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1.  Role of coronary physiology in the contemporary management of coronary artery disease 
Coronary artery disease (CAD) remains the leading cause of death worldwide with approximately 1 in 30 patients with stable CAD experiencing death or acute myocardial infarction each year. The presence and extent of resultant myocardial ischaemia has been shown to confer an increased risk of adverse outcomes. Whilst, optimal medical therapy (OMT) forms the cornerstone of the management of patients with stable CAD, a significant number of patients present with ischaemia refractory to OMT. Historically coronary angiography alone has been used to determine coronary lesion severity in both stable and acute settings. It is increasingly clear that this approach fails to accurately identify the haemodynamic significance of lesions; especially those that are visually “intermediate” in severity. Revascularisation based upon angiographic appearances alone may not reduce coronary events above OMT. Technological advances have enabled the measurement of physiological indices including the fractional flow reserve, the index of microcirculatory resistance and the coronary flow reserve. The integration of these parameters into the routine management of patients presenting to the cardiac catheterization laboratory with CAD represents a critical adjunctive tool in the optimal management of these patients by identifying patients that would most benefit from revascularisation and importantly also highlighting patients that would not gain benefit and therefore reducing the likelihood of adverse outcomes associated with coronary revascularisation. Furthermore, these techniques are applicable to a broad range of patients including those with left main stem disease, proximal coronary disease, diabetes mellitus, previous percutaneous coronary intervention and with previous coronary artery bypass grafting. This review will discuss current concepts relevant to coronary physiology assessment, its role in the management of both stable and acute patients and future applications.
PMCID: PMC4317608
Ischaemia; Coronary physiology; Coronary flow reserve; Fractional flow reserve; Coronary artery disease
2.  A Unique Human Mycoplasma Protein that Generically Blocks Antigen-Antibody Union 
Science (New York, N.Y.)  2014;343(6171):656-661.
We report the discovery and crystal structure of a human mycoplasma protein, Protein M, which binds with high affinity to antibodies, predominantly through attachment to the variable region of the κ and λ light chains. Protein M broadly blocks antibody-antigen union and its mechanism of inhibition is of considerable interest because, as a diversity system, the binding mode of each antibody is different. Protein M thus appears to function by a mechanism that is independent of the sequences of members of the extensive antibody repertoire. By anchoring to conserved regions of the antibody light chains, Protein M is in a position to extend its large C-terminal domain over the antibody combining site and block entrance to macromolecular antigens.
PMCID: PMC3987992  PMID: 24503852
3.  Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model 
PLoS ONE  2015;10(2):e0116861.
Electronic cigarettes (E-cigs) have experienced sharp increases in popularity over the past five years due to many factors, including aggressive marketing, increased restrictions on conventional cigarettes, and a perception that E-cigs are healthy alternatives to cigarettes. Despite this perception, studies on health effects in humans are extremely limited and in vivo animal models have not been generated. Presently, we determined that E-cig vapor contains 7x1011 free radicals per puff. To determine whether E-cig exposure impacts pulmonary responses in mice, we developed an inhalation chamber for E-cig exposure. Mice that were exposed to E-cig vapor contained serum cotinine concentrations that are comparable to human E-cig users. E-cig exposure for 2 weeks produced a significant increase in oxidative stress and moderate macrophage-mediated inflammation. Since, COPD patients are susceptible to bacterial and viral infections, we tested effects of E-cigs on immune response. Mice that were exposed to E-cig vapor showed significantly impaired pulmonary bacterial clearance, compared to air-exposed mice, following an intranasal infection with Streptococcus pneumonia. This defective bacterial clearance was partially due to reduced phagocytosis by alveolar macrophages from E-cig exposed mice. In response to Influenza A virus infection, E-cig exposed mice displayed increased lung viral titers and enhanced virus-induced illness and mortality. In summary, this study reports a murine model of E-cig exposure and demonstrates that E-cig exposure elicits impaired pulmonary anti-microbial defenses. Hence, E-cig exposure as an alternative to cigarette smoking must be rigorously tested in users for their effects on immune response and susceptibility to bacterial and viral infections.
PMCID: PMC4317176  PMID: 25651083
4.  Redox regulation of cardiomyocyte cell cycling via an ERK1/2 and c-Myc-dependent activation of cyclin D2 transcription 
Adult mammalian cardiomyocytes have a very limited capacity to proliferate, and consequently the loss of cells after cardiac stress promotes heart failure. Recent evidence suggests that administration of hydrogen peroxide (H2O2), can regulate redox-dependent signalling pathway(s) to promote cardiomyocyte proliferation in vitro, but the potential relevance of such a pathway in vivo has not been tested. We have generated a transgenic (Tg) mouse model in which the H2O2-generating enzyme, NADPH oxidase 4 (Nox4), is overexpressed within the postnatal cardiomyocytes, and observed that the hearts of 1–3 week old Tg mice pups are larger in comparison to wild type (Wt) littermate controls. We demonstrate that the cardiomyocytes of Tg mouse pups have increased cell cycling capacity in vivo as determined by incorporation of 5-bromo-2′-deoxyuridine. Further, microarray analyses of the transcriptome of these Tg mouse hearts suggested that the expression of cyclin D2 is significantly increased. We investigated the molecular mechanisms which underlie this more proliferative phenotype in isolated neonatal rat cardiomyocytes (NRCs) in vitro, and demonstrate that Nox4 overexpression mediates an H2O2-dependent activation of the ERK1/2 signalling pathway, which in turn phosphorylates and activates the transcription factor c-myc. This results in a significant increase in cyclin D2 expression, which we show to be mediated, at least in part, by cis-acting c-myc binding sites within the proximal cyclin D2 promoter. Overexpression of Nox4 in NRCs results in an increase in their proliferative capacity that is ablated by the silencing of cyclin D2. We further demonstrate activation of the ERK1/2 signalling pathway, increased phosphorylation of c-myc and significantly increased expression of cyclin D2 protein in the Nox4 Tg hearts. We suggest that this pathway acts to maintain the proliferative capacity of cardiomyocytes in Nox4 Tg pups in vivo and so delays their exit from the cell cycle after birth.
•Cardiomyocyte cell cycling is under redox control in vivo.•Nox4 is a potential source of ROS regulating this process.•Redox activation of ERK1/2 promotes cyclin D2 transcription via c-myc activation.•Promotion of proliferation via increased cyclin D2 may be useful therapeutically.
PMCID: PMC4312357  PMID: 25450615
BrdU, bromodeoxyuridine; AdNox4, adenoviral Nox4; AdβGal, adenoviral β-galactosidase; PEG, polyethylene glycol; Wt, wild type; Tg, transgenic; NRC, neonatal rat cardiomyocyte; Cardiomyocyte proliferation; ERK1/2; Nox4; Cyclin D2; Redox signalling; c-Myc
5.  Functional Brain Networks and White Matter Underlying Theory-of-Mind in Autism 
Human beings constantly engage in attributing causal explanations to one’s own and to others’ actions, and theory-of-mind (ToM) is critical in making such inferences. Although children learn causal attribution early in development, children with autism spectrum disorders (ASDs) are known to have impairments in the development of intentional causality. This functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) study investigated the neural correlates of physical and intentional causal attribution in people with ASDs. In the fMRI scanner, 15 adolescents and adults with ASDs and 15 age- and IQ-matched typically developing peers made causal judgments about comic strips presented randomly in an event-related design. All participants showed robust activation in bilateral posterior superior temporal sulcus at the temporo-parietal junction (TPJ) in response to intentional causality. Participants with ASDs showed lower activation in TPJ, right inferior frontal gyrus and left premotor cortex. Significantly weaker functional connectivity was also found in the ASD group between TPJ and motor areas during intentional causality. DTI data revealed significantly reduced fractional anisotropy in ASD participants in white matter underlying the temporal lobe. In addition to underscoring the role of TPJ in ToM, this study found an interaction between motor simulation and mentalizing systems in intentional causal attribution and its possible discord in autism.
PMCID: PMC3871731  PMID: 22977198
functional MRI; theory-of-mind; intentional causality; physical causality; causal attribution; diffusion tensor imaging; fractional anisotropy; functional connectivity; autism
6.  Probing the human estrogen receptor-α binding requirements for phenolic mono- and di-hydroxyl compounds: A combined synthesis, binding and docking study 
Bioorganic & medicinal chemistry  2013;22(1):303-310.
Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERβ over ERα, and was also 25-fold specific for agonist ERβ versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERβ, versus with Thr299 in the antagonist form. But, the presence of this aliphatic hydroxyl is not required in all compounds, since mono-hydroxyl (phenolic) compounds bind ERα with high affinity, via hydroxyl hydrogen bonding interactions with the ERα Arg394/Glu353/water triad, and van der Waals interactions with the rest of the molecule.
PMCID: PMC4013293  PMID: 24315190
Estrogen receptor; Docking; Phenolic; Breast cancer; Endocrine disruptor
7.  Highly thermostable GH39 β-xylosidase from a Geobacillus sp. strain WSUCF1 
BMC Biotechnology  2014;14(1):963.
Complete enzymatic hydrolysis of xylan to xylose requires the action of endoxylanase and β-xylosidase. β-xylosidases play an important part in hydrolyzing xylo-oligosaccharides to xylose. Thermostable β-xylosidases have been a focus of attention as industrially important enzymes due to their long shelf life and role in the relief of end-product inhibition of xylanases caused by xylo-oligosaccharides. Therefore, a highly thermostable β-xylosidase with high specific activity has significant potential in lignocellulose bioconversion.
A gene encoding a highly thermostable GH39 β-xylosidase was cloned from Geobacillus sp. strain WSUCF1 and expressed in Escherichia coli. Recombinant β-xylosidase was active over a wide range of temperatures and pH with optimum temperature of 70°C and pH 6.5. It exhibited very high thermostability, retaining 50% activity at 70°C after 9 days. WSUCF1 β-xylosidase is more thermostable than β-xylosidases reported from other thermophiles (growth temperature ≤ 70°C). Specific activity was 133 U/mg when incubated with p-nitrophenyl xylopyranoside, with Km and Vmax values of 2.38 mM and 147 U/mg, respectively. SDS-PAGE analysis indicated that the recombinant enzyme had a mass of 58 kDa, but omitting heating prior to electrophoresis increased the apparent mass to 230 kDa, suggesting the enzyme exists as a tetramer. Enzyme exhibited high tolerance to xylose, retained approximately 70% of relative activity at 210 mM xylose concentration. Thin layer chromatography showed that the enzyme had potential to convert xylo-oligomers (xylobiose, triose, tetraose, and pentaose) into fermentable xylose. WSUCF1 β-xylosidase along with WSUCF1 endo-xylanase synergistically converted the xylan into fermentable xylose with more than 90% conversion.
Properties of the WSUCF1 β-xylosidase i.e. high tolerance to elevated temperatures, high specific activity, conversion of xylo-oligomers to xylose, and resistance to inhibition from xylose, make this enzyme potentially suitable for various biotechnological applications.
PMCID: PMC4300165  PMID: 25532585
Lignocellulose; Biofuels; β-xylosidase; Thermostable
8.  The local, global, and neural aspects of visuospatial processing in autism spectrum disorders 
Neuropsychologia  2013;51(14):2995-3003.
Behavioral studies have documented a relative advantage in some aspects of visuospatial cognition in autism although it is not consistently found in higher functioning individuals with autism. The purpose of this functional neuroimaging study was to examine the neural activity in high functioning individuals with autism while they performed a block design task that systematically varied with regard to whether a global pattern was present. Participants were 14 adults with high-functioning autism and 14 age and IQ matched typical controls. The task was to identify a missing block in target figures which had either an obvious global shape or was an arbitrary array of blocks. Behavioral results showed intact, but not superior, performance in our participants with autism. A key group difference was that the participants with autism showed reliably greater activation in occipital and parietal regions in both tasks suggesting an increased reliance of the autism group on posterior brain areas to mediate visuospatial tasks. Thus, increased reliance on relatively posterior brain regions in itself may not guarantee superior performance as seen in the present study.
PMCID: PMC3900283  PMID: 24184351
Autism; fMRI; global-local processing; block design task
10.  Primary intracranial Parachordoma: An unusual tumor in brain 
Surgical Neurology International  2014;5(Suppl 14):S506-S511.
Parachordomas are rare soft tissue tumors commonly occurring in limbs, chest, Abdomen, and back. The World Health Organization (WHO) classification includes parachordomas in the same group as mixed tumors and myoepitheliomas. Exact histogenesis of this tumor is unclear.
Case Description:
A 52-year-old male presented with headache and blurring of vision since one month. Preoperative computed tomography (CT) scan of brain revealed left parieto-occipital tumor extending up to the trigone. Total excision of the tumor was done. Histopathologically, the tumor was composed of relatively uniform cells with eosinophilic cytoplasm in a myxoid stroma and with cartilaginous and osseous metaplasia. The tumoral cells were immunoreactive for cytokeratin, epithelial membrane antigen (EMA), S-100, and vimentin. The constellation of findings revealed the tumor to be parachordoma. Magnetic resonance imaging (MRI) brain during follow-up at one year showed no recurrent tumor. No adjuvant therapy was given to this patient.
This is the first reported case of primary intracranial parachordoma. It is difficult to diagnose the lesion preoperatively by imaging alone. Long-term follow-up is necessary in view of few reports in literature of recurrence and metastasis, of parachordomas in other anatomical locations.
PMCID: PMC4258724  PMID: 25525557
Brain tumor; brain; intracranial parachordoma; parachordoma
11.  Hormone Suppression with GnRH Antagonist Promotes Spermatogenic Recovery from Transplanted Spermatogonial Stem Cells in Irradiated Cynomolgus Monkeys 
Andrology  2013;1(6):886-898.
Hormone suppression given before or after cytotoxic treatment stimulates recovery of spermatogenesis from endogenous and transplanted spermatogonial stem cells (SSC) and restores fertility in rodents. To test whether the combination of hormone suppression and transplantation could enhance the recovery of spermatogenesis in primates, we irradiated (7 Gy) the testes of 12 adult cynomolgus monkeys and treated 6 of them with GnRH-antagonist (GnRH-ant) for 8 weeks. At the end of this treatment, we transfected cryopreserved testicular cells with GFP-lentivirus and autologously transplanted them back into one of the testes. The only significant effect of GnRH-ant treatment on endogenous spermatogenesis was an increase in the percentage of tubules containing differentiated germ cells (tubule differentiation index; TDI) in the sham-transplanted testes of GnRH-ant-treated monkeys compared to radiation-only monkeys at 24 weeks after irradiation. Although transplantation alone after irradiation did not significantly increase the TDI, detection of lentiviral DNA in the sperm of one radiation-only monkey indicated that some transplanted cells colonized the testis. However, the combination of transplantation and GnRH-ant clearly stimulated spermatogenic recovery as evidenced by several observations in the GnRH-ant-treated monkeys receiving transplantation: (a) significant increases (~20%) in the volume and weight of the testes compared to the contralateral sham-transplanted testes and/or to the transplanted testes of the radiation-only monkeys; (b) increases in TDI compared to the transplanted testes of radiation-only monkeys at 24 weeks (9.6% vs. 2.9%; P=0.05) and 44 weeks (16.5% vs. 6.1%, P=0.055); (c) detection of lentiviral sequences in the sperm or testes of five of the GnRH-ant–treated monkeys; and (d) significantly higher sperm counts than in the radiation-only monkeys. Thus hormone suppression enhances spermatogenic recovery from transplanted SSC in primates and may be a useful tool in conjunction with spermatogonial transplantation to restore fertility in men after cancer treatment.
PMCID: PMC3889638  PMID: 24124124
Radiation; spermatogenesis; infertility; transplantation; GnRH-antagonist
12.  A role for Rab27 in neutrophil chemotaxis and lung recruitment 
BMC Cell Biology  2014;15(1):39.
Neutrophils are a critical part of the innate immune system. Their ability to migrate into infected or injured tissues precedes their role in microbial killing and clearance. We have previously shown that Rab27a can promote neutrophil migration by facilitating uropod release through protease secretion from primary granule exocytosis at the cell rear. Rab27b has been implicated in primary granule exocytosis but its role in neutrophil migration has not been investigated.
Here we found Rab27b to be expressed in bone marrow derived neutrophils and Rab27b knockout (Rab27b KO) along with Rab27a/b double knockout (Rab27DKO) neutrophils exhibited impaired transwell migration in vitro in response to chemokines MIP-2 and LTB4. Interestingly, no additional defect in migration was observed in Rab27DKO neutrophils compared with Rab27b KO neutrophils. In vivo, Rab27DKO mice displayed severe impairment in neutrophil recruitment to the lungs in a MIP-2 dependent model but not in an LPS dependent model.
These data taken together implicate Rab27b in the regulation of neutrophil chemotaxis, likely through the regulation of primary granule exocytosis.
PMCID: PMC4221698  PMID: 25359237
Rab27; Neutrophil; Chemotaxis; Exocytosis
13.  The role of mirroring and mentalizing networks in mediating action intentions in autism 
Molecular Autism  2014;5(1):50.
The ability to interpret agents’ intent from their actions is a vital skill in successful social interaction. However, individuals with autism spectrum disorders (ASD) have been found to have difficulty in attributing intentions to others. The present study investigated the neural mechanisms of inferring intentions from actions in individuals with ASD.
Functional magnetic resonance imaging (fMRI) data were acquired from 21 high-functioning young adults with ASD and 22 typically developing (TD) control participants, while making judgments about the means (how an action is performed) and intention (why an action is performed) of a model’s actions.
Across both groups of participants, the middle and superior temporal cortex, extending to temporoparietal junction, and posterior cingulate cortex, responded significantly to inferring the intent of an action, while inferior parietal lobule and occipital cortices were active for judgments about the means of an action. Participants with ASD had significantly reduced activation in calcarine sulcus and significantly increased activation in left inferior frontal gyrus, compared to TD peers, while attending to the intentions of actions. Also, ASD participants had weaker functional connectivity between frontal and posterior temporal regions while processing intentions.
These results suggest that processing actions and intentions may not be mutually exclusive, with reliance on mirroring and mentalizing mechanisms mediating action understanding. Overall, inferring information about others’ actions involves activation of the mirror neuron system and theory-of-mind regions, and this activation (and the synchrony between activated brain regions) appears altered in young adults with ASD.
PMCID: PMC4210608  PMID: 25352976
Action; Intention; Means; fMRI; Autism spectrum disorders; Mirror neuron system; Theory-of-mind
15.  Enhanced parietal cortex activation during location detection in children with autism 
Visuospatial processing has been found to be mediated primarily by two cortical routes, one of which is unique to recognizing objects (occipital-temporal, ventral or “what” pathway) and the other to detecting the location of objects in space (parietal-occipital, dorsal or “where” pathway). Considering previous findings of relative advantage in people with autism in visuospatial processing, this functional MRI study examined the connectivity in the dorsal and ventral pathways in high-functioning children with autism.
Seventeen high-functioning children and adolescents with autism spectrum disorders (ASD) and 19 age-and-IQ-matched typically developing (TD) participants took part in this study. A simple visual task involving object recognition and location detection was used. In the MRI scanner, participants were shown grey scale pictures of objects (e.g., toys, household items, etc.) and were asked to identify the objects presented or to specify the location of objects relative to a cross at the center of the screen.
Children with ASD, relative to TD children, displayed significantly greater activation in the left inferior parietal lobule (especially the angular gyrus) while detecting the location of objects. However, there were no group differences in brain activity during object recognition. There were also differences in functional connectivity, with the ASD participants showing decreased connectivity of the inferior temporal area with parietal and occipital areas during location detection.
The results of this study underscore previous findings of an increased reliance on visuospatial processing (increased parietal activation) for information processing in ASD individuals. In addition, such processing may be more local, focal, and detailed in ASD as evidenced from the weaker functional connectivity.
Electronic supplementary material
The online version of this article (doi:10.1186/1866-1955-6-37) contains supplementary material, which is available to authorized users.
PMCID: PMC4190580  PMID: 25302083
fMRI; Autism; Dorsal; Ventral; Visual system; Functional connectivity; Object recognition; Location detection
16.  The implications of brain connectivity in the neuropsychology of autism 
Neuropsychology review  2014;24(1):16-31.
Autism is a neurodevelopmental disorder that has been associated with atypical brain functioning. Functional connectivity MRI (fcMRI) studies examining neural networks in autism have seen an exponential rise over the last decade. Such investigations have led to characterization of autism as a distributed neural systems disorder. Studies have found widespread cortical underconnectivity, local overconnectivity, and mixed results suggesting disrupted brain connectivity as a potential neural signature of autism. In this review, we summarize the findings of previous fcMRI studies in autism with a detailed examination of their methodology, in order to better understand its potential and to delineate the pitfalls. We also address how a multimodal neuroimaging approach (incorporating different measures of brain connectivity) may help characterize the complex neurobiology of autism at a global level. Finally, we also address the potential of neuroimaging-based markers in assisting neuropsychological assessment of autism. The quest for a biomarker for autism is still ongoing, yet new findings suggest that aberrant brain connectivity may be a promising candidate.
PMCID: PMC4059500  PMID: 24496901
autism; fMRI; functional connectivity; underconnectivity; effective connectivity; white matter integrity
17.  Plasmin promotes foam cell formation by increasing macrophage catabolism of aggregated low density lipoprotein 
The plasmin/plasminogen system is involved in atherosclerosis. However, the mechanisms by which it stimulates disease are not fully defined. A key event in atherogenesis is the deposition of LDL on arterial walls where it is modified, aggregated and retained. Macrophages are recruited to clear the lipoproteins, and they become foam cells. The goal of this study was to assess the role of plasmin in macrophage uptake of aggregated LDL and foam cell formation.
Approach and Results
Plasminogen treatment of macrophages catabolizing aggregated LDL significantly accelerated foam cell formation. Macrophage interaction with aggregated LDL increased the surface expression of urokinase-type plasminogen activator receptor and plasminogen activator activity, resulting in increased ability to generate plasmin at the cell surface. The high local level of plasmin cleaves cell-associated aggregated LDL, allowing a portion of the aggregate to become sequestered in a nearly sealed, yet extracellular, acidic compartment. The low pH in the plasmin-induced compartment allows lysosomal enzymes, delivered via lysosome exocytosis, greater activity, resulting in more efficient cholesteryl ester hydrolysis and delivery of a large cholesterol load to the macrophage, thereby promoting foam cell formation.
These findings highlight a critical role for plasmin in the catabolism of aggregated LDL by macrophages and provide a new context for considering the atherogenic role of plasmin.
PMCID: PMC3716867  PMID: 23702659
Atherosclerosis; foam cell; plasmin; macrophage; aggregated low density lipoprotein
18.  Diagnostic Value of PCR in Genitourinary Tuberculosis 
Genitourinary tuberculosis is a disease of the genitourinary system which includes the entire urinary tract and reproductive system. Genital tuberculosis is an important cause of female infertility, especially in developing nations like India. In the present study, a total of 257 clinical specimens comprising of endometrial biopsy (109), endometrial curetting (42), menstrual blood (8), semen (17), placenta (11) and urine (70) were collected from patients and subjected for PCR, Culture and AFB detection. The endometrial biopsy, endometrial curetting, menstrual blood, semen, placenta, urine showed 30.2, 45.2,12.5, 5.8, 27.2, 31.4 %, positivity rate for tuberculosis by PCR, 7.3, 9.5, 25.0, 0, 9, 8.5 % by culture and 1.8, 2.3, 0, 0, 0, 2.8 % respectively by AFB smear. Being a novel, rapid technique, PCR is the method of choice for rapid diagnosis and management of genitourinary tuberculosis shared with the other concerned tests. This study reveals that genital tuberculosis can occur in any age group, however, the majority of patients were from reproductive age (nearly 75 % of them were from 20–45 years of age) group.
PMCID: PMC3689327  PMID: 24426229
Polymerase chain reaction; MPB64; Bactec 460; Genitourinary tuberculosis
20.  Peri-operative management of hysterostomy in a parturient with complete heart block, placenta accreta and intrauterine death 
BMC Anesthesiology  2014;14:49.
Complete heart block in pregnancy has serious implications particularly during the period of delivery. This is more so if the delivery is an operative one as the presence of heart block may produce haemodynamic instability in the intra operative period. We report a unique case of a pregnant mother with complete heart block undergoing hysterostomy, complicated by placenta accreta and intrauterine death.
Case presentation
A 37 year old Malaysian Chinese parturient was admitted at 25 weeks gestation following a scan which suggested intrauterine death and placenta accreta. She was diagnosed to have congenital complete heart block after her first delivery eight years previously but a pacemaker was never inserted. These medical conditions make her extremely likely to experience massive bleeding and haemodynamic instability. Among the measures taken to optimise her pre-operatively were the insertion of a temporary intravenous pacemaker and embolization of the uterine arteries to minimize peri-operative blood loss. She successfully underwent surgery under general anesthesia, which was relatively uneventful and was discharged well on the fourth post-operative day.
Congenital heart block in pregnancies in the presence of potential massive bleeding is best managed by a team, with meticulous pre-operative optimization. Suggested strategies would include insertion of a temporary pacemaker and embolization of the uterine arteries to reduce the risk of the patient getting into life threatening situations.
PMCID: PMC4083103  PMID: 25002831
Complete heart block; Pregnancy; Hysterostomy; Hysterectomy
21.  Bromfenac ophthalmic solution for the treatment of postoperative ocular pain and inflammation: safety, efficacy, and patient adherence 
Ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used by clinicians to manage ocular inflammation and pain following cataract surgery. Over the past decade, the US Food and Drug Administration has approved multiple topical NSAIDs for these purposes, including several reformulated products. One of these medications, bromfenac ophthalmic solution, has a long and extensive history, with proven efficacy and safety in patients following cataract surgery. The evolution of bromfenac ophthalmic solution over the years has involved either lowering the concentration of the active ingredient or extending the dosing interval to improve patient adherence/compliance. This review will focus on the history and progression of bromfenac ophthalmic solution and report the available patient preference and adherence data regarding this ocular NSAID throughout its evolution.
PMCID: PMC4077855  PMID: 25028541
cataract surgery; nonsteroidal anti-inflammatory drugs; COX inhibitors
22.  Advances in Monitoring and Management of Shock 
Shock continues to be the proximate cause of death for many childhood diseases and imposes a significant burden. Early recognition and treatment of pediatric shock, regardless of etiology, decreases mortality and improves outcome. In addition to the conventional parameters (e.g., heart rate (HR), systolic blood pressure (SBP), urine output (UOP), and central venous pressure (CVP)), biomarkers and non-invasive methods of measuring cardiac output are now available to monitor and treat shock. In this article, we emphasize how fluid resuscitation is the cornerstone of shock resuscitation although the choice and amount of fluid may vary based on the etiology of shock. Other emerging treatments for shock i.e., temperature control, extracorporeal membrane oxygenation (ECMO)/Ventricular Assist Devices (VAD) are also discussed briefly in this article.
PMCID: PMC3644114  PMID: 23639660
Pediatric sepsis; septic shock; Cardiac output monitoring
24.  Role of Dried Fruits of Carissa carandas as Anti-Inflammatory Agents and the Analysis of Phytochemical Constituents by GC-MS 
BioMed Research International  2014;2014:512369.
Inflammation plays an important role in various diseases with high prevalence within populations such as rheumatoid arthritis, ulcer, atherosclerosis, and asthma. Many drugs are available in the market for inflammatory diseases. They exhibit several unwanted side effects to humans. Therefore, alternative treatments with safer compounds are needed. Carissa carandas plant is used in traditional medicinal system for its various diseases curing property. In the present study, we examined the anti-inflammatory effects of dried fruit methanol extract on carrageenan-induced hind paw edema in rats. C. carandas was defatted with petroleum ether, followed by methanol extraction. The methanol extracts of the dried fruits of Carissa carandas were given orally to the experimental rats caused significant activity (P ≤ 0.05) when compared with the control group. The maximum inhibition of paw edema was found to be in Group V, that is, 76.12% with inhibition of paw volume in a dose-dependent manner. The anti-inflammatory activity of the methanol extract of the dried fruits shows that the presence of potential constituents present in this extract may provide assistance in the drug discovery process. The phytochemical compounds of the extract were screened by GC-MS analysis and it was found that 11 compounds are present in methanol extract of dried fruits of Carissa carandas.
PMCID: PMC4022248  PMID: 24877106
25.  An fMRI Investigation of Working Memory and its Relationship with Cardiorespiratory Fitness in Pediatric Posterior Fossa Tumor Survivors who received Cranial Radiation Therapy 
Pediatric blood & cancer  2012;60(4):669-675.
The present study investigated the relationship between cardiorespiratory fitness and executive functioning in pediatric brain tumor survivors who received cranial radiation. This population is known to show executive dysfunction and lower rates of aerobic exercise compared to peers.
Nine adolescent survivors of pediatric posterior fossa tumor completed an n-back working memory task during a functional MRI scan, as well as cardiorespiratory fitness testing on a cycle ergometer.
Neuroimaging findings indicated typical activation patterns associated with working memory, mainly in the frontal-parietal network. Higher cardiorespiratory fitness was related to better performance on a behavioral measure of working memory and more efficient neural functioning.
This study provides preliminary evidence that cardiorespiratory fitness may be related to executive functioning, particularly working memory, in pediatric brain tumor survivors. Descriptions of the brain regions recruited for working memory by pediatric brain tumor survivors may be used to inform future interventions or indicators of treatment efficacy.
PMCID: PMC3541446  PMID: 23042746
Brain Neoplasms; Neuropsychology; Executive Function; Physical Fitness; Magnetic Resonance Imaging

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