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1.  Keeping Cool in the Operating Room 
PMCID: PMC4251350  PMID: 25593543
2.  Multimodality imaging of renal inflammatory lesions 
World Journal of Radiology  2014;6(11):865-873.
Spectrum of acute renal infections includes acute pyelonephritis, renal and perirenal abscesses, pyonephrosis, emphysematous pyelonephritis and emphysematous cystitis. The chronic renal infections that we routinely encounter encompass chronic pyelonephritis, xanthogranulomatous pyelonephritis, and eosinophilic cystitis. Patients with diabetes, malignancy and leukaemia are frequently immunocompromised and more prone to fungal infections viz. angioinvasive aspergillus, candida and mucor. Tuberculosis and parasitic infestation of the kidney is common in tropical countries. Imaging is not routinely indicated in uncomplicated renal infections as clinical findings and laboratory data are generally sufficient for making a diagnosis. However, imaging plays a crucial role under specific situations like immunocompromised patients, treatment non-responders, equivocal clinical diagnosis, congenital anomaly evaluation, transplant imaging and for evaluating extent of disease. We aim to review in this article the varied imaging spectrum of renal inflammatory lesions.
PMCID: PMC4241493  PMID: 25431641
Imaging modalities; Renal infection; Cystitis; Pyelonephritis; Pyonephrosis; Xanthogranulomatous; Magnetic resonance imaging
3.  Effect of Peer Counselling by Mother Support Groups on Infant and Young Child Feeding Practices: The Lalitpur Experience 
PLoS ONE  2014;9(11):e109181.
Our primary objective was to evaluate the effect of peer counselling by mother support groups (MSG's) in improving the infant and young child feeding (IYCF) practices in the community.
We conducted this repeated-measure before and after study in the Lalitpur district of Uttar Pradesh, India between 2006 and 2011. We assessed the IYCF practices before and after creating MSG's within the community. The feeding practices were reassessed at two time points–2 (T1) and 5 years (T2) after the intervention and compared with that of the pre-intervention phase (T0).
The total population covered by the project from the time of its initiation was 105000. A total of 425 (T0), 480 (T1) and 521 (T2) mother infant pairs were selected from this population. There was significant improvement in the following IYCF practices in the community (represented as %; adjOR (95% CI, p) such as initiation of breast feeding within 1 hour at both T1 (71% vs. 11%); 19.6 (13.6, 28.2, p = <0.0001)and T2 (62% vs. 11%); 13.3 (9.4, 18.9, p = <0.0001); use of prelacteal feeds at both T1 (67% vs. 15%); 12.6 (CI: 9.0, 17.6, p<0.0001) and T2 (67% vs. 5%); 44.4 (28.8, 68.4, p = <0.0001); rates of exclusive breast feeding for 6 months at both T1 (50% vs. 7%); 13.6 (7.6, 25.0, p = <0.0001) and T2 (60% vs. 7%); 20.5 (11.3, 37.2, p = <0.0001); initiation of complementary feeding at T1 (85% vs. 54%); 5.6 (3.6, 8.7, p = <0.0001) and T2 (96% vs. 54%); 22.9 (11.8, 44.1, p = <0.0001) and complementary feeding along with continued breast feeding at both T1 (36% vs. 4.5%); 6 (1.15, 31.4, p = 0.033) and T2 (42% vs. 4.5%); 8.06 (1.96, 49.1, p = 0.005) as compared to pre-intervention period (T0) after adjusting for important social and demographic variables.
Peer counseling by MSG's improved the IYCF practices in the district and could be sustained.
PMCID: PMC4219670  PMID: 25369452
4.  Skeletal dysplasias: A radiographic approach and review of common non-lethal skeletal dysplasias 
World Journal of Radiology  2014;6(10):808-825.
Skeletal dysplasias are not uncommon entities and a radiologist is likely to encounter a suspected case of dysplasia in his practice. The correct and early diagnosis of dysplasia is important for management of complications and for future genetic counselling. While there is an exhaustive classification system on dysplasias, it is important to be familiar with the radiological features of common dysplasias. In this article, we enumerate a radiographic approach to skeletal dysplasias, describe the essential as well as differentiating features of common non-lethal skeletal dysplasias and conclude by presenting working algorithms to either definitively diagnose a particular dysplasia or suggest the most likely differential diagnoses to the referring clinician and thus direct further workup of the patient.
PMCID: PMC4209426  PMID: 25349664
Skeletal dysplasia; Short limb dwarfism; Rhizomelia; Radiograph; Skeletal survey; Review; Spondylopepiphyseal dysplasia; Multiple epiphyseal dysplasia; Achondroplasia; Algorithm; Approach
5.  Biomedical waste disposal: A systems analysis 
In view of the contemporary relevance of BMW Management, a system analysis of BMW management was conducted to ascertain the views of Service hospitals/HCE's on the current system in BMW management in-vogue; to know the composition and quantity of waste generated; to get information on equipment held & equipment required and to explore the possibility of outsourcing, its relevance and feasibility.
A qualitative study in which various stake holders in BMW management were studied using both primary (Observation, In-depth Interview of Key Personnel, Group Discussions: and user perspective survey) and secondary data.
All the stake holders were of the opinion that where ever possible outsourcing should be explored as a viable method of BMW disposal. Waste generated in Colour code Yellow (Cat 1,2,3,5,6) ranged from 64.25 to 27.345 g/day/bed; in Colour code Red (Cat 7) from 19.37 to 10.97 g/day/bed and in Colour code Blue (Cat 4) from 3.295 to 3.82 g/day/bed in type 1 hospitals to type 5 hospitals respectively.
Outsourcing should be explored as a viable method of BMW disposal, were there are government approved local agencies. Facilities authorized by the Prescribed Authority should be continued and maintained where outsourcing is not feasible.
PMCID: PMC3862903  PMID: 24600142
Biomedical waste; Systems analysis; Qualitative study
6.  MRI in central nervous system infections: A simplified patterned approach 
World Journal of Radiology  2014;6(9):716-725.
Recognition and characterization of central nervous system infections poses a formidable challenge to the neuro-radiologist. Imaging plays a vital role, the lesions typically being relatively inaccessible to tisue sampling. The results of an accurate diagnosis are endlessly rewarding, given the availability of excellent pharmacological regimen. The availability of numerous magnetic resonance (MR) sequences which provide functional and molecular information is a powerful tool in the hands of the radiologist. However, the plethora of sequences and the possibilities on each sequence is also intimidating, and often confusing as well as time consuming. While a large number of reviews have already described in detail the possible imaging findings in each infection, we intend to classify infections based on their imaging characteristics. In this review we describe an algorithm for first classifying the imaging findings into patterns based on basic MR sequences (T1, T2 and enhancement pattern with Gadolinium), and then sub-classify them based on more advanced molecular and functional sequences (Diffusion, Perfusion, Susceptibility imaging, MR Spectroscopy). This patterned approach is intended as a guide to radiologists in-training and in-practice for quickly narrowing their list of differentials when faced with a clinical challenge. The entire content of the article has also been summarised in the form of flow-charts for the purpose of quick reference.
PMCID: PMC4176788  PMID: 25276314
Central nervous system; Infection; Magnetic resonance imaging; Magnetic resonance spectroscopy; Perfusion weighted magnetic resonance imaging; Diffusion weighted magnetic resonance imaging
7.  Does PTEN Loss Impair DNA Double-Strand Break Repair by Homologous Recombination? 
The tumor suppressor PTEN is frequently lost in cancer cells, resulting in altered radiation and drug sensitivity. However, the role of PTEN in DNA repair is controversial. Detailed studies in prostate cancer cells now indicate PTEN does not regulate RAD51 expression or homologous recombination and is not a biomarker for PARP inhibitor sensitivity.
PMCID: PMC4151559  PMID: 22179663
8.  Role of 53BP1 in the Regulation of DNA Double-Strand Break Repair Pathway Choice 
Radiation research  2013;181(1):1-8.
The p53-binding protein 1 (53BP1) is a well-known DNA damage response (DDR) factor, which is recruited to nuclear structures at the site of DNA damage and forms readily visualized ionizing radiation (IR) induced foci. Depletion of 53BP1 results in cell cycle arrest in G2/M phase as well as genomic instability in human as well as mouse cells. Within the DNA damage response mechanism, 53BP1 is classified as an adaptor/mediator, required for processing of the DNA damage response signal and as a platform for recruitment of other repair factors. More recently, specific 53BP1 contributions to DSB repair pathway choice have been recognized and are being characterized. In this review, we have summarized recent advances in understanding the role of 53BP1 in regulating DNA DSBs repair pathway choice, variable diversity joining [V(D)J] recombination and class-switch recombination (CSR).
PMCID: PMC4133096  PMID: 24320053
9.  METRIC (MREnterography or ulTRasound in Crohn’s disease): a study protocol for a multicentre, non-randomised, single-arm, prospective comparison study of magnetic resonance enterography and small bowel ultrasound compared to a reference standard in those aged 16 and over 
BMC Gastroenterology  2014;14:142.
Crohn’s disease (CD) is a lifelong, relapsing and remitting inflammatory condition of the intestine. Medical imaging is crucial for diagnosis, phenotyping, activity assessment and detecting complications. Diverse small bowel imaging tests are available but a standard algorithm for deployment is lacking. Many hospitals employ tests that impart ionising radiation, of particular concern to this young patient population. Magnetic resonance enterography (MRE) and small bowel ultrasound (USS) are attractive options, as they do not use ionising radiation. However, their comparative diagnostic accuracy has not been compared in large head to head trials. METRIC aims to compare the diagnostic efficacy, therapeutic impact and cost effectiveness of MRE and USS in newly diagnosed and relapsing CD.
METRIC (ISRCTN03982913) is a multicentre, non-randomised, single-arm, prospective comparison study. Two patient cohorts will be recruited; those newly diagnosed with CD, and those with suspected relapse. Both will undergo MRE and USS in addition to other imaging tests performed as part of clinical care. Strict blinding protocols will be enforced for those interpreting MRE and USS. The Harvey Bradshaw index, C-reactive protein and faecal calprotectin will be collected at recruitment and 3 months, and patient experience will be assessed via questionnaires. A multidisciplinary consensus panel will assess all available clinical and imaging data up to 6 months after recruitment of each patient and will define the standard of reference for the presence, localisation and activity of disease against which the diagnostic accuracy of MRE and USS will be judged. Diagnostic impact of MRE and USS will be evaluated and cost effectiveness will be assessed. The primary outcome measure is the difference in per patient sensitivity between MRE and USS for the correct identification and localisation of small bowel CD.
The trial is open at 5 centres with 46 patients recruited. We highlight the importance of stringent blinding protocols in order to delineate the true diagnostic accuracy of both imaging tests and discuss the difficulties of diagnostic accuracy studies in the absence of a single standard of reference, describing our approach utilising a consensus panel whilst minimising incorporation bias.
Trial registration
METRIC - ISRCTN03982913 – 05.11.13.
PMCID: PMC4134460  PMID: 25110044
Crohn’s disease; Inflammatory bowel disease; MRE; USS; Consensus panel
10.  Developing a dancer wellness program employing developmental evaluation 
Wellness programs are being increasingly employed with performing artists. Given their aim of reducing injuries, injury tracking is commonly employed as an outcome measure. Evaluating the development and process of a wellness program can also enhance its effectiveness. Developmental evaluation offers one methodological framework within which to conduct such investigations. This paper reports on a 2-year process involving feedback from professional ballet dancers, management and artistic staff, and healthcare providers at a ballet company in order to develop a dancer screening and wellness program. Following a consultation phase, an initial program composed of an expanded medical team and annual injury prevention screen was proposed. Alongside implementation with 30 professional ballet dancers, formal and informal feedback was sought from stakeholders and members across all levels of the ballet company to facilitate ongoing development, evaluation, and revision of the wellness program. The use of a process informed by developmental evaluation helped identify strengths and limitations within the screening process. The collective expertise of the assessors was used to modify the components and process of the screen to strive for ecological appropriateness. The process also fostered buy-in from all involved. Participant feedback helped refine the medical team available to the dancers and influenced the treatment and referral pathways via which dancers are able to access each member of the medical team. Furthermore, reflective discussions with artistic and management staff brought to light potential interactions between repertoire programming, fitness, and injury patterns. This prompted a reconsideration of how artists are trained and supported. Evaluation methods that focus on experiences and insight gained during program development stand to result in more efficient screening programs and health-promotion models and, ultimately, healthier performing artists.
PMCID: PMC4090754  PMID: 25071689
performing artists; wellness programs; developmental evaluation; screening; health
11.  Hippocampal volumetry: Normative data in the Indian population 
Mesial temporal sclerosis (MTS) is the most common cause of temporal lobe epilepsy. Quantitative analysis of the hippocampus using volumetry is commonly being used in the diagnosis of MTS and is being used as a marker in prognostication of seizure control. Although normative data for hippocampal volume (HV) is available for the western population, no such data is available for the Indian population.
The aim of the study was to establish normative data for HV for the Indian population, which can aid in the accurate diagnosis of MTS.
Materials and Methods:
Magnetic resonance imaging (MRI) scans of 200 healthy volunteers were acquired using a 3 Tesla (3T) MRI scanner. Manual segmentation and volumetry was done using Siemens Syngo software. The data was analyzed using two tailed t-test to detect associations between HV and age, gender, and education. The data so obtained was also correlated with the data available from the rest of the world.
A mean HV of 2.411 cm3 (standard deviation -0.299) was found in the study, which was significantly smaller when compared to the data from the western population. The right hippocampus was larger than the left, with a mean volume of 2.424 cm3 and 2.398 cm3, respectively. HV was detected to be significantly higher in males. No association was found between HV and age and education.
The values obtained in this study may be adopted as a standard in the evaluation of patients with intractable epilepsy.
PMCID: PMC4162010  PMID: 25221393
Manual hippocampal volumetry; manual hippocampal segmentation; mesial temporal sclerosis; normative data
12.  T-cell-specific deletion of Mof blocks their differentiation and results in genomic instability in mice 
Mutagenesis  2013;28(3):263-270.
Ataxia telangiectasia patients develop lymphoid malignancies of both B- and T-cell origin. Similarly, ataxia telangiectasia mutated (Atm)-deficient mice exhibit severe defects in T-cell maturation and eventually develop thymomas. The function of ATM is known to be influenced by the mammalian orthologue of the Drosophila MOF (males absent on the first) gene. Here, we report the effect of T-cell-specific ablation of the mouse Mof (Mof) gene on leucocyte trafficking and survival. Conditional Mof Flox/Flox (Mof F/F) mice expressing Cre recombinase under control of the T-cell-specific Lck proximal promoter (Mof F/F/Lck-Cre +) display a marked reduction in thymus size compared with Mof F/F/Lck-Cre – mice. In contrast, the spleen size of Mof F/F/Lck-Cre + mice was increased compared with control Mof F/F/Lck-Cre – mice. The thymus of Mof F/F/Lck-Cre + mice contained significantly reduced T cells, whereas thymic B cells were elevated. Within the T-cell population, CD4+CD8+ double-positive T-cell levels were reduced, whereas the immature CD4–CD8– double-negative (DN) population was elevated. Defective T-cell differentiation is also evident as an increased DN3 (CD44–CD25+) population, the cell stage during which T-cell receptor rearrangement takes place. The differentiation defect in T cells and reduced thymus size were not rescued in a p53-deficient background. Splenic B-cell distributions were similar between Mof F/F/Lck-Cre + and Mof F/F/Lck-Cre – mice except for an elevation of the κ light-chain population, suggestive of an abnormal clonal expansion. T cells from Mof F/F/Lck-Cre + mice did not respond to phytohaemagglutinin (PHA) stimulation, whereas LPS-stimulated B cells from Mof F/F/Lck-Cre + mice demonstrated spontaneous genomic instability. Mice with T-cell-specific loss of MOF had shorter lifespans and decreased survival following irradiation than did Mof F/F/Lck-Cre – mice. These observations suggest that Mof plays a critical role in T-cell differentiation and that depletion of Mof in T cells reduces T-cell numbers and, by an undefined mechanism, induces genomic instability in B cells through bystander mechanism. As a result, these mice have a shorter lifespan and reduced survival after irradiation.
PMCID: PMC3630520  PMID: 23386701
13.  Extracellular brain pH with or without hypoxia is a marker of profound metabolic derangement and increased mortality after traumatic brain injury 
Cerebral hypoxia and acidosis can follow traumatic brain injury (TBI) and are associated with increased mortality. This study aimed to evaluate a relationship between reduced pHbt and disturbances of cerebral metabolism. Prospective data from 56 patients with TBI, receiving microdialysis and Neurotrend monitoring, were analyzed. Four tissue states were defined based on pHbt and PbtO2: 1—low PbtO2/pHbt, 2—low pHbt/normal PbtO2, 3—normal pHbt/low PbtO2, and 4—normal pHbt/PbtO2). Microdialysis values were compared between the groups. The relationship between PbtO2 and lactate/pyruvate (LP) ratio was evaluated at different pHbt levels. Proportional contribution of each state was evaluated against mortality. As compared with the state 4, the state 3 was not different, the state 2 exhibited higher levels of lactate, LP, and glucose and the state 1—higher LP and reduced glucose (P<0.001). A significant negative correlation between LP and PbtO2 (rho=−0.159, P<0.001) was stronger at low pHbt (rho=−0.201, P<0.001) and nonsignificant at normal pHbt (P=0.993). The state 2 was a significant discriminator of mortality categories (P=0.031). Decreased pHbt is associated with impaired metabolism. Measuring pHbt with PbtO2 is a more robust way of detecting metabolic derangements.
PMCID: PMC3587815  PMID: 23232949
brain ischemia; brain trauma; energy metabolism; microdialysis; neurocritial care; pH
15.  Outcome of Surgery for Benign Prostatic Hyperplasia-Is It Predictable? 
Aim: The study was done to evaluate the pre-operative and intra operative factors which influence the post-operative outcome in patients undergoing surgery for Benign Prostatic Hyperplasia (BPH).
Setting and Design: It was carried out prospectively at a university college hospital in northern India.
Material & Methods: The study was carried out prospectively in 31 patients who underwent surgery for BPH (TURP – 50, Open Prostatectomy – 10).
Various pre-operative and intra-operative parameters were studied by means of a detailed history and examination, IPS score, urodynamic evaluation & cystoscopic examination. Their effect on post-operative outcome was evaluated by measuring changes in IPSS, maximum and average flow rates, and fall in PSA values.
Statistical Analysis: Repeated measure ANNOVA was applied to calculate the significance of preoperative factors on post operative outcome (IPSS, Q max and Q av).
Results: All parameters studied in the patients improved significantly following surgery.
Patients who had pre-operative urinary retention and catheter at the time of surgery had significant improvement in both subjective (IPSS ,p=.oo4) and objective (maximum & average flow rates p=.04) parameters studied. Patients with larger prostrate had a significantly better maximum flow rate (p=.03) and IPSS at 3 months post-operatively. Similarly, patients with larger bladder capacity (more than 150 ml), better compliance (more than 6 ml per cm of water) and lower post-voidal residue (less than 60ml) had better post-operative outcome.
Conclusion: Patients with pre-operative urinary retention, shorter duration of bladder catheterization, lower post voidal residue, high IPSS score, larger prostrate, larger bladder capacity and compliance had a significantly better outcome following surgery for BPH as assessed by various parameters studied.
PMCID: PMC3919415  PMID: 24551658
International prostate symptom score; Benign Prostatic Hyperplasia; Transurethral resection of prostate
16.  Malignant rhabdoid tumor of liver 
Malignant rhabdoid tumor (MRT) is a rare, but aggressive tumor commonly arising from the kidney in young children. Extrarenal MRT has been reported in the literature in various other sites including the liver, pelvis, CNS, abdomen, heart and other soft-tissues. Reported herein are the presentation, radiology, histopathology, immunohistochemistry, treatment and outcome of a 6 month infant with primary MRT of liver.
PMCID: PMC3935299  PMID: 24604983
Children; liver; malignant rhabdoid tumor
17.  Pediatric vs adult pulmonary tuberculosis: A retrospective computed tomography study 
AIM: To compare the manifestations of chest tuberculosis (TB) in pediatric and adult patients based on contrast enhanced computed tomography of chest.
METHODS: This was a retrospective study consisting of 152 patients of chest TB including 48 children and 104 adults who had undergone contrast enhanced computed tomography of chest prior to treatment. The patterns and severity of parenchymal, mediastinal and pleural manifestations were analyzed and compared among different age groups.
RESULTS: Parenchymal changes observed include consolidation, air space nodules, miliary TB, cavitation, bronchiectasis and fibrosis and these were noted in 60% of children, 71% of adolescents and 76.9% of adults. These changes were more common in right upper lobe in all age groups. There was no significant difference in the frequency of these changes (except nodules) in different age groups. Centrilobular nodules were seen less commonly in children less than 10 years (P = 0.028). Pleural effusion was noted in 28 (18.42%) patients and pericardial effusion in 8 (5.3%) patients. No significant difference in the serosal involvement is seen among children and adults. Mediastinal adenopathy was seen 70% of children, 76.3% adolescents and 76.9% of adults and paratracheal nodes were seen most frequently. Nodes had similar features (except matting) among all age groups. Matting of nodes was seen more commonly in children (P = 0.014).
CONCLUSION: Pediatric chest tuberculosis can have severe parenchymal lesions and nodal involvement similar to adults. The destructive lung changes observed in children needs immediate attention in view of the longer life span they have and hence in formulating optimal treatment strategies.
PMCID: PMC4145651  PMID: 25254177
Tuberculosis; Pulmonary; Primary tuberculosis; Children; Computed tomography
18.  The Value of Magnetic Resonance Cholangio-Pancreatography (MRCP) in the Detection of Choledocholithiasis 
Introduction: Magnetic Resonance Cholangio-Pancreatography (MRCP) is a non-invasive radiological investigation which can be performed rapidly and which does not expose the patients to ionised radiations or iodinated contrast material. The present study was conducted to evaluate the role of MRCP in detection of Common Bile Duct (CBD) stones in patients with suspected choledocholithiasis.
Material and Methods: This prospective study included 30 patients with a suspicion of choledocholithiasis which was based on clinical evaluation, biochemical or radiological investigations. Ultrasonography and MRCP were performed in all patients. All patients underwent open surgery. CBD exploration was performed in all patients, either due to presence of palpable stones or due to the presence of dilated CBD (> 7 mm). Demonstration of CBD stones intra-operatively was considered the ‘gold standard’ for their presence, defined as stones visualised and extracted or attempted for extraction during surgical CBD exploration.
Results: Intra–operatively, 21 (70%) out of 30 patients had cholelithiasis. 26 (86.67%) out of 30 patients had dilated CBD stones intra-operatively. In 20 (66.67%) out of 30 patients, choledocholithiasis was detected intra-operatively. The sensitivity, specificity, positive and negative predictive value of ultrasonography in detecting CBD stones in the present study was 65%, 60%, 76.47% and 46.15% respectively. The sensitivity, specificity, positive and negative predictive value of MRCP in diagnosis of CBD stones in the present study was 95%, 90%, 95% and 90% respectively.
Conclusions: MRCP is a non–invasive investigation without complications and it has high sensitivity, specificity and positive and negative predictive values in detection of CBD stones. MRCP should be done in all cases with a suspicion of CBD stones, where facilities and expertise are available.
PMCID: PMC3809643  PMID: 24179904
Choledocholithiasis; MRCP; ERCP
19.  Percutaneous transhepatic portal vein stenting in a patient with benign non-transplant postoperative portal vein stenosis: A case report 
Extrahepatic portal vein stenosis is caused by a variety of benign and malignant diseases and results in development of symptoms due to portal hypertension. Benign post-surgical adhesions causing portal vein stenosis in non-transplant population is an uncommon etiology of portal hypertension. Endovascular treatment of such patients with angioplasty and stenting is uncommonly reported in literature. We report a case of portal hypertension caused by benign postoperative portal vein fibrosis, successfully treated by self-expandable metallic stent.
PMCID: PMC3932579  PMID: 24604941
Portal hypertension; portal vein stenosis; portal vein stenting
20.  Lamin A/C Depletion Enhances DNA Damage-Induced Stalled Replication Fork Arrest 
Molecular and Cellular Biology  2013;33(6):1210-1222.
The human LMNA gene encodes the essential nuclear envelope proteins lamin A and C (lamin A/C). Mutations in LMNA result in altered nuclear morphology, but how this impacts the mechanisms that maintain genomic stability is unclear. Here, we report that lamin A/C-deficient cells have a normal response to ionizing radiation but are sensitive to agents that cause interstrand cross-links (ICLs) or replication stress. In response to treatment with ICL agents (cisplatin, camptothecin, and mitomycin), lamin A/C-deficient cells displayed normal γ-H2AX focus formation but a higher frequency of cells with delayed γ-H2AX removal, decreased recruitment of the FANCD2 repair factor, and a higher frequency of chromosome aberrations. Similarly, following hydroxyurea-induced replication stress, lamin A/C-deficient cells had an increased frequency of cells with delayed disappearance of γ-H2AX foci and defective repair factor recruitment (Mre11, CtIP, Rad51, RPA, and FANCD2). Replicative stress also resulted in a higher frequency of chromosomal aberrations as well as defective replication restart. Taken together, the data can be interpreted to suggest that lamin A/C has a role in the restart of stalled replication forks, a prerequisite for initiation of DNA damage repair by the homologous recombination pathway, which is intact in lamin A/C-deficient cells. We propose that lamin A/C is required for maintaining genomic stability following replication fork stalling, induced by either ICL damage or replicative stress, in order to facilitate fork regression prior to DNA damage repair.
PMCID: PMC3592031  PMID: 23319047
21.  Aortoesophageal fistula in a child 
Aortoesophageal fistulae (AEF) are rare and are associated with very high mortality. Foreign body ingestions remain the commonest cause of AEF seen in children. However in a clinical setting of tuberculosis and massive upper GI bleed, an AEF secondary to tuberculosis should be kept in mind. An early strong clinical suspicion with good quality imaging and endoscopic evaluation and timely aggressive surgical intervention helps offer the best possible management for this life threatening disorder. Our case is a 10-year-old boy who presented to the pediatric emergency with massive bouts of haemetemesis and was investigated and managed by multidisciplinary team effort in the emergency setting.
PMCID: PMC3760313  PMID: 24019646
Aorto-esophageal fistula; children; tuberculosis
22.  SHIFT: Server for hidden stops analysis in frame-shifted translation 
BMC Research Notes  2013;6:68.
Frameshift is one of the three classes of recoding. Frame-shifts lead to waste of energy, resources and activity of the biosynthetic machinery. In addition, some peptides synthesized after frame-shifts are probably cytotoxic which serve as plausible cause for innumerable number of diseases and disorders such as muscular dystrophies, lysosomal storage disorders, and cancer. Hidden stop codons occur naturally in coding sequences among all organisms. These codons are associated with the early termination of translation for incorrect reading frame selection and help to reduce the metabolic cost related to the frameshift events. Researchers have identified several consequences of hidden stop codons and their association with myriad disorders. However the wealth of information available is speckled and not effortlessly acquiescent to data-mining. To reduce this gap, this work describes an algorithmic web based tool to study hidden stops in frameshifted translation for all the lineages through respective genetic code systems.
This paper describes SHIFT, an algorithmic web application tool that provides a user-friendly interface for identifying and analyzing hidden stops in frameshifted translation of genomic sequences for all available genetic code systems. We have calculated the correlation between codon usage frequencies and the plausible contribution of codons towards hidden stops in an off-frame context. Markovian chains of various order have been used to model hidden stops in frameshifted peptides and their evolutionary association with naturally occurring hidden stops. In order to obtain reliable and persuasive estimates for the naturally occurring and predicted hidden stops statistical measures have been implemented.
This paper presented SHIFT, an algorithmic tool that allows user-friendly exploration, analysis, and visualization of hidden stop codons in frameshifted translations. It is expected that this web based tool would serve as a useful complement for analyzing hidden stop codons in all available genetic code systems. SHIFT is freely available for academic and research purpose at
PMCID: PMC3598200  PMID: 23432998
Frameshift; Reading frames; Hidden stop codons; Codon usage
23.  Crossed fused renal ectopia: Challenges in diagnosis and management 
Crossed fused renal ectopia is a rare congenital malformation, which is reported to be usually asymptomatic but may have varied presentations. This survey was conducted to study the clinical profile and the challenges posed in the management of this entity.
Materials and Methods:
Retrospective analysis of 6 patients diagnosed to have crossed fused renal ectopia during 1997-2010. The diagnosis was confirmed during surgical exploration in one patient. In one patient it was detected on antenatal ultrasonography and in the other 4 patients it was detected during investigations for abdominal pain, abdominal mass, anorectal malformation and urinary tract infection.
The left moiety was crossed and fused with the right moiety in 4 cases. Ultrasonography was found to be a good screening investigation with useful diagnostic contributions from CT scans, radionuclide scintigraphy and magnetic resonance urography. Micturating cystourethrography revealed presence of VUR in 4 cases, 3 of whom have undergone ureteric reimplantation. Two patients required pyeloplasty for pelviureteric junction obstruction; in one of these patients the upper ureter was entrapped in the isthmus. In one patient, a non-functioning moiety resulted in nephrectomy. All children were asymptomatic at last follow-up with stable renal functions.
Crossed fused renal ectopia was detected in most patients during investigation for other problems. It was found more commonly in boys. The left moiety was crossed to the right in the majority of cases. Associated urological problems were found in most cases and required the appropriate surgical management.
PMCID: PMC3628252  PMID: 23599575
Congenital anomalies of kidney; crossed fused renal ectopia; fusion anomalies of kidney
24.  Interaction between Brain Chemistry and Physiology after Traumatic Brain Injury: Impact of Autoregulation and Microdialysis Catheter Location 
Journal of Neurotrauma  2011;28(6):849-860.
Bedside monitoring of cerebral metabolism in traumatic brain injury (TBI) with microdialysis is gaining wider clinical acceptance. The objective of this study was to examine the relationship between the fundamental physiological neuromonitoring modalities intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygen (PbtO2), and cerebrovascular pressure reactivity index (PRx), and cerebral chemistry assessed with microdialysis, with particular focus on the lactate/pyruvate (LP) ratio as a marker of energy metabolism. Prospectively collected observational neuromonitoring data from 97 patients with TBI, requiring neurointensive care management and invasive cerebral monitoring, were analyzed. A linear mixed model analysis was used to account for individual patient differences. Perilesional tissue chemistry exhibited a significant independent relationship with ICP, PbtO2 and CPP thresholds, with increasing LP ratio in response to decrease in PbtO2 and CPP, and increase in ICP. The relationship between CPP and chemistry depended upon the state of PRx. Within the studied physiological range, tissue chemistry only changed in response to increasing ICP or drop in PbtO2<1.33 kPa (10 mmHg). In agreement with previous studies, significantly higher levels of cerebral lactate (p<0.001), glycerol (p=0.013), LP ratio (p<0.001) and lactate/glucose (LG) ratio (p=0.003) were found in perilesional tissue, compared to “normal” brain tissue (Mann-Whitney test). These differences remained significant following adjustment for the influences of other important physiological parameters (ICP, CPP, PbtO2, PbtCO2, PRx, and brain temperature; mixed linear model), suggesting that they may reflect inherent tissue properties related to the initial injury. Despite inherent biochemical differences between less-injured brain and “perilesional” cerebral tissue, both tissue types exhibited relationships between established physiological variables and biochemistry. Decreases in perfusion and oxygenation were associated with deteriorating neurochemistry and these effects were more pronounced in perilesional tissue and when cerebrovascular reactivity was impaired.
PMCID: PMC3113421  PMID: 21488707
autoregulation; brain injury; CPP; ICP; microdialysis
25.  Incontinence and mood disorder: is there an association? 
BMJ Case Reports  2010;2010:bcr07.2009.2118.
A variety of psychiatric disorders including depression have been reported in patients suffering from incontinence. It is uncertain if the association between incontinence and depression is causal or is related to a third common factor. We report the case of a 48-year-old man who presented with incontinence of urine and faeces along with a severe depressive episode. No organic cause could be identified for the incontinence. The depressive symptoms as well as the incontinence resolved with treatment with reboxetine and aripiprazole. However, the patient developed a manic episode. This case supports the hypothesis that incontinence and depression may share a common pathogenesis. The authors review the literature to investigate this linkage. The combination of aripiprazole and reboxetine should be used cautiously when treating first episode depression as it can induce a manic switch. Previous reports of manic switch with aripiprazole and reboxetine are reviewed.
PMCID: PMC3028471  PMID: 22315640

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