HRCT evaluation and immunohistochemistry of bronchiectatic airways: is there a relationship?

published_or_final_versio

Functional significance of CT quantified bronchial wall thickening in bronchbiectasis

published_or_final_versio

Parkinsonism and dystonia: Clinical spectrum and diagnostic clues

The links between the two archetypical basal ganglia disorders, dystonia and parkinsonism, are manifold and stem from clinical observations, imaging studies, animal models and genetics. The combination of both, i.e. the syndrome of dystonia-parkinsonism, is not uncommonly seen in movement disorders clinics and has a myriad of different underlying aetiologies, upon which treatment and prognosis depend. Based on a comprehensive literature review, we delineate the clinical spectrum of disorders presenting with dystonia-parkinsonism. The clinical approach depends primarily on the age at onset, associated neurological or systemic symptoms and neuroimaging. The tempo of disease progression, and the response to L-dopa are further important clues to tailor diagnostic approaches that may encompass dopamine transporter imaging, CSF analysis and, last but not least, genetic testing. Later in life, sporadic neurodegenerative conditions are the most frequent cause, but the younger the patient, the more likely the cause is unravelled by the recent advances of molecular genetics that are focus of this review. Here, knowledge of the associated phenotypic spectrum is key to guide genetic testing and interpretation of test results. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna

A survey of falls in people with dystonia.

ObjectiveDystonia is a chronic and sometimes progressive neurological disorder causing abnormalities in movement and function. We conducted a preliminary survey to investigate whether people with dystonia experience falls and to identify contributing factors to falls in this population.MethodsAn online survey of people with dystonia was conducted in November 2015. Respondents were asked to complete demographic information, three questionnaires (the Falls Self-Efficacy Scale International [FES-I], the Activities-based Balance Confidence Scale [ABC] and the Functional Disability Questionnaire [FDQ]), and to report any falls sustained during the previous 6 months.ResultsThirty-nine percent of the 122 respondents reported falling in the previous 6 months and 65% of fallers were diagnosed with dystonia not affecting the lower limbs. Fallers reported lower falls self-efficacy and balance confidence with higher functional disability. Both falling scales correlated with self-reported functional disability. Linear regression analysis for falls prediction revealed the variables FES-I and FDQ accounted for almost 30% of the falls in this dystonia population.ConclusionThis survey indicates that fear of falling and balance confidence are impaired in people with dystonia, possibly impacting on function and falls. Further investigation into balance, function and falls in this population is required

Association of 25-Hydroxyvitamin D Deficiency in Pediatric Epileptic Patients

How to Cite This Article: Chaudhuri IR, Mridula KR, Rathnakishore Ch, Balaraju B, Bandaru VCS. Association of 25-Hydroxyvitamin D Deficiency in Pediatric Epileptic Patients. Iran J Child Neurol. Spring 2017; 11(2):48-56. Abstract Objective Epilepsy is a chronic neurological disorder requiring long-term therapy using antiepileptic medications. Reports have incriminated long-term antiepileptic drugs use in deficiency of vitamin D and bone diseases in all age groups. We aimed to investigate the association between serum 25-hydroxyvitamin D levels and pediatric epilepsy in Indian patients. Materials & Methods We prospectively recruited 100 pediatric epilepsy patients, on monotherapy for minimum one-year duration, and 50 age and sex matched controls. This study was carried out at Yashoda Hospital, India from 2011-2014. All cases and controls underwent tests for serum 25-hydroxyvitamin D, alkaline phosphatase, serum calcium and phosphorus levels. Results Patients with 25-hydroxyvitamin D deficiency were significantly higher among cases (45%) than controls (24%). Mean alkaline phosphatase was significantly higher in cases and mean serum calcium was significantly lower (8.3±1.5) in cases. Amongst antiepileptic drugs, carbamazepine and sodium valproate were significantly associated with 25-hydroxyvitamin D deficiency. Risk of vitamin D deficiency was highest with sodium valproate usage (odds:4.0;95%CI 1.4-11.6) followed by carbamazepine use (odds: 2.7; 95%CI 1.0-6.8). After adjustment using multiple logistic regression, antiepileptic drugs showed independent association with 25-hydroxyvitamin D deficiency (odds:2.2;95%CI 0.9-4.5). Conclusion 25-hydroxyvitamin D deficiency was significantly associated with use of carbamazepine and sodium valproate in pediatric epilepsy.References 1. Santhosh NS, Sinha S, Satishchandra P. Epilepsy: Indian perspective. Ann Indian Acad Neurol2014;17(Suppl 1):S3-11. 2. Sridharan R, Murthy BN. Prevalence and pattern of epilepsy in India. Epilepsia 1999;40:631-66. 3. RainaSK,RazdanS,NandaR.Prevalence of neurological disorders in children less than 10 years of age in RS Pura town of Jammu and Kashmir. J Pediatr Neurosci 2011; 6:103-05. 4. Misra A, Aggarwal A, Singh O, Sharma S. Effect of carbamazepine therapy on vitamin D and parathormone in epileptic children. Pediatr Neurol 2010 Nov;43:320- 24. 5. Lazzari AA, Dussault PM, Thakore-James M, Gagnon D, Baker E, Davis SA et al.Prevention of bone loss and vertebral fractures in patients with chronic epilepsy-antiepileptic drug and osteoporosis prevention trial. Epilepsia 2013;54:1997-2004.6. Menon B, Harinarayan CV. The effect of anti epileptic drug therapy on serum 25-hydroxyvitamin D and parameters of calcium and bone metabolism a longitudinal study. Seizure 2010;19:153-58. 7. Chaudhuri JR, Mridula KR, Alladi S, Anamika A, Umamahesh U, Balaraju B et al. Serum 25-hydroxyvitamin D deficiency in ischemic stroke and subtypes in Indian patients. J Stroke 2014;16:44-50. 8. Fisher RS, van Emde Boas W, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46:470-72. 9. Chaudhuri JR, Mridula KR, Anamika A, Boddu DB, Misra PK, Lingaiah A et al. Deficiency of 25-hydroxyvitamin d and dyslipidemia in Indian subjects. J Lipids 2013;2013:623420. 10. Gniatkowska-Nowakowska A. Fractures in epilepsy children. Seizure 2010;19:324-25. 11. Shellhaas RA, Barks AK, Joshi SM. Prevalence and risk factors for vitamin D insufficiency among children with epilepsy. Pediatr Neurol 2010;42:422-26. 12. Nettekoven S, Strohle A, Trunz B, Wolters M, Hoffmann S, Horn R, et al. Lichtinghagen R, Welkoborsky HJ, Tuxhorn I, Hahn A. Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy. Eur J Pediatr 2008;167:1369-77. 13. Rajantie J, Lamberg-Allardt C, Wilska M. Dose carbamazepine treatment lead to need of extera vitamin D in some mentally retarded children. Acta Pediatr Scand 1984;73:325-28. 14. Jekovec-Vrhovsek M, Kocijancic A, Prezelj J. Effect of vitamin D and calcium on bone mineral density in children with CP and epilepsy in full-term care. Dev Med Child Neurol 2000;42:403-05. 15. Pack AM. The Association between Antiepileptic Drugs and Bone Disease. Epilepsy Currents 2003; 3:91-95. 16. Babayigit A, Dirik E, Bober E, Cakmakci H. Adverse effects of antiepileptic drugs on bone mineral density. Pediatr Neurol 2006;35:177-81. 17. Pack AM. The impact of long-term antiepileptic drug use on bone health. Advanced Students 2005;5:S567-71.18. Voudris KA, Attilakos A, Katsarou E, Garoufi A, Dimou S, Skardoutsou A,et al. Early alteration in bone metabolism in epileptic children receiving carbamazepine monotherapy owing to the induction of hepatic drug-metabolizing enzymes. J Child Neurol 2005; 20: 513-16. 19. Malik R, Mohapatra JN, Kabi BC, Halder R. 5 Hydroxy Cholecalciferol Levels in Infants with Hypocalcemic Seizures J Nutr Food Sci 2014; 4:3 20. Razazizan N, Mirmoeini M, Daeichin S, Ghadiri K. Comparison of 25-hydroxy vitamin D, calcium and alkaline phosphatase levels in epileptic and non-epileptic children. Acta Neurol Taiwan 2013;22:112-16. 21. Krishnamoorthy G, Karande S, Ahire N, Mathew L, Kulkarni M. Bone Metabolism Alteration on Antiepileptic Drug Therapy. Indian J Pediatr 2009; 76 : 377-83. 22. Valsamis HA, Arora SK, Labban B, McFarlane SI.Antiepileptic drugs and bone metabolism. Nutr Metab (Lond) 2006;3:36 23. MintzerS, Boppana P, Toguri J, DeSantis A. Vitamin D levels and bone turnover in epilepsy patients taking carbamazepine or oxcarbamazepine. Epilepsia 2006;47:510-15. 24. Pack AM, Morrell MJ. Adverse effect of antiepileptic drug on bone structure: Epidemiology mechanisms and therapeutic indications.CNS Drugs 2001;15:633-42. 25. Yaghini O, Tonekaboni SH, Amir Shahkarami SM, Ahmad Abadi F, Shariat F, Abdollah Gorji F. Bone mineral density in ambulatory children with epilepsy. Indian J Pediatr 2015;82:225-29. 26. Verrotti A, Greco R, Morgese G, Chiarelli F. Increased bone turnover in epileptic patients treated with carbamazepine. Ann Neurol 2000;47: 385-88. 27. Ginige N,de Silva KSH, Wanigasinghe JK, Gunawardane NS, Munasinghe TMJ. Effects of long term anti epileptic drugs on serum vitamin D levels and bone profile in a cohort of Sri Lankan children. Int J Pediatr Endocrinol 2015,2015(Suppl 1):P66. 28. Hosseinpour F, Ellfolk M, Norlin M, Wikvall K. Phenobarbital suppresses vitamin D3 25-hydroxylase expression: a potential new mechanism for drug-induced osteomalacia. Biochem Biophys Res Commun 2007;357:603-07. 29. Heo K, Rhee Y, Lee HW, Lee SA, Shin DJ, Kim WJ, et al. The effect of topiramate monotherapy on bone mineral density and markers of bone and mineral metabolism in premenopausal women with epilepsy. Epilepsia 2011;52:1884-89. 30. Zhou C, Assem M, Tay JC, Watkins PB, Blumberg B, Schuetz EG, et al.Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. J Clin Invest 2006;116:1703-12. 31. Pascussi JM, Robert A, Nguyen M, Walrant-Debray O, Garabedian M, Martin P, et al.. Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest 2005;115:177- 86. 32. Holick MF. Stay tuned to PXR: an orphan actor that may not be D-structive only to bone. J Clin Invest 2005;115:32- 4. 33. Perucca E. Clinical implications of hepatic microsomal enzyme induction by antiepileptic drugs. Pharmacol Ther 1987;33:139-44. 34. Koch HU, Kraft D, von Herrath D, Schaefer K. Influence of diphenylhydantoin and phenobarbital on intestinal calcium transport in the rat. Epilepsia 1972;13:829-41. 35. Weinstein RS, Bryce GF, Sappington LJ, King DW, Gallagher BB. Decreased serum ionized calcium and normal vitamin D metabolite levels with anticonvulsant drug treatment. J Clin Endocrinol Metab 1984;58:1003-09. 36. Onodera K, Takahashi A, Sakurada S, Okano Y. Effects of phenytoin and/or vitamin K2 (menatetrenone) on bone mineral density in the tibia of growing rats. Life Sci 2002; 70: 1533-42. 37. Vernillo AT, Rifkin BR, Hauschka PV. Phenytoin affects osteoblastic secretion from osteoblastic rat osteosarcoma 17/2.8 cells in culture. Bone 1990;11:309-12. 38. Guo C, Ronen GM, Atkinson SA. Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy. Epilepsia 2001; 42:1141-47. 39. Nakken KO, Tauboll E. Bone loss associated with use of antiepileptic drugs. Expert Opin Drug Saf 2010;9:561-71. 40. Lee RH,Lyles KW, Colon-Emeric C. A review of the effect of anticonvulsant medications on bone mineral density and fracture risk. Am J Geriatr Pharmacother 2010; 8:34-46. 41. Teagarden DL, Meador KJ, Loring DW. Low vitamin D levels are common in patients with epilepsy. Epilepsy Res 2014;108:1352-56. 42. Wu FJ, Sheu SY, Lin HC. Osteoporosis is associated with antiepileptic drugs: a population-based study. Epileptic Disord 2014;16:333-42. 43. Cansu A, Yesilkaya E, Serdaroglu A, Hirfanoglu TL, Camurdan O, Gulbahar O, et al. Evaluation of bone turnover in epileptic children using oxcarbazepine. Pediatr Neurol 2008;39:266-71. 44. Bergqvist AG, Schall JI, Stallings VA. Vitamin D status in children with intractable epilepsy, and impact of the ketogenic diet. Epilepsia 2007;48:66-71. 45. Nicolaidou P, Georgouli H, Kotsalis H, Matsinos Y, Papadopoulou A, Fretzayas A, et al.Effects of anticonvulsant therapy on vitamin D status in children: Prospective monitoring study. J Child Neurol 2006;21:205-09. 46. Farhat G, Yamout B, Mikati MA, Demirjian S, Sawaya R, El-Hajj Fuleihan G. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurol 2002;58:1348-53. 47. Harijan P, Khan A, Hussain N. Vitamin D deficiency in children with epilepsy: Do we need to detect and treat it? J Pediatr Neurosci 2013;8:5-10. 48. Mikati MA, Dib L, Yamout B, Sawaya R, Rahi AC, Fuleihan Gel-H. Two randomized vitamin D trials in ambulatory patients on anticonvulsants: Impact on bone. Neurol 2006; 67:2005-14. 49. Bianchini G, Mazzaferro S, Mancini U, Bianchi AR, Donato G, Massimetti C,et al.Calcium phosphorus changes in chronic anticonvulsant therapy: effects of administration of 25 hydroxy vitamin D3 on secondary hyperparathyroidism. Acta Vitaminol Enzymol 1983;5:229-34. 50. Drezner MK. Treatment of anticonvulsant drug – induced bone disease. Epilepsy Behav 2004;5:S41-7. 51. Howard JM. Anticonvulsant induced bone disease. Editorial. Arch Neurol 2004;58:1352-53

Cascaded two-photon nonlinearity in a one-dimensional waveguide with multiple two-level emitters

We propose and theoretically investigate a model to realize cascaded optical nonlinearity with few atoms and photons in one-dimension (1D). The optical nonlinearity in our system is mediated by resonant interactions of photons with two-level emitters, such as atoms or quantum dots in a 1D photonic waveguide. Multi-photon transmission in the waveguide is nonreciprocal when the emitters have different transition energies. Our theory provides a clear physical understanding of the origin of nonreciprocity in the presence of cascaded nonlinearity. We show how various two-photon nonlinear effects including spatial attraction and repulsion between photons, background fluorescence can be tuned by changing the number of emitters and the coupling between emitters (controlled by the separation).Comment: 6 pages, 4 figure

A hybrid fuzzy sliding-mode control for a three-phase shunt active power filter

This document is the Accepted Manuscript version of the following article: Mohamed Abdeldjabbar Kouadria, Tayeb Allaoui, and Mouloud Denai, ‘A hybrid fuzzy sliding-mode control for a three-phase shunt active power filter’, Energy Systems, Vol. 8 (2): 297-308, March 2016. The final publication is available at Springer via http://dx.doi.org/10.1007/s12667-016-0198-4.This paper describes the hybrid fuzzy sliding-mode control (HFSMC) for a three phase shunt active shunt filter for the power quality improvement. The Power Quality (PQ) problems in power distribution systems are not new but only recently the effects of these problems have gained public awareness. These non-linear loads are constructed by nonlinear devices in which the current is not proportional to the applied voltage. For the harmonic elimination different methods are used, but in this paper a novel fuzzy logic controller for a three-phase shunt active power filter for the power quality improvement such as reactive power and harmonic current compensation generated due to nonlinear loads. The hybrid fuzzy sliding-mode control (HFSMC) approach is proposed such that it can be applied with advantages to both fuzzy and sliding-mode controller. Simulation results are presented to demonstrate the effectiveness of the control strategy. The results are found to be quite satisfactory to mitigate harmonic distortions, reactive power compensation and power quality improvement.Peer reviewedFinal Accepted Versio

Immunomodulatory Protective Effects of Rb9 Cyclic-Peptide in a Metastatic Melanoma Setting and the Involvement of Dendritic Cells

The cyclic VHCDR3-derived peptide (Rb9) from RebMab200 antibody, directed to a NaPi2B phosphate-transport protein, displayed anti-metastatic melanoma activity at 50-300 mu g intraperitoneally injected in syngeneic mice. Immune deficient mice failed to respond to the peptide protective effect. Rb9 induced increased CD8+ T and low Foxp3+ T cell infiltration in lung metastases and high IFN-gamma and low TGF-beta in lymphoid organs. The peptide co-localized with F-actin and a nuclear site in dendritic cells and specifically bound to MIF and CD74 in a dot-blot setting. Murine bone-marrow dendritic cells preincubated with Rb9 for 6 h were treated with MIF for short time periods. The modulated responses showed stimulation of CD74 and inhibition of pPI3K, pERK, and pNF-kappa B as compared to MIF alone. Rb9 in a melanoma-conditioned medium, stimulated the M1 type conversion in bone marrow-macrophages. Functional aspects of Rb9 in vivo were studied in therapeutic and prophylactic protocols using a melanoma metastatic model. In both protocols Rb9 exhibited a marked anti-melanoma protection. Human dendritic cells were also investigated showing increased expression of surface markers in response to Rb9 incubation. Rb9 either stimulated or slightly inhibited moDCs submitted to inhibitory (TGF-beta and IL-10) or activating (LPS) conditions, respectively. Lymphocyte proliferation was obtained with moDCs stimulated by Rb9 and tumor cell lysate. In moDCs from cancer patients Rb9 exerted immunomodulatory activities depending on their functional status. The peptide may inhibit over-stimulated cells, stimulate poorly activated and suppressed cells, or cause instead, little phenotypic and functional alterations. Recently, the interaction MIF-CD74 has been associated to PD-L1 expression and IFN-gamma, suggesting a target for melanoma treatment. The effects described for Rb9 and the protection against metastatic melanoma may suggest the possibility of a peptide reagent that could be relevant when associated to modern immunotherapeutic procedures