Neurologic Complications of Varicella-Zoster Virus Infection

Varicella-zoster virus (VZV) causes a diverse spectrum of neurologic complications: aseptic meningitis, encephalitis, cerebral infarction associated with granulomatous vasculitis, myelitis, and cranial polyneuropathy. These VZV-associated central nervous system (CNS) diseases usually result from reactivation of latent infection in immunosuppressive conditions, such as old age, diabetes mellitus, cancer, human immunodeficiency virus (HIV) infection, and the use of immunosuppressive drugs. However, they also occur in immunocompetent subjects. Since VZV antigen or DNA is often detected in the cerebrospinal fluid of these patients, it is thought that reactivated VZV reaches the central nervous system by direct spread from latently infected sensory ganglia. Analysis of cerebrospinal fluid by PCR is important for the diagnosis of VZV-associated CNS diseases particularly in the absence of exanthema/herpes zoster. Clinicians should be aware of the neurologic complications of VZV infection, because early acyclovir therapy is necessary for these disorders

In vitro nonalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions, and its treatment involves curing the patients without liver transplantation. Understanding the mechanism of NAFLD initiation and progression would enable the development of new diagnostic tools and drugs; however, until now, the underlying mechanisms of this condition remain largely unknown owing to the lack of experimental settings that can simplify the complicated NAFLD process in vitro. Microphysiological systems (MPSs) have long been used to recapture human pathophysiological conditions in vitro for applications in drug discovery. However, polydimethylsiloxane (PDMS) is used in most of these MPSs as the structural material; it absorbs hydrophobic molecules, such as free fatty acids (FFAs), which are the key components that initiate NAFLD. Therefore, the current PDMS-based MPSs cannot be directly applied to in vitro NAFLD modeling. In this work, we present an in vitro NAFLD model with an MPS made of cyclo-olefin polymer (COP), namely COP-MPS, to prevent absorption of FFAs. We demonstrated the induction of NAFLD-like phenotype in HepaRG hepatocyte-like cells cultured in the COP-MPS by treatment with FFAs. The FFAs induced lipid accumulation in the HepaRG cells, resulting in inactivation of the apoptotic cells. We believe that the proposed COP-MPS can contribute toward the investigation of NAFLD mechanisms and identification of new drugs to prevent the progression of liver disease and thus avoid liver transplantation

Five Prognostic Factors for Readmission in Patients Over 75 Years Old with Worsening Heart Failure

Heart failure （HF） is a common disease in elderly patients, particularly in those presenting as readmission for worsening HF. While recent studies have revealed mortality-associated factors in this population, little is known about prognostic factors associated with worsening HF. To investigate this clinical evidence gap in patients aged over 75 years, we retrospectively investigated 165 patients hospitalized for HF at Showa University Hospital, of whom 65 （39.4％） were readmitted for worsening HF. We extracted the candidate variables based on univariate analysis, and then elucidated the independent prognostic factors by multivariate analysis. Compared with non-readmitted patients, readmitted patients with worsening HF had lower left ventricular ejection fraction （LVEF） （39％ vs. 50％, P＝0.002） and body mass index （BMI） （19.9kg/m2 vs. 21.4kg/m2, P＝0.007）, higher levels of B-type natriuretic peptide （BNP） （478pg/ml vs. 198pg/ml, P＜0.001）, and heart rate （HR） （71.0 beats/min vs. 67.0 beats/min, P＝0.021） upon discharge during the primary admission. Multivariate logistic analysis identified LVEF ＜40％, BMI ＜21kg/m2, BNP ≥500pg/ml, Charlson score ≥3, and HR ≥70 beats/min upon initial discharge as independent prognostic factors. Based on these factors, readmission for worsening HF was more frequent in those with our proposed risk score of ≥3.0 than in those with a risk score ＜3.0 （P＜0.001）, and we suggested five prognostic factors for HF patients over 75 years old. Our proposed risk score combines these factors and might predict readmission for worsening HF in the elderly population

Free Flap Blood Flow Evaluated Using Two-Dimensional Laser Speckle Flowgraphy

Objective. We investigated the efficiency of laser speckle flowgraphy for evaluating blood flow in free flaps used for plastic surgery. Methods. We measured blood flow using a visual laser meter capable of providing two-dimensional color graphic representations of flow distribution for a given area using a dynamic laser speckle effect. Using laser speckle flowgraphy, we examined the blood flow of 20 free flaps applied following the excision of head and neck tumors. Results. After anastomosis of the feeding and draining blood vessels and sewing the flap, musculocutaneous (MC) flaps showed significantly lower blood flow than jejunal or omental flaps (P < .05). The ratio of blood flow decrease from the edge to the center was significantly greater in MC flaps than in jejunal or omental flaps (P < .001). Conclusion. Laser speckle flowgraphy is useful for the perioperative measurement of blood flow in free flaps used in plastic surgery. This method is a highly useful, practical, and reliable tool for assessing cutaneous blood flow and is expected to be applicable to several clinical fields

Beneficial Effects of Cocoa in Perivascular Mato Cells of Cerebral Arterioles in SHR-SP (Izm) Rats

As previously reported, the cerebral arterioles are surrounded by unique perivascular Mato cells. They contain many inclusion bodies rich in hydrolytic enzymes, and have strong uptake capacity. They are thus considered scavenger cells of vascular and neural tissues in steady-state. In this study, employing hypertensive SHR-SP (Izm) rats, the viability of Mato cells was investigated. In hypertensive rats, the capacity for uptake of horse radish peroxidase (HRP) and the activity of acid phosphatase (ACPase) of Mato cells were markedly reduced, and on electron-microscopic examination Mato cells were found to include heterogeneous contents and appeared electron-dense and degenerated. Vascular cells exhibited some signs of pathology. However, in hypertensive rats fed chow containing 0.25% cocoa, the uptake capacity and ACPase activity of Mato cells for HRP were enhanced, and on electron-microscopic examination Mato cells appeared healthy, with mitochondria with nearly normal profiles. Signs of pathology in vascular cells were also decreased. Superoxides may impair Mato cells and vascular cells

Hemorrhagic infarction at 33 days after birth in a healthy full-term neonate

Intraparenchymal hemorrhage in the full-term neonate rarely occurs more than 2 weeks after birth, and its definitive cause remains unclear. In the present report, a case of a patient with intraparenchymal hemorrhage occurring 33 days after birth is described. Histological examination of the brain tissue obtained during hematoma evacuation through craniotomy showed hemorrhagic infarction. Patent foramen ovale may have been present and this may have led to spontaneous paradoxical cerebral embolism followed by hemorrhagic infarction

Quantitative non-canonical amino acid tagging based proteomics identifies distinct patterns of protein synthesis rapidly induced by hypertrophic agents in cardiomyocytes, revealing new aspects of metabolic remodeling

Cardiomyocytes undergo growth and remodeling in response to specific pathological or physiological conditions. Pathological myocardial growth is a risk factor for cardiac failure to which faster protein synthesis is a major driving element. We aimed to quantify the rapid effects of different pro-hypertrophic stimuli on the synthesis of specific proteins in ARVC and to determine whether such effects are due to alterations on mRNA abundance or the translation of specific mRNAs. Cardiomyocytes have very low rates of protein synthesis, posing a challenging problem in terms of studying changes in the synthesis of specific proteins, which also applies to other non-dividing primary cells. To address this, an optimized QuaNCAT LC/MS method was used to selectively quantify newly synthesized proteins in such cells. The study showed both classical (phenylephrine; PE) and more recent (insulin) pathological cardiac hypertrophic agents increased the synthesis of proteins involved in glycolysis, the Krebs cycle / beta-oxidation, and sarcomeric components. However, insulin increased synthesis of many metabolic enzymes to a greater extent than PE. Using a novel validation method, we confirmed that synthesis of selected candidates is indeed up-regulated by PE and insulin. Synthesis of all proteins studied was upregulated by signaling through mTORC1 without changes in their mRNA levels, showing the key importance of translational control in the rapid effects of hypertrophic stimuli. Expression of PKM2 was upregulated in rat hearts following TAC. This isoform possesses specific regulatory properties that may be involved in metabolic remodeling and as a novel candidate biomarker. Levels of translation factor eEF1 also increased during TAC, likely contributing to faster cell mass accumulation. Interestingly, PKM2 and eEF1 were not up-regulated in pregnancy or exercise induced CH, suggesting them as pathological CH specific markers. The study methods may be of utility to the examination of protein synthesis in primary cells

Lack of association between PER3 variable number tandem repeat and circadian rhythm sleep-wake disorders.

Circadian rhythm sleep-wake disorders (CRSWDs) are characterized by disturbed sleep-wake patterns. Wegenotyped a PER3 variable number tandem repeat (VNTR) in 248 CRSWD individuals and 925 controls andfound no significant association between the VNTR and CRSWDs or morningness-eveningness (diurnal)preferences in the Japanese population. Although the VNTR has been associated with circadian and sleep phenotypes in some other populations, the polymorphism may not be a universal genetic marker

Generation of medaka gene knockout models by target-selected mutagenesis

We have established a reverse genetics approach for the routine generation of medaka (Oryzias latipes) gene knockouts. A cryopreserved library of N-ethyl-N-nitrosourea (ENU) mutagenized fish was screened by high-throughput resequencing for induced point mutations. Nonsense and splice site mutations were retrieved for the Blm, Sirt1, Parkin and p53 genes and functional characterization of p53 mutants indicated a complete knockout of p53 function. The current cryopreserved resource is expected to contain knockouts for most medaka genes