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A male patient in his 80s was brought to our emergency room with a one-day history of general malaise and cough. He had received a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination seven days earlier. He initially presented with respiratory failure, and an alveolar hemorrhage was suspected. The patient was intubated and admitted to the intensive care unit. We suspected that the alveolar hemorrhage was caused by acute respiratory distress syndrome (ARDS). Treatment including high-dose corticosteroid therapy and venovenous extracorporeal membrane oxygenation (ECMO) was initiated, however, the patient did not respond to treatment and died 35 days after admission. Pathological autopsy revealed diffuse alveolar damage (DAD) and idiopathic diffuse alveolar hemorrhage (DAH) consistent with ARDS. ARDS should be considered as a differential diagnosis when a patient develops respiratory symptoms after receiving the SARS-CoV-2 vaccine., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kawano et al.)

Targeted protein degradation via the ubiquitin-proteasome system has emerged as one of the most promising drug discovery modalities. Autophagy, another intracellular degradation system, can target a wide range of nonproteinous substrates as well as proteins, but its application to targeted degradation is still in its infancy. Our previous work revealed a relationship between guanine modification of cysteine residues on intracellular proteins and selective autophagy, resulting in the first autophagy-based degraders, autophagy-targeted chimeras (AUTACs). Based on the research background, all the reported AUTACs compounds contain cysteine as a substructure. Here, we examine the importance of this substructure by conducting SAR studies and report significant improvements in the degrader's activity by replacing cysteine with other moieties. Several derivatives showed sub-μM range degrading activity, demonstrating the increased practical value of AUTACs.

Post-transcriptional modifications of tRNA are crucial for their core function. The inosine (I; 6-deaminated adenosine) at the first position in the anticodon of tRNA Arg (ICG) modulates the decoding capability and is generally considered essential for reading CGU, CGC, and CGA codons in eubacteria. We report here that the Bacillus subtilis yaaJ gene encodes tRNA-specific adenosine deaminase and is non-essential for viability. A β-galactosidase reporter assay revealed that the translational activity of CGN codons was not impaired in the yaaJ -deletion mutant. Furthermore, tRNA Arg (CCG) responsible for decoding the CGG codon was dispensable, even in the presence or absence of yaaJ . These results strongly suggest that tRNA Arg with either the anticodon ICG or ACG has an intrinsic ability to recognize all four CGN codons, providing a fundamental concept of non-canonical wobbling mediated by adenosine and inosine nucleotides in the anticodon. This is the first example of the four-way wobbling by inosine nucleotide in bacterial cells. On the other hand, the absence of inosine modification induced +1 frameshifting, especially at the CGA codon. Additionally, the yaaJ deletion affected growth and competency. Therefore, the inosine modification is beneficial for translational fidelity and proper growth-phase control, and that is why yaaJ has been actually conserved in B. subtilis .

Intercellular cleaning via autophagy is crucial for maintaining cellular homeostasis, and impaired autophagy has been associated with the accumulation of protein aggregates that can contribute to neurological diseases. Specifically, the loss-of-function mutation in the human autophagy-related gene 5 (ATG5) at E122D has been linked to the pathogenesis of spinocerebellar ataxia in humans. In this study, we generated two homozygous C. elegans strains with mutations (E121D and E121A) at positions corresponding to the human ATG5 ataxia mutation to investigate the effects of ATG5 mutations on autophagy and motility. Our results showed that both mutants exhibited a reduction in autophagy activity and impaired motility, suggesting that the conserved mechanism of autophagy-mediated regulation of motility extends from C. elegans to humans., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2023 by the authors.)

Aim: In Japan, no training course is dedicated to postcardiac arrest care (PCAC), including venoarterial extracorporeal membrane oxygenation (VA-ECMO); thus, faculty members of the Japanese Circulation Society developed an original, comprehensive PCAC training course. This report reviews the development, implementation, and refinement of this PCAC training course., Methods: We examined the preserved data from the Japanese Circulation Society PCAC training courses between 2014 and 2020. Data related to the learning content and number of the attendees and instructors were collected and summarized., Results: Sixteen courses were held between August 2014 and February 2020, before the coronavirus disease 2019 (COVID-19) pandemic. A total of 677 health care providers participated: 351 doctors, 225 nurses, 62 perfusionists, five emergency medical professionals, and two pharmacists. Thirty-two attendees' data were missing. The core learning contents of all the courses included a standardized postcardiac arrest algorithm, targeted temperature management, VA-ECMO cannulation skills, and postcannulation management. Concerning curriculum evolution, extracorporeal cardiopulmonary resuscitation simulation, postarrest neurological examination and monitoring, and ultrasound-guided Seldinger technique training were added in the 4th, 5th, and 13th courses, respectively., Conclusion: The Japanese Circulation Society PCAC training course has been developed and refined to provide an organized, comprehensive opportunity for health care providers to acquire specific knowledge and skills in PCAC and VA-ECMO., (© 2022 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Background: The prevalence of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) has been increasing rapidly worldwide. However, guidelines or clinical studies do not provide sufficient data on ECPR practice. The aim of this study was to provide real-world data on ECPR for patients with OHCA, including details of complications., Methods: We did a retrospective database analysis of observational multicenter cohort study in Japan. Adult patients with OHCA of presumed cardiac etiology who received ECPR between 2013 and 2018 were included. The primary outcome was favorable neurological outcome at hospital discharge, defined as a cerebral performance category of 1 or 2., Results: A total of 1644 patients with OHCA were included in this study. The patient age was 18-93 years (median: 60 years). Shockable rhythm in the initial cardiac rhythm at the scene was 69.4%. The median estimated low flow time was 55 min (interquartile range: 45-66 min). Favorable neurological outcome at hospital discharge was observed in 14.1% of patients, and the rate of survival to hospital discharge was 27.2%. The proportions of favorable neurological outcome at hospital discharge in terms of shockable rhythm, pulseless electrical activity, and asystole were 16.7%, 9.2%, and 3.9%, respectively. Complications were observed during ECPR in 32.7% of patients, and the most common complication was bleeding, with the rates of cannulation site bleeding and other types of hemorrhage at 16.4% and 8.5%, respectively., Conclusions: In this large cohort, data on the ECPR of 1644 patients with OHCA show that the proportion of favorable neurological outcomes at hospital discharge was 14.1%, survival rate at hospital discharge was 27.2%, and complications were observed during ECPR in 32.7%., (© 2022. The Author(s).)

Anopheles gambiae sensu lato complex (An. gambiae s.l.) describes a group of nine morphologically indistinguishable members that vary in their distribution, ability to transmit malaria, and susceptibility to pyrethroids. Here, we recorded the spatial patterns of PCR-identified An. gambiae s.l. complex species collected from four sites in Cross River State, Nigeria that represented three different ecological zones. Trapping was conducted between October 2015 and June 2016. Anopheles gambiae s.l. complex species identification was performed using species-specific primers followed by An. gambiae and An. coluzzii differentiation using the restriction fragment length polymorphism (RFLP) method. Bivariate and multivariate logistic regression models were used to identify ecological and seasonal variables closely associated with An. coluzzii and An. gambiae distribution. Out of 1,388 An. gambiae s.l. successfully amplified, 1,074 (77.4%) were An. coluzzii, 278 (20%) were An. gambiae, and 25 (1.8%) were hybrids (An. coluzzii/An. gambiae). A very small number of An. arabiensis (0.8%, n = 11) were also collected. Statistical analysis indicated that An. coluzzii is predominant in Guinea-savannah and tropical rainforest, and is highly associated with rainy seasons, while, An. gambiae is prevalent in mangrove swamp forest during dry seasons. Only 13 An. gambiae s.l. females were infected with Plasmodium falciparum (P. falciparum). The sporozoite infection rate was higher in mangrove swamp forest (53.8%, n = 7) than in rain forest (38.5%, n = 5) followed by Guinea-savannah (7.7%, n = 1) ecological zones. These results provide important insights for strategic planning of malaria control programs in Nigeria., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Ticks are important vectors of various pathogenic protozoa, bacteria and viruses that cause serious and life-threatening illnesses in humans and animals worldwide. Estimating tick-borne pathogen prevalence in tick populations is necessary to delineate how geographical differences, environmental variability and host factors influence pathogen prevalence and transmission. This study identified ticks and tick-borne pathogens in samples collected from June 2016 to December 2017 at seven sites within the Coastal, Sudan and Guinea savanna ecological zones of Ghana., Methods: A total of 2016 ticks were collected from domestic animals including cattle, goats and dogs. Ticks were morphologically identified and analysed for pathogens such as Crimean-Congo haemorrhagic fever virus (CCHFV), Alkhurma haemorrhagic fever virus (AHFV), Rickettsia spp. and Coxiella burnetii using polymerase chain reaction assays (PCR) and sequence analysis., Results: Seven species were identified, with Amblyomma variegatum (60%) most frequently found, followed by Rhipicephalus sanguineus sensu lato (21%), Rhipicephalus spp. (9%), Hyalomma truncatum (6%), Hyalomma rufipes (3%), Rhipicephalus evertsi (1%) and Rhipicephalus (Boophilus) sp. (0.1%). Out of 912 pools of ticks tested, Rickettsia spp. and Coxiella burnetii DNA was found in 45.6% and 16.7% of pools, respectively, whereas no CCHFV or AHFV RNA were detected. Co-infection of bacterial DNA was identified in 9.6% of tick pools, with no statistical difference among the ecozones studied., Conclusions: Based on these data, humans and animals in these ecological zones are likely at the highest risk of exposure to rickettsiosis, since ticks infected with Rickettsia spp. displayed the highest rates of infection and co-infection with C. burnetii, compared to other tick-borne pathogens in Ghana., (© 2022. The Author(s).)

Background: The effect of in-hospital rapid cooling by intravenous ice-cold fluids for comatose survivors of out-of-hospital cardiac arrest (OHCA) is unclear., Methods and results: From the J-PULSE-HYPO study registry, data for 248 comatose survivors with return of spontaneous circulation (ROSC) who were treated with therapeutic hypothermia (34℃ for 12-72 h) after witnessed shockable OHCA were extracted. Patients were divided into 2 groups by the median collapse-to-ROSC interval (18 min), and then into 2 groups by cooling method (rapid cooling by intravenous ice-cold fluids vs. standard cooling). The primary endpoint was favorable neurological outcome (Cerebral Performance Category of 1 or 2) at 30 days after OHCA. In the whole cohort, the shorter collapse-to-ROSC interval group had significantly higher favorable neurological outcome than the longer collapse-to-ROSC interval group (78.2% vs. 46.8%, P<0.001). In the shorter collapse-to-ROSC interval group, no significant difference was observed in favorable neurological outcome between the 2 cooling groups (rapid cooling group: 79.4% vs. standard cooling group: 77.0%, P=0.75). In the longer collapse-to-ROSC interval group, however, favorable neurological outcome was significant higher in the rapid cooling group than in the standard cooling group (60.7% vs. 33.3%, P<0.01) and the adjusted odds ratio after rapid cooling was 3.069 (95% confidence interval 1.423-6.616, P=0.004)., Conclusions: In-hospital rapid cooling by intravenous ice-cold fluids improved neurologically intact survival in comatose survivors whose collapse-to-ROSC interval was delayed over 18 min after shockable OHCA.

Arbovirus transmission by Aedes mosquitoes has long been a significant problem in Africa. In West Africa, Aedes vector management faces significant challenges; lack of recent Aedes distributional data and potential distributional modeling hinder effective vector control and pose serious public health issues. In this study, larval and adult mosquitoes were collected from four study sites in Enugu State, Nigeria every other month between November 2017 and September 2018. A total number of 2997 Aedes mosquitoes were collected and identified, and 59 positive field occurrence points for both Aedes adult and larvae were recorded. A total of 18 positive occurrence points were used for modeling. Ecological Niche Models (ENMs) were used to estimate the current geographic distribution of Aedes species ( spp. ) in Enugu State, south-east Nigeria, and mosquito presence was used as a proxy for predicting risk of disease transmission. Maximum Entropy distribution modeling or "MaxEnt" was used for predicting the potential suitable habitats, using a portion of the occurrence records. A total of 23 environmental variables (19 bioclimatic and four topographic) were used to model the potential geographical distribution area under current climatic conditions. The most suitable habitat for Aedes spp. was predicted in the northern, central, and southeastern parts of Enugu State with some extensions in Anambra, Delta, and Edo States in the west, and Ebonyi State in the east. Seasonal temperature, precipitation of the wettest month, mean monthly temperature range, elevation, and precipitation of the driest months were the highest estimated main variable contributions associated with the distribution of Aedes spp. We found that Aedes spp. prefer to be situated in environmental conditions where precipitation of wettest month ranged from 265 to 330 mm, precipitation of driest quarter ranged from 25 to 75 mm while precipitation of wettest quarter ranged from 650 to 950 mm. Aedes mosquitoes, such as Ae. aegypti and Ae. albopictus, pose a significant threat to human health, hence, the results of this study will help decision makers to monitor the distribution of these species and establish a management plan for future national mosquito surveillance and control programs in Nigeria., Competing Interests: All authors declare that there is no conflict of interest.

Background: To date, no study has comprehensively analyzed the association between neuromuscular blockade (NMB) during target temperature management (TTM) and the neurological outcomes after out-of-hospital cardiac arrest (OHCA) using a multicenter dataset. We aimed to examine the association between NMB during TTM after cardiac arrest and neurological outcomes after OHCA., Methods: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry. The exposure of the current study was the use of NMB during TTM. The primary outcome was favorable neurological outcome, i.e., a cerebral performance category of 1-2, at hospital discharge., Results: Of the 452 patients with OHCA enrolled in the J-PULSE-HYPO study, 431 were analyzed. NMB was used in 353 patients (81.9%). Multivariable logistic regression analysis revealed that NMB use was not independently associated with favorable outcomes [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.42-2.18; p = .918)] or survival at discharge (OR, 0.83; 95% CI, 0.31-2.02; p = .688). After adjusting the covariates, the predicted probabilities did not reveal significant differences between NMB use and non-NMB use in the respective mean (95% CI) values for favorable neurological outcomes [53.6 (50.2-57.0) % vs. 58.0 (50.4-65.6) %, p = .304], and survival rates [77.1 (74.7-79.5) % vs. 75.8 (70.5-81.0) %, p = .647]., Conclusions: The NMB use during TTM was not associated with favorable neurological outcomes and survival rate in patients with OHCA., Competing Interests: Declaration of Competing Interest The authors have declared no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Degrader technologies, which enable the chemical knockdown of disease-causing proteins, are promising for drug discovery. After two decades of research, degraders using the ubiquitin-proteasome system (UPS) are currently in clinical trials. However, the UPS substrates are mainly limited to soluble proteins. Autophagy-targeting chimeras and autophagosome-tethering compounds are degraders that use autophagy, which has functions complementary to the UPS. They can degrade organelles and aggregate-prone proteins, making them promising treatments against age-related conditions such as mitochondrial dysfunction and neurodegenerative diseases. The molecular mechanism of selective autophagy is an ongoing research topic, which explains why autophagy-based degraders were not available until recently. In this review, we introduce four classifications of selective autophagy mechanisms to facilitate the understanding of the degrader design., Competing Interests: Declaration of interests Tohoku University has filed patent applications on AUTACs that are described in this article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend that comatose patients with return of spontaneous circulation after cardiac arrest have targeted temperature management (TTM). However, the duration of TTM remains to be elucidated. Methods and Results: We conducted a cluster randomized trial in 10 hospitals to compare 12-24 vs. 36 h of cooling in patients with cardiac arrest who received TTM. The primary outcome was the incidence, within 1 month, of complications including bleeding requiring transfusion, infection, arrhythmias, decreasing blood pressure, shivering, convulsions, and major adverse cardiovascular events. Secondary outcomes were mortality and favorable neurological outcome (Cerebral Performance Categories 1-2) at 3 months. Random-effects models with clustered effects were used to calculate risk ratios (RR). Data of 185 patients were analyzed (12- to 24-h group, n=100 in 5 hospitals; 36-h group, n=85 in 5 hospitals). The incidence of complications within 1 month did not differ between the 2 groups (40% vs. 34%; RR 1.04, 95% confidence interval [CI] 0.67-1.61, P=0.860). Favorable neurological outcomes at 3 months were comparable between the 2 groups (64% vs. 62%; RR 0.91, 95% CI 0.72-1.14, P=0.387). Conclusions: TTM at 34℃ for 12-24 h did not significantly reduce the incidence of complications. This study did not show superiority of TTM at 34℃ for 12-24 h for neurologic outcomes., Competing Interests: S.Y. is a member of Circulation Reports’ Editorial Team. None of the authors have any financial interests to disclose and any further conflicts of interest to declare., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Aim: A lack of known guidelines for the provision of extracorporeal cardiopulmonary resuscitation (ECPR) to patients with out-of-hospital cardiac arrest (OHCA) has led to variability in practice between hospitals even in the same country. Because variability in ECPR practice has not been completely examined, we aimed to describe the variability in ECPR practice in patients with OHCA from the emergency department (ED) to the intensive care units (ICU)., Methods: An anonymous online questionnaire to examine variability in ECPR practice was completed in January 2020 by 36 medical institutions who participated in the SAVE-J II study. Institutional demographics, inclusion and exclusion criteria, initial resuscitation management, extracorporeal membrane oxygenation (ECMO) initiation, initial ECMO management, intra-aortic balloon pumping/endotracheal intubation/management during coronary angiography, and computed tomography criteria were recorded., Results: We received responses from all 36 institutions. Four institutions (11.1%) had a hybrid emergency room. Cardiovascular surgery was always involved throughout the entire ECMO process in only 14.7% of institutions; 60% of institutions had formal inclusion criteria and 50% had formal exclusion criteria. In two-thirds of institutions, emergency physicians carried out cannulation. Catheterization room was the leading location of cannulation (48.6%) followed by ED (31.4%). The presence of formal exclusion criteria significantly increased with increasing ECPR volume ( P for trend <0.001). Intra-aortic balloon pumping was routinely initiated in only 25% of institutions. Computed tomography was routinely carried out before coronary angiography in 25% of institutions., Conclusions: We described the variability in ECPR practice in patients with OHCA from the ED to the ICU., Competing Interests: Approval of the research protocol: Approval number 19‐R155. Informed consent: N/A. Registry and registration no. of the study/trial: Not applicable. Animal studies: N/A. Conflict of interest: None., (© 2021 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

The genus Nipponodrasterius Kishii, 1966 was established as a member of the subfamily Conoderinae Fleutiaux, 1919 (now tribe Oophorini Gistel, 1848; subfamily Agrypninae Candèze, 1857) based on N. alpicola . The genus was suggested to be unlikely to belong to Agrypninae because it lacks diagnostic features of the Agrypninae. However, there are no taxonomic treatments for the genus or species. Here, we review the status of the genus and species by examining the holotype of N. alpicola . Consequently, the genus was found to be a junior synonym of the genus Gamepenthes Fleutiaux, 1928 and N. alpicola was found to be a junior synonym of G. pictipennis (Lewis, 1894). We review all species of Gamepenthes in Japan and provide a key to species., (Kôichi Arimoto, Hisayuki Arimoto.)

Background: Whether hospital bed number and rapid response system (RRS) call rate is associated with the clinical outcomes of patients who have RRS activations is unknown. We test a hypothesis that hospital volume and RRS call rates are associated with the clinical outcomes of patients with RRSs., Methods: This is a retrospective chart analysis of an existing dataset associated with In-Hospital Emergency Registry in Japan. In the present study, 4818 patients in 24 hospitals from April 2014 to March 2018 were analyzed. Primary outcome variable was an unplanned intensive care unit (ICU) admission after RRS activation., Results: In the primary analysis of the study using a multivariate analysis adjusting potential confounding factors, higher RRS call rate was significantly associated with decreased unplanned ICU admissions (P < 0.0001, Odds ratio [OR] 0.95, 95% confidence interval [CI] 0.92-0.98), but there was no significant association of hospital volume with unplanned ICU admissions (P = 0.44). In the secondary analysis of the study, there was a non-significant trend of increased cardiac arrest on arrival at the location of the RRS provider at large-volume hospitals (P = 0.084, OR 1.16, 95% CI 0.98-1.38). Large-volume hospitals had a significantly higher 1-month mortality rate (P = 0.0040, OR 1.10, 95% CI 1.03-1.18)., Conclusion: Hospitals with increased RRS call rates had significantly decreased unplanned ICU admission in patients who had RRS activations. Patients who had RRS activations at large-volume hospitals had an increased 1-month mortality rate., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Targeted degradation is a promising new modality in drug discovery that makes it possible to reduce intracellular protein levels with small molecules. It is a complementary approach to the conventional protein knockdown typically used in laboratories and may offer a way to approach the currently undruggable human proteome. Recently, the first autophagy-mediated degraders, called AUTACs, were developed based on observations in a xenophagy study.

Aim: The European Resuscitation Council guidelines recommend a slow rate of rewarming of 0.25 °C/h-0.5 °C/h for out-of-hospital cardiac arrest (OHCA) patients receiving therapeutic hypothermia (TH). Conversely, a very slow rewarming of 1 °C/day is generally applied in Japan. The rewarming duration ranged from less than 24 h up to more than 50 h. No randomized control trials have examined the optimal rewarming speed for TH in OHCA patients. Therefore, we examined the association between the rewarming duration and neurological outcomes in OHCA patients who received TH., Methods: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry, a multicenter prospective cohort study. Patients suffering from OHCA who received TH (target temperature, 34 °C) after the return of spontaneous circulation from 2005 to 2011 in 14 hospitals throughout Japan were enrolled. The rewarming duration was defined as the time from the beginning of rewarming at a target temperature of 34 °C until reaching 36 °C. The primary outcome was an unfavorable neurological outcome at hospital discharge, i.e., a cerebral performance category of 3-5., Results: The J-PULSE-HYPO study enrolled 452 OHCA patients. Of these, 328 were analyzed; 79.9% survived to hospital discharge, of which 56.4% had a favorable neurological outcome. Multivariable logistic regression analysis revealed that the rewarming duration was independently associated with unfavorable neurological outcomes [odds ratio (per 5 h), 0.89; 95% confidence interval, 0.79-0.99; p =  0.032]., Conclusion: A longer rewarming duration was significantly associated with and was an independent predictor of favorable neurological outcomes in OHCA patients who received TH., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Spinal cord injury (SCI) with atlantoaxial dislocation (AAD) is often fatal. We present the case of a resuscitated patient with AAD and traumatic subarachnoid hemorrhage (SAH) at the craniovertebral junction (CVJ)., Case Presentation: We present the case of an 84-year-old man who suffered an observed cardiopulmonary arrest. Cardiopulmonary resuscitation was initiated and spontaneous circulation returned. In the emergency room, the patient's Glasgow Coma Scale was 3 (E1V1M1). No spontaneous respiration was noted. Neuroimaging revealed SAH at the CVJ. Contrast-enhanced computed tomography (CT) revealed a vessel running through the left C2/3 intervertebral foramen into the spinal canal. The ventral space of spinal cord revealed contrast enhancement. Angiography revealed extravasation from the spinal branch of the left vertebral artery, without venous filling. It did not appear to be a vascular malformation with an arteriovenous shunt, but rather a traumatic laceration of the artery. Plain CT and CT angiography suggested AAD. Magnetic resonance imaging revealed injury to the medulla oblongata and upper cervical spinal cord, with AAD and retrodental subligamentous hemorrhage. We embolized the branch of the left vertebral artery and performed a C1 laminectomy. The patient moved his extremities postoperatively., Discussion: This was a case of injury to the medulla oblongata and upper cervical spinal cord due to AAD with SAH. This is the first report of resuscitated case of traumatic AAD with SAH in the CVJ. Traumatic AAD should be included in the differential diagnosis in case of SAH in CVJ, which may be misdiagnosed as intrinsic SAH., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© International Spinal Cord Society 2019.)

Protein silencing represents an essential tool in biomedical research. Targeted protein degradation (TPD) strategies exemplified by PROTACs are rapidly emerging as modalities in drug discovery. However, the scope of current TPD techniques is limited because many intracellular materials are not substrates of proteasomal clearance. Here, we described a novel targeted-clearance strategy (autophagy-targeting chimera [AUTAC]) that contains a degradation tag (guanine derivatives) and a warhead to provide target specificity. As expected from the substrate scope of autophagy, AUTAC degraded fragmented mitochondria as well as proteins. Mitochondria-targeted AUTAC accelerated both the removal of dysfunctional fragmented mitochondria and the biogenesis of functionally normal mitochondria in patient-derived fibroblast cells. Cytoprotective effects against acute mitochondrial injuries were also seen. Canonical autophagy is viewed as a nonselective bulk decomposition system, and none of the available autophagy-inducing agents exhibit useful cargo selectivity. With its target specificity, AUTAC provides a new modality for research on autophagy-based drugs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We propose a new low VπL, fully-crystalline, accumulation modulator design based on a thin horizontal gate oxide slot fin waveguide, on bonded double Silicon-on-Insulator (SOI). A combination of anisotropic wet etching and the mirrored crystal alignment of the top and bottom SOI layers allows us for the first time to selectively pattern the bottom layer from above. Simulations presented herein show a VπL = 0.17Vcm. Fin-waveguides and passive Mach-Zehnder Interferometer (MZI) devices with fin-waveguide phase shifters have been fabricated, with the fin-waveguides having a transmission loss of 5.8dB/mm and a 13.5nm thick internal gate oxide slot.

In metropolitan areas, shallow groundwater temperatures are affected by anthropogenic heat sources. The resulting thermal conditions in the subsurface are highly site-specific, and spatial and temporal trends have only been revealed for a few cities. In this study, the anthropogenic heat input is quantified for 15 locations in Osaka, Japan using an analytical, one-dimensional conductive heat transport model. Mean anthropogenic fluxes into the subsurface are determined annually between 2003 and 2011. The model depicts fluxes from buildings and from different land cover types separately. The main objective is to compare the predicted annual mean heat input to heat storage increase, and to identify site-specific factors relevant for the thermal evolution of the underground at each well location. Our results indicate that mean fluxes from asphalt covered areas (0.28 ± 0.07 W/m 2 ) and from buildings (0.32 ± 0.18 W/m 2 ) are significantly higher than fluxes from unpaved (0.06 ± 0.06 W/m 2 ) and grass-covered (-0.04 ± 0.06 W/m 2 ) areas. Furthermore, the temporal variation of mean fluxes from buildings is stable over the studied time period, while annual mean fluxes from asphalt, grass and unpaved areas vary as much as 0.8 MJ/m 2 . Still, the uncertainty associated with the combined annual heat input of all heat sources is slightly higher than the changes between the years. Overall, the predicted cumulative heat input (2003 to 2011) at the wells ranges from 4 MJ/m 2 to 60 MJ/m 2 . Comparing these results to heat storage increase, additional local heat fluxes, such as from construction work or a sewage treatment plant, have to be considered for about 1/3 of the wells. In addition, it becomes apparent that a significant percentage of determined anthropogenic heat input is not stored in the urban aquifer and heat input is predicted to be considerably higher than heat storage increase., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Early rehabilitation is widely recommended for acute-stroke patients. We tested the hypothesis that the functional prognosis of stroke patients receiving daily early rehabilitation in a clinical practice setting is generally better than that of patients receiving rehabilitation only on weekdays., Materials and Methods: We analyzed hospitalized patients who experienced either cerebral infarctions or cerebral hemorrhages and subsequently underwent rehabilitation at our hospital between October 2010 and September 2014. We examined the association between training frequency and activities of daily living improvements, as indicated by the Barthel Index (BI) effectiveness., Results: In total, 661 patients with cerebral infarctions and 245 with intracerebral hemorrhages (ICHs) were analyzed. The BI effectiveness was highest for patients receiving high-frequency therapy following cerebral infarction. In addition, multiple linear regression analysis indicated that BI effectiveness was significantly and positively correlated with high-frequency therapy (coefficient, 0.072; 95% confidence interval, 0.019-0.126; p < 0.01) in patients with cerebral infarctions. There was no significant difference in BI effectiveness between therapeutic protocols for patients with ICHs., Conclusion: This retrospective cohort study demonstrated that extensive therapy can result in functional recovery in patients with cerebral infarctions. Implications for Rehabilitation Early intervention with intensive rehabilitation therapy is important for improving the functional recovery of patients during acute-care hospitalization. Few acute hospitals provide more than 2 h of daily rehabilitation for patients with acute stroke. In a daily clinical practice setting, this clinical study demonstrates a direct relationship between early intervention with intensive rehabilitation therapy and good functional recovery of stroke patients in an acute ward.

Mobile phone technology has led to implementation of portable and inexpensive microscopes. Light-emitting diode (LED) array microscopes support various multicontrast imaging by flexible illumination patterns of the LED array that can be achieved without changing the optical components of the microscope. Here, we demonstrate a mobile-phone-based LED array microscope to realize multimodal imaging with bright-field, dark-field, differential phase-contrast, and Rheinberg illuminations using as few as 37 LED bulbs. Using this microscope, we obtained high-contrast images of living cells. Furthermore, by changing the color combinations of Rheinberg illumination, we were able to obtain images of living chromatic structures with enhanced or diminished contrast. This technique is expected to be a foundation for high-contrast microscopy used in modern field studies.

Objectives: Bradycardia during therapeutic hypothermia has been reported to be a predictor of favorable neurologic outcomes in out-of-hospital cardiac arrests. However, bradycardia occurrence rate may be influenced by the target body temperature. During therapeutic hypothermia, as part of the normal physiologic response, heart rate decreases in the cooling phase and increases during the rewarming phase. We hypothesized that increased heart rate during the rewarming phase is another predictor of favorable neurologic outcomes. To address this hypothesis, the study aimed to examine the association between heart rate response during the rewarming phase and neurologic outcomes in patients having return of spontaneous circulation after out-of-hospital cardiac arrest., Design: A secondary analysis of the Japanese Population-based Utstein style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia registry, which was a multicenter prospective cohort study., Setting: Fourteen hospitals throughout Japan., Patients: Patients suffering from out-of-hospital cardiac arrest who received therapeutic hypothermia after the return of spontaneous circulation from 2005 to 2011., Intervention: None., Measurements and Main Results: This study enrolled 452 out-of-hospital cardiac arrest patients, of which 354 were analyzed, and 80.2% survived to hospital discharge, of which 57.3% had a good neurologic outcome. Heart rate response was calculated using heart rate data recorded during therapeutic hypothermia in the abovementioned registry. Heart rate response in the rewarming phase (heart rate response-rewarming) was calculated as follows: (heart rate [post rewarming]-heart rate [pre rewarming])/heart rate (pre rewarming) × 100. The primary outcome was an unfavorable neurologic outcome at hospital discharge, that is, a Cerebral Performance Category of 3-5. Multivariable logistic regression analysis was performed to determine the association between heart rate response-rewarming and unfavorable neurologic outcomes. Multivariable logistic regression analysis showed that heart rate response-rewarming was independently associated with unfavorable outcomes (odds ratio [per 10% change], 0.86; 95% CI, 0.78-0.96; p = 0.004)., Conclusions: Increased heart rate in the approximately 48-hour rewarming phase during therapeutic hypothermia was significantly associated with and was an independent predictor of favorable neurologic outcomes during out-of-hospital cardiac arrest.

House flies (Musca domestica) are worldwide agricultural pests with estimated control costs at $375 million annually in the U.S. Non-target effects and widespread resistance challenge the efficacy of traditional chemical control. Double stranded RNA (dsRNA) has been suggested as a biopesticide for M. domestica but a phenotypic response due to the induction of the RNAi pathway has not been demonstrated in adults. In this study female house flies were injected with dsRNA targeting actin-5C or ribosomal protein (RP) transcripts RPL26 and RPS6. Ovaries showed highly reduced provisioning and clutch reductions of 94-99% in RP dsRNA treated flies but not in actin-5C or GFP treated flies. Gene expression levels were significantly and specifically reduced in dsRNA injected groups but remained unchanged in the control dsGFP treated group. Furthermore, injections with an Aedes aegypti conspecific dsRNA designed against RPS6 did not impact fecundity, demonstrating species specificity of the RNAi response. Analysis of M. domestica tissues following RPS6 dsRNA injection showed significant reduction of transcript levels in the head, thorax, and abdomen but increased expression in ovarian tissues. This study demonstrates that exogenous dsRNA is specifically effective and has potential efficacy as a highly specific biocontrol intervention in adult house flies. Further work is required to develop effective methods for delivery of dsRNA to adult flies.

Group A Streptococcus (GAS) is deleterious pathogenic bacteria whose interaction with blood vessels leads to life-threatening bacteremia. Although xenophagy, a special form of autophagy, eliminates invading GAS in epithelial cells, we found that GAS could survive and multiply in endothelial cells. Endothelial cells were competent in starvation-induced autophagy, but failed to form double-membrane structures surrounding GAS, an essential step in xenophagy. This deficiency stemmed from reduced recruitment of ubiquitin and several core autophagy proteins in endothelial cells, as demonstrated by the fact that it could be rescued by exogenous coating of GAS with ubiquitin. The defect was associated with reduced NO-mediated ubiquitin signaling. Therefore, we propose that the lack of efficient clearance of GAS in endothelial cells is caused by their intrinsic inability to target GAS with ubiquitin to promote autophagosome biogenesis for xenophagy.

A 49-year-old woman suffered hydrocephalus after subarachnoid hemorrhage, and underwent a lumboperitoneal(LP)shunt operation. X-ray imaging revealed that a spinal catheter inserted into the cranial side from L2/3 turned caudally at the Th12 level. Postoperative numbness and pain of the left buttocks and posterior femoral region persisted. The spinal catheter was pulled about 5 cm to improve flexure, and was reconnected 10 months after the shunt procedure. Symptoms improved, but a similar symptom developed one and a half years later. The spinal catheter was torn at the connection to the shunt valve. The catheter curved to the left side of the spinal cord and the catheter tip was located around the right Th12/L1 intervertebral foramen. We continued observations with analgesics, but symptoms did not subside. The shunt was removed 16 months after symptom relapse, and symptoms disappeared immediately. Bent insertion of the lumbar catheter is a potential cause of lower limb neuropathy after LP shunt operation. Attention must also be paid to the continuity of the catheter in follow-up after shunt procedures.

Because of the scanty pipeline of antibiotics newly obtained from nature, chemical modification of established drugs is one of the major streams of current antibacterial research. Intuitive and easy-to-use assays are critical for identifying drug candidates with novel modes of action. In this study, we demonstrated that metabolic fluorescent staining of growing cell walls is a powerful tool for mode-of-action analyses of antibiotics using Streptococcus pyogenes. A set of major cell-wall-inhibiting antibiotics (bacitracin, D-cycloserine, flavomycin, oxacillin, ramoplanin, and vancomycin) was employed to validate the potential of the assay. The mechanistic differences of these antibiotics were successfully observed. For instance, D-cycloserine treatment induced fluorescently stained, excessive peripheral cell wall growth. This may indicate that the switch from the peripheral growth stage to the succeeding septal growth was disturbed by the treatment. We then applied this assay to analyze a series of vancomycin derivatives. The assay was sufficiently sensitive to detect the effects of single-site chemical modification of vancomycin on its modes of action. This metabolic fluorescent labeling method is easy to perform, especially because it does not require radiolabeled substrates. Thus, it is suitable for the preliminary evaluation of antibacterial mechanisms during antibacterial research.

Alaolacon Candèze, 1865 is found to be a senior synonym of Eumoeus Candèze, 1874, Luzonicus Fleutiaux, 1916 and Tharopsides Fleutiaux, 1918. Alaolacon is represented by Alaolacon bakeri (Fleutiaux, 1916), comb. n. , Alaolacon candezei Fleutiaux, 1928, Alaolacon cyanipennis Candèze, 1865, Alaolacon fujiokai sp. n. , Alaolacon griseus Candèze, 1874, Alaolacon megalopus sp. n. , Alaolacon murrayi (Candèze, 1874), comb. n. , and Alaolacon philippinensis nom. n. This genus is redescribed based on the descriptions of three species, Alaolacon candezei , Alaolacon fujiokai , and Alaolacon megalopus as well as the examination of the holotypes of Alaolacon cyanipennis and Alaolacon murrayi comb. n. Males of the genus Alaolacon exhibit 12-segmented and biflabellate antennae, and the females exhibit 11-segmented and subpectinate antennae. A key to species is provided.

Nitric oxide (NO) raises the intracellular 3',5'-cyclic guanosine monophosphate (cGMP) level through the activation of soluble guanylate cyclase and, in the presence of reactive oxygen species (ROS), reacts with biomolecules to produce nitrated cGMP derivatives. 8-Nitro-cGMP was the first endogenous cGMP derivative discovered in mammalian cells (2007) and was later found in plant cells. Among the six nitrogen atoms in this molecule, the one in the nitro group (NO 2 ) comes from NO. This chapter asserts that this newly found cGMP is undoubtedly one of the major physiological cNMPs. Multiple studies suggest that its intracellular abundance might exceed that of unmodified cGMP. The characteristic chemical feature of 8-nitro-cGMP is its ability to modify proteinous cysteine residues via a stable sulfide bond. In this posttranslational modification, the nitro group is detached from the guanine base. This modification, termed "protein S-guanylation," is known to regulate the physiological functions of several important proteins. Furthermore, 8-nitro-cGMP participates in the regulation of autophagy. For example, in antibacterial autophagy (xenophagy), S-guanylation accumulates around invading bacterial cells and functions as a "tag" for subsequent clearance of the organism via ubiquitin modifications. This finding suggests the existence of a system for recognizing the cGMP structure on proteins. Autophagy induction by 8-nitro-cGMP is mechanistically distinct from the well-described starvation-induced autophagy and is independent of the action of mTOR, the master regulator of canonical autophagy.

Background/purpose: Near-infrared (NIR) light with high water absorption enables us to visualize the water content distribution appeared in the superficial skin layer. The light penetration depth with the wavelength of 1920 nm is almost 100 μm from the skin surface. Thus, the water distribution in the stratum corneum can be effectively imaged by detecting the wavelength band around 1920 nm. The aim of this article was to measure the time-lapse behavior of the tiny droplet of the moisturizer spreading on the skin surface by imaging in 1920 nm wavelength band for investigating the correlation with the traditional index of the skin condition such as the water content and transepidermal water loss (TEWL)., Methods: Experiment is performed with three moisturizer products and seven volunteer subjects. The NIR image is acquired by an originally designed imaging scope equipped with the white light of the strong brightness [super continuum (SC) light], the bandpass filter with the center wavelength of 1920 nm, and the NIR image sensor. A tiny droplet of the moisturizer is put on the surface of the skin and the time-lapse images are saved. Each acquired image is analyzed from a view point of the droplet area and elapsed time for absorption into the skin. The water content and TEWL of all subjects are measured by the conventional electrical method for investigating the relationship with the measured droplet dynamics parameters., Results: Elapsed time for moisturizer droplet to be absorbed into the skin, the droplet area just before absorption for three moisturizer products, skin water contents, and TEWL for seven subjects were measured and correlation coefficients for each parameters were calculated. It was found that the skin with higher water contents or lower TEWL absorbed the moisturizer faster and spreads moisturizer wider. Also absorption and spreading speed depend on moisturizer property (moisturizing or fresh) which is originated from the moisturizer constituents., Conclusion: The correlation values between the moisturizer dynamics on the skin surface and the traditional index of the skin property were clarified. It was found that the skin with the high water content or low TEWL absorbs the moisturizer droplet fast. The spreading area depends not only on the skin property but on the constituents of the moisturizers., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A novel blood-brain barrier (BBB)-permeable compound 10 was discovered, wherein the nitroxide moiety was linked to a nicotine acetylcholine receptor ligand. It was applied as a probe for electron paramagnetic resonance (EPR) imaging of the mouse brain. The results demonstrated that the newly synthesized compound 10 exhibited BBB permeability. These findings provide an essential discovery for in vivo EPR imaging., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Kendomycin, an ansamycin-type natural product first reported in 1996, possesses a series of attractive bioactivities and a unique all-carbon macrocyclic skeleton. To the date, seven total syntheses, two formal total syntheses and a number of synthetic studies on this hot molecule have been reported. In this short review article, we mainly survey and comment on these efforts regarding the difficult macrocyclization strategies.

Recently, the BG-Sentinel® trap (BGS) trap has been reconfigured for increased durability during harsh field conditions. We evaluated the attractiveness of this redesigned trap, BG-Sentinel 2® (BGS2), and its novel granular lure cartridge system relative to the original trap and lure. Granular lures containing different combinations of lactic acid, ammonia, hexanoic acid, and octenol were also evaluated. Lure cartridges with all components except octenol trapped significantly more Aedes albopictus than lures containing octenol. This new granular lure combination and original BG-Lure® system were paired with BGS and BGS2 traps to compare relative attractiveness of the lures and the traps. All evaluations were conducted under field conditions in a suburban neighborhood in northeastern Florida from July to October 2014. Overall, the average numbers of Ae. albopictus collected by BGS or BGS2 were similar regardless of the lure type (i.e., mesh bag versus granules) (P  =  0.56). The functionality and durability of both trap models are discussed.

Aim: Our study aimed at filling the fundamental knowledge gap on the characteristics of regional brain oxygen saturation (rSO2) levels in out-of-hospital cardiac arrest (OHCA) patients with or without return of spontaneous circulation (ROSC) upon arrival at the hospital for estimating the quality of cardiopulmonary resuscitation and neurological prognostication in these patients., Methods: We enrolled 1921 OHCA patients from the Japan - Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry and measured their rSO2 immediately upon arrival at the hospital by near-infrared spectroscopy using two independent forehead probes (right and left). We also assessed the percentage of patients with a good neurological outcome (defined as cerebral performance categories 1 or 2) 90 days post cardiac arrest., Results: After 90 days, 79 (4%) patients had good neurological outcomes and a median lower rSO2 level of 15% (15-20%). Compared to patients without ROSC upon arrival at the hospital, those with ROSC had significantly higher rSO2 levels (56% [39-65%] vs. 15% [15-17%], respectively; P<0.01), and significantly correlated right- and left-sided regional brain oxygen saturation levels (R=0.94 vs. 0.66, respectively). In both groups, the percentage of patients with a good 90-day neurological outcome increased significantly in proportion to their rSO2 levels upon arrival at the hospital (P<0.01)., Conclusion: Our data indicate that measuring rSO2 levels might be effective for both monitoring the quality of resuscitation and neurological prognostication in patients with OHCA., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Aim: This study investigated the value of regional cerebral oxygen saturation (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest intervention outcomes., Methods: We enrolled 1195 patients with out-of-hospital cardiac arrest of presumed cardiac cause from the Japan-Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary endpoint was a good neurologic outcome (cerebral performance categories 1 or 2 [CPC1/2]) 90 days post-event., Results: A total of 68 patients (6%) had good neurologic outcomes. We found a mean rSO2 of 21%±13%. A receiver operating characteristic curve analysis indicated an optimal rSO2 cut-off of ≥40% for good neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity 0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of patients with high (≥40%) and low (<40%) rSO2, respectively. Even without return of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic outcomes. Multivariate analyses indicated that high rSO2 was independently associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients with high rSO2 showed favourable neurologic prognoses if they had undergone therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However, 24% (25/103) of those with high rSO2 did not undergo these procedures and exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25])., Conclusion: rSO2 is a good indicator of 90-day neurologic outcomes for post-cardiac arrest intervention patients., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: It is important to devise efficient and easy methods of detecting colorectal tumours to reduce mortality from colorectal cancer. Dual-wavelength excitation autofluorescence intensity can be used to visualize colorectal tumours. Therefore, we evaluated dual-wavelength excitation autofluorescence images of colorectal tumours obtained with a newly developed, high-sensitivity complementary metal-oxide-semiconductor (CMOS) imager., Methods: A total 107 colorectal tumours (44 adenomas, 43 adenocarcinomas with intramucosal invasion, and 20 sessile serrated adenoma/polyps [SSA/Ps]) in 98 patients who underwent endoscopic tumour resection were included. The specimens were irradiated with excitation light at 365 nm and 405 nm, and autofluorescence images measured with a 475 ± 25-nm band pass filter were obtained using a new, high-sensitivity CMOS imager. Ratio images (F365ex/F405ex) were created to evaluate the lesion brightness compared with that of normal mucosa, and specimens were categorized into a no signal or high signal group., Results: Adenomas and adenocarcinomas were depicted in 87 ratio images, with 86.2% (n = 75) in the High signal group. SSA/P was depicted in 20 ratio images, with 70.0% (n = 14) in the High signal group., Conclusions: Dual-wavelength excitation autofluorescence images of colorectal tumours can be acquired using our high-sensitivity CMOS imager, and are useful in detecting colorectal tumours.

The Aedes mosquito vectors of dengue virus (DENV) and chikungunya virus (CHIKV) are attracted to specific host cues that are not generated by traditional light traps. For this reason multiple companies have designed traps to specifically target those species. Recently the standard trap for DENV and CHIKV vectors, the BG-Sentinel (BGS) trap, has been remodeled to be more durable and better suited for use in harsh field conditions, common during military operations, and relabeled the BG-Sentinel 2 (BGS2). This new trap was evaluated against the standard Centers for Disease Control and Prevention (CDC) light trap, Zumba Trap, and BG-Mosquitito Trap to determine relative effectiveness in collecting adult Aedes aegypti and Ae. albopictus. Evaluations were conducted under semifield and field conditions in suburban areas in northeastern Florida from May to August 2014. The BGS2 trap collected more DENV and CHIKV vectors than the standard CDC light trap, Zumba Trap, and BG-Mosquitito Trap, but attracted fewer species, while the BG-Mosquitito Trap attracted the greatest number of mosquito species.

Metabolism-based autofluorescence redox imaging is one of the promising options for non-invasive screening of digestive tumors. In this paper, autofluorescence from fluorescent coenzymes such as NADH and FAD related to cellular metabolism as well as total hemoglobin and oxygen saturation are analyzed based on a point spectrum. As a redox index based on the metabolism, the ratio of the 450nm-490nm fluorescence intensities for 365nm and 405nm excitation wavelengths (F365/F405) is used. Although F365/F405 is a good index in many samples, inversion and weakened contrast are observed. A Simplified models with and without collagen based on Lambert-Beer law are built to explain how F365/F405 depicts the tumor region.

Background: Therapeutic hypothermia (TH) is a standard strategy to reduce brain damage in post-cardiac arrest syndrome (PCAS) patients. However, it is unknown whether the target temperature should be adjusted for PCAS patients in different states., Methods: Participants in the J-PULSE-Hypo study database were divided into lower (32.0-33.5 °C; Group L) or moderate (34.0-35.0 °C; Group M) temperature groups. Primary outcome was a favourable neurological outcome (proportion of patients with a Glasgow-Pittsburgh Cerebral Performance Category [CPC] of 1-2 on day 30). We compared between the two groups and in subgroups of patients divided by age and resuscitation interval (interval from collapse to return of spontaneous circulation) by propensity score (PS) analysis., Results: Overall, 467 participants were analysed. The proportions of patients with favourable neurological outcomes were as follows (Group L vs. Group M) (OR; Odds ratio): all patients, 64 % (n = 42) vs. 55 % ((n = 424) (PS; OR 1.381 (0.596-3.197)), P = 0.452) and resuscitation interval ≤ 30 min, 88 % (n = 24) vs. 64 % ((n = 281) (PS; OR 7.438 (1.769-31.272)), P = 0.007)., Conclusions: PCAS patients with a resuscitation interval of <30 min may be candidates for TH with a target temperature of <34 °C., Trial Registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000001935; available at: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000002348&language=J.

Objective: We report the technique of three-dimensional computed tomography angiography (3D CTA)+two-dimensional computed tomographic (2D CT) imaging as an adjunct in early surgery for a ruptured anterior communicating artery (ACoA) aneurysm by adopting an anterior interhemispheric approach. These combined imaging modalities provide accurate intraoperative anatomical information., Methods: To produce images for an anterior interhemispheric approach, 3D CTA+2D coronal CT images, which are perpendicular to the direction of the surgical approach at three levels (brain surface, genu of the corpus callosum and aneurysm neck), were constructed. We also produced two 3D CTA+2D CT images of the lamina terminalis, with a horizontal 10-degree difference, to clarify the vascular architecture around the aneurysm stereotactically, as well as the dissection point and direction to open the lamina terminalis. Furthermore, we produced a 3D CTA+2D sagittal CT image at the midline, which allowed us to understand the anatomical architecture of the aneurysm, planum sphenoidale and tuberculum sellae. In addition, four different 3D CTA aneurysm images were produced for deciding the clip size preoperatively., Results: The imaging findings in 28 patients with 28 ACoA aneurysms facilitated early clipping. Based on these 3D CTA+2D CT images, we conducted aneurysm surgery, and successfully performed neck clipping via an anterior interhemispheric approach., Conclusion: The combination of 3D CTA and 2D CT images is a feasible and useful method of image guidance for ACoA aneurysm microsurgery.

Background/purpose: We investigate the measurement sensitivity for the water content distribution in Near-infrared (NIR) imaging ranging up to 2 μm., Methods: To evaluate the sensitivity, our attention is focused to the light penetration depth in the skin tissue because the thickness of a layer where the water content can be varied is very thin and deep light penetration decreases the signal variation. The light penetration depths in the wavelengths of 1300, 1450, and 1920 nm are calculated theoretically based on the Monte Carlo light transport simulation., Results: It is clarified that the wavelength of 1920 nm gives the smallest penetration depth. A NIR imaging experiment is demonstrated to verify the difference of imaging sensitivity. The experiment result shows that the NIR image taken at 1920 nm gives the most sensitive measurement of the water content distribution in skin., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Because the initial (on admission) Glasgow Coma Scale (GCS) examination has not been fully evaluated in comatose survivors of cardiac arrest (CA) who receive therapeutic hypothermia (TH), the aim of the present study was to determine any association between the admission GCS motor score and neurologic outcomes in patients with out-of-hospital CA who receive TH., Methods and results: In the J-PULSE-HYPO study registry, patients with bystander-witnessed CA were eligible for inclusion. Patients were divided into 3 groups based on GCS motor score (1, 2-3, and 4-5) to assess various effects on neurologic outcome. Univariate and multivariate analyses were performed to identify independent predictors of good neurologic outcome at 90 days. Of 452 patients, 302 were enrolled. There was a significant difference among the 3 patient groups with regard to neurologic outcome at 90 days in the univariate analysis. Multiple logistic regression analyses showed that the GCS motor score on admission, age >65 years, bystander cardiopulmonary resuscitation, the time from collapse to return of spontaneous circulation, and pupil size <4 mm were independent predictors of a good neurologic outcome at 90 days in cases of CA (GCS motor score, 4-5: odds ratio, 8.18; 95% confidence interval: 1.90-60.28; P<0.01)., Conclusions: GCS motor score is an independent predictor of good neurologic outcome at 90 days in patients sustaining out-of-hospital CA who receive TH.

Intravenous tissue plasminogen activator (IVtPA) is effective for the treatment of acute stroke. Although IVtPA is easily administered and is effective in many cases, the clinical condition of some patients can worsen after the initiation of thrombolytic therapy due to sustained cerebrovascular insufficiency. In such cases, several additional treatment options to re-establish cerebral perfusion are available, including superficial temporal artery to middle cerebral artery bypass. However, it is recommended that invasive procedures should be avoided soon after IVtPA administration because tPA is believed to exert prolonged fibrinolytic effects may continue for more than 24 hours. We described three cases of emergency superficial temporal artery to middle cerebral artery bypass performed within 24 hours of IVtPA administration, and discussed the safety of such procedures. We believe that superficial temporal artery to middle cerebral artery bypass can be safely performed even within 24 hours after IVtPA administration.

Symptomatic cervical carotid artery stenosis is one of the common causes of ischemic stroke in octogenarians. The records for 90 consecutive patients with symptomatic cervical carotid artery stenosis treated by carotid endarterectomy(CEA)were analyzed retrospectively. The patients were divided into two groups:21 patients aged 80 years or over and 69 patients aged less than 80 years. CT angiography revealed that ulcer formation was significantly more common and the length of carotid artery stenosis was significantly greater in the octogenarians. Histological examination of the plaque revealed no significant difference between the two groups in terms of ulcer formation, lipid content, and intraplaque hemorrhage. However, all three of these pathological findings were present in a significantly higher number of octogenarians. No significant difference was observed for new ischemic lesions on diffusion-weighted MR imaging, neurological complications, or cardiac and pulmonary complications. However, treatment with an albumin preparation and loop diuretics was significantly more common in octogenarians after CEA. The present study suggests that with careful postoperative management CEA can be safely performed in symptomatic patients aged 80 years or over with almost the same risk as that for patients aged less than 80 years.

Background: The failures of recent studies intended to prevent cerebral vasospasm have moved the focus of research into delayed cerebral ischemia away from cerebral artery constriction towards other mechanisms. Recent accumulating evidence has suggested that early brain injury is also involved in the development of delayed cerebral ischemia, and that hydrogen can prevent early brain injury. Therefore, we have established a combination therapy of intravenous hydrogen infusion and intra-cisternal magnesium sulfate infusion for the treatment of both early brain injury and cerebral vasospasm. The present randomized controlled clinical trial is designed to investigate the effects of this novel therapeutic strategy on the occurrence of cerebral vasospasm, delayed cerebral ischemia, and clinical outcomes after high-grade subarachnoid hemorrhage., Methods: This study is a randomized, double-blind, placebo-controlled design to be conducted in two hospitals. A total of 450 patients with high-grade subarachnoid hemorrhage will be randomized to one of three arms: (i) Mg + H2 group, (ii) Mg group, and (iii) control group. Patients who are assigned to the Mg + H2 group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous hydrogen-rich fluid infusion (200 mL) twice a day for 14 days. Patients who are assigned to the Mg group will receive intra-cisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Patients who are assigned to the control group will receive intra-cisternal Ringer solution without magnesium sulfate at 20 mL/h for 14 days and intravenous normal glucose-electrolyte solution (200 mL) without added hydrogen twice a day for 14 days. Primary outcome measures will be occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures will be modified Rankin scale score at 3, 6, and 12 months and biochemical markers., Discussion: The present protocol for a randomized, placebo-controlled study of intravenous hydrogen therapy with intra-cisternal magnesium infusion is expected to establish the efficacy and safety of this therapeutic strategy., Trial Registration Umin-Ctr: UMIN000014696.