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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.  Oncologic outcomes in men with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institution international study 
BMC Urology  2015;15:79.
The presence of lymph nodes (LN) within the prostatic anterior fat pad (PAFP) has been reported in several recent reports. These PAFP LNs rarely harbor metastatic disease, and the characteristics of patients with PAFP LN metastasis are not well-described in the literature. Our previous study suggested that metastatic disease to the PAFP LN was associated with less severe oncologic outcomes than those that involve the pelvic lymph node (PLN). Therefore, the objective of this study is to assess the oncologic outcome of prostate cancer (PCa) patients with PAFP LN metastasis in a larger patient population.
Data were analyzed on 8800 patients from eleven international centers in three countries. Eighty-eight patients were found to have metastatic disease to the PAFP LNs (PAFP+) and 206 men had isolated metastasis to the pelvic LNs (PLN+). Clinicopathologic features were compared using ANOVA and Chi square tests. The Kaplan-Meier method was used to calculate the time to biochemical recurrence (BCR).
Of the eighty-eight patients with PAFP LN metastasis, sixty-three (71.6 %) were up-staged based on the pathologic analysis of PAFP and eight (9.1 %) had a low-risk disease. Patients with LNs present in the PAFP had a higher incidence of biopsy Gleason score (GS) 8–10, pathologic N1 disease, and positive surgical margin in prostatectomy specimens than those with no LNs detected in the PAFP. Men who were PAFP+ with or without PLN involvement had more aggressive pathologic features than those with PLN disease only. However, there was no significant difference in BCR-free survival regardless of adjuvant therapy. In 300 patients who underwent PAFP LN mapping, 65 LNs were detected. It was also found that 44 out of 65 (67.7 %) nodes were located in the middle portion of the PAFP.
There was no significant difference in the rate of BCR between the PAFP LN+ and PLN+ groups. The PAFP likely represents a landing zone that is different from the PLNs for PCa metastasis. Therefore, the removal and pathologic analysis of PAFP should be adopted as a standard procedure in all patients undergoing radical prostatectomy.
Electronic supplementary material
The online version of this article (doi:10.1186/s12894-015-0070-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4521494  PMID: 26231860
Lymph node metastases; Prostate anterior fat pad; Prostate cancer
4.  What happens to your brain on the way to Mars 
Science advances  2015;1(4):e1400256.
As NASA prepares for the first manned spaceflight to Mars, questions have surfaced concerning the potential for increased risks associated with exposure to the spectrum of highly energetic nuclei that comprise galactic cosmic rays. Animal models have revealed an unexpected sensitivity of mature neurons in the brain to charged particles found in space. Astronaut autonomy during long-term space travel is particularly critical as is the need to properly manage planned and unanticipated events, activities that could be compromised by accumulating particle traversals through the brain. Using mice subjected to space-relevant fluences of charged particles, we show significant cortical- and hippocampal-based performance decrements 6 weeks after acute exposure. Animals manifesting cognitive decrements exhibited marked and persistent radiation-induced reductions in dendritic complexity and spine density along medial prefrontal cortical neurons known to mediate neurotransmission specifically interrogated by our behavioral tasks. Significant increases in postsynaptic density protein 95 (PSD-95) revealed major radiation-induced alterations in synaptic integrity. Impaired behavioral performance of individual animals correlated significantly with reduced spine density and trended with increased synaptic puncta, thereby providing quantitative measures of risk for developing cognitive decrements. Our data indicate an unexpected and unique susceptibility of the central nervous system to space radiation exposure, and argue that the underlying radiation sensitivity of delicate neuronal structure may well predispose astronauts to unintended mission-critical performance decrements and/or longer-term neurocognitive sequelae.
PMCID: PMC4500198  PMID: 26180843
5.  Comparison of VIM and STN DBS for Parkinsonian Resting and Postural/Action Tremor 
Resting tremor is common in Parkinson’s disease (PD), but up to 47% of PD patients have action tremor, which is sometimes resistant to medications. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus or subthalamic nucleus (STN) is effective for medication-refractory tremor in PD, though it remains unclear whether STN DBS is as effective as VIM DBS for postural/action tremor related to PD.
We carried out a single-center retrospective review of patients with medication-refractory resting, postural, and action PD tremor, treated with either VIM or STN DBS between August 2004 and March 2014. We assessed the degree of improvement using items 20 and 21 of the Unified Parkinson’s Disease Rating Scale (UPDRS) motor scale and examined the proportion of patients achieving tremor arrest.
A total of 18 patients were analyzed, 10 treated with STN and eight treated with VIM, with similar off-medication motor UPDRS scores. There was no significant difference in improvement in tremor scores or in the proportion of patients experiencing tremor arrest between the two stimulation sites. Overall, 56% and 72% of patients experienced complete absence of postural/action tremor and resting tremor, respectively, at last follow-up.
This study demonstrated excellent outcomes on both resting and postural/action tremor after either VIM or STN DBS. Resting tremor improved to a greater degree than postural/action tremor in both groups. These results suggest that a large randomized controlled trial is needed to show a superior effect of one target on PD tremor.
PMCID: PMC4502347  PMID: 26196027
Action tremor; Parkinson’s disease; deep brain stimulation
6.  Defining the Optimal Window for Cranial Transplantation of Human Induced Pluripotent Stem Cell-Derived Cells to Ameliorate Radiation-Induced Cognitive Impairment 
The authors report the beneficial cognitive effects of transplanting induced pluripotent stem cell-derived human neural stem cells in the irradiated rodent brain and how these cells differentiate and mitigate neuroinflammation throughout multiple hippocampal subfields. Given the absence of efficacious treatment options for the devastating side effects of cranial radiotherapy, stem cell therapy may provide a viable solution for this long-term mental health problem afflicting cancer survivors.
Past preclinical studies have demonstrated the capability of using human stem cell transplantation in the irradiated brain to ameliorate radiation-induced cognitive dysfunction. Intrahippocampal transplantation of human embryonic stem cells and human neural stem cells (hNSCs) was found to functionally restore cognition in rats 1 and 4 months after cranial irradiation. To optimize the potential therapeutic benefits of human stem cell transplantation, we have further defined optimal transplantation windows for maximizing cognitive benefits after irradiation and used induced pluripotent stem cell-derived hNSCs (iPSC-hNSCs) that may eventually help minimize graft rejection in the host brain. For these studies, animals given an acute head-only dose of 10 Gy were grafted with iPSC-hNSCs at 2 days, 2 weeks, or 4 weeks following irradiation. Animals receiving stem cell grafts showed improved hippocampal spatial memory and contextual fear-conditioning performance compared with irradiated sham-surgery controls when analyzed 1 month after transplantation surgery. Importantly, superior performance was evident when stem cell grafting was delayed by 4 weeks following irradiation compared with animals grafted at earlier times. Analysis of the 4-week cohort showed that the surviving grafted cells migrated throughout the CA1 and CA3 subfields of the host hippocampus and differentiated into neuronal (∼39%) and astroglial (∼14%) subtypes. Furthermore, radiation-induced inflammation was significantly attenuated across multiple hippocampal subfields in animals receiving iPSC-hNSCs at 4 weeks after irradiation. These studies expand our prior findings to demonstrate that protracted stem cell grafting provides improved cognitive benefits following irradiation that are associated with reduced neuroinflammation.
PMCID: PMC4275007  PMID: 25391646
Induced pluripotent stem cell-derived human neural stem cells; Transplantation; Radiation; Cognition; Hippocampus; Novel place recognition; Fear conditioning
7.  Extraskeletal Chondroma of the Gluteal Region Along with Sporadic Neurofibroma - An Unusual Presentation 
Extraskeletal or soft tissue chondroma is a benign cartilaginous tumour that predominantly involves the hands and feet. We present a rare case of gluteal extraskeletal chondroma in a 55-year-old Indian female. She presented with right gluteal mass measuring 5 cm in greatest dimension. The diagnosis was provided through histopathological examination of completely excised tumour mass. The patient also had sporadic neurofibroma in the supraclavicular region. Such a unique association has not been reported till date in the English literature. We describe the clinical and histopathological characteristics of our case, emphasizing the first reported association of extraskeletal chondroma and sporadic neurofibroma.
PMCID: PMC4484077  PMID: 26155485
Buttock; Soft tissue tumour; Supraclavicular
8.  Pneumocephalus in cerebellopontine angle and meningitis secondary to chronic otitis media in a child 
Pneumocephalus is a rare complication of chronic otitis media. Despite its rarity intra-cranial air carries a potential risk of increased intra-cranial pressure or meningitis, which requires immediate therapy. A 10-year-old child presented to us with complaints of fever, headache, vomiting, and decreased hearing from left ear. He had history of left ear discharge since 2 years. Clinical examination revealed neck rigidity and left chronic otitis media. Contrast enhanced computed axial tomography scan of head [Figures 1 and 2] showed pneumocephalus in left cerebellopontine angle, opacification of left middle ear and nonpneumatisation of left mastoid. Child was immediately put on empirical intravenous antibiotics and decongestants. He showed clinical improvement in 3 days. Pneumocephalus secondary to chronic otitis media is extremely rare; we are reporting one such case in a child with review of literature.
PMCID: PMC4481802  PMID: 26167031
Meningitis; neurogenic complications; otitis media; pneumocephalus
9.  Consequences of Low Dose Ionizing Radiation Exposure on the Hippocampal Microenvironment 
PLoS ONE  2015;10(6):e0128316.
The response of the brain to irradiation is complex, involving a multitude of stress inducible pathways that regulate neurotransmission within a dynamic microenvironment. While significant past work has detailed the consequences of CNS radiotherapy following relatively high doses (≥ 45 Gy), few studies have been conducted at much lower doses (≤ 2 Gy), where the response of the CNS (like many other tissues) may differ substantially from that expected from linear extrapolations of high dose data. Low dose exposure could elicit radioadaptive modulation of critical CNS processes such as neurogenesis, that provide cellular input into hippocampal circuits known to impact learning and memory. Here we show that mice deficient for chemokine signaling through genetic disruption of the CCR2 receptor exhibit a neuroprotective phenotype. Compared to wild type (WT) animals, CCR2 deficiency spared reductions in hippocampal neural progenitor cell survival and stabilized neurogenesis following exposure to low dose irradiation. While radiation-induced changes in microglia levels were not found in WT or CCR2 deficient animals, the number of Iba1+ cells did differ between each genotype at the higher dosing paradigms, suggesting that blockade of this signaling axis could moderate the neuroinflammatory response. Interestingly, changes in proinflammatory gene expression were limited in WT animals, while irradiation caused significant elevations in these markers that were attenuated significantly after radioadaptive dosing paradigms in CCR2 deficient mice. These data point to the importance of chemokine signaling under low dose paradigms, findings of potential significance to those exposed to ionizing radiation under a variety of occupational and/or medical scenarios.
PMCID: PMC4456101  PMID: 26042591
10.  Craniopharyngioma and epidermoid tumour in same child: a rare association 
BMJ Case Reports  2013;2013:bcr2013009421.
Simultaneous occurrence of histologically different primary brain tumours is rare, and its preoperative diagnosis is still challenging. The explanations for the simultaneous occurrence of different primary intracranial tumours in the absence of phacomatoses or prior radiation exposure are at present hypothetical, and these tumours could be simply coincidental. Herein, we report a case of a boy presenting with features of raised intracranial pressure and right-sided sensorineural hearing loss. Brain MRI revealed two different neoplastic pathologies at different sites: an intrasellar and suprasellar craniopharyngioma and a right cerebello-pontine angle epidermoid. To the best of our knowledge, this is the first report in literature of a craniopharyngioma coexisting with an epidermoid, in the same individual.
PMCID: PMC3703010  PMID: 23737578
11.  Post-transfusion purpura: a rare and life-threatening aetiology of thrombocytopenia 
BMJ Case Reports  2013;2013:bcr2013008860.
We present a middle-aged man with history of lung adenocarcinoma, who was admitted with massive haemoptysis secondary to severe thrombocytopenia. Two weeks prior he was started on enoxaparin for a newly diagnosed pulmonary embolus and at that time required blood transfusions for anaemia. Our initial diagnosis was heparin-induced thrombocytopenia. His platelet count, however, did not improve despite receiving argatroban and platelet transfusions. Hence, we suspected post-transfusion purpura (PTP) and started him on intravenous immunoglobulin which brought his platelet count to normal levels. The serotonin-release assay was negative and platelet-antibody test was positive confirming PTP as our diagnosis. The patient eventually was transferred to hospice care because of the advanced stage lung cancer and died of respiratory failure.
PMCID: PMC3669804  PMID: 23709534
12.  Plexiform Schwannoma of Lumbar Region 
Plexiform schwannoma is an unusual peripheral nerve sheath tumor. It can mimic plexiform neurofibroma. A five-year-old girl presented with painful swelling in left lumbar region. Radiologic investigations showed a multinodular tumor in the subcutaneous plane of lumbosacral region. A complete excision and histopathologic examination revealed a plexiform tumor composed of hypocellular and hypercellular areas with verocay bodies. The tumor cells showed strong positivity for S-100 protein, rendering a final diagnosis of plexiform schwannoma. The child has been free of recurrence in 12-month follow-up.
PMCID: PMC4448099  PMID: 26064806
Schwannoma; Plexiform; Soft tissue; Lumbar
13.  Incidental Findings on Cone Beam Computed Tomography and Reasons for Referral by Dental Practitioners in Indore City (M.P) 
Introduction: Cone beam computed tomography is a new diagnostic innovation to dental imaging. Despite the use of CBCT in oral and maxillofacial imaging, reports on its use either by individual practitioners or referral patterns to CBCT centers is lacking. Hence, a study was conducted to determine incidental findings on CBCT and reasons for referral by dental practitioners in Indore city.
Materials and Methods: A retrospective analysis of 795 records that were referred for CBCT imaging at Institutional and Oracal CBCT Centre, Indore was undertaken. Referrals from both within and outside institution, as well as from private practitioners were considered. The reason for CBCT referral, provision diagnosis, final diagnosis and any incidental diagnosis were recorded.
Results: This retrospective chart audit revealed that 56.7 % were male and 43.3% were females. Greatest source of patients was referred by oral surgeons (21.9%) followed by oral and maxillofacial radiologist (14.2%) and prosthodontist (9.3%). The most common reason for referral was for implant analysis (24.2%) and the most common incidental finding diagnosed by CBCT was oral malignancies.
Conclusion: In Institutional set-up, CBCT referrals were mostly for the reason of planning implant placement followed by trauma whereas private practitioners used CBCT mostly for implant placement followed by impaction. CBCT was being utilized more by Oral surgeons in private sector whereas it in an Institutional setup majority of referrals from Department of Oral Diagnosis and Radiology. Findings that were most commonly diagnosed incidentally on CBCT were Orofacial malignancies followed maxillary sinus pathologies.
PMCID: PMC4378801  PMID: 25859519
CBCT; Referral pattern; Incidental finding
14.  Functional Consequences of Radiation-Induced Oxidative Stress in Cultured Neural Stem Cells and the Brain Exposed to Charged Particle Irradiation 
Antioxidants & Redox Signaling  2014;20(9):1410-1422.
Aims: Redox homeostasis is critical in regulating the fate and function of multipotent cells in the central nervous system (CNS). Here, we investigated whether low dose charged particle irradiation could elicit oxidative stress in neural stem and precursor cells and whether radiation-induced changes in redox metabolism would coincide with cognitive impairment. Results: Low doses (<1 Gy) of charged particles caused an acute and persistent oxidative stress. Early after (<1 week) irradiation, increased levels of reactive oxygen and nitrogen species were generally dose responsive, but were less dependent on dose weeks to months thereafter. Exposure to ion fluences resulting in less than one ion traversal per cell was sufficient to elicit radiation-induced oxidative stress. Whole body irradiation triggered a compensatory response in the rodent brain that led to a significant increase in antioxidant capacity 2 weeks following exposure, before returning to background levels at week 4. Low dose irradiation was also found to significantly impair novel object recognition in mice 2 and 12 weeks following irradiation. Innovation: Data provide evidence that acute exposure of neural stem cells and the CNS to very low doses and fluences of charged particles can elicit a persisting oxidative stress lasting weeks to months that is associated with impaired cognition. Conclusions: Exposure to low doses of charged particles causes a persistent oxidative stress and cognitive impairment over protracted times. Data suggest that astronauts subjected to space radiation may develop a heightened risk for mission critical performance decrements in space, along with a risk of developing long-term neurocognitive sequelae. Antioxid. Redox Signal. 20, 1410–1422.
PMCID: PMC3936501  PMID: 23802883
15.  IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice 
PLoS ONE  2015;10(3):e0121070.
Classical activation of macrophages (caMph or M1) is crucial for host protection against Mycobacterium tuberculosis (Mtb) infection. Evidence suggests that IL-4/IL-13 alternatively activated macrophages (aaMph or M2) are exploited by Mtb to divert microbicidal functions of caMph. To define the functions of M2 macrophages during tuberculosis (TB), we infected mice deficient for IL-4 receptor α on macrophages (LysMcreIL-4Rα-/lox) with Mtb. We show that absence of IL-4Rα on macrophages does not play a major role during infection with Mtb H37Rv, or the clinical Beijing strain HN878. This was demonstrated by similar mortality, bacterial burden, histopathology and T cell proliferation between infected wild-type (WT) and LysMcreIL-4Rα-/lox mice. Interestingly, we observed no differences in the lung expression of inducible nitric oxide synthase (iNOS) and Arginase 1 (Arg1), well-established markers for M1/M2 macrophages among the Mtb-infected groups. Kinetic expression studies of IL-4/IL-13 activated bone marrow-derived macrophages (BMDM) infected with HN878, followed by gene set enrichment analysis, revealed that the MyD88 and IL-6, IL-10, G-CSF pathways are significantly enriched, but not the IL-4Rα driven pathway. Together, these results suggest that IL-4Rα-macrophages do not play a central role in TB disease progression.
PMCID: PMC4366092  PMID: 25790379
16.  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
17.  Endoscopic endonasal trans-sphenoid management of craniopharyngiomas 
Asian Journal of Neurosurgery  2015;10(1):10-16.
Craniopharyngiomas treatment has been challenging because of their anatomical location. The endoscopic endonasal (EE) trans-sphenoidal approach is indicated in sellar, supra sellar, selected intraventricular lesions in adults and children. We are reporting our initial experience of 44 patients managed by EE approach.
Materials and Methods:
This is a retrospective study of 44 craniopharyngiomas. The goal of surgery was gross-total resection in all cases. All patients underwent pre- and post-operative comprehensive ophthalmological and endocrinological evaluation. Lumbar drain at the start of the operation was used in all cases with tumor larger than 3 cm maximum diameter. Binostril technique vascularized nasoseptal flap and multilayer closure of the dural defect were used. Wide sphenoidotomy, posterior ethmoidectomy, tuberculum selle, and planum removal were performed in all cases. Perioperative antibiotic prophylaxis was used for 72 h.
There were 44 patients of age ranging from 8 to 65 (mean: 42) years. Diameter of the tumor varied from 3.1 cm to 6.6 cm (average: 4.3 cm). Visual and pituitary dysfunctions were observed in 44 and 33, respectively, before surgery. Vision improvement, gross-total removal, cerebrospinal fluid (CSF) leak and recurrence were observed in 34, 26, four and six patients, respectively. Average follow-up was 19 months.
Endoscopic endonasal trans-sphenoidal approach for craniopharyngioma is safe and effective alternative to transcranial approach in selected patients. Although this technique is associated with effective tumor removal and improved visual outcome, CSF leak, and endocrine dysfunctions remain a major challenge.
PMCID: PMC4352621  PMID: 25767569
Brain neoplasm; craniopharyngioma; endoscopy; intracranial neoplasm; neoplasm; surgical endoscopy
18.  Plasma cell leukaemia: a management conundrum 
Oxford Medical Case Reports  2014;2014(9):159-161.
Primary plasma cell leukaemia in a young transplant eligible patient brings forth a number of perplexing questions and many remain unanswered. There are good data to suggest the superiority of novel agents over conventional chemotherapy regimens, however choosing between autologous and allogeneic haematopoietic stem cell transplant in first remission remains a therapeutic conundrum. We report a case of primary plasma cell leukaemia in a young patient and the dilemmas in its management.
PMCID: PMC4370024  PMID: 25988065
19.  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
20.  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
21.  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
22.  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
23.  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
24.  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

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