Involvement of the Thalamus, Hippocampus, and Brainstem in Hypsarrhythmia of West Syndrome: Simultaneous Recordings of Electroencephalography and fMRI Study.

BACKGROUND AND PURPOSE: West syndrome is a developmental and epileptic encephalopathy characterized by epileptic spasms, neurodevelopmental regression, and a specific EEG pattern called hypsarrhythmia. Our aim was to investigate the brain activities related to hypsarrhythmia at onset and focal epileptiform discharges in the remote period in children with West syndrome using simultaneous electroencephalography and fMRI recordings. MATERIALS AND METHODS: Fourteen children with West syndrome underwent simultaneous electroencephalography and fMRI at the onset of West syndrome. Statistically significant blood oxygen level-dependent responses related to hypsarrhythmia were analyzed using an event-related design of 4 hemodynamic response functions with peaks at 3, 5, 7, and 9 seconds after the onset of each event. Six of 14 children had focal epileptiform discharges after treatment and underwent simultaneous electroencephalography and fMRI from 12 to 25 months of age. RESULTS: At onset, positive blood oxygen level-dependent responses were seen in the brainstem (14/14 patients), thalami (13/14), basal ganglia (13/14), and hippocampi (13/14), in addition to multiple cerebral cortices. Group analysis using hemodynamic response functions with peaks at 3, 5, and 7 seconds showed positive blood oxygen level-dependent responses in the brainstem, thalamus, and hippocampus, while positive blood oxygen level-dependent responses in multiple cerebral cortices were seen using hemodynamic response functions with peaks at 5 and 7 seconds. In the remote period, 3 of 6 children had focal epileptiform discharge-related positive blood oxygen level-dependent responses in the thalamus, hippocampus, and brainstem. CONCLUSIONS: Positive blood oxygen level-dependent responses with hypsarrhythmia appeared in the brainstem, thalamus, and hippocampus on earlier hemodynamic response functions than the cerebral cortices, suggesting the propagation of epileptogenic activities from the deep brain structures to the neocortices. Activation of the hippocampus, thalamus, and brainstem was still seen in half of the patients with focal epileptiform discharges after adrenocorticotropic hormone therapy.

Unwillingness to cooperate with COVID-19 contact tracing in Japan.

OBJECTIVES: Contact tracing for COVID-19 relies heavily on the cooperation of individuals with authorities to provide information of contact persons. However, few studies have clarified willingness to cooperate and motivation to provide information for contact tracing. This study sought to describe willingness to cooperate and motivation to report contact persons for COVID-19 contact tracing among citizens in Japan, and to assess any associated sociodemographic factors. STUDY DESIGN: Cross-sectional study. METHODS: This was an online-based survey using quota sampling. Participants were asked about their willingness to cooperate in reporting contacts for COVID-19 contact tracing if they tested positive. Participants also responded to questions regarding their reasons for cooperating or not cooperating and provided sociodemographic data. Multiple logistic regression analysis was performed to clarify associations between sociodemographic factors and willingness to cooperate. RESULTS: This study included 2844 participants. The proportion of participants who were not willing to cooperate in reporting contacts was 27.6%, with their main reasons being concerns about causing trouble for the other person and being criticised for revealing their names. Willingness to cooperate was lower among men, young adults and those with an educational level less than a university degree. CONCLUSIONS: To improve the effectiveness of contact tracing, educational campaigns, such as reducing the fear and stigma associated with COVID-19, may be important. Furthermore, it is essential to understand that individuals may have contacts whom they do not wish to disclose to others and to be considerate when handling such situations.

Occurrence of human respiratory syncytial virus in summer in Japan.

In temperate zones, human respiratory syncytial virus (HRSV) outbreaks typically occur in cold weather, i.e. in late autumn and winter. However, recent outbreaks in Japan have tended to start during summer and autumn. This study examined associations of meteorological conditions with the numbers of HRSV cases reported in summer in Japan. Using data from the HRSV national surveillance system and national meteorological data for summer during the period 2007-2014, we utilized negative binomial logistic regression analysis to identify associations between meteorological conditions and reported cases of HRSV. HRSV cases increased when summer temperatures rose and when relative humidity increased. Consideration of the interaction term temperature × relative humidity enabled us to show synergistic effects of high temperature with HRSV occurrence. In particular, HRSV cases synergistically increased when relative humidity increased while the temperature was ⩾28·2 °C. Seasonal-trend decomposition analysis using the HRSV national surveillance data divided by 11 climate divisions showed that summer HRSV cases occurred in South Japan (Okinawa Island), Kyushu, and Nankai climate divisions, which are located in southwest Japan. Higher temperature and higher relative humidity were necessary conditions for HRSV occurrence in summer in Japan. Paediatricians in temperate zones should be mindful of possible HRSV cases in summer, when suitable conditions are present.

Electronic and Optical Properties of Single Wall Carbon Nanotubes.

In this article, we overview our recent theoretical works on electronic and optical properties of carbon nanotubes by going from the background to the perspectives. Electronic Raman spectra of metallic carbon nanotubes give a new picture of Raman processes. Thermoelectricity of semiconducting nanotubes gives a general concept of the confinement effect on the thermoelectric power factor. Selective excitation of only a single phonon mode is proposed by the pulsed train technique of coherent phonon spectroscopy. Occurrence of both two and four fold degeneracy in the carbon nanotube quantum dot is explained by difference group velocities and the intra/inter valley scattering near the hexagonal corner of the Brillouin zone.

Characterization of influenza outbreaks in Lebanon during the 2013/14 and 2014/15 seasons.

Despite the significant burden of influenza outbreaks, active disease monitoring has been largely absent in the Middle East, including Lebanon. In this study we characterized influenza virus in 440 nasopharyngeal swabs collected from patients with acute respiratory infections during two influenza seasons in Lebanon. Influenza A(H3N2) was dominant in the 2013/14 season while the A(H1N1)pdm09 and B/Yamagata strains were most prevalent in the 2014/15 season. All tested isolates were susceptible to 4 neuraminidase inhibitors (oseltamivir, zanamivir, peramivir and laninamivir). Genetic analysis of the haemagglutinin gene revealed multiple introductions of influenza viruses into Lebanon from different geographic sources during each season. Additionally, large data gaps were identified in the Middle East region, as indicated by the lack of current influenza sequences in the database from many countries in the region.

Raman spectroscopy of transition metal dichalcogenides.

Raman spectroscopy of transition metal dichalcogenides (TMDs) is reviewed based on our recent theoretical and experimental works. First, we discuss the semi-classical and quantum mechanical description for the polarization dependence of Raman spectra of TMDs in which the optical dipole transition matrix elements as a function of laser excitation energy are important for understanding the polarization dependence of the Raman intensity and Raman tensor. Overviewing the symmetry of TMDs, we discuss the dependence of the Raman spectra of TMDs on layer thickness, polarization, laser energy and the structural phase. Furthermore, we discuss the Raman spectra of twisted bilayer and heterostructures of TMDs. Finally, we give our perspectives on the Raman spectroscopy of TMDs.

Characterization of influenza outbreaks in Lebanon during the 2013/14 and 2014/15 seasons

Despite the significant burden of influenza outbreaks, active disease monitoring has been largely absent in the Middle East, including Lebanon. In this study we characterized influenza virus in 440 nasopharyngeal swabs collected from patients with acute respiratory infections during two influenza seasons in Lebanon. Influenza A[H3N2] was dominant in the 2013/14 season while the A[H1N1]pdm09 and B/Yamagata strains were most prevalent in the 2014/15 season. All tested isolates were susceptible to 4 neuraminidase inhibitors [oseltamivir, zanamivir, peramivir and laninamivir]. Genetic analysis of the haemagglutinin gene revealed multiple introductions of influenza viruses into Lebanon from different geographic sources during each season. Additionally, large data gaps were identified in the Middle East region, as indicated by the lack of current influenza sequences in the database from many countries in the region

Malgré la lourde charge que représentent les flambées de grippe, la surveillance active de la maladie était jusqu'à présent inexistante au Moyen-Orient, et notamment au Liban. Dans la présente étude, le virus de la grippe a été caractérisé dans 440 sécrétions rhinopharyngées prélevées par écouvillonnage chez des patients ayant souffert d'infections respiratoires aiguës pendant deux saisons grippales au Liban. Le virus de la grippe A[H3N2] était prédominant pendant la saison 2013/2014, tandis que celui de la grippe A[H1N1]pdm09 et les souches de grippe B/Yamagata étaient les plus courants pendant la saison 2014/2015. Tous les isolats testés étaient sensibles à quatre inhibiteurs de la neuraminidase [l'oseltamivir, le zanamivir, le peramivir, et le laninamivir]. L'analyse génétique du gène de l'hémagglutinine a révélé de multiples introductions des virus de la grippe au Liban, depuis différentes sources géographiques au cours de chaque saison. De plus, d'importantes lacunes dans les données ont été constatées dans la région du Moyen-Orient, comme le montre l'absence des séquences génétiques actuelles de la grippe dans les bases de données de nombreux pays de la region

Delayed norovirus epidemic in the 2009-2010 season in Japan: potential relationship with intensive hand sanitizer use for pandemic influenza.

Norovirus (NoV) epidemics normally peak in December in Japan; however, the peak in the 2009-2010 season was delayed until the fourth week of January 2010. We suspected intensive hand hygiene that was conducted for a previous pandemic influenza in 2009 as the cause of this delay. We analysed the NoV epidemic trend, based on national surveillance data, and its associations with monthly output data for hand hygiene products, including alcohol-based skin antiseptics and hand soap. The delayed peak in the NoV incidence in the 2009-2010 season had the lowest number of recorded cases of the five seasons studied (2006-2007 to 2010-2011). GII.4 was the most commonly occurring genotype. The monthly relative risk of NoV and monthly output of both alcohol-based skin antiseptics and hand soap were significantly and negatively correlated. Our findings suggest an association between hand hygiene using these products and prevention of NoV transmission.

Activation of Nesfatin-1-Containing Neurones in the Hypothalamus and Brainstem by Peripheral Administration of Anorectic Hormones and Suppression of Feeding via Central Nesfatin-1 in Rats.

Peripheral anorectic hormones, such as glucagon-like peptide (GLP)-1, cholecystokinin (CCK)-8 and leptin, suppress food intake. The newly-identified anorectic neuropeptide, nesfatin-1, is synthesised in both peripheral tissues and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. In the present study, we examined the effects of i.p. administration of GLP-1 and CCK-8 and co-administrations of GLP-1 and leptin at subthreshold doses as confirmed by measurement of food intake, on nesfatin-1-immunoreactive (-IR) neurones in the hypothalamus and brainstem of rats by Fos immunohistochemistry. Intraperitoneal administration of GLP-1 (100 µg/kg) caused significant increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the supraoptic nucleus (SON), the area postrema (AP) and the nucleus tractus solitarii (NTS) but not in the paraventricular nucleus (PVN), the arcuate nucleus (ARC) or the lateral hypothalamic area (LHA). On the other hand, i.p. administration of CCK-8 (50 µg/kg) resulted in marked increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the SON, PVN, AP and NTS but not in the ARC or LHA. No differences in the percentage of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the nuclei of the hypothalamus and brainstem were observed between rats treated with saline, GLP-1 (33 µg/kg) or leptin. However, co-administration of GLP-1 (33 µg/kg) and leptin resulted in significant increases in the number of nesfatin-1-IR neurones expressing Fos-immunoreactivity in the AP and the NTS. Furthermore, decreased food intake induced by GLP-1, CCK-8 and leptin was attenuated significantly by pretreatment with i.c.v. administration of antisense nesfatin-1. These results indicate that nesfatin-1-expressing neurones in the brainstem may play an important role in sensing peripheral levels of GLP-1 and leptin in addition to CCK-8, and also suppress food intake in rats.

Possible Involvement of the Rat Hypothalamo-Neurohypophysial/-Spinal Oxytocinergic Pathways in Acute Nociceptive Responses.

Oxytocin (OXT)-containing neurosecretory cells in the parvocellular divisions of the paraventricular nucleus (PVN), which project to the medulla and spinal cord, are involved in various physiological functions, such as sensory modulation and autonomic processes. In the present study, we examined OXT expression in the hypothalamo-spinal pathway, as well as the hypothalamo-neurohypophysial system, which includes the magnocellular neurosecretory cells in the PVN and the supraoptic nucleus (SON), after s.c. injection of saline or formalin into the hindpaws of transgenic rats that express the OXT and monomeric red fluorescent protein 1 (mRFP1) fusion gene. (i) The numbers of OXT-mRFP1 neurones that expressed Fos-like immunoreactivity (-IR) and OXT-mRFP1 intensity were increased significantly in the magnocellular/parvocellular PVN and SON after s.c. injection of formalin. (ii) OXT-mRFP1 neurones in the anterior parvocellular PVN, which may project to the dorsal horn of the spinal cord, were activated by s.c. injection of formalin, as indicated by a significant increases of Fos-IR and mRFP1 intensity intensity. (iii) Formalin injection caused a significant transient increase in plasma OXT. (iv) OXT, mRFP1 and corticotrophin-releasing hormone mRNAs in the PVN were significantly increased after s.c. injection of formalin. (v) An intrathecal injection of OXT-saporin induced hypersensitivity in conscious rats. Taken together, these results suggest that the hypothalamo-neurohypophysial/-spinal OXTergic pathways may be involved in acute nociceptive responses in rats.

Monoiodoacetic acid induces arthritis and synovitis in rats in a dose- and time-dependent manner: proposed model-specific scoring systems.

OBJECTIVE: In a rat monoiodoacetic acid (MIA)-induced arthritis model, the amount of MIA commonly used was too high, resulting in rapid bone destruction. We examined the effect of MIA concentrations on articular cartilage and infrapatellar fat pad (IFP). We also established an original system for "macroscopic cartilage and bone score" and "IFP inflammation score" specific to the rat MIA-induced arthritis model. DESIGN: Male Wistar rats received a single intra-articular injection of MIA in the knee. The amount of MIA was 0.1, 0.2, 0.5, and 1 mg respectively. Articular cartilage was evaluated at 2-12 weeks. IFP was also observed at 3-14 days. RESULTS: Macroscopically, low MIA doses induced punctate depressions on the cartilage surface, and cartilage erosion proceeded slowly over 12 weeks, while higher MIA doses already induced cartilage erosion at 2 weeks, followed by bone destruction. MIA macroscopic cartilage and bone score, OARSI histological score, and Mankin score increased in a dose- and time-dependent manner. The IFP inflammation score peaked at 5 days in low dose groups, then decreased, while in high dose groups, the IFP score continued to increase over 14 days due to IFP fibrosis. CONCLUSIONS: Punctate depressions, cartilage erosion, and bone destruction were observed in the MIA-induced arthritis model. The macroscopic cartilage and bone scoring enabled the quantification of cartilage degeneration and demonstrated that MIA-induced arthritis progressed in a dose- and time-dependent manner. IFP inflammation scores revealed that 0.2 mg MIA induced reversible synovitis, while 1 mg MIA induced fibrosis of the IFP body.

Efficacy of platinum combination chemotherapy after first-line gefitinib treatment in non-small cell lung cancer patients harboring sensitive EGFR mutations

Purpose. Gefitinib is an effective first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, whether second-line platinum combination chemotherapy after first-line gefitinib treatment shows similar effects to first-line platinum combination chemotherapy in these patients remains unclear. Therefore, we here aimed to investigate the efficacy of platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations. Methods/patients. We retrospectively evaluated the clinical effects of second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations (exon 19 deletion or exon 21 L858R mutation) at five institutions. All patients were initially treated with gefitinib (250 mg/day) followed by platinum combination chemotherapy as second-line chemotherapy. Results. Between January 2006 and December 2012, 42 patients [8 men, 34 women; median age, 63 years (range 39–75 years)] were enrolled. The overall response rate, disease control rate, and median progression-free survival (PFS) were 26.2, 61.9 %, and 5.1 months, respectively, after the second-line treatment. The corresponding values for first-line gefitinib treatment were 69.0, 95.2 %, and 11.1 months, respectively. Moreover, second-line platinum combination chemotherapy with pemetrexed or bevacizumab-containing regimens was independently associated with improved PFS. Conclusions. Second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations was effective and showed equivalent outcomes to first-line platinum combination chemotherapy. After failure of first-line gefitinib therapy, second-line platinum combination chemotherapy with pemetrexed or bevacizumab might result in improved PFS (AU)

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Efficacy of platinum combination chemotherapy after first-line gefitinib treatment in non-small cell lung cancer patients harboring sensitive EGFR mutations.

PURPOSE: Gefitinib is an effective first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. However, whether second-line platinum combination chemotherapy after first-line gefitinib treatment shows similar effects to first-line platinum combination chemotherapy in these patients remains unclear. Therefore, we here aimed to investigate the efficacy of platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations. METHODS/PATIENTS: We retrospectively evaluated the clinical effects of second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations (exon 19 deletion or exon 21 L858R mutation) at five institutions. All patients were initially treated with gefitinib (250 mg/day) followed by platinum combination chemotherapy as second-line chemotherapy. RESULTS: Between January 2006 and December 2012, 42 patients [8 men, 34 women; median age, 63 years (range 39-75 years)] were enrolled. The overall response rate, disease control rate, and median progression-free survival (PFS) were 26.2, 61.9%, and 5.1 months, respectively, after the second-line treatment. The corresponding values for first-line gefitinib treatment were 69.0, 95.2%, and 11.1 months, respectively. Moreover, second-line platinum combination chemotherapy with pemetrexed or bevacizumab-containing regimens was independently associated with improved PFS. CONCLUSIONS: Second-line platinum combination chemotherapy after first-line gefitinib treatment in NSCLC patients harboring sensitive EGFR mutations was effective and showed equivalent outcomes to first-line platinum combination chemotherapy. After failure of first-line gefitinib therapy, second-line platinum combination chemotherapy with pemetrexed or bevacizumab might result in improved PFS.

The spatial diffusion of norovirus epidemics over three seasons in Tokyo.

We studied the spatial trend of norovirus (NoV) epidemics using sentinel gastroenteritis surveillance data for patients aged <15 years (n = 140) in the Tokyo area for the 2006-2007 to 2008-2009 seasons utilizing the kriging method of geographical information system (GIS). This is the first study of the spreading pattern of NoV epidemics using sentinel surveillance data. Correlations of sentinel cases between the seasons and with demographic data were examined to identify the trend and related factors. A similar pattern of diffusion was observed over the seasons, and its mean correlation between seasons was significantly high. A higher number of cases were found in the peripheral area, which surrounds the most populated central area, and showed a correlation with the ratio of the children population (r = 0·321, P < 0·01) and the ratio of residents in larger families (r = 0·263, P < 0·01). While NoV susceptibility remained, the results suggest a transmission route in the local community as a possible epidemic factor. Prevention with focus on the peripheral area is desirable.

Molecular epidemiology and antimicrobial susceptibility of Clostridium difficile isolated from a university teaching hospital in Japan.

Clostridium difficile infection control strategies require an understanding of its epidemiology. In this study, we analysed the toxin genotypes of 130 non-duplicate clinical isolates of C. difficile from a university hospital in Tokyo, Japan. Multilocus sequence typing (MLST) and eBURST analysis were performed for these isolates and nine strains previously analysed by polymerase chain reaction (PCR) ribotyping. Minimum inhibitory concentrations (MICs) were determined for six antibiotics, and the bacterial resistance mechanisms were investigated. Ninety-five toxigenic strains (73%), including seven tcdA-negative, tcdB-positive and cdtA/cdtB-negative strains (A(-)B(+)CDT(-)) and three A(+)B(+)CDT(+) strains, and 35 (27%) non-toxigenic strains, were classified into 23 and 12 sequence types, respectively. Of these, sequence type (ST)17 (21.8%) was the most predominant. MLST and eBURST analysis showed that 139 strains belonged to seven groups and singletons, and most A(+)B(+)CDT(-) strains (98%, 89/91) were classified into group 1. All isolates were susceptible to metronidazole, vancomycin and meropenem; the ceftriaxone, clindamycin and ciprofloxacin resistance rates were 49, 59 and 99%, respectively. Resistance rates to ceftriaxone and clindamycin were higher in toxigenic strains than in non-toxigenic strains (P < 0.001). All ST17 and ST81 strains were resistant to these antibiotics. The clindamycin- and fluoroquinolone-resistant strains carried erm(B) and mutations in GyrA and/or GyrB, respectively. To our knowledge, this is the first MLST-based study of the molecular epidemiology of toxigenic and non-toxigenic strains in Japan, providing evidence that non-toxigenic and toxigenic strains exhibit high genetic diversity and that toxigenic strains are more likely than non-toxigenic strains to exhibit multidrug resistance.

A complex regulatory network coordinating cell cycles during C. elegans development is revealed by a genome-wide RNAi screen.

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development.

Clinicopathological and prognostic significance of interleukin-8 expression and its relationship to KRAS mutation in lung adenocarcinoma.

BACKGROUND: On the basis of our recent findings of oncogenic KRAS-induced interleukin-8 (IL-8) overexpression in non-small cell lung cancer, we assessed the clinicopathological and prognostic significances of IL-8 expression and its relationship to KRAS mutations in lung adenocarcinomas. METHODS: IL-8 expression was examined by quantitative RT-PCR using 136 of surgical specimens from lung adenocarcinoma patients. The association between IL-8 expression, clinicopathological features, KRAS or EGFR mutation status and survival was analysed. RESULTS: IL-8 was highly expressed in tumours from elderly patients or smokers and in tumours with pleural involvement or vascular invasion. In a non-smokers' subgroup, IL-8 level positively correlated with age. IL-8 was highly expressed in tumours with KRAS mutations compared with those with EGFR mutations or wild-type EGFR/KRAS. Lung adenocarcinoma patients with high IL-8 showed significantly shorter disease-free survival (DFS) and overall survival (OS) than those with low IL8. DFS and OS were significantly shorter in the patients with mutant KRAS/high IL-8 than in those with wild-type KRAS/low IL-8. Cox regression analyses demonstrated that elevated IL-8 expression correlated with unfavourable prognosis. CONCLUSIONS: Our findings suggest that IL-8 expression is associated with certain clinicopathological features including age and is a potent prognostic marker in lung adenocarcinoma, especially in oncogenic KRAS-driven adenocarcinoma.