Background and PurposeMiddle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012.MethodsWe evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described.ResultsFour of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2–3 weeks.ConclusionsNeuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.

Huntington's disease is caused by CAG trinucleotide expansions in the gene encoding huntingtin. Nterminal fragments of huntingtin with polyglutamine produce aggregates in the endosome-lysosomal system, where proteolytic fragments of huntingtin is generated. Heat shock protein 70 (HSP70) prevents the formation of protein aggregates, but the effect of HSP70 on the huntingtin in the endosome-lysosomal system is unknown. This study was to determine whether HSP70 alters the distribution of huntingtin in endosome-lysosomal system. HSP70 expressing stable cells (NIH/3T3 or cerebral hybrid cell line A1) were generated, and mutant [(CAG) 100 ] huntingtin was transiently overexpressed. Analysis of subcellular distribution by immnuocytochemistry or proteolysis cleavage by Western blotting was performed. 18 CAG repeat wild type [WT; (CAG)18] huntingtin was used as a control. Cells with huntingtin showed patterns of endosomelysosomal accumulation, from a 'dispersed vacuole (DV)' type into a coalescent 'perinuclear vacuole (PV)' type over time. In WT huntingtin, HSP70 increased the cells with the PV types that enhanced the proteolytic cleavage of huntingtin. However, HSP70 reduced cells of the DV and PV types expressing mutant huntingtin, that result in less proteolysis than that of control. In addition, intranuclear inclusions were formed only in mutant cells, which was not affected by HSP70. These results suggest that HSP70 alters the distribution of huntingtin in the endosomelysosomal system, and that this contributes to huntingtin proteolysis.Keywords: endosomes; HSP70 heat-shock proteins; Huntington disease; lysosome IntroductionHuntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by progressive chorea leading to severe debilitation and death within 15-20 years. Selective neuronal loss in the neostriatum and cortex causes choreic movement and dementia (Ross et al., 1997). The gene defective in HD is located on chromosome 4p16.3 (Lesperance et al., 1995) and is translated into huntingtin, a 350 kDa ubiquitous protein (Ide et al., 1995;Sharp et al., 1995). Moreover, increased CAG trinucleotide repeats in exon 1 lead to polyglutamine expansion in the N-terminus of huntingtin and are responsible for neurodegeneration in the HD brain (MacDonald et al., 1993, The Huntington's Disease Collaborative Research Group). The intracellular aggregates observed in the HD human brain and in transgenic mice are mainly formed by proteolysis of the N-terminus region in mutant huntingtin (Davies et al., 1997;DiFiglia et al., 1997), and are related to cellular toxicity (Cooper et al., 1998;Zala et al., 2005;Benchoua et al., 2006;Scheibel and Buchner, 2006).In dying neurons of the HD brain, huntingtinHeat shock protein 70 alters the endosome-lysosomal localization of huntingtin Huntingtin and HSP70 39 aberrantly accumulates in perinuclear regions and in numerous punctate cytoplasmic structures that resemble the endosomal-lysosomal system (Sapp et al., 1997). In an in vitro model of HD, using a ...

The Addenbrooke's Cognitive Examination (ACE) is a valid dementia-screening test that is a simple and effective instrument. We aimed to assess the diagnostic accuracy of the Korean version of the ACE (K-ACE) in a Korean population. A total of 115 subjects (50 with Alzheimer's dementia [AD], 26 with mild cognitive impairment [MCI], and 39 controls) who visited the Neurology Outpatient Clinic of Seoul Medical Center were included. The ACE was translated and modified to create the K-ACE. The sensitivity, specificity, area under the curve, reliability, and Verbal-Language/Orientation-Memory ratio were evaluated. The receiver-operating characteristic (ROC) curve was used to determine the optimal cutoff score in screening for dementia. The ROC curves showed the superiority of the K-ACE over the Korean Mini-Mental Status Examination in the diagnosis of AD and MCI. The optimal cutoff of the K-ACE for the identification of AD was 68/69, which had a sensitivity of 90% and a specificity of 84%. The K-ACE is a short, reliable, and valid neuropsychological test battery used to screen for dementia in the Korean elderly.

Recent studies have documented that testosterone relaxes several smooth muscles by modulating K + channel activities. Smooth muscles of seminal vesicles play a fundamental role in ejaculation, which might involve testosterone. This study was aimed to assess the role of testosterone in seminal vesicular motility by studying its effects on contractile agents and on the ion channels of single vesicular myocytes in a rabbit model. The contractile responses of circular smooth muscle strips of rabbit seminal vesicles to norepinephrine (10μM), a high concentration of KCl (70 mM), and testosterone (10μM) were observed. Single vesicular myocytes of rabbit were isolated using proteolytic enzymes including collagenase and papain. Inside-out, attached, and whole-cell configurations were examined using the patch clamp technique. The applications of 10μ M norepinephrine or 70 mM KCl induced tonic contractions, and 10μM testosterone (pharmacological concentration) evoked dose-dependent relaxations of these precontracted strips. Various K + channel blockers, such as tetraethylammonium (TEA; 10 mM), iberiotoxin (0.1μM), 4-aminopyridine (4-AP, 10μM), or glibenclamide (10μM) rarely affected these relaxations. Single channel data (of inside-out and attached configurations) of BK channel activity were also hardly affected by testosterone (10μM). On the other hand, however, testosterone reduced L-type Ca 2+ currents significantly, and found to induce acute relaxation of seminal vesicular smooth muscle and this was mediated, at least in part, by Ca 2+ current inhibition in rabbit.

Writing Committee of Korean clinical practice guidelines for secondary prevention of stroke has reviewed recent randomized controlled trials of cilostazol published after the fi rst edition of Korean clinical practice guidelines that considered evidences published before June 2007. Two clinical trials and 1 meta-analysis which compared cilostazol directly with aspirin in the prevention of stroke in patients with cerebral infarction or transient ischemic attack (TIA) were identifi ed and included for the current guideline update. Review of fi ndings indicates that cilostazol as compared to aspirin achieved a greater reduction of stroke as well as composite vascular events of stroke, myocardial infarction, and vascular death. For safety, cilostazol was associated with fewer major bleeding events than aspirin. Accordingly, new recommendations for cilostazol are made for prevention of stroke in the setting of noncardioembolic stroke or TIA. Changes in the guidelines necessitated by new evidences will be continuously refl ected in future guidelines.