A nuclear localization signal and a membrane association domain contribute to the cellular localization of the Tobacco mosaic virus 126-kDa replicase protein

A transient expression system using onion epidermal cells was used to investigate domains of the Tobacco mosaic virus (TMV) 126-kDa replicase protein involved in cellular localization. Initially, a nuclear localization signal (NLS), identified within the amino-terminus of the 126-kDa protein, was investigated for its functionality using fusion constructs containing the green fluorescent protein (GFP). Fusion of the amino-terminal 70 amino acids of the 126-kDa protein, containing the NLS, to a beta-glucuronidase-GFP open reading frame (ORF), directed the accumulation of fluorescence to the nucleus. In contrast, similar constructs lacking the NLS or containing a mutated NLS sequence failed to accumulate within the nucleus. Additional investigations using GFP fusion constructs containing the first 178 or 388 amino acids of the 126-kDa protein also displayed nuclear localization. However, fusion constructs encoding the first 781 amino acids or the entire 126-kDa ORF did not accumulate within the nucleus but instead associated with the endoplasmic reticulum (ER), forming spot-like inclusions. Thus, a dominant ER association domain exists between amino acids 388 and 781 of the 126-kDa protein. Interestingly, a full-length 126-kDa GFP fusion construct encoding a nonfunctional NLS mutation also localized to the ER but did not form inclusions. Furthermore, a TMV mutant containing the same nonfunctional NLS mutation failed to replicate in protoplasts. Together these findings suggest that both the NLS and the ER retention domain contribute to the functional localization of the 126-kDa protein.     

Posterior reversible encephalopathy syndrome in a patient of organophosphate poisoning

A 32-year-old male presented with a history of consuming some organophosphorous compound with suicidal intention. He was treated with atropine, pralidoxime, ventilator support. During stay patient had persistent irritability, tachycardiaand hypertension despite sedation and labetalol infusion. He developed headache, visual blurring hemiparesis and focal seizures. Magnetic resonance imaging of the brain revealed multifocal hyperintensities mainly in subcortical areas of parietal and occipital regions in T2-weighted images, with increased values of Apparent Diffusion Coefficient, suggesting posterior reversible encephalopathy syndrome (PRES). The possibilities of PRES caused by organophosphorous poisoning either due to hypertension caused by autonomic deregulation or direct neurological toxicity has been discussed.     

Clinical predictors of high risk histopathology in retinoblastoma

Background

Previous studies show that clinical features at presentation, in retinoblastoma patients, like glaucoma and neovascularization of iris are associated with a higher incidence of high risk histopathology findings (HRF) in enucleated eyes. Herein, we analyze association between clinical features at time of enucleation and occurrence of HRF including invasion of anterior chamber, iris, ciliary body, choroid (massive), sclera, extrascleral tissue, optic nerve beyond lamina cribrosa, and optic nerve cut end, in a large series of eyes enucleated for retinoblastoma.

Procedure

We retrospectively studied demographic, clinical, and histopathology findings in all retinoblastoma patients who underwent primary enucleation at our center, over a 5 years duration. Statistical analysis was done to find any association between clinical features at presentation and the presence of HRF.

Results

Three hundred twenty‐six eyes were studied. Median age of presentation was 2 years. Glaucoma was the most common clinical finding at presentation apart from leucocoria. Out of 326 enucleated eyes, 28 (8.6%) had extrascleral and/or optic nerve transection invasion. Among remaining 298 eyes, with completely resected tumor, 115 (38.6%) had massive choroidal invasion, 54 (17%) had retrolaminar optic nerve invasion, and 24 (7%), 29 (9%), and 23(7%) had anterior chamber, iris, and ciliary body invasion, respectively. Age more than 2 years, lag period more than 3 months, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were associated with occurrence of three or more HRF on univariate analysis.

Conclusions

Clinical variables including older age, longer lag period, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were strongly associated with occurrence of HRF in this study. Pediatr Blood Cancer 2012; 58: 356–361. © 2011 Wiley Periodicals, Inc.     

Survey instruments used in clinical and epidemiological research on waterpipe tobacco smoking: a systematic review

Background  

The primary objective was to systematically review the medical literature for instruments validated for use in epidemiological and clinical research on waterpipe smoking.     

Phenotypic spectrum and genetics of SCN2A‐related disorders,treatment options,and outcomes in epilepsy and beyond

Pathogenic variants in the SCN2A gene are associated with a variety of neurodevelopmental phenotypes, defined in recent years through multicenter collaboration. Phenotypes include benign (self‐limited) neonatal and infantile epilepsy and more severe developmental and epileptic encephalopathies also presenting in early infancy. There is increasing evidence that an important phenotype linked to the gene is autism and intellectual disability without epilepsy or with rare seizures in later childhood. Other associations of SCN2A include the movement disorders chorea and episodic ataxia. It is likely that as genetic testing enters mainstream practice that new phenotypic associations will be identified. Some missense, gain of function variants tend to present in early infancy with epilepsy, whereas other missense or truncating, loss of function variants present with later‐onset epilepsies or intellectual disability only. Knowledge of both mutation type and functional consequences can guide precision therapy. Sodium channel blockers may be effective antiepileptic medications in gain of function, neonatal and infantile presentations.     

Olivopontocerebellar atrophy in a young patient: A case report with radiologic findings

BackgroundOlivopontocerebellar atrophy (OPCA) is a term that encompasses an increasing number of neurodegenerative syndromes that lack a unique pathogenesis but are known to result from a disruption in the relationship between the cerebellar cortex, dentate nucleus, and the inferior olivary nuclei. OPCA can be difficult to diagnose on clinical grounds only and recent data suggests that OPCA affects 3–5 individuals in every 100,000 and may constitute almost 6% of patients diagnosed with atypical parkinsonism.Case reportHerein, we report the case of a 36-year-old female that initially developed dysarthria and gait abnormalities and subsequently presented with progressive neurologic signs and symptoms. A routine MRI of the brain was performed and high-resolution images were taken through the entire posterior fossa which showed prominent widening of the CSF spaces in the posterior fossa, cerebellar atrophy and reduction in the size of the pons, consistent with a diagnosis of OPCA.ConclusionOlivopontocerebellar atrophy is challenging condition to diagnose on a clinical basis, and hence requires corroboration of clinical and physical examination findings with radiologic findings. MRI of the brain is the gold standard in assessing OPCA and is an extremely valuable imaging modality in distinguishing OPCA from other neurological disorders and allows for the precise determination of OPCA subtypes.     

Leiomyoma Infarction after Uterine Artery Embolization: Influence of Embolic Agent and Leiomyoma Size and Location on Outcome

Purpose

To study the factors that might impact infarction of individual uterine leiomyomas and total tumor burden after uterine artery embolization (UAE).

ICD coding for epilepsy: Past,present, and future—A report by the International League Against Epilepsy Task Force on ICD codes in epilepsy

The World Health Organization (WHO) International Classification of Diseases (ICD) has been used to classify causes of morbidity and mortality such as epilepsy for more than 50 years. The aims of this critical commentary are to do the following: (1) Introduce the ICD classification, summarize the ICD‐9 and ICD‐10 codes for epilepsy and seizures, and discuss the challenges of mapping epilepsy codes between these two versions; (2) discuss how the ICD‐9 and ICD‐10 relate to the revised International League Against Epilepsy (ILAE) terminology and concepts for classification of seizures and epilepsies; (3) discuss how ICD‐coded data have been used for epilepsy care and research and briefly examine the potential impact of the international ICD‐10 clinical modifications on research; (4) discuss the upcoming ICD‐11 codes and the role of the epilepsy community in their development; and (5) discuss how the ICD‐11 will conform more closely to the current ILAE terminology and classification of the epilepsies and seizures and its potential impact on clinical care, surveillance, and public health and research.     

Objective predictors of ‘early tolerance’ to ventral intermediate nucleus of thalamus deep brain stimulation in essential tremor patients

Objective

To identify pre-operative clinical and computerized spiral analysis characteristics that may help ascertain which patients with Essential Tremor (ET) will exhibit ‘early tolerance’ to ventral intermediate nucleus of thalamus (Vim) deep brain stimulation (DBS).