Neuroimaging in Cerebral Palsy – Report from North India

How to Cite This Article: Aggarwal A, Mittal H, Debnath SKR, Rai A. Neuroimaging in Cerebral Palsy–Report from North India. Iran J Child Neurol. 2013 Autumn; 7(3):41- 46. ObjectiveOnly few Indian reports exist on neuroimaging abnormalities in children with cerebral palsy (CP) from India. Materials & MethodsWe studied the clinico-radiological profile of 98 children diagnosed as CP at a tertiary centre in North India. Relevant investigations were carried out to determine the etiology. ResultsAmong the 98 children studied, 80.5% were males and 22.2% were premature. History of birth asphyxia was present in 41.9%. Quadriplegic CP was seen in 77.5%, hemiplegic in 11.5%, and diplegic in 10.5%. Other abnormalities were microcephaly (60.5%), epilepsy (42%), visual abnormality (37%), and hearing abnormality (20%). Neuroimaging was abnormal in 94/98 (95.91%).Abnormalities were periventricular white matter abnormalities (34%), deep grey matter abnormalities (47.8%), malformations (11.7%), and miscellaneous lesions (6.4%). Neuroimaging findings did not relate to the presence of birth asphyxia, sex, epilepsy, gestation, type of CP, or microcephaly. ConclusionsNeuroimaging is helpful for etiological diagnosis, especially malformations.  ReferencesSinghi PD, Ray M, Suri G. Clinical spectrum of cerebral palsy in north India-an analysis of 1000 cases. J Trop Pediatr 2002 48(3); 162-6.Sharma P, Sharma U, Kabra A. Cerebral Palsy-Clinical Profile and Predisposing Factors. Indian Pediatr 1999;36(10):1038-42.Nelson KB, Ellenberg JH. Antecedents of cerebral palsy. Multivariate analysis of risk. N Engl J Med 1986 315(2):81-6.Krägeloh-Mann I, Horber V. The role of magnetic resonance imaging in elucidating the pathogenesis of cerebral palsy: a systematic review. Dev Med Child Neurol 2007; 49(2):144-51.Rosenbaum P, Paneth N, Leviton A, Goldstein M, Bax M, Damiano D, et al. A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol Suppl 2007;109:8-14.http://www.newbornwhocc.org/pdf/database.pdfRikomen R, Raumanvrita S, Sinivuori E, Seppala T. Changing pattern of cerebral palsy in southwest region of Finland. Acta Pediatr Scand 1989; 78(4):581-7.Pharaoh POD, Plat MJ, Cooke T. The changing epidemiology of cerebral palsy. Arch Dis Child 1996;75(3): F169-73.Eischer PS, Batshaw M. Cerebral Palsy. Ped Clin North Am 1993;40(3):537-51.Bax M, Tydeman BA, Flodmark O. Clininical and MRI correlates of cerebral palsy: the European Cerebral PalsyStudy. JAMA 2006; 296(13):1602-08.Korzeniewski SJ, Birbeck G, DeLano MC, Potchen MJ, Paneth N. A systematic review of neuroimaging for cerebral palsy. Journal of Child Neurology 2008;23(2):216-27.Robinson MN, Peake LJ, Ditchfield MR, Reid SM. Magnetic Resonance imaging findings in population based cohort of children with cerebral palsy Dev Med Child Neurol 2009; 51(1):39-45.Shevell M, Ashwal S, Donley D, Flint J, Gingold M, Hirtz D, et al. Practice parameter: Evaluation of the child with global developmental delay: Report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society. Neurology 2003; 60(3); 367-80.Ashwal S, Russman BS, Blasco PA, Miller G, Sandler A, Shevell M, et al. Practice parameter: diagnostic assessment of the child with cerebralpalsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2004; 23;62(6): 851-63.

Predictors of Practice of breast self-examination among women in District Ambala (Haryana)

Background: Breast cancer is the most common cancer among women and its early detection is critical to improve survival. Breast self-examination is a cheap, basic and non-intellectual method to detect breast cancer. Aims and objectives: 1To determine the knowledge, attitude and practices regarding breast self-examination2. To explain the various factors which affect the practice of BSE Material and Methods: The present study was carried out among 300 women residing in rural and urban areas of district Ambala using a self-designed pretested semi-structured questionnaire. Results: In this study 127 (42.3%) of the participants had heard of BSE and 107 (35.7%) of the participants knew how to perform BSE.  Overall, 47.7%, 30.3%, and 22% of the study participants had poor (<50%), medium (50–75%), and good knowledge (>75) on BSE, respectively. Educational qualification, knowing the three positions to perform BSE, knowing how often should BSE be done, taught how to do BSE, BSE is a useful tool to detect breast cancer were seen to be significantly associated   with practice of BSE. Conclusion: This study elucidates that the knowledge as well as practice of BSE was significantly low in the population. This study provides insights into the various factors which affect the practice of BSE

Intrinsically Disordered C-Terminal Tails of \u3cem\u3eE. coli\u3c/em\u3e Single-Stranded DNA Binding Protein Regulate Cooperative Binding to Single-Stranded DNA

The homotetrameric Escherichia coli single-stranded DNA binding protein (SSB) plays a central role in DNA replication, repair and recombination. E. coli SSB can bind to long single-stranded DNA (ssDNA) in multiple binding modes using all four subunits [(SSB)65 mode] or only two subunits [(SSB)35 binding mode], with the binding mode preference regulated by salt concentration and SSB binding density. These binding modes display very different ssDNA binding properties with the (SSB)35 mode displaying highly cooperative binding to ssDNA. SSB tetramers also bind an array of partner proteins, recruiting them to their sites of action. This is achieved through interactions with the last 9 amino acids (acidic tip) of the intrinsically disordered linkers (IDLs) within the four C-terminal tails connected to the ssDNA binding domains. Here, we show that the amino acid composition and length of the IDL affects the ssDNA binding mode preferences of SSB protein. Surprisingly, the number of IDLs and the lengths of individual IDLs together with the acidic tip contribute to highly cooperative binding in the (SSB)35 binding mode. Hydrodynamic studies and atomistic simulations suggest that the E. coli SSB IDLs show a preference for forming an ensemble of globular conformations, whereas the IDL from Plasmodium falciparum SSB forms an ensemble of more extended random coils. The more globular conformations correlate with cooperative binding

KAP-1 promotes resection of broken DNA ends not protected by γ-H2AX and 53BP1 in G1-phase lymphocytes

The resection of broken DNA ends is required for DNA double-strand break (DSB) repair by homologous recombination (HR) but can inhibit normal repair by nonhomologous end joining (NHEJ), the main DSB repair pathway in G(1)-phase cells. Antigen receptor gene assembly proceeds through DNA DSB intermediates generated in G(1)-phase lymphocytes by the RAG endonuclease. These DSBs activate ATM, which phosphorylates H2AX, forming γ-H2AX in flanking chromatin. γ-H2AX prevents CtIP from initiating resection of RAG DSBs. Whether there are additional proteins required to promote resection of these DNA ends is not known. KRAB-associated protein 1 (KAP-1) (TRIM28) is a transcriptional repressor that modulates chromatin structure and has been implicated in the repair of DNA DSBs in heterochromatin. Here, we show that in murine G(1)-phase lymphocytes, KAP-1 promotes resection of DSBs that are not protected by H2AX and its downstream effector 53BP1. In these murine cells, KAP-1 activity in DNA end resection is attenuated by a single-amino-acid change that reflects a KAP-1 polymorphism between primates and other mammalian species. These findings establish KAP-1 as a component of the machinery that can resect DNA ends in G(1)-phase cells and suggest that there may be species-specific features to this activity

Restoration of Corneal Transparency by Mesenchymal Stem Cells

Summary Transparency of the cornea is indispensable for optimal vision. Ocular trauma is a leading cause of corneal opacity, leading to 25 million cases of blindness annually. Recently, mesenchymal stem cells (MSCs) have gained prominence due to their inflammation-suppressing and tissue repair functions. Here, we investigate the potential of MSCs to restore corneal transparency following ocular injury. Using an in vivo mouse model of ocular injury, we report that MSCs have the capacity to restore corneal transparency by secreting high levels of hepatocyte growth factor (HGF). Interestingly, our data also show that HGF alone can restore corneal transparency, an observation that has translational implications for the development of HGF-based therapy

Association of Cutibacterium acnes with human thyroid cancer

IntroductionThe diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations, sparse efforts have been made to characterize the microbes associated with thyroid cancer. In this study, we examine the microbial profile of thyroid cancer.MethodsWe sequenced the whole transcriptome of 70 thyroid cancers (40 papillary and 30 anaplastic). Using Infectious Pathogen Detector IPD 2.0, we analysed the relative abundance of 1060 microbes across 70 tumours from patients with thyroid cancer against 118 tumour samples from patients with breast, cervical, colorectal, and tongue cancer.ResultsOur analysis reveals a significant prevalence of Cutibacterium acnes in 58.6% thyroid cancer samples compared to other cancer types (p=0.00038). Immune cell fraction analysis between thyroid cancer samples with high and low Cutibacterium loads identify enrichment of immunosuppressive cells, including Tregs (p=0.015), and other anti-inflammatory cytokines in the tumour microenvironment, suggesting an immune evasion/immunosuppression milieu is associated with the infection. A higher burden of Cutibacterium acnes was also found to be associated with poor survival defining a distinct sub-group of thyroid cancer.ConclusionCutibacterium acnes is associated with immune suppression and poor prognosis in a subpopulation of thyroid cancer. This study may help design novel therapeutic measures involving appropriate antibiotics to manage the disease better

What do we know about chronic kidney disease in India: first report of the Indian CKD registry

<p>Abstract</p> <p>Background</p> <p>There are no national data on the magnitude and pattern of chronic kidney disease (CKD) in India. The Indian CKD Registry documents the demographics, etiological spectrum, practice patterns, variations and special characteristics.</p> <p>Methods</p> <p>Data was collected for this cross-sectional study in a standardized format according to predetermined criteria. Of the 52,273 adult patients, 35.5%, 27.9%, 25.6% and 11% patients came from South, North, West and East zones respectively.</p> <p>Results</p> <p>The mean age was 50.1 ± 14.6 years, with M:F ratio of 70:30. Patients from North Zone were younger and those from the East Zone older. Diabetic nephropathy was the commonest cause (31%), followed by CKD of undetermined etiology (16%), chronic glomerulonephritis (14%) and hypertensive nephrosclerosis (13%). About 48% cases presented in Stage V; they were younger than those in Stages III-IV. Diabetic nephropathy patients were older, more likely to present in earlier stages of CKD and had a higher frequency of males; whereas those with CKD of unexplained etiology were younger, had more females and more frequently presented in Stage V. Patients in lower income groups had more advanced CKD at presentation. Patients presenting to public sector hospitals were poorer, younger, and more frequently had CKD of unknown etiology.</p> <p>Conclusions</p> <p>This report confirms the emergence of diabetic nephropathy as the pre-eminent cause in India. Patients with CKD of unknown etiology are younger, poorer and more likely to present with advanced CKD. There were some geographic variations.</p

Development and Application of Computational Drug Design Methods Against Microbial Pathogen Enzymes

The overall objective of this research is to develop new computational protocols that address some of the current challenges in computational drug design, and to use them in the identification of novel small molecules that inhibit enzymes essential for viral or bacterial replication and survival. In this dissertation, we target a cysteine protease from the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and a condensing enzyme from the B. anthracis fatty acid biosynthesis pathway. The SARS-CoV 3-Chymotrypsin-like protease (3CLpro), vital for SARS-CoV replication, and the condensing enzyme, beta-Ketoacyl-acyl carrier protein synthase III (FabH), essential for the B. anthracis fatty acid biosynthesis pathway, serve as selective targets for novel antiviral and antibacterial drug design, respectively. We have developed a structure-based virtual screening protocol to identify novel small molecules active against SARS CoV 3CLpro. Through the use of a tiered docking approach and consensus scoring function we have obtained considerable enrichment of true positives compared to the individual scoring functions. SARS-CoV 3CLpro shows large movements of active site loops as well as side chain flexibility of the binding pocket residues. In our screening protocol, we have incorporated a combination of docking and pharmacophore based approaches to overcome some of the challenges of protein flexibility. Nearly half a million compounds from the ZINC database were screened using the developed protocol, leading to the identification of several compounds with micromolar activity. The structure activity relationship using the active and inactive compounds was also developed to provide guidance for compound optimization. Recently, additional experimental inhibitory data against 3CLpro was obtained from experimental screening of an in-house compound collection in our laboratory, and the public release on PubChem of results from an HTS campaign through the NIH Molecular Libraries Program. We used this data to re-validate our structure-based screening protocol. Additionally, the availability of sufficient ligand data allowed us to use a ligand-based approach to find novel scaffolds active against 3CLpro. The structural determinants for FabH-inhibitor binding are poorly understood. We first characterized the FabH binding pocket using computational solvent mapping and identified hot spot residues making dominant contributions to the binding affinity. The results show good agreement with the protein-inhibitor interactions observed in the co-crystal structures. These insights can serve as a guideline for designing and optimizing lead compounds. We also developed a reliable and computationally efficient protocol for virtual screening against FabH. A comprehensive pharmacophore based screening protocol was developed taking advantage of all the structure and inhibitor information available in the literature. Three different approaches were used for pharmacophore query generation for screening the ZINC library. Three compounds were selected and their binding to the baFabH active site was confirmed using fluorescence quenching experiments. The structural and energetic analysis of the putative ligands suggest that they bind to the key hot spots identified in this work

Bethe-Salpeter qqq dynamics: electromagnetic properties of baryons

The Bethe-Salpeter model for qq&#x0305; and qqq systems under harmonic confinement, previously found to fit the qq&#x0305; and qqq mass spectra of light (u,d,s) quarks rather well with a universal spring constant (&#969; = 0.15 GeV) and the concerned quark mass (mud = 0.28 GeV, ms = 0.35 GeV) is employed to predict some crucial electromagnetic properties of baryons as a generalization of a similar method recently developed for the electromagnetic interaction of qq&#x0305; mesons. The major successes, in which the relativistic features of the model have played a crucial role, are in respect of magnetic moments of baryons and the charge radius of the proton, all in very good agreement with experiment with no free parameters. In particular, &#956;p=2.796 (2.793) nuclear magnetons and &lt;rp2&gt;1/2=0.86 (0.87) fm. The helicity amplitudes A3/2 and A1/2 for &#916;&#8594;N&#947; also reveal an improved fit to data over previous quark-model calculations. The significance of these results is discussed in relation to contemporary confinement models