East Syndrome Research Articles

Personnel Contamination During PPE Removal

The secondary cases of Ebola virus disease in the U.S. — and of Middle East respiratory syndrome in South Korea — highlight limitations in current strategies for preventing transmission of infectious agents in the healthcare setting. Contamination of hospital surfaces and of healthcare workers' skin and clothing contributes to the spread of pathogens and can affect the safety of …

Outbreak of Middle East Respiratory Syndrome (MERS): A Public Health Concern

No Abstract AvailableJournal of Current and Advance Medical Research, 2015;2(2):28-29

Abstract 113: Renal Phenotype of Inwardly Rectifying Potassium Channel Kcnj16 (Kir 5.1) Knockout in the Dahl Salt-Sensitive Rats

The inward-rectifying channels play an important role in the control of resting membrane potential and tubular homeostasis in the kidney. Kcnj16 (Kir 5.1) form a heteromeric channel with Kcnj10 (Kir 4.1) at the basolateral membranes of aldosterone-sensitive distal nephron (ASDN); mutations in the human KCNJ10 gene result in SeSAME)/EAST syndrome, a complex disorder that includes salt wasting and hypokalemic alkalosis. To illuminate the importance of Kcnj16 (Kir 5.1) in the context of a disease state in vivo, we generated a Kcnj16 knockout rat model in Dahl salt-sensitive (SS) background by using ZFN technology. ZFN against Kcnj16 caused a 18-bp in-frame deletion that occurred in the second protein transmembrane domain. IHC analysis demonstrated highly specific expression of Kcnj16 on the basolateral membranes of ASDN in the control kidneys of SS rats, which was completely abolished in Kcnj16-/- rats. The electrophysiological recording of K+ channels in the CCD basolateral membrane revealed activity of only homomeric Kcnj10 channels (21 pS channel in Kcnj16-/- rats compared to both 41 and 21 pS channels in SS rats). Thus, these data provide evidence of successful knock out of this protein and consequent degradation of the channel in renal tubules. The Kcnj16-/- knockout in SS rat induces electrolyte imbalance, epileptic seizures and result in changes in development (37% reduction in body and 54% in kidney mass). The mean arterial pressure was significantly lower in Kcnj16-/- compared to SS rats (91.3±1.8 to 104.7±5.5 mmHg) when animals were fed a low salt (0.4%) diet. Knockout of Kcnj16 resulted in hypokalemia (4.25±0.09 vs 2.08±0.12 mmol/L in serum of control vs KO rats), hypermagnesemia (0.49±0.02 vs 0.63±0.01 mmol/L in serum of control vs KO rats), and FSGS. Urea electrolyte balance was also disturbed compared to control animals. Importantly, change of the diet to high salt (4%) caused mortality of KO rats within 1-2 days. These data demonstrate critical role of Kcnj16 channels in renal salt handling and in the development of salt-sensitive hypertension.

Vasopressin-induced stimulation of the Na+-activated K+ channels is responsible for maintaining the basolateral K+ conductance of the thick ascending limb (TAL) in EAST/SeSAME syndrome

The renal phenotype of EAST syndrome, a disease caused by the loss-of-function-mutations of Kcnj10 (Kir4.1), is a reminiscence of Gitelman's syndrome characterized by the defective function in the distal convoluted tubule (DCT). The aim of the present study is to test whether antidiuretic hormone (vasopressin)-induced stimulation of the Na+-activated 80–150pS K+ channel is responsible for compensating the lost function of Kcnj10 in the thick ascending limb (TAL) of subjects with EAST syndrome. Immunostaining and western blot showed that the expression of aquaporin 2 (AQP2) was significantly higher in Kcnj10−/− mice than those of WT littermates, suggesting that the disruption of Kcnj10 stimulates vasopressin response in the kidney. The role of vasopressin in stimulating the basolateral K+ conductance of the TAL was strongly indicated by the finding that the application of arginine-vasopressin (AVP) hyperpolarized the membrane in the TAL of Kcnj10−/− mice. Application of AVP significantly stimulated the 80–150pS K+ channel in the TAL and this effect was blocked by tolvaptan (V2 receptor antagonist) or by inhibiting PKA. Moreover, the water restriction for 24h significantly increased the probability of finding the 80–150pS K+ channel and the K+ channel open probability in the TAL. The application of a membrane permeable cAMP analog also mimicked the effect of AVP and activated this K+ channel, suggesting that cAMP–PKA pathway stimulates the 80–150pS K+ channels. The role of the basolateral K+ conductance in maintaining transcellular Cl− transport is further suggested by the finding that the inhibition of basolateral K+ channels significantly diminished the AVP-induced stimulation of the basolateral 10pS Cl− channels. We conclude that vasopressin stimulates the 80–150pS K+ channel in the TAL via a cAMP-dependent mechanism. The vasopressin-induced stimulation of K+ channels is responsible for compensating lost function of Kcnj10 thereby rescuing the basolateral K+ conductance which is essential for the transport function in the TAL.

Current status of Middle East respiratory syndrome in children

Since Middle East respiratory syndrome (MERS) was first reported in 2012, the severe clinical symptoms and high mortality have been concerned.The epidemiology, possible pathogenesis, clinical manifestations (especially in children), treatment and counter measures of MERS were reviewed in this paper. Key words: Middle East respiratory syndrome; Coronavirus; Child; Treatment; Prevention

A review on the epidemiology of Middle East Respiratory Syndrome

A review on the epidemiology of Middle East Respiratory Syndrome

Epidemiological investigation on human coronovirus infection in hospitalized children with lower respiratory tract infection in Shanghai

Objective To investigate the epidemiological and clinical characteristics of human coronovirus (HCoV) infection in hospitalized children with acute lower respiratory tract infection (ALRTI) in Shanghai. Methods A retrospective cohort study was conducted between October 2009 and September 2012. Five hundred and fifty-four cases of ALRTI in children under 5 years were enrolled. HCoV and other respiratory viruses in archival nasopharyngeal aspirate specimens were detected by a commercial Seeplex RV12 ACE detection kit. HCoV pan-family reverse transcription polymerase chain reaction (PCR) was performed to screen all known six HCoV, including HCoV-229E, HCoV-OC43, severe acute respiratory syndrome (SARS)-CoV, HCoV-NL63, HCoV-HKU1, and real-time PCR was performed to screen Middle East respiratory syndrome (MERS)-CoV. MEGA5.0 software was used to perform sequence alignment and phylogenetic tree analysis. Results In 554 samples, at least one virus was identified in 273 cases (48.56%) and HCoV was detected in 18 cases (3.25%), among which 13 were HCoV-OC43/HKU1 positive, 5 HCoV-229E/NL63 positive. No high pathogenic MERS-CoV and SARS-CoV were detected. The median age of 18 children with HCoV infection was 18 months (1–48 months) with 12 boys and 6 girls. Seventeen cases had fever, 11 cough, 9 tachypenea and 1 wheeze. Seven received oxygen therapy, and 6 were admitted to intensive care unit for treatment. Two who was in ordinary ward were coinfected with adenovirus and human rhinovirus. All 18 cases recovered or improved on discharge. Six was infected in autumn, 5 in winter, 3 in spring and 4 in summer. Of 8 HCoV-positive samples which were sequenced, each 3 samples belonged to HKU1 and 229E subtypes, respectively, and each 1 belonged to OC43 and NL63 subtypes, respectively. Conclusions HCoV is a relatively common viral pathogen among hospitalized young children with ALRTI in Shanghai. No high pathogenic MERS-CoV is detected. HCoV can cause severe infection with favorable outcome. Key words: Human coronovirus; Lower respiratory tract infections; Child

Healthcare-Associated MERS-CoV Outbreak

Because of its high mortality rate, Middle East respiratory syndrome coronavirus (MERS-CoV) infection has received much attention since its

Lessons learned from Middle East respiratory syndrome coronavirus cluster in Korea

중동호흡기증후군 사태의 교훈 595 2015년 5월 20일 국내에서 중동호흡기증후군(Middle East respiratory syndrome, MERS; 메르스) 확진 환자가 처음 발생한 것을 시작으로 7월 6일 현재 확진 환자 1,860명, 사망자 33명이 발생하였다[1]. 사우디아라비아의 메르스 코 로나바이러스 발생 이후 우리나라는 공식적으로 가장 많은 확진 환자가 발생한 국가이며 메르스 코로나바이러스 클러 스터가 병원을 중심으로 발생하여 우리나라의 감염병관리 역량의 부실을 전 세계에 보여주는 계기가 되었다[2]. 이번 사태는 메르스 바이러스에게 낙타보다 대한민국 보건의료체 계가 더 좋은 숙주라는 사실을 확인시켜 주었다는 지적과 같 이 우리 사회의 전반적 보건의료체계 문제점이 드러났다[3]. 메르스 사태의 경험과 교훈에 관한 본 특집은 향후 재발방 지와 정책마련의 측면에서 매우 중요한 의미를 갖는다. 대한 감염학회가 제시한 의견에 의하면 노출된 환자와 의료진의 규모가 전 세계적으로 유례없는 숫자이며, 메르스는 지역사 회에서는 밀접접촉에 의한 비말전파가 감염경로이지만 병원 의 경우 에어로졸이 생성되는 상황에서 더 먼 거리에서 전 파가 가능하므로 이에 대한 관리와 격리시설 확보유지가 매 우 중요함을 지적하고 있다. 또한 발열 환자에 대한 선별치 료 기능과 폐렴 환자를 선제적으로 격리치료하는 것이 필요 하다는 지적은 앞으로 우리나라 감염관리에 있어서 매우 중 요한 개선방향이다[4]. 응급실 감염관리 역량강화의 경우 3차병원 응급실 체류기 간 증가, 응급실 감염에 취약한 감염방지시설 및 장비, 환자 와 보호자들이 통제가 되지 않는 개방형 응급실 문제 등을 지적하고 있는 Lee [5]의 연구는 주목할 만하다. 특히 우리 나라 상위 20개 응급센터의 평균 재실기간은 14.5시간, 응 급실 인력부족문제, 그리고 응급실 과밀화 등을 해결하기 위 해서는 현재 응급의료에 대한 보험수가 원가보전율이 72% 인 문제점을 근본적으로 해결하여야 하며 구체적으로는 응 급실 과밀화와 체류시간 감소, 응급실 의료인력 확충을 시급 히 해결하여야 한다. 응급실 의료인력 확충의 경우 권역응급 의료센터는 내원환자 30,000명당 최소 5명의 전담 전문의가 있어야 한다는 인력기준은 주목할 만한 내용이다[5]. 국민들의 병원이용문화와 간병 및 방문문화의 개선은 의 료전달체계의 정상화라는 목표 하에 추진되어야 할 것이 다. 포괄간호제도의 도입, 격리실 이용에 대한 건강보험 급 중동호흡기증후군 사태의 교훈 최 재 욱 | 고려대학교 의과대학 예방의학교실, 환경의학연구소, 대한의사협회 의료정책연구소 Lessons learned from Middle East respiratory syndrome coronavirus cluster in Korea Jae Wook Choi, MD Department of Preventive Medicine, Korea University College of Medicine, Institute for Occupational and Environmental Health, Korea University, Research Institute for Healthcare Policy, Korean Medical Association, Seoul, Korea

Distal convoluted tubule.

The distal convoluted tubule (DCT) is a short nephron segment, interposed between the macula densa and collecting duct. Even though it is short, it plays a key role in regulating extracellular fluid volume and electrolyte homeostasis. DCT cells are rich in mitochondria, and possess the highest density of Na+/K+-ATPase along the nephron, where it is expressed on the highly amplified basolateral membranes. DCT cells are largely water impermeable, and reabsorb sodium and chloride across the apical membrane via electroneurtral pathways. Prominent among this is the thiazide-sensitive sodium chloride cotransporter, target of widely used diuretic drugs. These cells also play a key role in magnesium reabsorption, which occurs predominantly, via a transient receptor potential channel (TRPM6). Human genetic diseases in which DCT function is perturbed have provided critical insights into the physiological role of the DCT, and how transport is regulated. These include Familial Hyperkalemic Hypertension, the salt-wasting diseases Gitelman syndrome and EAST syndrome, and hereditary hypomagnesemias. The DCT is also established as an important target for the hormones angiotensin II and aldosterone; it also appears to respond to sympathetic-nerve stimulation and changes in plasma potassium. Here, we discuss what is currently known about DCT physiology. Early studies that determined transport rates of ions by the DCT are described, as are the channels and transporters expressed along the DCT with the advent of molecular cloning. Regulation of expression and activity of these channels and transporters is also described; particular emphasis is placed on the contribution of genetic forms of DCT dysregulation to our understanding.

MERS-CoV Replicates in the Upper Respiratory Tracts of Camels

Camels have been implicated as one source of human infection with Middle East respiratory syndrome coronavirus (MERS-CoV; NEJM JW Infect Dis Apr 25

Transmission of MERS-CoV to Household Contacts

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a human respiratory pathogen that can cause life-threatening illness. It was first

Travel implications of emerging coronaviruses: SARS and MERS-CoV.

SummaryThe emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and of the Middle East Syndrome Cornavirus (MERS-CoV) caused widespread fear and concern for their potential threat to global health security. There are similarities and differences in the epidemiology and clinical features between these two diseases. The origin of SARS-COV and MERS-CoV is thought to be an animal source with subsequent transmission to humans. The identification of both the intermediate host and the exact route of transmission of MERS-CoV is crucial for the subsequent prevention of the introduction of the virus into the human population. So far MERS-CoV had resulted in a limited travel-associated human cases with no major events related to the Hajj.

Epidemiological and clinical features of human coronavirus in hospitalized children with respiratory infections in Chongqing

Objective To detect the existence of Middle East respiratory syndrome coronavirus (MERS-CoV) in the hospitalized children with respiratory infection in Chongqing area and study the clinical symptoms associated with the detection of 4 human coronaviruses (HCoV): HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 types. Methods Nasopharyngeal aspirates collected over a 4-year period (from Jul.2009 to Jun.2013) from pediatric inpatients with respiratory infection were analyzed for the presence of 5 coronavirus subtypes by using multi-nested polymerase chain reaction and sensitive real-time polymerase chain reaction assays.The clinical characteristics associated with coronavirus infection were examined. Results MERS-CoV was not found and other 4 coronaviruses were positive in 74(3.38%) of 2 188 children, in which 31(1.42%), 21(0.96%), 6(0.27%) and 15 (0.69%) specimens were positive for subtypes HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1, respectively, and 1 case was co-detected with HCoV-229E and HCoV-NL63.HCoV infection was sporadic in the whole year, of which HCoV-229E and HCoV-NL63 infection mainly occurred in summer and autumn, while HCoV-OC43 in summer and HCoV-HKU1 in winter.Of the 74 children, 56(75.7%) were male, 36(48.6%)were at ages of 0-6 months and 19(25.7%)at 7-12 months, and 20(27.0%) had underlying diseases .The clinical symptoms of HCoV infection included cough(66/74 cases, 89.2%), sputum(53/74 cases, 71.6%), wheezing(39/74 cases, 52.7%), fever(33/74 cases, 44.6%)and diarrhea(26/74 cases, 35.1%). Most patients were diagnosed as pneumonia(54/74 cases, 73.0%), including 10 cases of severe pneumonia.Fifty patients were co-infected with another respiratory virus, in which respiratory syncytial virus was the mostly detected.HKU1 was the most likely to detect in the co-infected group.Patients who were co-infected with another respiratory virus were more likely to have cough and wheezing than sole-infected patients (P<0.05). Conclusions No MERS-CoV existed in the hospitalized children with respiratory infection in Chongqing area and HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 are of low prevalent.HCoV that primarily infects male infants less than 1 year old and lead to lower respiratory tract infection, especially in children with underlying diseases and plays a role in severe pneumonia disease. Key words: Middle East respiratory syndrome coronavirus; Coronavirus; Molecular epidemiology; Respiratory infection; Child

Serologic Evidence of MERS-CoV Infection in Dromedaries in Africa

Recent studies provide virologic and serologic evidence that the Middle East respiratory syndrome coronavirus (MERS-CoV) has been circulating among dromedary camels (NEJM JW Infect Dis Apr 25 2014). Many camels in the Arabian Peninsula come from Africa. In two recent studies, researchers assessed whether the animals might be infected before reaching the Middle East. Corman and colleagues tested samples collected between 1992 and 2013 from dromedaries in three regions in Kenya. Among 774 serum …

Camels and MERS-CoV: New Results, Little Clarity

Several recent studies provide details that, taken together, yield a fuller picture of the ecology of the Middle East respiratory syndrome coronavirus

Association of host tropism of Middle East syndrome coronavirus with the amino acid structure of host cell receptor dipeptidyl peptidase 4.

The Middle East syndrome coronavirus (MERS-CoV) is a recently emerging betacoronavirus with high fatality. Recently, dipeptidyle peptidase (CD26, DPP4) was identified as the host cell receptor for MERS-CoV. Interestingly, despite of common presence of DPP4 receptors the binding and infection of various cells shows imminent variability. In this report, we provide a tool for prediction of the host tropism of the virus based on the host receptor binding interface. We found out that, in the binding of MERS-CoV to cells the amino acid residues in lancets 4 and 5 of DPP4 receptor, namely K267, Q286, T288, R317, R336, Q344 A291, L294, and I295 are involved. Changes in these residues correspond to profound decrease in virus binding to cells. The nine residues at the interface between the virus spikes and the lancets 4 and 5 of host DPP4 can be used as a predictive tool for the host tropism and virus affinity to host cell receptors.

MERS-CoV: Virologic Confirmation in Camels

In October 2013, laboratory-confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infection was recorded in two men who were exposed both to animals and to each other on a Qatari farm. Investigators collected serum and rectal and nasal swab specimens from all 14 dromedary camels on the farm for virologic study, as well as stool samples from three …

Epilepsy in kcnj10 Morphant Zebrafish Assessed with a Novel Method for Long-Term EEG Recordings

We aimed to develop and validate a reliable method for stable long-term recordings of EEG activity in zebrafish, which is less prone to artifacts than current invasive techniques. EEG activity was recorded with a blunt electrolyte-filled glass pipette placed on the zebrafish head mimicking surface EEG technology in man. In addition, paralysis of agarose-embedded fish using D-tubocurarine excluded movement artifacts associated with epileptic activity. This non-invasive recording technique allowed recordings for up to one hour and produced less artifacts than impaling the zebrafish optic tectum with a patch pipette. Paralyzed fish survived, and normal heartbeat could be monitored for over 1h. Our technique allowed the demonstration of specific epileptic activity in kcnj10a morphant fish (a model for EAST syndrome) closely resembling epileptic activity induced by pentylenetetrazol. This new method documented that seizures in the zebrafish EAST model were ameliorated by pentobarbitone, but not diazepam, validating its usefulness. In conclusion, non-invasive recordings in paralyzed EAST syndrome zebrafish proved stable, reliable and robust, showing qualitatively similar frequency spectra to those obtained from pentylenetetrazol-treated fish. This technique may prove particularly useful in zebrafish epilepsy models that show infrequent or conditional seizure activity.

KCNJ10 Mutations Display Differential Sensitivity to Heteromerisation with KCNJ16

Background/Aims: Mutations in the inwardly-rectifying K⁺-channel KCNJ10/Kir4.1 cause autosomal recessive EAST syndrome (epilepsy, ataxia, sensorineural deafness and tubulopathy). KCNJ10 is expressed in the distal convoluted tubule of the kidney, stria vascularis of the inner ear and brain glial cells. Patients diagnosed clinically with EAST syndrome were genotyped and mutations in KCNJ10 were studied functionally. Methods: Patient DNA was amplified and sequenced, and new mutations were identified. Mutant and wild-type KCNJ10 constructs were cloned and heterologously expressed in Xenopus oocytes. Whole-cell K⁺ currents were measured by 2-electrode voltage clamping and channel expression was analysed by Western blotting. Results: We identified 3 homozygous mutations in KCNJ10 (p.F75C, p.A167V and p.V91fs197X), with mutation p.A167V previously reported in a compound heterozygous state. Oocytes expressing wild-type human KCNJ10 showed inwardly rectified currents, which were significantly reduced in all of the mutants (p < 0.001). Specific inhibition of KCNJ10 currents by Ba²⁺ demonstrated a large residual function in p.A167V only, which was not compatible with causing disease. However, co-expression with KCNJ16 abolished function in these heteromeric channels almost completely. Conclusion: This study provides an explanation for the pathophysiology of the p.A167V KCNJ10 mutation, which had previously not been considered pathogenic on its own. These findings provide evidence for the functional cooperation of KCNJ10 and KCNJ16. Thus, in vitro ascertainment of KCNJ10 function may necessitate co-expression with KCNJ16.