Hospital Occupancy and its Effect on Emergency Department Evaluation.

STUDY OBJECTIVE: To examine whether hospital occupancy was associated with increased testing and treatment during emergency department (ED) evaluations, resulting in reduced admissions. METHODS: We analyzed the electronic health records of an urban academic ED. We linked data from all ED visits from October 1, 2010, to May 29, 2015, with daily hospital occupancy (inpatients/total staffed beds). Outcome measures included the frequency of laboratory testing, advanced imaging, medication administration, and hospitalizations. We modeled each outcome using multivariable negative binomial or logistic regression, as appropriate, and examined their association with daily hospital occupancy quartiles, controlling for patient and visit characteristics. We calculated the adjusted outcome rates and relative changes at each daily hospital occupancy quartile using marginal estimating methods. RESULTS: We included 270,434 ED visits with a mean patient age of 48.1 (standard deviation 19.8) years; 40.1% were female, 22.8% were non-Hispanic Black, and 51.5% were commercially insured. Hospital occupancy was not associated with differences in laboratory testing, advanced imaging, or medication administration. Compared with the first quartile, the third and fourth quartiles of daily hospital occupancy were associated with decreases of 1.5% (95% confidence interval [CI] -2.9 to -0.2; absolute change -0.6 percentage points [95% CI -1.2 to -0.1]) and 4.6% (95% CI -6.0 to -3.2; absolute change -1.9 percentage points [95% CI -2.5 to -1.3]) in hospitalizations, respectively. CONCLUSION: The lack of association between hospital occupancy and laboratory testing, advanced imaging, and medication administration suggest that changes in ED testing or treatment did not facilitate the decrease in admissions during periods of high hospital occupancy.

Vestibular Migraine.

PURPOSE OF REVIEW: To explore recent developments in vestibular migraine (VM). RECENT FINDINGS: This review discusses the current diagnostic criteria for VM in the adult and pediatric populations, as proposed by the International Headache Society and Bárány Society. Recent VM studies confirm the prior findings and reveal new insights, including the wide range of vestibular symptoms, symptoms in the attack-free period, and triggers. Many patients experience persistent vestibular symptoms, even in the absence of acute attacks, which often significantly impact patients' quality of life. The syndrome of benign recurrent vertigo and its relationship to migraine, VM, and Meniere's disease is also discussed. There is a dearth of randomized controlled trials in VM treatment. Prospective and retrospective studies support the benefit of many migraine treatments are effective in VM, including neuromodulation, and calcitonin gene-related peptide monoclonal antibodies. VM affects almost 3% of the population, but remains under-diagnosed. Recent diagnostic criteria can help clinicians diagnose VM in adults and children.

LMBD1 protein participates in cell mitosis by regulating microtubule assembly.

LMBD1 was previously demonstrated to regulate the endocytosis of insulin receptor on the cell surface and to mediate the export of cobalamin from the lysosomes to the cytosol, but little is known about its function in mitosis. In this study, interactome analysis data indicate that LMBD1 is involved in cytoskeleton regulation. Both immunoprecipitation and GST pulldown assays demonstrated the association of LMBD1 with tubulin. Immunofluorescence staining also showed the colocalization of LMBD1 with microtubule in both interphase and mitotic cells. LMBD1 specifically accelerates microtubule assembly dynamics in vitro and antagonizes the microtubule-disruptive effect of vinblastine. In addition, LMBRD1-knockdown impairs mitotic spindle formation, inhibits tubulin polymerization, and diminishes the mitosis-associated tubulin acetylation. The reduced acetylation can be reversed by ectopic expression of LMBD1 protein. These results suggest that LMBD1 protein stabilizes microtubule intermediates. Furthermore, embryonic fibroblasts derived from Lmbrd1 heterozygous knockout mice showed abnormality in microtubule formation, mitosis, and cell growth. Taken together, LMBD1 plays a pivotal role in regulating microtubule assembly that is essential for the process of cell mitosis.

Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Suppresses Type I and Type III Interferon Induction by Targeting RIG-I Signaling.

Type I and type III interferons (IFNs) are the frontline of antiviral defense mechanisms that trigger hundreds of downstream antiviral genes. In this study, we observed that MERS-CoV nucleocapsid (N) protein suppresses type I and type III IFN gene expression. The N protein suppresses Sendai virus-induced IFN-ß and IFN-λ1 by reducing their promoter activity and mRNA levels, as well as downstream IFN-stimulated genes (ISGs). Retinoic acid-inducible gene I (RIG-I) is known to recognize viral RNA and induce IFN expression through tripartite motif-containing protein 25 (TRIM25)-mediated ubiquitination of RIG-I caspase activation and recruitment domains (CARDs). We discovered that MERS-CoV N protein suppresses RIG-I-CARD-induced, but not MDA5-CARD-induced, IFN-ß and IFN-λ1 promoter activity. By interacting with TRIM25, N protein impedes RIG-I ubiquitination and activation and inhibits the phosphorylation of transcription factors IFN-regulatory factor 3 (IRF3) and NF-κB that are known to be important for IFN gene activation. By employing a recombinant Sindbis virus-EGFP replication system, we showed that viral N protein downregulated the production of not only IFN mRNA but also bioactive IFN proteins. Taken together, MERS-CoV N protein functions as an IFN antagonist. It suppresses RIG-I-induced type I and type III IFN production by interfering with TRIM25-mediated RIG-I ubiquitination. Our study sheds light on the pathogenic mechanism of how MERS-CoV causes disease.IMPORTANCE MERS-CoV causes death of about 35% of patients. Published studies showed that some coronaviruses are capable of suppressing interferon (IFN) expression in the early phase of infection and MERS-CoV proteins can modulate host immune response. In this study, we demonstrated that MERS-CoV nucleocapsid (N) protein suppresses the production of both type I and type III IFNs via sequestering TRIM25, an E3 ubiquitin ligase that is essential for activating the RIG-I signaling pathway. Ectopic expression of TRIM25 rescues the suppressive effect of the N protein. In addition, the C-terminal domain of the viral N protein plays a pivotal role in the suppression of IFN-ß promoter activity. Our findings reveal how MERS-CoV evades innate immunity and provide insights into the interplay between host immune response and viral pathogenicity.

Hepatitis C Virus NS3 Protein Plays a Dual Role in WRN-Mediated Repair of Nonhomologous End Joining.

Hepatitis C virus (HCV) NS3 protein possesses protease and helicase activities and is considered an oncoprotein in virus-derived hepatocellular carcinoma. The NS3-associated oncogenesis has been studied but not fully understood. In this study, we have identified novel interactions of the NS3 protein with DNA repair factors, Werner syndrome protein (WRN) and Ku70, in both an HCV subgenomic replicon system and Huh7 cells expressing NS3. HCV NS3 protein inhibits WRN-mediated DNA repair and reduces the repair efficiency of nonhomologous end joining. It interferes with Ku70 recruitment to the double-strand break sites and alters the nuclear distribution of WRN-Ku repair complex. In addition, WRN is a substrate of the NS3/4A protease; the level of WRN protein is regulated by both the proteasome degradation pathway and HCV NS3/4A protease activity. The dual role of HCV NS3 and NS3/4A proteins in regulating the function and expression level of the WRN protein intensifies the effect of impairment on DNA repair. This may lead to an accumulation of DNA mutations and genome instability and, eventually, tumor development.IMPORTANCE HCV infection is a worldwide problem of public health and a major contributor to hepatocellular carcinoma. The single-stranded RNA virus with RNA-dependent RNA polymerase experiences a high error rate and develops strategies to escape the immune system and hepatocarcinogenesis. Studies have revealed the involvement of HCV proteins in the impairment of DNA repair. The present study aimed to further elucidate mechanisms by which the viral NS3 protein impairs the repair of DNA damage. Our results clearly indicate that HCV NS3/4A protease targets WRN for degradation, and, at the same time, diminishes the repair efficiency of nonhomologous end joining by interfering with the recruitment of Ku protein to the DNA double-strand break sites. The study describes a novel mechanism by which the NS3 protein influences DNA repair and provides new insight into the molecular mechanism of HCV pathogenesis.

Low free T3 to free T4 ratio was associated with low muscle mass and impaired physical performance in community-dwelling aged population.

In aged population, the association of thyroid hormones on physical performance, especially within their normal range, has yet to be elucidated. In this study, individuals with low serum free T3/free T4 were likely to have low muscle mass and impaired physical performance. PURPOSE: We aimed to evaluate the associations of muscle mass, strength, and physical performance with thyroid hormone in an aged euthyroid population from a community-based cohort. METHODS: We examined 918 men aged over 60 years and 1215 postmenopausal women from the Ansung cohort study. Appendicular skeletal muscle mass divided by square of height (ASM/ht2) was used as the muscle mass index. Hand grip strength was measured using a hydraulic dynamometer. Physical performance was assessed using the short physical performance battery (SPPB). RESULTS: Participants with higher tertiles of free T3 and free T3/free T4 were younger and had higher ASM/ht2, stronger hand grip strength, and higher SPPB scores than those in the lower tertiles. In adjusted models, men within higher tertiles of free T3 had higher ASM/ht2 compared with those within lower tertiles (p = 0.033), whereas subjects with higher tertiles of free T4 had lower ASM/ht2 compared with those within lower tertiles (p = 0.043). Subjects within higher tertiles of free T3/free T4 had higher ASM/ht2 (p < 0.001) and better physical performance (p = 0.048) than those within lower tertiles after adjustments. However, free T3, free T4, or free T3/free T4 was not related to hand grip strength after adjustment for covariates. CONCLUSION: Our results thus indicate that in an aged euthyroid population, low serum free T3/free T4 was a better index for low muscle mass and impaired physical performance than serum free T3 or free T4 alone.

Romosozumab or alendronate for fracture prevention in East Asian patients: a subanalysis of the phase III, randomized ARCH study.

Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. Among high-risk postmenopausal East Asian women, romosozumab followed by alendronate was associated with lower incidences of fractures vs alendronate alone. Romosozumab demonstrates potential to address an unmet need in osteoporosis management in Asia. INTRODUCTION: Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. The global ARCH study demonstrated superiority of romosozumab followed by alendronate in reducing fracture risk in high-risk postmenopausal osteoporotic women vs alendronate alone. We report outcomes among ARCH East Asian patients. METHODS: In ARCH, 4093 postmenopausal osteoporotic women with fragility fracture were randomized 1:1 to monthly romosozumab 210 mg or weekly alendronate 70 mg for 12 months, both followed by open-label alendronate. Primary endpoints were incidence of new vertebral fracture (VF) at 24 months and clinical fracture at primary analysis (confirmed fractures in ≥ 330 patients and all patients had opportunity to attend month 24 visit). This post hoc analysis was not powered to detect fracture-rate differences. RESULTS: This analysis included 275 patients from Hong Kong, Korea, and Taiwan. Romosozumab followed by alendronate reduced risk of new VFs at 24 months by 60% (P = 0.11) and clinical fractures at primary analysis by 44% (P = 0.15) vs alendronate alone. Romosozumab followed by alendronate significantly increased mean bone mineral density at 24 months from baseline by a further 9.0%, 3.3%, and 3.0% at the lumbar spine, total hip, and femoral neck vs alendronate alone. Adverse event (AE) rates, including positively adjudicated serious cardiovascular AEs (1.6% vs 1.4% at 12 months for romosozumab vs alendronate), were similar across treatment groups. CONCLUSIONS: Consistent with the global analysis, romosozumab followed by alendronate was associated with lower incidences of new vertebral, clinical, non-vertebral, and hip fractures vs alendronate alone among East Asian patients.

Search for Sub-eV Sterile Neutrinos at RENO.

We report a search result for a light sterile neutrino oscillation with roughly 2200 live days of data in the RENO experiment. The search is performed by electron antineutrino (ν[over ¯]_{e}) disappearance taking place between six 2.8 GW_{th} reactors and two identical detectors located at 294 m (near) and 1383 m (far) from the center of the reactor array. A spectral comparison between near and far detectors can explore reactor ν[over ¯]_{e} oscillations to a light sterile neutrino. An observed spectral difference is found to be consistent with that of the three-flavor oscillation model. This yields limits on sin^{2}2θ_{14} in the 10^{-4}≲|Δm_{41}^{2}|≲0.5 eV^{2} region, free from reactor ν[over ¯]_{e} flux and spectrum uncertainties. The RENO result provides the most stringent limits on sterile neutrino mixing at |Δm_{41}^{2}|≲0.002 eV^{2} using the ν[over ¯]_{e} disappearance channel.

Treatment of lower limb ischaemia in patients with diabetes.

Diabetic chronic limb-threatening ischaemia is a challenging clinical problem with patients at high risk of diabetic foot ulceration (DFU) and limb loss. Patients often remain asymptomatic even in the presence of severe pedal ischaemia until first presenting with tissue loss such as DFU or frank gangrene. Limb salvage units should have the facilities and expertise to provide multidisciplinary team-based holistic care through best medical therapy, rapid diagnosis, prompt revascularisation with endovascular or open surgical techniques and expert wound management. Endovascular revascularisation has become the first line strategy in contemporary clinical practice because of similar outcomes in wound healing and amputation rates in most patients when compared with open surgery. The primary goal is restoration of pulsatile in-line blood flow to the ankle or foot, with an angiosome-directed approach possibly achieving superior outcomes especially in diabetics with poor collaterals. A comprehensive overview of conventional endovascular techniques (such as antegrade true lumen and subintimal approaches), advanced techniques for complex disease (such as retrograde subintimal and pedal-plantar loop approaches or even deep venous arterialisation) and the various treatment options are described. Diabetic limb salvage rates can be excellent with suitable multidisciplinary expertise and care.

Fuel-Composition Dependent Reactor Antineutrino Yield at RENO.

We report a fuel-dependent reactor electron antineutrino (ν[over ¯]_{e}) yield using six 2.8 GW_{th} reactors in the Hanbit nuclear power plant complex, Yonggwang, Korea. The analysis uses 850 666 ν[over ¯]_{e} candidate events with a background fraction of 2.0% acquired through inverse beta decay (IBD) interactions in the near detector for 1807.9 live days from August 2011 to February 2018. Based on multiple fuel cycles, we observe a fuel ^{235}U dependent variation of measured IBD yields with a slope of (1.51±0.23)×10^{-43} cm^{2}/fission and measure a total average IBD yield of (5.84±0.13)×10^{-43} cm^{2}/fission. The hypothesis of no fuel-dependent IBD yield is ruled out at 6.6σ. The observed IBD yield variation over ^{235}U isotope fraction does not show significant deviation from the Huber-Mueller (HM) prediction at 1.3 σ. The measured fuel-dependent variation determines IBD yields of (6.15±0.19)×10^{-43} and (4.18±0.26)×10^{-43} cm^{2}/fission for two dominant fuel isotopes ^{235}U and ^{239}Pu, respectively. The measured IBD yield per ^{235}U fission shows the largest deficit relative to the HM prediction. Reevaluation of the ^{235}U IBD yield per fission may mostly solve the reactor antineutrino anomaly (RAA) while ^{239}Pu is not completely ruled out as a possible contributor to the anomaly. We also report a 2.9 σ correlation between the fractional change of the 5 MeV excess and the reactor fuel isotope fraction of ^{235}U.

Characteristics of morphologic macular abnormalities in neuroimmunology practice.

BACKGROUND: Morphologic macular abnormalities (MMAs) are frequently seen on macular optical coherence tomography (OCT) imaging in neuroimmunology practice, yet studies pragmatically assessing prevalence and risk factors of MMAs to date are limited. OBJECTIVE: To describe the characteristics of MMAs in a neuroimmunology-based academic practice. METHODS: Cross-sectional study of 1450 patients (2900 eyes) who underwent spectral-domain macular OCT between June 2010 and June 2012. The association between MMAs and demographic variables was analyzed using mixed-effects logistic regression. Odds ratios (ORs) were calculated per 5-year age increments. RESULTS: MMAs were observed in 338/2872 eyes (11.7%) of 232/1445 participants (16.1%). The most common abnormalities identified, included drusen (6.0%), epiretinal membrane (ERM; 5.5%), and microcystoid macular pathology (MMP; 1.9%). Overall, patients with MMAs were older (OR: 1.79, p = 5 × 10-5) and more likely to be males (OR: 2.45, p = 0.014). In particular, advancing age was associated with higher risk of drusen and ERM (OR: 1.80 and 4.26, p = 2 × 10-5 and 7 × 10-3, respectively). MMP prevalence declined with age (OR: 0.73, p = 0.015) and was associated with African-American ethnicity (OR: 15.0, p = 5 × 10-5). CONCLUSION: Unexpected or incidental MMAs are common in patients assessed with OCT in neuroimmunology practice, emphasizing the importance of comprehensive OCT image review for risk stratification and appropriate ophthalmology referral.

Cognitive decline in association with hyposmia in idiopathic rapid eye movement sleep behavior disorder: a prospective 2-year follow-up study.

BACKGROUND AND PURPOSE: The aim was to analyze the characteristics and progression of cognitive dysfunction in non-demented idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with baseline olfactory function. METHODS: From a prospective polysomnography-confirmed iRBD cohort, 25 patients (16 patients in 2-year follow-up) and 13 normal controls were included. Initial and 2-year follow-up cognitive functions were analyzed with olfactory function and 18 F-fluorinated-N-3-fluoropropyl-2ß-carboxymethoxy-3ß-(4-iodophenyl)-nortropane (18 F-FP-CIT) uptake in deep nuclei initially. RESULTS: Idiopathic RBD patients had impaired attention, memory and executive function compared to controls. Baseline cognitive tests were comparable between the iRBD subgroups with and without hyposmia. 18 F-FP-CIT uptake tended to be lower in the hyposmic group than in the normosmic group. The olfactory test score was positively correlated with amygdala uptake in iRBD patients (P = 0.027). After 2 years, visuospatial and verbal memory dysfunction worsened more in hyposmics than in normosmics. Lower initial olfactory test score was associated with more severe declines in verbal memory function. CONCLUSIONS: Hyposmia may be a predictive sign of cognitive decline in iRBD patients.

The Spectrum of Vestibular Migraine: Clinical Features, Triggers, and Examination Findings.

OBJECTIVE: To assess the ictal symptoms, interictal symptoms, psychiatric comorbidities, and interictal neuro-otologic examination findings in vestibular migraine (VM). METHODS: Retrospective chart review of 491 patients seen from August 2014 until March 2018 at a tertiary neurology referral center for vestibular disorders to identify patients fulfilling the 2012 VM criteria. RESULTS: One hundred and thirty-one patients (105 women) were identified. Mean age of VM onset was 44.3 (±13.7) years. Preceding the onset of vestibular symptoms, most had migraine (57.3%) and motion sickness (61.1%). It was common to have a family history of migraine (50.8%) and episodic vestibular symptoms (28.1%). Common ictal symptoms were triggered (visually induced and head-motion) and spontaneous vertigo, accompanied by photophobia and phonophobia (118/131 [90.1%] patients), nausea (105/131 [80.2%] patients), aural symptoms (79/131 [60.3%] patients), and headache (65/131 [49.6%] patients). Interictally, many experienced visually induced (116/131 [88.6%] patients), head-motion (86/131 [65.6%] patients), and persistent (67/131 [51.1%] patients) dizziness. Psychiatric comorbidities include anxiety (92/131 [70.2%] patients), depression (53/131 [40.5%] patients), insomnia (38/131 [29.0%] patients), phobic disorders (15/131 [11.5%] patients), and psychogenic disorders (11/131 [8.4%] patients). Common triggers were stress (52/131 [39.7%] patients), bright lights (35/131 [26.7%] patients), weather changes (34/131 [26.0%] patients), and sleep deprivation (34/131 [26.0%] patients). Interictal neuro-otologic examination was abnormal in 56/131 (42.7%), usually hyperventilation-induced, head-shaking-induced, vibration-induced, and positional nystagmus. The most common balance-test finding was impaired sharpened Romberg's test (22/130 [16.9%] patients). CONCLUSIONS: In this single center study, we found that VM typically affects women in their 40s, with a personal and family history of migraine. Typical ictal symptoms were triggered and spontaneous vertigo, associated with photophobia and phonophobia, nausea, aural symptoms, and headache. Interictal vestibular symptoms, comorbid psychiatric disorders, and non-specific interictal neuro-otologic findings were common.

Vestibular Migraine: How to Sort it Out and What to Do About it.

BACKGROUND: Vestibular migraine (VM) is the most common neurologic cause of vertigo in adults and results in significant utilization of health care resources, but remains under-recognized and underdiagnosed. EVIDENCE ACQUISITION: Review of literature in PubMed using the following terms: vestibular migraine, migraine-associated vertigo, vertiginous migraine, benign recurrent vertigo, migraine-associated dizziness, migraine, migraine treatment, Meniere disease (MD), vertebrobasilar ischemia (VBI), posterior circulation stroke, benign paroxysmal positional vertigo, and episodic-ataxia Type 2 (EA2). RESULTS: VM can manifest with a variety of vestibular symptoms, including spontaneous vertigo, triggered vertigo, positional vertigo, and head-motion dizziness. Patients may report more than 1 vestibular symptom. Episodes of vertigo are often, but not always, accompanied by headache. Auditory symptoms are frequently associated with VM attacks and may mimic the manifestations of MD. Other migrainous features that accompany VM attacks include photophobia, phonophobia, osmophobia, and visual aura. Interictally, patients may suffer from persistent dizziness or isolated paroxysmal vestibular symptoms. Mood disorders (particularly anxiety) are often found in VM. Abnormal neuro-otologic findings are not uncommon in patients with VM. Differential diagnoses for VM include MD, VBI, EA2, and migraine with brainstem aura. For rescue treatment, triptans, vestibular suppressants, and/or antiemetic agents may be considered. Pharmacologic migraine preventives (antiepileptics, beta-blockers, and antidepressants) are often useful. CONCLUSIONS: The keys to correctly diagnosing VM is identifying a relationship between vestibular symptoms and migrainous features and being aware of the heterogeneity of manifestations of this enigmatic, but treatable, condition. The principles of treatment of VM include rescue therapy, lifestyle modification, nonpharmacologic migraine preventives, pharmacologic migraine prophylaxis, and treatment of comorbidities.

Measurement of Reactor Antineutrino Oscillation Amplitude and Frequency at RENO.

The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (ν[over ¯]_{e}) oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) ν[over ¯]_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor ν[over ¯]_{e} is observed in the deficit of the measured number of ν[over ¯]_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=[2.68±0.12(stat)±0.07(syst)]×10^{-3} eV^{2}.

Nucleocapsid protein-dependent assembly of the RNA packaging signal of Middle East respiratory syndrome coronavirus.

BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) consists of a positive-sense, single-stranded RNA genome and four structural proteins: the spike, envelope, membrane, and nucleocapsid protein. The assembly of the viral genome into virus particles involves viral structural proteins and is believed to be mediated through recognition of specific sequences and RNA structures of the viral genome. METHODS AND RESULTS: A culture system for the production of MERS coronavirus-like particles (MERS VLPs) was determined and established by electron microscopy and the detection of coexpressed viral structural proteins. Using the VLP system, a 258-nucleotide RNA fragment, which spans nucleotides 19,712 to 19,969 of the MERS-CoV genome (designated PS258(19712-19969)ME), was identified to function as a packaging signal. Assembly of the RNA packaging signal into MERS VLPs is dependent on the viral nucleocapsid protein. In addition, a 45-nucleotide stable stem-loop substructure of the PS258(19712-19969)ME interacted with both the N-terminal domain and the C-terminal domain of the viral nucleocapsid protein. Furthermore, a functional SARS-CoV RNA packaging signal failed to assemble into the MERS VLPs, which indicated virus-specific assembly of the RNA genome. CONCLUSIONS: A MERS-oV RNA packaging signal was identified by the detection of GFP expression following an incubation of MERS VLPs carrying the heterologous mRNA GFP-PS258(19712-19969)ME with virus permissive Huh7 cells. The MERS VLP system could help us in understanding virus infection and morphogenesis.

Horizontal Direction-Changing Positional Nystagmus and Vertigo: A Case of Vestibular Migraine Masquerading as Horizontal Canal BPPV.

Episodic positional vertigo is typically due to benign paroxysmal positional vertigo (BPPV) but may also be a manifestation of vestibular migraine. Distinguishing vestibular migraine from BPPV is essential since the treatment of each disorder is markedly different. The 31-month clinical course of a 41-year-old woman with vestibular migraine causing recurrent positional vertigo is described. During vestibular migraine attacks, she developed left-beating nystagmus in the upright position with removal of fixation, and geotropic horizontal nystagmus during the supine roll test. Interictally, her exam demonstrated positional apogeotropic horizontal nystagmus with the supine roll test, more intense in the supine head left position. Her vestibular migraine was successfully controlled with topiramate and eletriptan.

Recombinant growth hormone therapy for prepubertal children with idiopathic short stature in Korea: a phase III randomized trial.

PURPOSE: Several studies have evaluated the effects of growth hormone (GH) on auxological and biochemical parameters in children with non-GH-deficient, idiopathic short stature (ISS). This study evaluated the efficacy and safety of Growtropin®-II (recombinant human GH) in Korean patients with ISS. METHODS: This was a 1-year, open-label, multicenter, phase III randomized trial of Growtropin®-II in Korean patients with ISS. In total, 70 prepubertal subjects (39 males, 31 females) between 4 and 12 years of age were included in the study. All patients were naive to GH treatment. RESULTS: Annual height velocity was significantly higher in the treatment group (10.68 ± 1.95 cm/year) than the control group (5.72 ± 1.72, p < 0.001). Increases in height and weight standard deviation scores (SDSs) at 26 weeks were 0.63 ± 0.16 and 0.64 ± 0.46, respectively, for the treatment group, and 0.06 ± 0.15 and 0.06 ± 0.28, respectively, for the control group (p < 0.001). Serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) increased significantly in the treatment group at week 26 compared to baseline. However, the SDS for body mass index (BMI) at 26 weeks did not change significantly in either group. Growtropin®-II was well tolerated and safe over 1 year of treatment. CONCLUSIONS: One-year GH treatment for prepubertal children with ISS demonstrated increased annualized velocity, height and weight SDSs, and IGF-1 and IGFBP-3 levels, with a favorable safety profile. Further evaluations are needed to determine the optimal dose, final adult height, and long-term effects of ISS treatment.

Single allele Lmbrd1 knockout results in cardiac hypertrophy.

BACKGROUND/PURPOSE: LMBD1 protein, a type IV-B plasma membrane protein possessing nine putative trans-membrane domains, was previously demonstrated at cellular level to play a critical part in the signaling cascade of insulin receptor through its involvement in regulating clathrin-mediated endocytosis. However, at physiological level, the significance of LMBD1 protein in cardiac development remains unclear. METHODS: To understand the role of Lmbrd1 gene involved in the cardiac function, heterozygous knockout mice were used as an animal model system. The pathological outcomes were analyzed by micro-positron emission tomography, ECG acquisition, cardiac ultrasound, and immunohistochemistry. RESULTS: By studying the heterozygous knockout of Lmbrd1 (Lmbrd1+/-), we discovered that lack of Lmbrd1 not only resulted in the increase of cardiac-glucose uptake, pathological consequences were also observed. Here, we have distinguished that Lmbrd1+/- is sufficient in causing cardiac diseases through a pathway independent of the recessive vitamin B12 cblF cobalamin transport defect. Lmbrd1+/- mice exhibited an increase in myocardial glucose uptake and insulin receptor signaling that is insensitive to the administration of additional insulin. Pathological symptoms such as cardiac hypertrophy, ventricular tissue fibrosis, along with the increase of heart rate and cardiac muscle contractility were observed. As Lmbrd1+/- mice aged, the decrease in ejection fraction and fraction shortening showed signs of ventricular function deterioration. CONCLUSION: The results suggested that Lmbrd1 gene not only plays a significant role in mediating the energy homeostasis in cardiac tissue, it may also be a key factor in the regulation of cardiac function in mice.

Skeletal effects of vitamin D deficiency among patients with primary hyperparathyroidism.

Little is known about the association between vitamin D deficiency and the skeletal phenotypes in primary hyperparathyroidism (PHPT) patients. A low 25-hydroxyvitamin D level was associated with a low bone mineral density and deteriorated hip geometry in women with PHPT in an Asian population where vitamin D deficiency is prevalent. INTRODUCTION: Few studies have examined the effect of vitamin D deficiency on the bone health of primary hyperparathyroidism (PHPT) patients. METHODS: We investigated the skeletal effects of vitamin D deficiency in 79 PHPT patients by assessing bone mineral density (BMD), the trabecular bone score (TBS), and hip geometry, which were measured using dual-energy X-ray absorptiometry (27 men with median age 60 years [53;69]; 52 postmenopausal women with median age of 57 years [53;67]). Cross-sectional data were collected from subjects enrolled in an ongoing PHPT cohort study at Seoul National University Hospital from March 2008 to December 2015. RESULTS: We classified PHPT patients according to 25-hydroxyvitamin D (25(OH)D) levels (<20 vs. ≥20 ng/ml). After adjusting for age and body mass index, women with vitamin D deficiency had lower BMDs at the lumbar spine (LS) and femur neck (FN) than women who had sufficient levels of vitamin D (LS, 0.903 ± 0.138 vs. 0.998 ± 0.184 g/cm2; FN, 0.715 ± 0.084 vs. 0.791 ± 0.113 g/cm2; P < 0.05). However, the total hip BMD and the TBS were not significantly different between the two groups. In the hip geometry analysis, the cross-sectional area, cross-sectional moment of inertia, and section modulus were also significantly lower in women with vitamin D deficiency than in those without. No significant difference was found in the BMD, TBS, or hip geometry according to 25(OH)D levels in men. CONCLUSION: Vitamin D deficiency may be associated with a low BMD and deteriorated hip geometry in postmenopausal women with PHPT.