Review of meta-analyses on prevention of the common cold

かぜ症候群は誰でもしばしば罹患する疾患であり，自然治癒する疾患であるが，症状は数日続き，欠席や欠勤が余儀なくされる場合もある。かぜ症候群の予防について，現時点で，どの程度のエビエンスが蓄積されているかを検討するために，かぜ症候群の予防に関するメタ解析論文をレビューした。PubMed でかぜ症候群（インフルエンザを含む）の予防に関するメタ解析論文で，2007年以降に発表され，2017年12月末に検索可能な英語で発表されたものを検索した。プロバイオティクス，ビタミンD，エキナセアは２報以上メタ解析がなされており，かぜ症候群に対する有意な予防効果が示されていた。メタ解析が１報だけであるが，予防効果が認められた薬剤には漢方薬であるペラルゴニウム（ゼラニウム），亜鉛含有薬，多価機械的細菌溶解物があった。また，手指衛生とマスク着用，運動，そして，湿気とカビによる建物損傷の改修も，かぜ症候群の予防に有効と報告されていた。ビタミンC 等，予防効果があると考えられるものの，有意差が認められていないものもあり，今後さらなる検討が必要である。The common cold is frequently treated by family physicians. Although it is generally benign, the symptoms can last for several days, causing missed work and study days. To examine prevention of this condition, we searched the English literature for meta-analyses on prevention of the common cold including influenza on PubMed from 2007 to the end of 2017. There were at least two or more meta-analyses on probiotics, vitamin D, and echinacea, and all of them showed significant preventive effects of these agents. Although one meta-analysis showed that pelargonium, zinc, polyvalent mechanical bacterial lysate, hand hygiene and wearing masks, exercise, and repairing buildings damaged by dampness and mould offered significant preventive effects, vitamin C had only a marginal effect on prevention. Further examinations are needed to clarify the effects of various measures to prevent the common cold

Long‐lasting housing environment manipulation and acute loss of environmental enrichment impact BALB/c mice behaviour in multiple functional domains

Understanding environmental influences on individuals' behaviour is challenging. Here we have investigated the housing impact of 9 weeks of enriched environment (EE) and social isolation (SI) and the impact of abrupt deprivation of EE (enrichment removal: ER) on BALB/c mice. Compared with the widely used C57BL/6 strain in research, BALB/c synthesises serotonin less efficiently due to a genetic variation and thus may potentially represent human populations at higher risk of stress-related disorders. We assessed the effects of EE and SI by conducting a behavioural test battery and the effects of acute ER by monitoring homecage activities and social behaviour. We found that EE and SI impact BALB/c's physiological states and behavioural performances from lower to higher cognitive processes: increased body weight, increased rectal temperature, altered performance in motor and sensory tasks, the activity level in a novel environment and altered performance in tests of anxiety-like behaviour, stress-coping strategies and learning and memory. Furthermore, acute ER triggered stress/frustration-like behaviour in BALB/c, with increased aggression, increased social distancing and disrupted daily/nightly activities. Our results demonstrate that long-lasting housing manipulation such as EE and SI, impact behaviour via multilayered processes over a wide range of functional domains, and unforeseen change to a negative environment, ER, is a major stressor that causes behavioural and psychological consequences through environment-gene interactions, a model of direct relevance to human health

Three-dimensional observation and analysis of remineralization in dentinal caries lesions

The remineralization mechanism in dental caries lesions is not completely understood. This study reports on ultrastructural and chemical changes observed within arrested caries lesions. Carious human teeth were observed using scanning electron microscopy (SEM) and focused-ion-beam (FIB)-SEM. The crystals detected in the caries lesions were characterized by transmission electron microscopy (TEM), along with chemical element mapping using energy-dispersive spectroscopy (EDS)-STEM. FIB-SEM 3D reconstructions revealed a severely damaged dentin surface abundantly covered by bacteria. Although the dentin tubules were clogged up to a depth of 100 mu m, bacterial invasion into dentin tubules was not observed. TEM crystal analysis and EDS-STEM revealed the presence of Ca and P, as well as of Mg within the HAp crystals deposited inside the dentin tubules. It was concluded that extensive remineralization with deposition of Mg-HAp crystals had occurred in dentin tubules of caries-arrested dentin. Understanding the natural remineralization process is thought to be helpful for developing clinical biomimetic remineralization protocols

Selegiline ameliorates depression-like behavior in mice lacking the CD157/BST1 gene, a risk factor for Parkinson’s disease

Parkinson’s disease (PD), a neurodegenerative disorder, is accompanied by various non-motor symptoms including depression and anxiety, which may precede the onset of motor symptoms. Selegiline is an irreversible monoamine oxidase-B (MAO-B) inhibitor, and is widely used in the treatment of PD and major depression. However, there are few reports about the effects of selegiline on non-motor symptoms in PD. The aim of this study was to explore the antidepressant and anxiolytic effects of selegiline, using CD157/BST1 knockout (CD157 KO) mouse, a PD-related genetic model displaying depression and anxiety, compared with other antiparkinsonian drugs and an antidepressant, and was to investigate the effects of selegiline on biochemical parameters in emotion-related brain regions. A single administration of selegiline (1–10 mg/kg) dose-dependently reduced immobility time in the forced swimming test (FST) in CD157 KO mice, but not C57BL/6N wild-type (WT) mice. At 10 mg/kg, but not 3 mg/kg, selegiline significantly increased climbing time in CD157 KO mice. A single administration of the antiparkinsonian drugs pramipexole (a dopamine (DA) D2/D3 receptor agonist) or rasagiline (another MAO-B inhibitor), and repeated injections of a noradrenergic and specific serotonergic antidepressant (NaSSA), mirtazapine, also decreased immobility time, but did not increase climbing time, in CD157 KO mice. The antidepressant-like effects of 10 mg/kg selegiline were comparable to those of 10 mg/kg rasagiline, and tended to be stronger than those of 1 mg/kg rasagiline. After the FST, CD157 KO mice showed decreases in striatal and hippocampal serotonin (5-HT) content, cortical norepinephrine (NE) content, and plasma corticosterone concentration. A single administration of selegiline at 10 mg/kg returned striatal 5-HT, cortical NE, and plasma corticosterone levels to those observed in WT mice. In the open field test (OFT), repeated administration of mirtazapine had anxiolytic effects, and selegiline nonsignificantly ameliorated anxiety-like behaviors in CD157 KO mice. In the social interaction and preference tests, repeated mirtazapine ameliorated the high anxiety and low sociability of CD157 KO mice, whereas selegiline did not. These results indicate that selegiline has antidepressant and mild anxiolytic effects in CD157 KO mice, and suggest that it is an effective antiparkinsonian drug for depressive and anxiety symptoms in PD patients with a CD157 single nucleotide polymorphism (SNP). © 2017 Kasai, Yoshihara, Lopatina, Ishihara and Higashida

Critical role of JSAP1 and JLP in axonal transport in the cerebellar Purkinje cells of mice

JNK/stress-activated protein kinase-associated protein 1 (JSAP1) and JNK-associated leucine zipper protein (JLP) are structurally related scaffolding proteins that are highly expressed in the brain. Here, we found that JSAP1 and JLP play functionally redundant and essential roles in mouse cerebellar Purkinje cell (PC) survival. Mice containing PCs with deletions in both JSAP1 and JLP exhibited PC axonal dystrophy, followed by gradual, progressive neuronal loss. Kinesin-1 cargoes accumulated selectively in the swollen axons of Jsap1/Jlp-deficient PCs. In addition, autophagy inactivation in these mice markedly accelerated PC degeneration. These findings suggest that JSAP1 and JLP play critical roles in kinesin-1-dependent axonal transport, which prevents brain neuronal degeneration. © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.Embargo Period (12 mouths

Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats

The RIβ subunit of cAMP-dependent protein kinase (PKA), encoded by Prkar1b, is a neuronal isoform of the type I regulatory subunit of PKA. Mice lacking the RIβ subunit exhibit normal long-term potentiation (LTP) in the Schaffer collateral pathway of the hippocampus and normal behavior in the open-field and fear conditioning tests. Here, we combined genetic, electrophysiological, and behavioral approaches to demonstrate that the RIβ subunit was involved in body tremor, LTP in the Schaffer collateral pathway, and fear conditioning memory in rats. Genetic analysis of WTC-furue, a mutant strain with spontaneous tremors, revealed a deletion in the Prkar1b gene of the WTC-furue genome. Prkar1b-deficient rats created by the CRISPR/Cas9 system exhibited body tremor. Hippocampal slices from mutant rats showed deficient LTP in the Schaffer collateral–CA1 synapse. Mutant rats also exhibited decreased freezing time following contextual and cued fear conditioning, as well as increased exploratory behavior in the open field. These findings indicate the roles of the RIβ subunit in tremor pathogenesis and contextual and cued fear memory, and suggest that the hippocampal and amygdala roles of this subunit differ between mice and rats and that rats are therefore beneficial for exploring RIβ function