A quick algorithmic review on management of viral infectious diseases in pediatric solid organ transplant recipients.

Pediatric solid organ transplant is a life-saving procedure for children with end-stage organ failure. Viral infections are a common complication following pediatric solid organ transplantation (SOT), which can lead to increased morbidity and mortality. Pediatric solid organ transplant recipients are at an increased risk of viral infections due to their immunosuppressed state. The most commonly encountered viruses include cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), adenoviruses, and BK polyomavirus. Prevention strategies include vaccination prior to transplantation, post-transplant prophylaxis with antiviral agents, and preemptive therapy. Treatment options vary depending on the virus and may include antiviral therapy and sometimes immunosuppression modification. This review provides a Quick Algorithmic overview of prevention and treatment strategies for viral infectious diseases in pediatric solid organ transplant recipient.

Neurologic Manifestations of Coronavirus Disease 2019 in Children: An Iranian Hospital-Based Study.

BACKGROUND: COVID-19 infection and its neurological manifestations were seen in children although less common than adults. The aim of this study was to determine the frequency of different types of neurologic findings of hospitalized children with COVID-19. ]. METHODS: This retrospective study was performed on hospitalized pediatric patients aged≤18 years with confirmed SARS-CoV-2 at Children's Medical Center Hospital. Neurological manifestations were defined as the presence of any of the following symptoms: seizure, altered mental status, behavioral/personality change, ataxia, stroke, muscle weakness, smell and taste dysfunctions, and focal neurological disorders. RESULTS: Fifty-four children with COVID-19 were admitted and their mean age was 6.94±4.06 years. Thirty-four of them (63%) were male. The most frequent neurological manifestation was seizure (19 [45%]) followed by muscle weakness (11 [26%]), loss of consciousness (10 [23%]), and focal neurological disorders (10 [23%]). Other neurological manifestations consisted of headache (n=7), movement disorders (n=6), behavioral/personality change (n=5), ataxia (n=3), and stroke (n=3). Twenty-nine percent of our patients had leukocytosis. A neutrophil count above 70% was seen in 31% of participants. Among our patients, 81% had a positive reverse-transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2. CONCLUSION: During the current pandemic outbreak, hospitalized children with COVID-19 should be evaluated for neurological signs because it is common among them and should not be under-estimated.

Early Childhood COVID-19: A Comparative Report of 20,506 Cases.

This report includes a retrospective analysis of 20506 children aged under 6 years old admitted with Coronavirus Disease of 2019 in Iranian hospitals. The total mortality rate was 2.9%, and 5.7% required mechanical ventilation. We demonstrate a higher mortality rate in comparison with existing studies as well as identifying clinical predictors of survival.

A case of Candida metapsilosis conjunctivitis in a neonate admitted to the cardiac heart intensive care unit.

Harmless commensal Candida species, especially uncommon and rare ones may rarely cause a serious infection. Candida metapsilosis is a recently described yeast that is phenotypically indistinguishable from Candida parapsilosis and molecular methods are essential for its identification. We report the first case of Candida conjunctivitis due to C. metapsilosis obtained from the eye discharge of a 40-day-old girl with congenital heart disease admitted to the cardiac intensive care unit (CICU). The yeast isolate was identified by sequencing the entire ITS1-5.8 rRNA-ITS2 region. Antifungal susceptibility testing performed according to the CLSI M27-A3 showed that the isolate was susceptible to amphotericin B, fluconazole, itraconazole, voriconazole, clotrimazole, nystatin, terbinafine, 5-fluorocytosine, and caspofungin. Differentiation of the fungal new species allows us the accurate diagnosis and treatment, and a better understanding the microbial epidemiology.

The first case of Wickerhamomyces anomalus fungemia in Iran in an immuneodeficient child, a review on the literature.

The incidence of invasive candidiasis in pediatric patients is increasing and is associated with significant morbidity and mortality. C. pelliculosa has been rarely reported as a human pathogen, however, it has been associated with serious nosocomial infections and clonal outbreaks with poor clinical outcomes in immunocompromised children were reported. Here, we describe the first case of candidemia due to Candida pelliculosa in a 5-year-old immunocompromised male suffered from Griscelli syndrome with hemophagocytic syndrome hospitalized in the pediatric intensive care unit (PICU), Tehran, Iran. In addition, the history of reported cases or case-series due to C. pelliculosa is reviewed.

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in children: update and new insights from the second report of an Iranian referral hospital.

INTRODUCTION: Here, we are sharing our second report about children affected by Multisystem Inflammatory Syndrome in Children (MIS-C). The aim of the present study was to update our knowledge about children with MIS-C. Furthermore, we tried to compare clinical manifestations, laboratory features and final outcome of patients based on disease severity, in order to better understanding of the nature of this novel syndrome. METHODS: This retrospective study was conducted at Children's Medical Center Hospital, the hub of excellence in paediatrics in Iran, located in Tehran, Iran. We reviewed medical records of children admitted to the hospital with the diagnosis of MIS-C from July 2020 to October 2021. RESULTS: One hundred and twenty-two patients enrolled the study. Ninety-seven (79.5%) patients had mild to moderate MIS-C (MIS-C without overlap with KD (n = 80); MIS-C overlapping with KD (n = 17)) and 25 (20.5%) patients showed severe MIS-C. The mean age of all patients was 6.4 ± 4.0 years. Nausea and vomiting (53.3%), skin rash (49.6%), abdominal pain (46.7%) and conjunctivitis (41.8%) were also frequently seen Headache, chest pain, tachypnea and respiratory distress were significantly more common in patients with severe MIS-C (P < 0.0001, P = 0.021, P < 0.0001 and P < 0.0001, respectively). Positive anti-N severe acute respiratory syndrome coronavirus 2 IgM and IgG were detected in 14 (33.3%) and 23 (46.9%) tested patients, respectively. Albumin, and vitamin D levels in children with severe MISC were significantly lower than children with mild to moderate MIS-C (P < 0.0001, P = 0.05). Unfortunately, 2 (1.6%) of 122 patients died and both had severe MIS-C. CONCLUSION: Patients with MIS-C in our region suffer from wide range of signs and symptoms. Among laboratory parameters, hypoalbuminemia and low vitamin D levels may predict a more severe course of the disease. Coronary artery dilation is frequently seen among all patients, regardless of disease severity.

Evaluation of human bocavirus as well as other well-known viral etiologic agents by PCR in the cerebrospinal fluid of children with clinical impression of viral meningoencephalitis referred to the Children's Medical Center in Tehran, Iran, from 2019 to 2020.

Viral meningoencephalitis is one of the most important diseases that most commonly affect children. In many cases of viral meningoencephalitis, the underlying cause of the disease is not identified, raising the possibility of a variety of pathogens that are not routinely tested. Bocaviruses belong to a newly identified class of viruses that have been reported in some studies to be associated with viral encephalitis. In the present study, we investigated the prevalence of bocaviruses and other viruses in the patients suspected of having viral encephalitis and their associations with various demographic and clinical variables. Two hundred patients with suspected viral meningoencephalitis referred to Children's Medical Center were studied from 2019 to 2020. Age, sex, length of hospitalization, and course of the disease were gathered. Cerebrospinal fluid (CSF) samples were taken from the patients and subjected to biochemical examinations and PCR to identify the underlying cause. Bocaviruses were detected in none of the DNA samples extracted from the CSF specimens. The most identified organisms were mumps and enteroviruses. In 92% of cases, the underlying cause was not identified. PCR-based identification of the underlying causes of viral meningoencephalitis in CSF specimens was not successful in most cases. Bocavirus was not found in any of the collected CSF samples. Further studies are required for drawing more accurate conclusions.

Children with SARS-CoV-2 infection during the novel coronaviral disease (COVID-19) outbreak in Iran: an alarming concern for severity and mortality of the disease.

BACKGROUND: The rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections led to public health crises globally and the number of pediatric patients with Coronavirus Disease 2019 (COVID-19) is still rising. The aim of this study was to describe the epidemiological, clinical, laboratory, and imaging features of hospitalized patients with COVID-19 at an Iranian referral pediatrics hospital and to compare these parameters between hospitalized patients with and without severe disease, multisystem inflammatory syndrome in children (MIS-C) and children with acute COVID-19, as well as deceased and discharged cases. METHODS: This study included hospitalized children and adolescents (≤ 18 years) with suspected COVID-19 who had positive results for SARS-CoV-2. RESULTS: Among the 262 patients with suspected COVID-19, 142 confirmed COVID-19 cases were included in the study. A total of 11 children were diagnosed as MIS-C. The majority of the cases with MIS-C were male, (n = 9, 82%) which is significantly higher than children (n = 61, 47%) with acute COVID-19 (P = 0.03). Fifty patients (35%) were shown to have a more severe form of COVID-19. Ninety percent of the cases (n = 45) with severe COVID-19 had comorbidities that was significantly higher than cases with non-severe or mild disease (n = 41, 45%; P < 0.0001). A mortality rate of 10% was reported (n = 14). Ninety-three percent of the deceased cases (n = 13) had comorbidities that were significantly higher than discharged patients (n = 73, 57%; P = 0.009). CONCLUSION: The increasing number of children with severe COVID-19 is cause for great concern. Underlying diseases, mainly cardiovascular diseases, cancer, and malignancies, are associated with greater risk of development of severe COVID-19 and even death in children. On the other hand, pediatric patients with MIS-C usually develop a milder form of the disease. However, evaluation specific immunological responses in children to explore the delayed inflammatory syndrome are highly recommended.

Candidemia among Hospitalized Pediatric Patients Caused by Several Clonal Lineages of Candida parapsilosis.

Candida parapsilosis is the second most common cause of candidemia in some geographical areas and in children in particular. Yet, the proportion among children varies, for example, from 10.4% in Denmark to 24.7% in Tehran, Iran. As this species is also known to cause hospital outbreaks, we explored if the relatively high number of C. parapsilosis pediatric cases in Tehran could in part be explained by undiscovered clonal outbreaks. Among 56 C. parapsilosis complex isolates, 50 C. parapsilosis were genotyped by Amplified Fragment Length Polymorphism (AFLP) fingerprinting and microsatellite typing and analyzed for nucleotide polymorphisms by FKS1 and ERG11 sequencing. AFLP fingerprinting grouped Iranian isolates in two main clusters. Microsatellite typing separated the isolates into five clonal lineages, of which four were shared with Danish isolates, and with no correlation to the AFLP patterns. ERG11 and FKS1 sequencing revealed few polymorphisms in ERG11 leading to amino-acid substitutions (D133Y, Q250K, I302T, and R398I), with no influence on azole-susceptibilities. Collectively, this study demonstrated that there were no clonal outbreaks at the Iranian pediatric ward. Although possible transmission of a diverse C. parapsilosis community within the hospital cannot be ruled out, the study also emphasizes the necessity of applying appropriately discriminatory methods for outbreak investigation.

Little Hearts Are Affected by COVID19: Importance of the Myocardial Systolic Evaluation.

Background: Identifying the cardiac changes could help design measures to recover the cardiovascular system and lessen the mortality and morbidity rate. Accordingly, this cross-sectional study was performed to evaluate the echocardiography indices which are indicators of the cardiac alterations of the children with COVID19 infection. Methods: This study was performed as a cross-sectional study evaluating echocardiography indices in children infected with COVID19. Fifteen children, known cases of the COVID19, and 14 healthy children were enrolled. Evaluated parameters include left ventricle ejection fraction (LVEF), left ventricle end-diastolic diameter (LVED), mitral valve Sa (MV Sa), Tricuspid annular plane systolic excursion (TAPSE), and laboratory parameters. Results: The participants' mean age and weight were 62.8 (±48.0) months and 19.95 (±15.67) kg, respectively. None of the laboratory and echocardiography parameters differed between males and females, between patients with and without positive past medical history, between the patients with and without respiratory tract symptoms, and between patients with and without GI tract symptoms (P.0.05). Patients had significantly higher TAPSE (p = 0.027), although MV Sa (p = 0.01) was significantly higher among healthy children. LV EF (p = 0.425) and LVED diameter (p = 0.603) were not different significantly. None of the patients had pericardial effusion, pleural effusion, and cardiac tamponade. Conclusion: The heart can be involved during the disease course in children, even at the level of echocardiography indices. This could contribute to a worse prognosis, higher morbidity, and mortality rate, especially in patients with overt myocardial involvement. Non-classic indicators, including LVEF, may not be conclusive for cardiac involvement in non-symptomatic patients.

SARS-CoV-2 RNAaemia in children: An Iranian referral hospital-based study.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is generally detected in nasopharyngeal swabs, viral RNA can be found in other samples including blood. Recently, associations between SARS-CoV-2 RNAaemia and disease severity and mortality have been reported in adults, while no reports are available in pediatric patients with coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the mortality, severity, clinical, and laboratory findings of SARS-CoV-2 RNA detection in blood in 96 pediatric patients with confirmed COVID-19. Among all patients, 6 (6%) had SARS-CoV-2 RNAaemia. Out of the six patients with SARS-CoV-2 RNAaemia, four (67%) had a severe form of the disease, and two out of the 6 patients with SARS-CoV-2 RNAaemia passed away (33%). Our results show that the symptoms more commonly found in the cases of COVID-19 in the study (fever, cough, tachypnea, and vomiting), were found at a higher percentage in the patients with SARS-CoV-2 RNAaemia. Creatine phosphokinase and magnesium tests showed significant differences between the positive and negative SARS-CoV-2 RNAaemia groups. Among all laboratory tests, magnesium and creatine phosphokinase could better predict SARS-CoV-2 RNAemia with area under the curve  levels of 0.808 and 0.748, respectively. In conclusion, 67% of individuals with SARS-CoV-2 RNAaemia showed a severe COVID-19 and one-third of the patients with SARS-CoV-2 RNAaemia passed away. Our findings suggest that magnesium and creatine phosphokinase might be considered as markers to estimate the SARS-CoV-2 RNAaemia.

Clinical Misdiagnosis of COVID-19 Infection with Confusing Clinical Course.

BACKGROUND: Similarities in the febrile course and other manifestations of some diseases may lead to clinical misdiagnosis of COVID-19 infection. Here, we report a case in a young child with a potentially confusing clinical course. Case Presentation. A 29-month-old boy presented with a 2-month history of fever. His PCR test for COVID-19 was positive, and there was pleural effusion plus positive findings in the lower left lobe of the lung on computed tomography scan. Mid-sized splenomegaly was found on abdominal ultrasound, and laboratory tests disclosed pancytopenia. In light of the atypical lymphocyte counts in laboratory tests, he underwent bone marrow aspiration. The suggested diagnosis was hemophagocytic lymphohistiocytosis, and prednisolone was initiated. Subsequently, Leishman-Donovan bodies were seen in the bone marrow aspirate, and treatment was started with amphotericin, which led to clinical improvement. CONCLUSION: In cases with vague clinical symptoms in tropical countries where other infectious diseases occur, possible simultaneous infection should be considered even during a pandemic. Familiarity with the possible differential diagnoses and appropriate, step-by-step consideration to rule out other possible causes are needed in all situations, and the coexistence of infectious disease should be considered in evaluating the clinical conditions of patients in tropical countries.

Catastrophic Brain Aspergillosis after Liver Transplantation.

Background. Liver transplantation has many complications. Because of receiving immunosuppressive regimens, infectious complications in these patients may have fatal results. Aspergillosis in solid organ recipients is one of the most common fungal infections that usually occur 1 month after transplantation. Aspergillus infection mainly involves the lungs. Although the central nervous system may get involved due to hematogenous spreading from lungs, isolated central nervous system involvement is rarely reported. Case Presentation. The patient was an 8-year-old boy, with a case of Wilson disease, who underwent liver transplantation due to acute fulminant hepatic failure. Four days after the surgery, he was affected by fever, agitation, loss of consciousness, hemiparesis, and focal seizure. Brain MRI showed abscess formation, whereas chest X-ray was normal. Intravenous antibiotics were initiated but the patient's condition was not improving; therefore, surgical drainage of the abscess was performed. The pathological investigation was compatible with aspergillosis. Antifungal therapy with voriconazole was administrated. His symptoms were resolved but unfortunately, brain lesions caused persistent vegetative state. Discussion. Aspergillus is a ubiquitous organism that mainly occurs in immunocompromised patients. Aspergillosis could be prevented by environmental modification such as installing high-efficiency particulate air filters. Chemoprevention with triazoles, echinocandins, and polyenes is also effective. Voriconazole is the drug of choice for aspergillosis treatment. Although voriconazole is a highly effective antifungal drug, cerebral aspergillosis is often fatal.

Invasive Rasamsonia argillacea infection in chronic granulomatous disease: Report of a new case and literature review.

Invasive Rasamsonia spp. infections are rare and usually associated with chronic granulomatous disease (CGD). We present a case of pulmonary and possible cerebral infection due to Rasamsonia argillacea in a girl with CGD receiving no primary antifungal prophylaxis. There was a fatal outcome despite the combination of antifungal therapy and surgical interventions. We also conducted a literature review on reported invasive Rasamsonia spp. infections in the setting of CGD.

The Coronavirus Disease 2019 (COVID-19) in Children: A Study in an Iranian Children's Referral Hospital.

BACKGROUND: Despite the worldwide spread of the coronavirus disease 2019 (COVID-19), the epidemiological and clinical patterns of the COVID-19 infection remain largely unclear, particularly among children. In this study, we explored the epidemiological characteristics, clinical patterns, and laboratory and imaging findings of pediatric patients with COVID-19. MATERIALS AND METHODS: From March 7 to March 30, 2020, there were a total of 35 patients who had confirmed COVID-19 infection by laboratory virus nucleic acid test (RT-PCR) assay with throat swab samples or typical chest CT manifestation compatible with COVID-19, in addition to a history of close contact with suspected or confirmed SARS-CoV-2 in family members. Information recorded included demographic data, medical history, exposure history, underlying comorbidities, symptoms, signs, laboratory findings and radiologic assessments, severity of disease, treatment, and mortality. RESULTS: The median age of the patients was 7.5 years (IQR=4-11; range=4 months to 15 years). A total of 63% were male. Cough was present in 80% of the patients, followed by fever (77%), nausea or vomiting (29%), diarrhea (26%), shortness of breath (29%), headache (20%), and myalgia (14%). Lymphopenia was present in 43% of the patients, thrombocytopenia in 9%, neutopenia in 8%, and leucopenia in 26%. We reported severe pneumonia in 40% of the hospitalized patients and 18 (51%) had underlying diseases. Of 35 patients, 11 had positive RT-PCR results (31%). The chest CT images of 24 patients (69%) suggested COVID-19, while their RT-PCR assays from throat swab samples were negative. CONCLUSION: This study demonstrates different clinical findings of pediatrics compared to the previous reports of children. Since a high rate of false negative RT-PCR test was observed, early detection of children with COVID-19 infection by CT is conducive to reasonable management and early treatment.

Antibiotic Susceptibility of Bacterial Agents Causing Meningitis in Children Older than 1 Month.

The frequency and antibiotic susceptibility of bacterial meningitis in children older than one month at Children's Medical Center during 2012-2017 were evaluated in this study. The CSF samples were cultured, and antibiotic sensitivity tests were performed. The samples were cultured on chocolate agar, blood agar (for gram positive) and Mkanky (for gram negative). The antimicrobial susceptibility of the isolates was determined using the disc diffusion method. In total, 72 samples were positive for bacterial infection where Staphylococcus epidermidis (20.8%) was seen most and Enterobacter (1.4%) and Pseudomonas aeruginosa (1.4%) was seen least. Most of these patients were under 1 year of the age and overall frequency of positive cultures of CSF in men (58.3%) was greater than women (41.7%). Bacterial meningitis has relatively diverse etiological factors that include; time of infection, geographical location and age. Most commonly seen bacteria were Staphylococcus aureus with S.epidermidis whereas, Escherichia coli and Pseudomonas aeruginosa was seen least. This result can be substantial in hospitalized patients, because these bacteria are also the result of nosocomial infections.

Species distribution and antifungal susceptibility profile of Candida isolates from blood and other normally sterile foci from pediatric ICU patients in Tehran, Iran.

As data on pediatric invasive candidiasis (IC) and the antifungal susceptibility pattern of associated isolates are scarce in Iran, this study aimed to determine species distribution and antifungal susceptibility profile of Candida species isolated from pediatric patients with suspected or documented IC. A total of 235 yeast strains recovered from normally sterile body fluids of patients admitted at the intensive care units of Children's Medical Centre, Tehran, Iran, were identified using CHROMagar Candida, molecular methods (ITS PCR-RFLP and sequencing), and MALDI-TOF. Susceptibility to amphotericin B, fluconazole, voriconazole, micafungin, and anidulafungin was determined according to the European on Antimicrobial Susceptibility testing reference microdilution method (EUCAST E.Def 7.3.1). Candida albicans (53.6%), C. parapsilosis (24.7%), and C. tropicalis (8.5%) were the most common species, followed by C. lusitaniae (4.3%), C. glabrata (3.0%), C. guilliermondii and C. orthopsilosis (each 1.7%), C. kefyr (1.3%), C. dubliniensis (0.8%), and C. intermedia (0.4%). Amphotericin B MICs were ≤1 mg/l for all Candida isolates. C. albicans isolates were susceptible to all five antifungal agents. All C. parapsilosis isolates categorised as intermediate to micafungin and anidulafungin, except two isolates that had the MICs >2 mg/l for micafungin. MIC50, MIC90, and MIC range for fluconazole were 0.25 mg/l, 1 mg/l, and 0.125 - ≥32 mg/l, respectively. Fluconazole and voriconazole showed 100% activity against the most prevalent Candida species. The low resistance rate, favorable safety profile and low cost of fluconazole make it a reasonable choice for treatment of candidemia/invasive candidemia in Iran.

Cinnarizine and sodium valproate as the preventive agents of pediatric migraine: A randomized double-blind placebo-controlled trial.

BACKGROUND: Few migraine preventive agents have been assessed in a pediatric population. We evaluated the safety and efficacy of cinnarizine and sodium valproate for migraine prophylaxis in children and adolescents. METHODS: We carried out a randomized double-blind placebo-controlled trial in the Children's Medical Center and Sina hospital, Tehran, Iran. Eligible participants were randomly assigned in 1:1:1 ratio via interactive web response system to receive either cinnarizine, sodium valproate, or placebo. The primary endpoints were the mean change in frequency and intensity of migraine attacks from baseline to the last 4 weeks of trial. The secondary endpoint was the efficacy of each drug in the prevention of migraine. The drug was considered effective if it decreased migraine frequency by more than 50% in the double-blind phase compared with the baseline. Safety endpoint was adverse effects that were reported by children or their parents. RESULTS: A total of 158 children participated. The frequency of migraine attacks significantly reduced compared to baseline in cinnarizine (difference: -8.0; 95% confidence interval (CI): -9.3 to -6.6), sodium valproate (difference: -8.3; 95% confidence interval: -9.3 to -7.2), and placebo (difference: -4.4; 95% confidence interval: -5.4 to -3.4) arms. The decrease was statistically greater in cinnarizine (difference: -3.6; 95% confidence interval: -5.5 to -1.6) and sodium valproate (difference: -3.9; 95% confidence interval: -5.8 to -1.9) arms, compared to placebo group. Children in all groups had significant reduction in intensity of episodes compared to baseline (cinnarizine: -4.6; 95% confidence interval: -5.2 to -4.0; sodium valproate: -4.0; 95% confidence interval: -4.8 to -3.3; placebo: -2.6; 95% confidence interval: -3.4 to -1.8). The decrease was statistically greater in cinnarizine (difference: -2.0; 95% confidence interval: -3.2 to -0.8) and sodium valproate (difference: -1.5; 95% confidence interval: -2.7 to -0.3) arms, compared to the placebo group. Seventy-one percent of individuals in the cinnarizine group, 66% of cases in the sodium valproate group, and 42% of people in the placebo arm reported more than 50% reduction in episodes at the end of the trial. The odds ratio for >50% responder rate was 3.5 (98.3% confidence interval: 1.3 to 9.3) for cinnarizine versus placebo and 2.7 (98.3% confidence interval: 1.0 to 6.9) for sodium valproate versus placebo. Nine individuals reported adverse effects (three in cinnarizine, five in sodium valproate, and one in the placebo group) and one case in the sodium valproate group discontinued the therapy due to severe sedation. CONCLUSION: Cinnarizine and sodium valproate could be useful in migraine prophylaxis in children and adolescents. Trial registration: IRCT201206306907N4.