These results indicate that the whole-brain LIPUS is an effective and non-invasive therapy for dementia by activating specific cells corresponding to each pathology, for which eNOS activation plays an important role as a common mechanism.

Objective-Left ventricular (LV) remodeling after acute myocardial infarction still remains an important issue in cardiovascular medicine. We have recently demonstrated that low-intensity pulsed ultrasound (LIPUS) therapy improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. In the present study, we aimed to demonstrate whether LIPUS also ameliorates LV remodeling after acute myocardial infarction and if so, to elucidate the underlying molecular mechanisms involved in the beneficial effects of LIPUS. Approach and Results-We examined the effects of LIPUS on LV remodeling in a mouse model of acute myocardial infarction, where the heart was treated with either LIPUS or no-LIPUS 3 times in the first week (days 1, 3, and 5). The LIPUS improved mortality and ameliorated post-myocardial infarction LV remodeling in mice. The LIPUS upregulated the expression of vascular endothelial growth factor, endothelial nitric oxide synthase, phosphorylated ERK, and phosphorylated Akt in the infarcted area early after acute myocardial infarction, leading to enhanced angiogenesis. Microarray analysis in cultured human endothelial cells showed that a total of 1050 genes, including those of the vascular endothelial growth factor signaling and focal adhesion pathways, were significantly altered by the LIPUS. Knockdown with small interfering RNA of either β1-integrin or caveolin-1, both of which are known to play key roles in mechanotransduction, suppressed the LIPUS-induced upregulation of vascular endothelial growth factor. Finally, in caveolin-1-deficient mice, the beneficial effects of LIPUS on mortality and post-myocardial infarction LV remodeling were absent. Conclusions-These results indicate that the LIPUS therapy ameliorates post-myocardial infarction LV remodeling in mice in vivo, for which mechanotransduction and its downstream pathways may be involved. (Arterioscler Thromb Vasc

We noted a new clinical syndrome with prominent cerebellar symptoms in apartment building residents in Kamisu, Japan. The well that provided drinking water contained diphenylarsinic acid, a degradation product of diphenylcyanoarsine or diphenylchloroarsine, which were developed for use as chemical weapons, inducing severe vomiting and sneezing. Characteristics of diphenylarsinic acid poisoning include brainstem-cerebellar and cerebral symptoms. Mental retardation associated with brain atrophy in magnetic resonance images was evident in some infants. We must be vigilant to prevent or minimize the effects of further diphenylarsinic acid poisoning in Japan or elsewhere.

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp a murine skin graft model, 12 and inhibits tumor necrosis factor (TNF)-α expression induced by lipopolysaccharides in a rat glioma cell line in vitro. 13 In addition, low-energy SW therapy exerts anti-inflammatory effects on orthopedic diseases, such as tendinitis, epicondylitis, plantar fasciitis and several inflammatory tendon diseases. 14 Infiltration of inflammatory cells (eg, macrophages) is critically important in wound healing after AMI, while excessive inflammatory responses deteriorates LV remodeling in the chronic phase. 15-17 In the present study, we thus examined whether SW therapy exerts beneficial anti-inflammatory effects in a rat model of AMI. MethodsThe present study conforms to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes ecent progress in emergency care and patient management has improved the prognosis of patients with acute myocardial infarction (AMI). 1-4 However, left ventricular (LV) remodeling after AMI still remains one of the unsolved problems. 5,6 Thus, it is crucial to develop new therapeutic strategies to suppress LV remodeling after AMI. We have developed a non-invasive angiogenic therapy with extracorporeal low-energy shock waves (SW), and have demonstrated its efficacy and safety in a porcine model of chronic myocardial ischemia 7 and patients with angina pectoris. 8,9 Furthermore, we have demonstrated that SW therapy ameliorates LV remodeling after AMI in pigs in vivo. 10,11 However, it remains to be examined whether SW therapy also exerts anti-inflammatory effects on AMI in addition to its angiogenic effects. Low-energy SW therapy suppresses the production of several cytokines, chemokines, and matrix metalloproteinases in Background: It has been previously demonstrated that extracorporeal low-energy shock-wave (SW) therapy ameliorates left ventricular (LV) remodeling through enhanced angiogenesis after acute myocardial infarction (AMI) in pigs in vivo. However, it remains to be examined whether SW therapy also exerts anti-inflammatory effects on AMI.

H. Molecular mechanisms of the angiogenic effects of low-energy shock wave therapy: roles of mechanotransduction. Am J Physiol Cell Physiol 311: C378 -C385, 2016. First published July 13, 2016; doi:10.1152/ajpcell.00152.2016.-We have previously demonstrated that low-energy extracorporeal cardiac shock wave (SW) therapy improves myocardial ischemia through enhanced myocardial angiogenesis in a porcine model of chronic myocardial ischemia and in patients with refractory angina pectoris. However, the detailed molecular mechanisms for the SW-induced angiogenesis remain unclear. In this study, we thus examined the effects of SW irradiation on intracellular signaling pathways in vitro. Cultured human umbilical vein endothelial cells (HUVECs) were treated with 800 shots of low-energy SW (1 Hz at an energy level of 0.03 mJ/mm 2 ). The SW therapy significantly upregulated mRNA expression and protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). The SW therapy also enhanced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2) and Akt. Furthermore, the SW therapy enhanced phosphorylation of caveolin-1 and the expression of HUTS-4 that represents ␤1-integrin activity. These results suggest that caveolin-1 and ␤1-integrin are involved in the SW-induced activation of angiogenic signaling pathways. To further examine the signaling pathways involved in the SW-induced angiogenesis, HUVECs were transfected with siRNA of either ␤ 1-integrin or caveolin-1. Knockdown of either caveolin-1 or ␤ 1-integrin suppressed the SW-induced phosphorylation of Erk1/2 and Akt and upregulation of VEGF and eNOS. Knockdown of either caveolin-1 or ␤1-integrin also suppressed SW-induced enhancement of HUVEC migration in scratch assay. These results suggest that activation of mechanosensors on cell membranes, such as caveolin-1 and ␤1-integrin, and subsequent phosphorylation of Erk and Akt may play pivotal roles in the SW-induced angiogenesis. shock wave; mechanotransduction; angiogenesis; caveolin-1; ␤1-integrin SHOCK WAVES (SW) have been clinically introduced for lithotripsy since the 1980s; urinary stones are broken up by highenergy SW (7). The waveform of an SW is similar to that of a blast wave, which is composed of discontinuous compression of leading shock propagating with supersonic speed, subsequent rarefaction, and negative pressure (27). Over the past 20 years, low-energy SW therapy has also been put into clinical application (3,17). We have previously demonstrated that low-energy SW (about 10% of the energy used for urolithotripsy treatment) significantly upregulated vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs) (25). Low-energy SW therapy has also been reported to enhance nitric oxide (NO) production via activation of endothelial NO synthase (eNOS) in vitro (23,24). We have demonstrated that extracorporeal low-energy cardiac SW therapy enhances angiogenesis and contractile function in a porcine model of chronic myocardial isc...

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We aimed to elucidate the range of the incubation period in patients infected with the SARS-CoV-2 Omicron variant in comparison with the Alpha variant. Contact tracing data from three Japanese public health centers (total residents, 1.06 million) collected following the guidelines of the Infectious Diseases Control Law were reviewed for 1589 PCR-confirmed COVID-19 cases diagnosed in January 2022. We identified 77 eligible symptomatic patients for whom the date and setting of transmission were known, in the absence of any other probable routes of transmission. The observed incubation period was 3.03 ± 1.35 days (mean ± SDM). In the log-normal distribution, 5th, 50th and 95th percentile values were 1.3 days (95% CI: 1.0–1.6), 2.8 days (2.5–3.1) and 5.8 days (4.8–7.5), significantly shorter than among the 51 patients with the Alpha variant diagnosed in April and May in 2021 (4.94 days ± 2.19, 2.1 days (1.5–2.7), 4.5 days (4.0–5.1) and 9.6 days (7.4–13.0), p < 0.001). As this incubation period, mainly of sublineage BA.1, is even shorter than that in the Delta variant, it is thought to partially explain the variant replacement occurring in late 2021 to early 2022 in many countries.

BackgroundH5N2 avian influenza virus infection of humans has not been reported thus far. The first H5N2 avian influenza infection of poultry in Japan occurred in Ibaraki.MethodsThe subjects were workers at 35 chicken farms in Ibaraki Prefecture, where the H5N2 virus or antibody was isolated from chickens. None of the subjects exhibited influenza symptoms. The H5N2-neutralizing antibody titers of the first and second paired sera samples were compared. To investigate the possible factors for this increase, the H5N2-neutralizing antibody titer (1:40 or more) was calculated for the second samples. A logistic regression analysis was performed to examine the association of these factors with H5N2-neutralizing antibody positivity.ResultsWe performed Wilcoxon matched-pairs signed-ranked test on data collected from 257 subjects, and determined that the H5N2 antibody titers of the second paired sera samples were significantly higher than those of the first samples (P < 0.001). The H5N2 antibody titers of paired sera of 13 subjects without a history of seasonal influenza vaccination within the previous 12 months increased 4-fold or more. The percentage of antibody positivity was 32% for subjects with a history of seasonal influenza vaccination (28% of all subjects) and 13% for those without a history of the same. The adjusted odds ratio of H5N2-neutralizing antibody positivity was 4.6 (95% confidence interval: 1.6-13.7) for those aged over 40 and 3.1 (95% confidence interval: 1.6-6.1) for those with a history of seasonal influenza vaccination within the previous 12 months.ConclusionThe results suggest that this may have been the first avian influenza H5N2 infection of poultry to affect humans. A history of seasonal influenza vaccination might be associated with H5N2-neutralizing antibody positivity.