital stay and follow-up. Minor complications of pleural effusion, fever, pain, and insignificant splenic infarct noted in 9 (36 %) patients. SAE is a technically feasible, safe, and effective method in the management of splenic injuries. Use of SAE as an adjunct to NOM of splenic injuries results improvement in hemoglobin, hematocrit levels, and SBP. SAE also reduces secondary splenectomy rate and hospital stay.
PMCID: PMC3824764  PMID: 24426477
Trauma; Splenic artery embolisation
7.  An extremely unusual presentation of isolated extrathoracic sarcoidosis of submandibular lymph node in a child 
A 12-year-old male child presented with left submandibular lymphadenopathy; excision biopsy revealed noncaseating granuloma with numerous Schaumann bodies in histopathology, suggestive of isolated extrathoracic sarcoidosis, which is an extremely rare entity in the pediatric age group.
PMCID: PMC4220331  PMID: 25378857
Extrathoracic; granuloma; lymphadenitis; sarcoidosis
8.  A study of mandibular fractures over a 5-year period of time: A retrospective study 
Contemporary Clinical Dentistry  2014;5(4):452-455.
This study aims to evaluate and compare with the existing literature on the etiology, pattern, gender, and anatomical distribution of mandibular fractures.
Materials and Methods:
The data of 225 cases were analyzed over a period of 5 years between March 2009 and November 2013. Of this 110 were unilateral, 23 bilateral, 18 symphysis and 74 multiple fractures.
Males are more affected than females. The peak incidence rate is occurring in 30-35 years of age group. The most common fracture site is parasymphysis and least common site is ramus of mandible. The most common etiological factor is road traffic accident (RTA) (45.3%) followed by falls (42.6%), assaults (8.9%), sport injuries (2.2%), and gunshot wounds (0.89%).
Thus, we conclude that RTA is the leading cause of mandibular fractures and males are more affected. The most common site is parasymphysis fracture in association with angle fracture. We observed that gender was significantly associated with body and angle fracture (P = 0.04) and significant relationship between etiology with multiple site fracture such as (parasymphysis-angle), (body-condyle), (body-angle), and (symphysis-condyle) was observed (P ≤ 0.05).
PMCID: PMC4229751  PMID: 25395758
Mandibular fracture; parasymphysis fracture; road traffic accident
9.  Crystal structure of (4Z)-1-(3,4-di­chloro­phen­yl)-4-[hy­droxy(4-methyl­phen­yl)methyl­idene]-3-methyl-4,5-di­hydro-1H-pyrazol-5-one 
The title compound, C18H14Cl2N2O2, crystallizes with two mol­ecules, A and B, in the asymmetric unit. In mol­ecule A, the dihedral angles between the central pyrazole ring and pendant di­chloro­benzene and p-tolyl rings are 2.18 (16) and 46.78 (16)°, respectively. In mol­ecule B, the equivalent angles are 27.45 (16) and 40.45 (18)°, respectively. Each mol­ecule features an intra­molecular O—H⋯O hydrogen bond, which closes an S(6) ring and mol­ecule A also features a C—H⋯O inter­action. In the crystal, weak C—H⋯π interactions and aromatic π–π stacking [shortest centroid–centroid separation = 3.707 (2) Å] generate a three-dimensional network.
PMCID: PMC4257223  PMID: 25484715
crystal structure; Schiff-base pyrazole derivative; hydrogen bonding; C—H⋯π inter­actions; aromatic π–π stacking
Gait and cognitive impairments in older adults mostly reflect the co-occurrence of two geriatric syndromes linked by common underlying brain substrates and pathologies. Gait control is predominately mediated by frontal subcortical circuits, which overlap with circuits controlling executive control and attention functions. These circuits are vulnerable to multiple age-related pathologies such as ischemia, inflammation, and neurodegeneration, which could ultimately cause cognitive, gait, or combined cognitive and gait impairments. The following review aims to describe various gait and cognitive classifications, gait based phenotypes, common underlying pathological processes, and provide a link between motor and cognitive impairments in an effort to predict the risk of dementia, as well as remediate impairments by applying appropriate interventions.
PMCID: PMC3859437  PMID: 24349877
Gait; cognition; gait phenotypes; inflammation; neurodegeneration; vascular; quantitative gait measurements; dual-task; dementia risk; remediation
12.  Extension of GWAS results for lipid-related phenotypes to extreme obesity using electronic health record (EHR) data and the Metabochip 
Frontiers in Genetics  2014;5:222.
A variety of health-related data are commonly deposited into electronic health records (EHRs), including laboratory, diagnostic, and medication information. The digital nature of EHR data facilitates efficient extraction of these data for research studies, including genome-wide association studies (GWAS). Previous GWAS have identified numerous SNPs associated with variation in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). These findings have led to the development of specialized genotyping platforms that can be used for fine-mapping and replication in other populations. We have combined the efficiency of EHR data and the economic advantages of the Illumina Metabochip, a custom designed SNP chip targeted to traits related to coronary artery disease, myocardial infarction, and type 2 diabetes, to conduct an array-wide analysis of lipid traits in a population with extreme obesity. Our analyses identified associations with 12 of 21 previously identified lipid-associated SNPs with effect sizes similar to prior results. Association analysis using several approaches to account for lipid-lowering medication use resulted in fewer and less strongly associated SNPs. The availability of phenotype data from the EHR and the economic efficiency of the specialized Metabochip can be exploited to conduct multi-faceted genetic association analyses.
PMCID: PMC4123014  PMID: 25147553
GWAS; lipids; obesity; EHR
13.  Crystal structure of (Z)-1-(3,4-dichlorophenyl)-3-methyl-4-[(naphthalen-1-yl­amino)(p-tolyl)methylidene]-1H-pyrazol-5(4H)-one 
The title Schiff base compound, C28H21Cl2N3O, was synthesized by the condensation of 1-(3,4-di­chloro­phen­yl)-3-methyl-4-(4-methyl­benzo­yl)-1H-pyrazol-5(4H)-one with 1-aminona­phthalene. The p-tolyl ring is normal to the pyrazole ring, with a dihedral angle of 88.02 (14)°, and inclined to the naphthalene ring system by 78.60 (12)°. The pyrazole ring is inclined to the naphthalene ring system and the di­chloro-substituted benzene ring by 63.30 (12) and 11.03 (13)°, respectively. The amino group and carbonyl oxygen atom are involved in an intra­molecular N—H⋯O hydrogen bond enclosing an S(6) ring motif. There is also a short C—H⋯O contact involving the carbonyl O atom and the adjacent benzene ring. In the crystal, mol­ecules are linked by C—H⋯π inter­actions, forming a three-dimensional structure.
PMCID: PMC4186144  PMID: 25309277
crystal structure; Schiff base; naphthalene; pyrazolone; pyrrole
14.  Apigenin induces DNA damage through the PKCδ-dependent activation of ATM and H2AX causing down-regulation of genes involved in cell cycle control and DNA repair 
Biochemical pharmacology  2012;84(12):1571-1580.
Apigenin, an abundant plant flavonoid, exhibits anti-proliferative and anti-carcinogenic activities through mechanisms yet not fully defined. In the present study, we show that the treatment of leukemia cells with apigenin resulted in the induction of DNA damage preceding the activation of the apoptotic program. Apigenin-induced DNA damage was mediated by p38 and protein kinase C-delta (PKCδ), yet was independent of reactive oxygen species or caspase activity. Treatment of monocytic leukemia cells with apigenin induced the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and histone H2AX, two key regulators of the DNA damage response, without affecting the ataxia-telangiectasia mutated and Rad-3-related (ATR) kinase. Silencing and pharmacological inhibition of PKCδ abrogated ATM and H2AX phosphorylation, whereas inhibition of p38 reduced H2AX phosphorylation independently of ATM. We established that apigenin delayed cell cycle progression at G1/S and increased the number of apoptotic cells. In addition, genome-wide mRNA analyses showed that apigenin-induced DNA damage led to down-regulation of genes involved in cell-cycle control and DNA repair. Taken together, the present results show that the PKCδ-dependent activation of ATM and H2AX define the signaling networks responsible for the regulation of DNA damage promoting genome-wide mRNA alterations that result in cell cycle arrest, hence contributing to the anti-carcinogenic activities of this flavonoid.
PMCID: PMC4097023  PMID: 22985621
Flavonoids; Apoptosis; DNA damage; PKC delta
15.  An invasive Mimosa in India does not adopt the symbionts of its native relatives 
Annals of Botany  2013;112(1):179-196.
Background and Aims
The large monophyletic genus Mimosa comprises approx. 500 species, most of which are native to the New World, with Central Brazil being the main centre of radiation. All Brazilian Mimosa spp. so far examined are nodulated by rhizobia in the betaproteobacterial genus Burkholderia. Approximately 10 Mya, transoceanic dispersal resulted in the Indian subcontinent hosting up to six endemic Mimosa spp. The nodulation ability and rhizobial symbionts of two of these, M. hamata and M. himalayana, both from north-west India, are here examined, and compared with those of M. pudica, an invasive species.
Nodules were collected from several locations, and examined by light and electron microscopy. Rhizobia isolated from them were characterized in terms of their abilities to nodulate the three Mimosa hosts. The molecular phylogenetic relationships of the rhizobia were determined by analysis of 16S rRNA, nifH and nodA gene sequences.
Key Results
Both native Indian Mimosa spp. nodulated effectively in their respective rhizosphere soils. Based on 16S rRNA, nifH and nodA sequences, their symbionts were identified as belonging to the alphaproteobacterial genus Ensifer, and were closest to the ‘Old World’ Ensifer saheli, E. kostiensis and E. arboris. In contrast, the invasive M. pudica was predominantly nodulated by Betaproteobacteria in the genera Cupriavidus and Burkholderia. All rhizobial strains tested effectively nodulated their original hosts, but the symbionts of the native species could not nodulate M. pudica.
The native Mimosa spp. in India are not nodulated by the Burkholderia symbionts of their South American relatives, but by a unique group of alpha-rhizobial microsymbionts that are closely related to the ‘local’ Old World Ensifer symbionts of other mimosoid legumes in north-west India. They appear not to share symbionts with the invasive M. pudica, symbionts of which are mostly beta-rhizobial.
PMCID: PMC3690997  PMID: 23712450
Mimosa hamata; Mimosa himalayana; Mimosa pudica; Thar Desert; nodulation; Cupriavidus; Burkholderia; Ensifer; bacterial symbionts; rhizobia; Betaproteobacteria; nitrogen fixation; arid regions
16.  Simple laceration wound of the eyelids? Always remember to look under the lids! 
PMCID: PMC3862826  PMID: 24600129
Eye lid laceration; Scleral tear; Global dehiscence
17.  Defining functional changes in the brain caused by targeted stereotaxic radiosurgery 
Translational cancer research  2014;3(2):124-137.
Brain tumor patients routinely undergo cranial radiotherapy, and while beneficial, this treatment often results in debilitating cognitive dysfunction. This serious and unresolved problem has at present, no clinical recourse, and has driven our efforts to more clearly define the consequences of different brain irradiation paradigms on specific indices of cognitive performance and on the underlying cellular mechanisms believed to affect these processes. To accomplish this we have developed the capability to deliver highly focused X-ray beams to small and precisely defined volumes of the athymic rat brain, thereby providing more realistic simulations of clinical irradiation scenarios. Using this technique, termed stereotaxic radiosurgery, we evaluated the cognitive consequences of irradiation targeted to the hippocampus in one or both hemispheres of the brain, and compared that to whole brain irradiation. While whole brain irradiation was found to elicit significant deficits in novel place recognition and fear conditioning, standard platforms for quantifying hippocampal and non-hippocampal decrements, irradiation targeted to both hippocampi was only found to elicit deficits in fear conditioning. Cognitive decrements were more difficult to demonstrate in animals subjected to unilateral hippocampal ablation. Immunohistochemical staining for newly born immature (doublecortin positive) and mature (NeuN positive) neurons confirmed our capability to target irradiation to the neurogenic regions of the hippocampus. Stereotaxic radiosurgery (SRS) of the ipsilateral hemisphere reduced significantly the number of doublecortin and NeuN positive neurons by 80% and 27% respectively. Interestingly, neurogenesis on the contralateral side was upregulated in response to stereotaxic radiosurgery, where the number of doublecortin and NeuN positive neurons increased by 22% and 36% respectively. Neuroinflammation measured by immunostaining for activated microglia (ED1 positive cells) was significantly higher on the ipsilateral versus contralateral sides, as assessed throughout the various subfields of the hippocampus. These data suggest that certain cognitive decrements are linked to changes in neurogenesis, and that the unilaterally irradiated brain exhibits distinct neurogenic responses that may be regulated by regional differences in neuroinflammation. Compensatory upregulation of neurogenesis on the contralateral hemisphere may suffice to maintain cognition under certain dose limits. Our results demonstrate unique cognitive and neurogenic consequences as a result of targeted stereotaxic radiosurgery, and suggest that these irradiation paradigms elicit responses distinct from those found after exposing the whole brain to more uniform radiation fields.
PMCID: PMC4043313  PMID: 24904783
Stereotaxic radiosurgery (SRS); radiation-induced cognitive dysfunction; neurogenesis; neuroinflammation
18.  Synchronized charge oscillations in correlated electron systems 
Scientific Reports  2014;4:4964.
Strongly correlated phases exhibit collective carrier dynamics that if properly harnessed can enable novel functionalities and applications. In this article, we investigate the phenomenon of electrical oscillations in a prototypical MIT system, vanadium dioxide (VO2). We show that the key to such oscillatory behaviour is the ability to induce and stabilize a non-hysteretic and spontaneously reversible phase transition using a negative feedback mechanism. Further, we investigate the synchronization and coupling dynamics of such VO2 based relaxation oscillators and show, via experiment and simulation, that this coupled oscillator system exhibits rich non-linear dynamics including charge oscillations that are synchronized in both frequency and phase. Our approach of harnessing a non-hysteretic reversible phase transition region is applicable to other correlated systems exhibiting metal-insulator transitions and can be a potential candidate for oscillator based non-Boolean computing.
PMCID: PMC4019945
19.  Spontaneous Cholecystocolic Fistula: Case Report 
Cholecystocolic fistula is a rare billiary-enteric fistula with variable clinical presentation. Despite modern diagnostic tool a high degree of suspicion is required to diagnose it preoperatively. These fistulae are treated by open as well as laparoscopic surgery, with no difference in intraoperative and postoperative complications. We are describing a 50-year-old female patient with the diagnosis of chronic cholecystitis with cholelithiasis, which was investigated with routine lab investigations, and abdominal ultrasonography but none of these gave us any clue to the presence of fistula, were discovered incidentally during an open surgery and were appropriately treated.
PMCID: PMC4003626  PMID: 24783121
Biliary-enteric fistula; Cholecystectomy; Cholelithiasis
20.  Concern for overtreatment using the AUA/ASTRO guideline on adjuvant radiotherapy after radical prostatectomy 
BMC Urology  2014;14:30.
Recently, three prospective randomized trials have shown that adjuvant radiotherapy (ART) after radical prostatectomy for the patients with pT3 and/or positive margins improves biochemical progression-free survival and local recurrence free survival. But, the optimal management of these patients after radical prostatectomy is an issue which has been debated continuously. The object of this study was to determine the necessity of adjuvant radiotherapy (ART) by reviewing the outcomes of observation without ART after radical prostatectomy (RP) in patients with pathologic indications for ART according to the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) guideline.
From a prospectively maintained database, 163 patients were eligible for inclusion in this study. These men had a pathological stage pT2–3 N0 with undetectable PSA level after RP and met one or more of the three following risk factors: capsular perforation, positive surgical margins, or seminal vesicle invasion. We excluded the patients who had received neoadjuvant hormonal therapy or adjuvant treatment, or had less than 24 months of follow-up. To determine the factors that influenced biochemical recurrence-free (BCR), univariate and multivariate Cox proportional hazards analyses were performed.
Among the 163 patients, median follow-up was 50.5 months (24.0-88.2 months). Of those men under observation, 27 patients had BCR and received salvage radiotherapy (SRT). The multivariate Cox analysis showed that BCR was marginally associated with pre-operative serum PSA (P = 0.082), and the pathologic GS (HR, 4.063; P = 0.001) was an independent predictor of BCR. More importantly, in 87 patients with pre-operative PSA < 6.35 ng/ml and GS ≤ 7, only 3 developed BCR.
Of the 163 patients who qualified for ART based on the current AUA/ASTRO guideline, only 27 (16.6%) developed BCR and received SRT. Therefore, using ART following RP using the current recommendation may be an overtreatment in an overwhelming majority of the patients.
PMCID: PMC4005471  PMID: 24708639
Radical prostatectomy; Radiotherapy; Biochemical recurrence
21.  An interesting case of rubeosis iridis with neovascular glaucoma in a young patient 
PMCID: PMC3862787  PMID: 24600098
Central retinal vein occlusion; Rubeosis iridis; Neovascular glaucoma
22.  Prenatal Cocaine Exposure Uncouples mGluR1 from Homer1 and Gq Proteins 
PLoS ONE  2014;9(3):e91671.
Cocaine exposure during gestation causes protracted neurobehavioral changes consistent with a compromised glutamatergic system. Although cocaine profoundly disrupts glutamatergic neurotransmission and in utero cocaine exposure negatively affects metabotropic glutamate receptor-type 1 (mGluR1) activity, the effect of prenatal cocaine exposure on mGluR1 signaling and the underlying mechanism responsible for the prenatal cocaine effect remain elusive. Using brains of the 21-day-old (P21) prenatal cocaine-exposed rats, we show that prenatal cocaine exposure uncouples mGluR1s from their associated synaptic anchoring protein, Homer1 and signal transducer, Gq/11 proteins leading to markedly reduced mGluR1-mediated phosphoinositide hydrolysis in frontal cortex (FCX) and hippocampus. This prenatal cocaine-induced effect is the result of a sustained protein kinase C (PKC)-mediated phosphorylation of mGluR1 on the serine residues. In support, phosphatase treatment of prenatal cocaine-exposed tissues restores whereas PKC-mediated phosphorylation of saline-treated synaptic membrane attenuates mGluR1 coupling to both Gq/11 and Homer1. Expression of mGluR1, Homer1 or Gα proteins was not altered by prenatal cocaine exposure. Collectively, these data indicate that prenatal cocaine exposure triggers PKC-mediated hyper-phosphorylation of the mGluR1 leading to uncoupling of mGluR1 from its signaling components. Hence, blockade of excessive PKC activation may alleviate abnormalities in mGluR1 signaling and restores mGluR1-regulated brain functions in prenatal cocaine-exposed brains.
PMCID: PMC3953582  PMID: 24626340
23.  Bladder neck contracture–incidence and management following contemporary robot assisted radical prostatectomy technique 
Prostate International  2014;2(1):12-18.
Bladder neck contracture (BNC) is a well-recognized complication following robot-assisted radical prostatectomy (RARP) for treatment of localized prostate cancer with a reported incidence of up to 1.4%. In this series, we report our institutional experience and management results.
A prospectively collected database of patients who underwent RARP by a single surgeon from 2006 to 2012 was reviewed. Watertight bladder neck to urethral anastomosis was performed over 18-French foley catheter. BNC was diagnosed by flexible cystoscopy in patients who developed symptoms of bladder outlet obstruction. Subsequently, these patients underwent cold knife bladder neck incisions. Patients then followed a strict self regimen of clean intermittent catheterization (CIC). We identify the patient demographics, incidence of BNC, associated risk factors and success of subsequent management.
Total of 930 patients who underwent RARP for localized prostate cancer was identified. BNC was identified in 15 patients, 1.6% incidence. Mean patient age and preoperative prostate-specific antigen was 58.8 years old and 7.83 ng/mL (range, 2.5–14.55 ng/mL) respectively. Mean estimated blood loss was 361±193 mL (range, 50–650 mL). Follow-up was mean of 23.4 months. Average time to BNC diagnosis was 5.5 months. In three patients, a foreign body was identified at bladder neck. On multivariate analysis, estimated blood loss was significantly associated with development of BNC. All patients underwent cystoscopy and bladder neck incision with a 3-month CIC regimen. Out of 15 index patients, none had a BNC recurrence over the follow-up period.
BNC was identified in 1.6% of patients in our series following RARP. Intraoperative blood loss was a significant risk factor for BNC. In 20% of BNC patients a migrated foreign body was noted at vesicourethral anastomosis. Primary management of patients with BNC following RARP should be bladder neck incision and self CIC regimen.
PMCID: PMC3970984  PMID: 24693529
Prostate cancer; Bladder neck contracture; Robotics
24.  Clinical evaluation of Deep Anterior Lamellar Keratoplasty (DALK) for stromal corneal opacities 
Corneal scars are commonly formed following many diseases of the eye like trauma, inflammation and infections. They lead to permanent diminution of vision which can be managed by Penetrating Keratoplasty (PK). PK is removing diseased as well as healthy tissues and is associated with many post-operative complications. Deep Anterior Lamellar Keratoplasty (DALK) is a relatively newer procedure which replaces only the diseased stroma, leaving the original corneal endothelium intact. This procedure is associated with lesser incidence of post-operative complications.
The study was conducted at a large tertiary care centre. 10 patients with stromal corneal scars were subjected to DALK and results were analysed after 06 months. Poor quality donor corneal tissue of B− and C grade was used in all cases.
7 out of 10 patients (70%) undergoing DALK had post-operative visual acuity of 6/24 or better. 03 patients who did not have adequate recovery of visual acuity were due to over-riding of the graft in 01 case (10%), fungal keratitis in 01 case (10%) and interface haze in 01 case (10%).
DALK is a promising new technique for management of superficial corneal stromal scars using poor quality donor corneal tissue. Initial results are encouraging with minimal complications.
PMCID: PMC3862359  PMID: 24532929
Lamellar keratoplasty; Superficial stromal corneal scars; Descemet's perforation; Graft rejection; Interface haze
25.  Development of computerized color vision testing as a replacement for Martin Lantern 
Development and standardization of computerized color vision testing as a replacement for Martin Lantern test. Non-randomized comparative trial.
All candidates of SSB, Allahabad, reporting for SMB underwent color vision testing at the eye dept by computerized eye test and currently available tests.
All candidates were subjected to Ishihara chart testing and those found to be CP III were subjected to the confirmatory test on Martin Lantern and the Software. Candidates requiring CP I standards for eligibility were tested on the same on Martin Lantern and on the new software method. On comparison between the Standard Martin Lantern and the Software, the results were consistent and comparable with 82 patients testing CP I on the Martin Lantern and 81 on the software. Of the CP III patients, 253 tested positive on the Standard lantern test as compared to 251 on the software and of the CP IV group, 147 tested positive on the Standard lantern and 149 by the software method.
It was found that the software replicated the existing Martin Lantern accurately and consistently. The Martin Lantern Software can be used as a replacement for existing old Lanterns which are not in production since the early 20th century.
PMCID: PMC3862463  PMID: 24532927
Color Vision; Lantern Tests; Martin Lantern; Ishihara

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