Phylogenetic molecular evolution and recombination analysis of complete genome of human parechovirus in Thailand

Human parechovirus (HPeV), which is a member of the Picornavirus group of viruses, is a pathogen that is reported to be associated with manifestations that include respiratory tract involvement, gastroenteritis, sepsis-like symptom, and central nervous system complication. Until now, nineteen genotypes have been identified. The lack of proofreading property of viral RNA-dependent RNA polymerase (RdRp) together with recombination among the intra- and inter-genotypes of the virus results in high diversity. However, data specific to the molecular evolutionary perspective of the complete genome of HPeV remains limited. This study aimed to analyze the phylogenetic, molecular evolution, and recombination characteristics of the complete genome of HPeV strains isolated in Thailand during 2009–2012. Fifty-eight samples that were previously confirmed to be HPeV positive and then evaluated for genotyping were subjected to complete genome amplification to generate ten overlapping PCR fragments using a set of in-house designed primers. The same position of the viral genome was read in triplicate using direct Sanger sequencing. All samples were classified into the same previously defined genotypes in both whole-genome and VP1 phylogenic tree. However, sample B1091/HPeV14/2011 exhibited discordant grouping between whole-genome and VP1 on the phylogenetic tree. Bootscan analysis revealed that B1091/HPeV14/2011 inherited from two genotypic viruses, including VP1 from HPeV14, and the rest of the genome from HPeV1B. The results of this study provide important insights into the molecular evolution of and recombination in the viral genome of HPeV that will improve and accelerate our ability to develop treatment and prophylactic strategies in the future.

HSV encephalitis after successful minimally invasive debridement for infected pancreatic necrosis: A case of rare central nervous system complication

Patients with acute pancreatitis (AP) often suffer tough complications, some of which are fatal. The early diagnosis and definite treatment of central nervous system (CNS) complications have not been fully achieved yet, which seriously affects the mortality of severe acute pancreatitis (SAP). We present a case of infected pancreatic necrosis (IPN) in a 62-year Chinese man who developed acute herpes simplex encephalitis (HSE) caused by herpes simplex virus type 1 (HSV-1) after favorable minimally invasive retroperitoneal approaches (MIRAs). The patient was successfully treated with 115 days stayed in our hospital. The MIRAs included image-guided retroperitoneal percutaneous catheter drainage (PCD), nephroscopic pancreatic necrosectomy (NPN), and ultrasonic pneumatic lithotripsy system (UPLS) assisted non-narcotic sinus track necrosectomy (NSN). HSE is relatively rare and potentially life threatening. We attempt to discuss the probable risk factors and how the relatively rare HSE are related to the patients of SAP with latent HSV.

Glycogen Synthase Kinase 3β Promotes Postoperative Cognitive Dysfunction by Inducing the M1 Polarization and Migration of Microglia

Postoperative cognitive dysfunction (POCD) is a common postoperative central nervous system complication, especially in the elderly. It has been consistently reported that the pathological process of this clinical syndrome is related to neuroinflammation and microglial proliferation. Glycogen synthase kinase 3β (GSK-3β) is a widely expressed kinase with distinct functions in different types of cells. The role of GSK-3β in regulating innate immune activation has been well documented, but as far as we know, its role in POCD has not been fully elucidated. Lithium chloride (LiCl) is a widely used inhibitor of GSK-3β, and it is also the main drug for the treatment of bipolar disorder. Prophylactic administration of lithium chloride (2 mM/kg) can inhibit the expression of proinflammatory mediators in the hippocampus, reduce the hippocampal expression of NF-κB, and increase both the downregulation of M1 microglial-related genes (inducible nitric oxide synthase and CD86) and upregulation of M2 microglial-related genes (IL-10 and CD206), to alleviate the cognitive impairment caused by orthopedic surgery. In vitro, LiCl reversed LPS-induced production of proinflammatory mediators and M1 polarization of microglia. To sum up these results, GSK-3β is a key contributor to POCD and a potential target of neuroprotective strategies.

Sirt1 Mediated High-Glucose-Induced Aβ Deposition and Cognitive Impairment through Activation of the TLR9/p53 Pathway

Background: Diabetic encephalopathy (DE) is a chronic central nervous system complication caused by diabetes mellitus (DM). β-amyloid (Aβ) deposition has been considered as the main cause of cognitive impairment in DE. Previous researches concerned the effect of canonical TLR9/Myd88 inflammatory pathway. However our study explored the function of non-inflammatory pathway of Toll-like receptor 9 (TLR9), acting on Sirt1 to influence Aβ deposition and cognitive function in DE.Results: We found that, compared with DM mice, TLR9-/-DM mice performed better learning ability and short-term memory, along with lower Aβ in hippocampi, but could be reversed by Sirt1 inhabition. Furthermore, in vitro, after intervention with high glucose and p53 over-expressed lentiviral infection, we observed the positive results of TLR9 inhibition, such as Sirt1 up-regulation, Aβ reduction or cognitive improvement, were altered (all P<0.05).Conclusions: we considered that TLR9/p53/Sirt1 signalling pathway induced by high glucose are one of molecular mechanisms underlying DE. These results not only confirm the importance of blood glucose management but also provide new insights for the diagnosis and treatment of DE.

Neuro-Sweet disease in a Japanese woman with Sjögren’s syndrome

Sweet disease (SD) is a multisystem inflammatory disorder characterised by fever, cutaneous erythematous plaques and aseptic neutrophilic infiltration of various organs. Neuro-Sweet disease (NSD) is a known rare central nervous system complication of SD. We describe a case of a 39-year-old Japanese woman who was diagnosed as NSD associated with Sjögren’s syndrome. She was successfully treated with systemic corticosteroid therapy.

Readmission Following Surgical Resection for Intractable Epilepsy: Nationwide Rates, Causes, Predictors, and Outcomes

BACKGROUND Hospital readmissions can be detrimental to patients and may interfere with the potential benefits of the therapeutic procedure. Government agencies have begun to focus on reducing readmissions; however, the etiology of readmissions is lacking. OBJECTIVE To report the national rates, risk factors, and outcomes associated with 30- and 90-d readmissions following surgery for intractable epilepsy. METHODS We queried the Nationwide Readmissions Database from January to September 2013 using International Classification of Diseases, Ninth Edition, Clinical Modification codes to identify all patients with intractable epilepsy, who underwent hemispherectomy (01.52), brain lobectomy (01.53), amydalohippocampectomy, or partial lobectomy (01.59). Predictor variables included epilepsy type, presurgical diagnostic testing, surgery type, medical complications, surgical complications, and discharge disposition. RESULTS In 1587 patients, the 30- and 90-d readmission rates were 11.5% and 16.8%, respectively. The most common reasons for readmission were persistent epilepsy, video electroencephalography monitoring, postoperative infection, and postoperative central nervous system complication. In multivariable analysis, risk factors associated with both 30- and 90-d readmission were Medicare payer status, lowest quartile of median income, depression, hemispherectomy, and postoperative complications (P &lt; .05). The only unique predictor of 30-d readmission was small bedsize hospital (P = .001). Readmissions within 30 d were associated with longer length of stay (6.8 vs 5.8 d), greater costs ($18 660 vs $15 515), and increased adverse discharges (26.4% vs 21.8%). CONCLUSION Following epilepsy surgery, most readmissions that occurred within 30 d can be attributed to management of persistent epilepsy and predicted by Medicare payer status, depression, and complications. These data can assist the clinician in preventing readmissions and assist policy makers determine which admissions are potentially avoidable.

Meningeal Melanomatosis: A Challenge for Timely Diagnosis

Neoplastic meningitis is a central nervous system complication that occurs in 3–5% of patients with cancer. Although most commonly seen in patients with disseminated disease, in a small percentage of patients, it may be the initial manifestation of cancer or even primitive in origin. In the absence of cancer history, the diagnosis of neoplastic meningitis may be challenging even for expert neurologists. Prognosis is poor, with a median overall survival of weeks from diagnosis. In the retrospective study herein, we described three cases of meningeal melanomatosis in patients without previous cancer history. The patients were diagnosed with significant delay (17 to 47 weeks from symptom onset) mainly due to the deferral in performing the appropriate testing. Even when the diagnosis was suspected, investigations by MRI, cerebrospinal fluid, or both proved at times unhelpful for confirmation. Prognosis was dismal, with a median survival of 4 weeks after diagnosis. Our observations are a cue to analyze the main pitfalls in the diagnosis of neoplastic meningitis in patients without cancer history and emphasize key elements that may facilitate early diagnosis.