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The Asian longhorned tick, Haemaphysalis longicornis Neumann (Ixodida: Ixodidae), is widely distributed across temperate East Asia, including Japan, and carries a variety of zoonotic diseases. The species includes bisexual and parthenogenetic lineages. Various aspects of these two lineages, such as their abundance ratio, genetic relationship, and population structure, remain unknown in island environments such as Japan that are isolated from the mainland. Therefore, in this study, 235 individuals were collected across 15 prefectures, and their mtDNA was analyzed to better understand the genetic population structure of this species in Japan. Haplotype analysis of the 631 bp cox1 region revealed the presence of 38 haplotypes, which showed for the first time that a large diversity of haplotypes is present in Japan. In addition, the calculated haplotype diversity was 0.889-equivalent to that reported in the study that examined haplotypes across a larger region in China. This indicates that Japan is a hotspot of genetic diversity of this species. The haplotype network of this species was divided into two major clades, but there were no clear geographical boundaries in the distributions of the haplotypes. However, a qualitative cline was observed in the distribution of sexual lineage, with the parthenogenetic lineage being more prevalent in northeastern Japan and the bisexual lineage being more prevalent in southwestern Japan. Future analysis combining the results of this paper with information from nuclear DNA and large-scale mtDNA analyses would facilitate a more detailed understanding of the population structure and historical distributions of the Asian longhorned tick., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: No approval of research ethics committees was required to accomplish the goals of this study because experimental work was conducted with an unregulated invertebrate species., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Selective distribution of cerebral blood flow (CBF) to vital brain regions likely occurs during rapid severe hypotension caused by tachyarrhythmia but has not yet been demonstrated. In this study, we aimed to test the hypothesis that CBF is differentially preserved between brain regions depending on the degree of hypotension. In anesthetized rats, CBF was measured in the motor cortex (MC), medial prefrontal cortex, amygdala, thalamus, dorsal hypothalamus, hippocampus, ventral tegmental area, dorsolateral periaqueductal gray (dlPAG), and parabrachial nucleus (PB) by using laser-Doppler flowmetry. Ventricular pacing was performed for 30 s at 550-800 beats/min. The cerebrovascular CO 2 response time and reactivity were evaluated during 5% CO 2 exposure. During 1-4 s of ventricular pacing, mean arterial pressure (MAP) rapidly decreased, with minor changes in central venous and intracranial pressures. CBF was relatively well maintained in brain regions other than the MC ( P s ≤ 0.012) when moderate hypotension occurred (-34 mmHg ≤ ΔMAP ≤ -15 mmHg), whereas severe hypotension (-54 mmHg ≤ ΔMAP ≤ -35 mmHg) induced selective CBF distribution to regions other than the MC, thalamus, and dlPAG. The cerebrovascular CO 2 response time/reactivity was rapid or high in the thalamus, dlPAG, and PB, which almost completely differed from the brain regions in which CBF was relatively maintained during pacing-induced severe hypotension. These results suggest that regional heterogeneity of CBF arises depending on the degree of tachyarrhythmia-induced hypotension. Clarifying the mechanisms and functions of CBF maintenance would be beneficial to syncope and cerebral ischemia management in patients with arrhythmia. NEW & NOTEWORTHY When lethal tachyarrhythmia occurs, survival is prioritized by counterregulating the cardiovascular system, which is driven by vital brain regions. However, whether limited cerebral blood flow is selectively distributed to vital brain regions is unknown. We demonstrated the preferential maintenance of cerebral blood flow in vital brain regions, depending on the degree of hypotension caused by ventricular pacing, in anesthetized rats. Our data may have clinical implications for syncope and cerebral ischemia management in patients with arrhythmia.

The risk of dysphagia and/or aspiration is determined using screening tests, such as the repeated saliva swallowing test and modified water swallowing test, which evaluate cued swallowing. However, humans masticate and swallow foods with various consistencies, forms, and amounts, without conscious awareness. Therefore, this study aimed to examine the difference in the behavior of masticatory and swallowing muscles during spontaneous versus cued swallowing through a series of mastication and swallowing processes by evaluating surface electromyogram (sEMG) signals. The effect of the consistency and amount of food on the behavior of these muscles was also investigated. The sEMG recordings of the masseter muscles and anterior belly of the digastric muscle for 12 subjects, and genioglossus muscle for 5 subjects were obtained. The genioglossus activity was recorded using custom-made ball electrodes. The test foods were cookies and tofu, in amounts of 2 g and 4 g. The normalized muscle activity (integrated EMG), duration of the muscle activity, initial activation timepoint of each muscle, and total duration of swallowing were compared among four conditions. The activity of each muscle was significantly higher during the swallowing of cookies than tofu, for 4 g vs 2 g, and for cued versus spontaneous swallowing. The duration of each muscle activity, initial activation timepoint, and total duration of swallowing were significantly longer for cookies versus tofu, for 4 g vs 2 g, and for spontaneous versus cued swallowing. These results suggest that the behavior of the masticatory and swallowing muscles is affected by cued swallowing and by the consistency and amount of food., (© 2023. The Author(s).)

Introduction Floods not only directly damage medical facilities but also hinder access to medical facilities, potentially disrupting local medical services. The scale of damage that medical facilities suffer from floods in Japan is unknown. In this study, we assessed the potential impact of floods on Japanese healthcare facilities by facility characteristics. Methods We conducted a cross-sectional study involving medical facilities registered in the Japan Medical Association Regional Medical Information System. Geographic data for the inundation area was obtained from open data of the Japanese government. Facilities that overlap with flooded areas were designated as affected facilities. The primary outcomes were the percentage of damaged facilities and beds. We calculated odds ratios (OR) and 95% confidence intervals (95%CI) using the Wald method to assess the impact of disaster base hospital designation on damage extent. Results We included 140,826 general clinics and 8,126 hospitals, which had 137,731 and 1,483,347 beds, respectively. The planned scale of flooding is estimated to affect 8.0% of general clinics and 10.8% of their beds. For hospitals, these figures were 8.8% and 7.8%, respectively. The maximum potential scale of flooding is estimated to affect 23.6% of general clinics and 23.9% of their beds. For hospitals, these figures were 22.5% and 20.6%, respectively. At the planned scale of flooding, there was no difference found in the rate of damaged facilities between disaster base hospitals and non-disaster base hospitals, and the rate of damaged beds was lower at non-disaster base hospitals (OR = 0.92, 95%CI = 0.71-1.18 for damaged facilities and OR = 0.79, 95%CI = 0.78-0.80 for damaged beds). At the maximum potential scale of flooding, there was no difference found in the expected damage between disaster base hospitals and non-disaster base hospitals (OR = 1.14, 95%CI = 0.95-1.38 for damaged facilities and OR = 0.99, 95%CI = 0.98-1.00 for damaged beds). Conclusion In Japan, floods can hinder nationwide medical functions, particularly in certain regions. Healthcare professionals should assess potential flood damage in advance and ensure that their workplace's business continuity plan includes appropriate countermeasures., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kaneko et al.)

Cerebral autoregulation is an important factor in prevention of cerebral ischemic events. We tested a traditional but unproven hypothesis that carotid sinus baroafferent signals contribute to dynamic cerebral autoregulation. Middle cerebral artery mean blood velocity (MCA V mean ) responses to thigh-cuff deflation-induced acute hypotension were compared between conditions using neck suction soon after cuff deflation, without or with a cushion wrapped around the upper neck, in nine healthy males (aged 25 ± 5 years). Neck suction was applied close to the hypotension. The MCA V mean response was expected to differ between conditions because the cushion was presumed to prevent the carotid sinus distension by neck suction. The cushion hindered bradycardia and depressor responses during sole neck suction. Thigh-cuff deflation decreased mean arterial blood pressure (MAP) and MCA V mean (Ps < 0.05) with an almost unchanged respiratory rate under both conditions. However, in the neck suction + cushion condition, subsequent MCA V mean restoration was faster and greater (Ps ≤ 0.0131), despite similar changes in MAP in both conditions. Thus, carotid sinus baroafferent signals would accelerate dynamic cerebral autoregulation during rapid hypotension in healthy young males. Elucidating the mechanism underlying cerebral neural autoregulation could provide a new target for preventing cerebral ischemic events., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Vasoconstriction during tachyarrhythmia contributes to maintenance of arterial pressure (AP) by decreasing peripheral blood flow. This cross-sectional observational study aimed to ascertain whether the relationship between peripheral blood flow and AP recovery occurs during both paroxysmal supraventricular (PSVT, n = 19) and ventricular tachycardias (VT, n = 17). Peripheral blood flow was evaluated using forearm tissue oxygen index (TOI), and mean AP (MAP) was measured using a catheter inserted in the brachial or femoral artery during an electrophysiological study. PSVT and VT rapidly decreased MAP with a comparable heart rate (P = 0.194). MAP recovered to the baseline level at 40 s from PSVT onset, but not VT. The forearm TOI decreased during both tachyarrhythmias (P ≤ 0.029). The TOI response was correlated with MAP recovery (i.e., MAP recovery from the initial rapid decrease) at 20-60 s from PSVT onset (r = -- 0.652 to - 0.814, P ≤ 0.0298); however, this association was not observed during VT. These findings persisted even after excluding patients who had taken vasoactive drugs. Thus, restricting peripheral blood flow was associated with MAP recovery during PSVT, but not VT. This indicates that AP recovery depends on the type of tachyarrhythmia: different cardiac output and/or vasoconstriction ability during tachyarrhythmia., (© 2023. The Author(s).)

Expansion of ticks and tick-borne diseases is of increasing concern worldwide. To decrease the risk of ticks and tick-borne diseases to public health, understanding the mechanisms of their current distribution and future expansion is needed. Although tick distribution has been studied globally on continents and large islands that are inhabited by large mammals, less attention has been paid to remote islands. However, small islands are often important stopover sites for migratory birds that may contribute to long-distance dispersal of ticks. Therefore, islands would be a suitable system to rule out potential effects of mammals and to evaluate the contribution of birds to the expansion of ticks and tick-borne diseases. We collected questing ticks by dragging cloths over vegetation on Tobishima Island, northern Japan, in summer 2021, and conducted a literature search of the distribution and avian hosts of hard tick. We found several southern species of ticks (Haemaphysalis hystricis, H. formosensis, H. cornigera, Amblyomma testudinarium, and Dermacentor bellulus) on the island. These species have rarely or never been reported from the mainland of Japan at similar latitudes or higher, where large mammals are found. They are known vectors of tick-borne diseases, such as severe fever with thrombocytopenia syndrome. The present study suggests that migratory birds may contribute to the expansion of ticks and tick-borne diseases, and a remote island may function as a front line and/or a hub for their expansion. Evaluating tick fauna on remote islands used by migratory birds might be useful to monitor the expansion., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Achieving rapid and complete reperfusion is the ultimate purpose for ischemic stroke with large vessel occlusion (LVO). Although mechanical thrombectomy (MT) had been a proverbially important procedure, medium vessel occlusion (MeVO) with thrombus migration can sporadically occur after MT. Moreover, the safe and effective approach for such had been unknown. We reported thrombolysis with intraarterial urokinase for MeVO with thrombus migration after MT., Methods: We included 122 patients who were treated by MT with LVO stroke at our institution between April 2019 and March 2021. Of 26 patients (21.3%) who developed MeVO with thrombus migration after MT, 11 (9.0%) underwent additional MT (MT group) and 15 (12.3%) received intraarterial urokinase (UK group). The procedure time; angiographically modified Treatment in Cerebral Ischemia Scale (mTICI); functional independence, which was defined as modified Rankin Scale 0-2, on day 30 or upon discharge; and symptomatic and asymptomatic intracerebral hemorrhage (ICH) were compared between the UK and MT groups., Results: The procedure time, mTICI, and asymptomatic ICH did not significantly differ between the groups. In the UK group, 8 of 15 (53.3%) patients obtained functional independence, and the functional independence rate was significantly higher in the UK group than in the MT group ( p  < 0.05). Symptomatic ICH did not occur in the UK group, and its incidence was significantly smaller than that in the MT group ( p  < 0.05)., Conclusion: The results of this study suggest that intraarterial urokinase for MeVO with thrombus migration after MT may safely improve angiographic reperfusion.

Objectives: This study aimed to prove the safety and efficacy of the contact aspiration using non-penetrating of thrombus (CANP) technique for the initial procedure for acute ischemic stroke and to increase operator familiarization with the technical aspects of the CANP technique., Materials and Methods: A total of 103 patients with large-vessel stroke who were treated using thrombectomy alone at our institution between April 2019 and March 2021 were included in this study. CANP technique was performed using a large lumen catheter (inner diameter, ≥0.060 in.) without penetrating a thrombus. Results of the CANP technique, including the procedure time; first-pass effect (FPE); angiographical recanalization; functional independence; thrombus migration; and intracerebral hemorrhage (ICH) were compared with combined technique., Results: A total of 77 patients (74.8%) were scheduled to undergo the CANP technique for initial procedure, and 50 (64.9%) attempted the CANP technique. Of 50 patients with CANP technique, 33 (66.0%) achieved angiographically good recanalization using CANP technique alone. FPE was achieved in 31 patients (62.0%) in CANP technique group; the rate of FPE was significantly higher (p = 0.008). Asymptomatic ICH were significantly smaller in the CANP technique group (p = 0.008). The median interval of only the CANP technique was 20 (IQR, 16-29.5) min for groin puncture to final recanalization, and was significantly faster (p < 0.001)., Conclusions: CANP technique was safe with low risk of hemorrhagic complication and effective for the initial procedure of acute ischemic stroke., Competing Interests: Declarations of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although flexible endoscopy is effective for intraventricular lesions, it is less frequently used for hemorrhagic cases. In some hemorrhagic strokes, blood clots may plunge into the cerebral aqueduct and cause acute obstructive hydrocephalus. A flexible endoscope can aspirate clots and prevent acute hydrocephalus., Methods: Here, we report four cases of hemorrhage: one of intracerebral hemorrhage and three of subarachnoid hemorrhages., Results: In all cases, acute hydrocephalus was not apparent upon admission. Sudden comatose occurred; computed tomography revealed acute obstructive hydrocephalus with a strangulated clot in the cerebral aqueduct. We performed aspiration of the strangulated clot using a flexible endoscope. Consciousness improved in all cases, and acute hydrocephalus was prevented in all cases., Conclusion: The use of simple flexible endoscopic aspiration for clots might be a beneficial and less-invasive procedure for acute obstructive hydrocephalus caused by a small clot with hemorrhagic stroke., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Artificial light at night (ALAN) is a major form of anthropogenic disturbance. ALAN attracts nocturnal invertebrates, which are a food source for nocturnal predators, including invasive species. Few studies quantify the effects of increased food availablity by ALAN on invasive vertebrate predators, and enhancement of food intake caused by ALAN may also be influenced by various environmental factors, such as proximitity to cities, moon phase, temperature, rainfall and wind speed. Revealing the potential impacts on invasive predators of ALAN-attracted invertebrates, and the influence of other factors on these effects, could provide important insights for the management of these predators. We constructed and supplied with artificial light field enclosures for invasive toads, and placed them at locations with different levels of ambient light pollution, in northeastern Australia. In addition, we determined the effect of rainfall, temperature, wind speed, and lunar phase on food intake in toads. We found that ALAN greatly increased the mass of gut contents of invasive toads compared to controls, but that the effect was increased in dark lunar phases, and when there were low ambient light pollution levels. Effects of rainfall, temperature and wind speed on food intake were comparatively weak. To avoid providing food resources to toads, management of ALAN in rural areas, and during dark lunar phases may be advisable. On the contrary, to effectively capture toads, trapping using lights as lures at such times and places should be more successful.

Natural oligonucleotides have many rotatable single bonds, and thus their structures are inherently flexible. Structural flexibility leads to an entropic loss when unwound oligonucleotides form a duplex with single-stranded DNA or RNA. An effective approach to reduce such entropic loss in the duplex-formation is the conformational restriction of the flexible phosphodiester linkage and/or sugar moiety. We here report the synthesis and biophysical properties of a novel artificial nucleic acid bearing an oxanorbornane scaffold (OxNorNA), where the adamant oxanorbornane was expected to rigidify the structures of both the linkage and sugar parts of nucleic acid. OxNorNA phosphoramidite with a uracil (U) nucleobase was successfully synthesized over 15 steps from a known sugar-derived cyclopentene. Thereafter, the given phosphoramidite was incorporated into the designed oligonucleotides. Thermal denaturation experiments revealed that oligonucleotides modified with the conformationally restricted OxNorNA-U properly form a duplex with the complementally DNA or RNA strands, although the T m values of OxNorNA-U-modified oligonucleotides were lower than those of the corresponding natural oligonucleotides. As we had designed, entropic loss during the duplex-formation was reduced by the OxNorNA modification. Moreover, the OxNorNA-U-modified oligonucleotide was confirmed to have extremely high stability against 3'-exonuclease activity, and its stability was even higher than those of the phosphorothioate-modified counterparts ( S p and R p). With the overall biophysical properties of OxNorNA-U, we expect that OxNorNA could be used for specialized applications, such as conformational fixation and/or bio-stability enhancement of therapeutic oligonucleotides (e.g., aptamers).

Central command, a feedforward signal from higher brain centers, regulates the cardiovascular system in association with exercise. Previous evidence suggests that nucleus (or nuclei) around the midbrain may contribute to generating spontaneous motor activity and concomitant cardiovascular responses. To examine which area within the midbrain is important for the spontaneous and synchronized responses, 18 rats were decerebrated at three levels (pre-midbrain, rostroventral midbrain, and caudal midbrain levels) and paralyzed with a neuromuscular blocker. Individual brain sections showed decerebration rostral to the pre-collicular level in the pre-midbrain preparation and, additionally, removal of the periaqueductal gray in the rostroventral midbrain preparation, and decerebration around the midcollicular level in the caudal midbrain preparation. Spontaneous motor activity occurred at frequency of 69 ± 27 times/h and accompanied increases in heart rate (by 15 ± 4 beats/min) and mean arterial blood pressure (by 54 ± 4 mmHg) in the pre-midbrain preparation. Similar motor and cardiovascular responses took place in the rostroventral midbrain preparation, while such responses hardly occurred in the caudal midbrain preparation. We next examined whether injection of a GABAergic receptor agonist (muscimol) in the ventral tegmental area (VTA) inhibits the spontaneous motor and cardiovascular responses in 6 pre-midbrain preparations. The occurrence of spontaneous motor activity and concomitant cardiovascular responses was inhibited clearly (P < 0.05) by injection of muscimol, but not saline. It is concluded that the VTA plays a pivotal role in the spontaneous and synchronized activation of the motor and cardiovascular systems in decerebrate rats., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to clarify the factors associated with requiring subacute surgery in patients with acute subdural hematoma (ASDH) treated conservatively at admission., Methods: Among the patients with ASDH admitted to our hospital from 2007 to 2018, we retrospectively reviewed data for 200 patients initially treated conservatively. We compared patients' characteristics, medical history, radiological findings, and clinical outcomes and differences between patients undergoing subacute surgery or no surgery., Results: Of the 200 patients treated conservatively, 17 (8.5%) patients underwent subacute surgery due to deterioration of their clinical and/or computed tomography (CT) findings, while 183 (91.5%) patients did not undergo subacute surgery. There were significant differences in the presence of focal neurological deficits, modified Rankin Scale scores, degree of midline shift, hematoma thickness, hematoma volume, cella media index, Sylvian fissure ratio, and hematoma density between the two groups., Conclusions: Large hematoma, brain atrophy, and hematoma density may be useful predictors for the need for subacute surgery in patients with ASDH treated conservatively at admission. Intensive investigation of clinical findings or CT images is warranted in patients with adverse prognostic factors, even if their initial symptoms are mild.

Character displacement is phenotypic divergence driven by competition (ecological character displacement) or reproductive interference (reproductive character displacement). Although previous studies have examined these phenomena separately, recent evidence suggests that reproductive interference can drive both reproductive and ecological character displacement, in that certain traits are related to both competition and reproduction. Thus, to evaluate the effect of competition, the effect of reproductive interference must be excluded. Here, we analysed ecological character displacement between non-congeneric frogs, which show little reproductive interference. Odorrana amamiensis inhabits the Amami and Tokunoshima Islands, Japan, whereas its non-congeneric competitor Babina subaspera inhabits the Amami Island. We tested three of the Schluter (2000) criteria for ecological character displacement: phenotypic changes in O. amamiensis between the two islands, phenotypic change related to prey preference, prey availability between the two islands. We demonstrated that the three criteria in Schluter (2000) were likely to be satisfied, indicating the occurrence of ecological character displacement in non-congeners without reproductive interference. Thus, we conclude that competition is potentially the main driver of this phenotypic divergence, and that non-congeners may be a suitable model for evaluating ecological character displacement in a variety of organisms, as the influence of reproductive interference can be excluded.

Extracranial carotid artery aneurysms are relatively rare. We present a case involving a giant aneurysm arising from the extracranial carotid artery. The patient was a 79-year-old woman. She had a pulsating mass in the right side of her neck. However, she was neurologically intact. Contrast-enhanced CT scans of the neck showed an enhanced mass lesion with a thrombus in the right side of her neck. Angiography revealed a saccular aneurysm 3.4 cm in size near the bifurcation site of the right common carotid artery into the external carotid artery. She underwent an urgent resection of the aneurysm and a carotid artery reconstruction. Postoperatively, she recovered well and the total resection of the lesion was angiographically confirmed. Histopathological examination revealed that the wall of the aneurysm had undergone fibrosis and contained a few elastic fibers and microhemorrhages. The wall of the aneurysm was also infiltrated by inflammatory cells. The surgical strategy for and appropriate preoperative evaluation of this rare disease was discussed.

Purpose: In assisted reproductive technology, normal zygotes are bipronuclear (2PN) during fertilization confirmation; however, sometimes, nonpronuclear zygotes (0PN) and monopronuclear zygotes (1PN) are found during routine observations., Methods: To elucidate the clinical usefulness of in vitro -fertilized embryos, we investigated the rates of clinical pregnancy, live birth, miscarriage, and congenital abnormality after transfer of frozen-thawed 1PN- and 0PN-derived single blastocysts at Denentoshi Ladies Clinic, Kanagawa, Japan., Results: The rates of pregnancy and live birth for 1PN-derived blastocysts obtained by conventional in vitro fertilization were 37.5% and 27.1%, respectively, which was not significantly different from those for 2PN-derived blastocysts; however, the rates for 0PN-derived blastocysts were significantly lower. The pregnancy and live birth rates for 0PN-derived embryos obtained by intracytoplasmic sperm injection (ICSI) were 45.7% and 34.8%, respectively, which was not significantly different from those for 2PN-derived blastocysts; however, the rates for 1PN-derived blastocysts were significantly lower (4.0% for both) than those for 2PN- and 0PN-derived blastocysts. No congenital abnormalities were found in infants resulting from transfer of 0PN- or 1PN-derived blastocysts., Conclusions: Both 1PN- and 0PN-derived blastocysts can be used for embryo transfer; however, care should be taken in making decisions about 1PN-derived blastocysts, especially if they are obtained by ICSI., Competing Interests: The authors declare no conflict of interest.

To determine whether output from the forebrain (termed central command) may descend early enough to increase cardiac and renal sympathetic outflows at the onset of voluntary exercise, we examined the changes in regional tissue blood flows of bilateral prefrontal cortices with near-infrared spectroscopy, precisely identifying the onset of voluntary ergometer 30-s exercise at 41 ± 2% of the maximal exercise intensity in humans. Prefrontal oxygenated-hemoglobin (Oxy-Hb) concentration was measured as index of regional blood flow unless deoxygenated-hemoglobin concentration remained unchanged. Prefrontal Oxy-Hb concentration increased significantly (P < 0.05) 5 s prior to the onset of exercise with arbitrary start, whereas such increase in prefrontal Oxy-Hb was absent before exercise abruptly started by a verbal cue. Furthermore, the increase in prefrontal Oxy-Hb observed at the initial 15-s period of exercise was greater with arbitrary start than cued start. The prefrontal Oxy-Hb, thereafter, decreased during the later period of exercise, irrespective of either arbitrary or cued start. The reduction in prefrontal Oxy-Hb had the same time course and response magnitude as that during motor-driven passive exercise. Cardiac output increased at the initial period of exercise, whereas arterial blood pressure and total peripheral resistance decreased. The depressor response was more pronounced (P < 0.05) with arbitrary start than cued start. Taken together, it is suggested that the increase in prefrontal Oxy-Hb observed prior to the onset of voluntary exercise may be in association with central command, while the later decrease in the Oxy-Hb during exercise may be in association with feedback stimulated by mechanical limb motion., (Copyright © 2015 the American Physiological Society.)

Purpose: Regular aerobic exercise has come to the forefront of non-pharmacological treatment for hypertension. In this line, post-exercise hypotension may have a potential tool for efficient blood pressure management. However, less is known about the influence of acute aerobic exercise on aortic pulse pressure (PP), an important property underlying the pathophysiology of cardiovascular disease. We tested the hypotheses that aortic PP would be attenuated with a single aerobic exercise and that its extent would be associated with the delayed return of reflected wave and the leg vasodilatory capacity., Methods: In 23 apparent healthy men (22 ± 4 years), hemodynamic variables and aortic pulse wave velocity (PWV) were measured before and 20 and 50 min after a 60-min bout of cycling exercise at moderate intensity (corresponding to 65-75 % heart rate reserve). Aortic pressure was estimated from applanation tonometrically measured radial arterial pressure waveform via general transfer function. Peak calf vascular dilatory capacity was measured with the ischemic exercise-induced hyperemia (via venous occlusion plethysmography)., Results: Finger, brachial, and aortic PP were significantly attenuated following the exercise. At 20 min after the exercise cessation, individual changes in aortic PWV significantly correlated with corresponding changes in aortic PP (r = 0.541, P < 0.05), but this correlation was no longer significant at 50 min after the exercise cessation. Peak calf vascular dilatory capacity was not associated with change in aortic PP., Conclusions: We conclude that in young men the aortic PP would be attenuated with the moderate-intensity dynamic exercise partly due to the delayed return of reflection wave from periphery.

Proximal large elastic arteries (ascending aorta and carotid artery) have an important role in buffering the pulsatile pressure generated from the left ventricle, which forwards continuous peripheral blood flow and protects the brain microcirculation from end-organ damage. Although compliance of distal conduit arteries (extremities' arteries) is attenuated by the nitric oxide synthase (NOS) inhibition, it is yet unknown whether compliance of proximal elastic arteries changes by the systemic NOS inhibition. To address this question, we measured central artery compliance in 17 young adults (26±1 years) who underwent intravenous infusions of N(G)-monomethyl-L-arginine (L-NMMA) or saline (placebo) on separate days. Following the systemic NOS inhibition, the mean arterial pressure (MAP), total peripheral resistance and aortic augmentation index were significantly increased. However, carotid artery compliance was not affected significantly (from 0.10±0.01 to 0.11±0.01 mm2) per mmHg) and the β-stiffness index (an index of arterial compliance adjusted for the distending pressure) tended to decrease (from 6.63±0.35 to 6.06±0.42 a.u., P=0.07). These parameters were not altered with saline infusion. Changes in the β-stiffness index tended to correlate negatively with the corresponding changes in MAP (r = -0.31, P=0.07). These results suggest that carotid artery compliance remains unchanged during the systemic NOS inhibition in spite of systemic vasoconstriction.

To prevent orthostatic hypotension, arterial blood pressure (BP) is neurally and hormonally regulated via increases in heart rate (HR) and peripheral vascular tone. After dynamic exercise, however, the latter arm is blunted because of the increased vasodilators in exercised muscles. Orthostatic tachycardia is likely a more important compensatory mechanism for post-exercise orthostatic intolerance in individuals who have higher leg vasodilator capacity, such as endurance-trained athletes. To test the hypothesis that regular endurance training was associated with the greater augmentation of tachycardia response to post-exercise orthostasis, we compared hemodynamic responses to 5-min 60° head-up tilt (HUT) before and after 60 min of cycling at 70% of HR reserve in the endurance-trained (n = 8) and sedentary men (n = 9). Calf peak vascular conductance was 62% greater in the endurance-trained than the sedentary (P < 0.001). After the exercise, the HUT-induced reduction of SV was significantly augmented in the endurance-trained (from -27.7 ± 6.9 to -33.7 ± 7.7 ml, P = 0.03) but not in their sedentary peers. Nevertheless, MAP was well maintained during post-exercise HUT even in the endurance-trained (from 81 ± 10 to 80 ± 8 mmHg). Tachycardia responses during sustained orthostasis were significantly increased in the sedentary (1.3-fold vs. pre-exercise) and more in the endurance-trained (2.0-fold). The augmented response of HUT-induced tachycardia was greater in the endurance-trained than the sedentary (P = 0.04). Additionally, cardiovagal baroreflex sensitivity (BRS), evaluated by the HR response to the hypotensive perturbation, was improved after the exercise in the endurance-trained (from -0.56 ± 0.32 to -1.03 ± 0.26 bpm/mmHg, P = 0.007) but not in the sedentary. These results suggest that in the endurance-trained men the increased orthostatic tachycardia and augmented cardiovagal BRS may favorably mitigate accumulated risks for orthostatic intolerance in the early phase of post-exercise.

Purpose: Near-infrared spectroscopy (NIRS) is widely used to investigate cerebral oxygenation and/or neural activation during physiological conditions such as exercise. However, NIRS-determined cerebral oxygenated hemoglobin (O2Hb) may not necessarily correspond to intracranial blood flow during dynamic exercise. To determine the selectivity of NIRS to assess cerebral oxygenation and neural activation during exercise, we examined the influence of changes in forehead skin blood flow (SkBF(head)) on NIRS signals during dynamic exercise., Methods: In ten healthy men (age: 20 ± 1 years), middle cerebral artery blood flow velocity (MCA V mean, via transcranial Doppler ultrasonography), SkBF(head) (via laser Doppler flowmetry), and cerebral O2Hb (via NIRS) were continuously measured. Each subject performed 60 % maximum heart rate moderate-intensity steady-state cycling exercise. To manipulate SkBF(head), facial cooling using a mist of cold water (~4 °C) was applied for 3 min during steady-state cycling., Results: MCA V mean significantly increased during exercise and remained unchanged with facial cooling. O2Hb and SkBF(head) were also significantly increased during exercise; however, both of these signals were lowered with facial cooling and returned to pre-cooling values with the removal of facial cooling. The changes in O2Hb correlated significantly with the relative percent changes in SkBF(head) in each individual (r = 0.71-0.99)., Conclusions: These findings suggest that during dynamic exercise NIRS-derived O2Hb signal can be influenced by thermoregulatory changes in SkBF(head) and therefore, may not be completely reflective of cerebral oxygenation or neural activation.

We have reported the upregulation of MARCO, a member of the class A scavenger receptor family, on the surface of murine and human dendritic cells (DCs) pulsed with tumor lysates. Exposure of murine tumor lysate-pulsed DCs to an anti-MARCO antibody led to loss of dendritic-like processes and enhanced migratory capacity. In this study, we have further examined the biological and therapeutic implications of MARCO expression by DCs. DCs generated from the bone marrow (bm) of MARCO knockout (MARCO⁻/⁻) mice were phenotypically similar to DCs generated from the bm of wild-type mice and produced normal levels of IL-12 and TNF-α when exposed to LPS. MARCO⁻/⁻ DCs demonstrated enhanced migratory capacity in response to CCL-21 in vitro. After subcutaneous injection into mice, MARCO⁻/⁻ TP-DCs migrated more efficiently to the draining lymph node leading to enhanced generation of tumor-specific IFN-γ producing T cells and improved tumor regression and survival in B16 melanoma-bearing mice. These results support targeting MARCO on the surface of DCs to improve trafficking and induction of anti-tumor immunity.

Introduction: Video-assisted thoracoscopic surgery is widely used for resecting early-stage non-small cell lung cancer. Segmentectomy and subsegmentectomy require a thorough knowledge of the 3-D bronchovascular anatomy of the lung. Previously, our department reported using a 3-D pulmonary model of a patient for thoracoscopic surgical treatment of non-small cell lung cancer. This study investigates multi-segmentectomy for patients with non-small cell lung cancer., Methods: Between July 2001 and January 2012, 943 patients underwent surgical resection of primary lung cancer. Of these, 11 patients had video-assisted thoracoscopic multi-subsegmentectomy. For preoperative simulation, virtual 3-D pulmonary models have been constructed since July 2001., Results: The mean age of patients was 69.2 ± 11.6 years (range, 43.0-86.0 years). Histological diagnoses included adenocarcinoma in eight patients, squamous cell carcinoma in two, and large cell carcinoma (neuroendocrine tumor) in one. Tumor size was ≤ 10 mm in one patient, 11-15 mm in four, 16-20 mm in four, and 21-25 mm in two. One patient was treated without lymphadenectomy, nine patients underwent additional hilar lymphadenectomy, and one patient underwent additional hilar and mediastinal lymphadenectomy. No patients were converted to thoracotomy. All patients had a macroscopically negative surgical margin. The pathological stage of patients was IA in nine patients, IB in one, and IIA in one. No pulmonary vessel injuries were found. Three patients had a prolonged lung air leak (> 6 days)., Conclusion: Using a reconstructed 3-D pulmonary model, this study demonstrates that video-assisted thoracoscopic multiple subsegmentectomy is feasible with adequate margins in selected patients., (© 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.)

Background: Resection of lung metastasis from malignant tumor of liver, biliary duct and pancreas has various controversial problems. These problems are that many patients have a progressive disease and there are few patients who can have resectable lesion. Generally the prognosis of these diseases is poor. In addition, the effect of pulmonary resection for lung metastasis from malignant tumor of liver, biliary duct and pancreas is unclear. We set out to investigate the outcome and usefulness of surgery in this group., Patients and Methods: From January 1999 to November 2012, 18 patients underwent a total of 21 surgeries. There were 11 men and 7 women with mean age of 66.6±10( range, 43 to 78). Primary diseases of these patients were hepatocellular carcinoma in 5, cholangiocellular carcinoma in 1, cholangiocarcinoma in 2 and pancreatic cancer in 10 patients., Results: Disease-free interval from 1st local therapy such as surgical treatment for primary lesion was 50.8±28.7(range, 19 to 107) months. Numbers of lung metastasis were 1 in 15, 2 in 4 patients and 3 in 1 patient. Many metastasis were in right lower lobe. Numbers of wedge resection were 13, segmentectomy were 4, lobectomy were 2 in these patients. Average of total survival time was 38±34 months. Four patients were dead. The 14 patients are alive and 7 patients had no recurrence. Adjuvant therapy such as chemotherapy was important. One-year all over survival rate after 1st pulmonary resection was 88%, 3 or 5-years was 73%. We think that it's was good result., Conclusion: There is a possibility that surgery for metastatic lung tumor from malignant tumor of liver, biliary duct and pancreas is useful by control of primary lesion and selecting of patients and adjuvant therapy such as chemotherapy.

This report describes a 3-dimensional (3-D) video-assisted thoracoscopic lung resection guided by a 3-D video navigation system having a patient-specific 3-D reconstructed pulmonary model obtained by preoperative simulation. A 78-year-old man was found to have a small solitary pulmonary nodule in the left upper lobe in chest computed tomography. By a virtual 3-D pulmonary model the tumor was found to be involved in two subsegments (S1 + 2c and S3a). Complete video-assisted thoracoscopic surgery bi-subsegmentectomy was selected in simulation and was performed with lymph node dissection. A 3-D digital vision system was used for 3-D thoracoscopic performance. Wearing 3-D glasses, the patient's actual reconstructed 3-D model on 3-D liquid-crystal displays was observed, and the 3-D intraoperative field and the picture of 3-D reconstructed pulmonary model were compared., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2013.)

Exercise training elicits morphological adaptations in the left ventricle (LV) and large-conduit arteries that are specific to the type of training performed (i.e., endurance vs. resistance exercise). We investigated whether the mode of chronic exercise training, and the associated cardiovascular adaptations, influence the blood pressure responses to orthostatic stimulation in 30 young healthy men (10 sedentary, 10 endurance trained, and 10 resistance trained). The endurance-trained group had a significantly larger LV end-diastolic volume normalized by body surface area (vs. sedentary and resistance-trained groups), whereas the resistance-trained group had a significantly higher LV wall thickness and aortic pulse wave velocity (PWV) compared with the endurance-trained group. In response to 60° head-up tilt (HUT), mean arterial pressure (MAP) rose in the resistance-trained group (+6.5 ± 1.6 mmHg, P < 0.05) but did not change significantly in sedentary and the endurance-trained groups. Systolic blood pressure (SBP) decreased in endurance-trained group (-8.3 ± 2.4 mmHg, P < 0.05) but did not significantly change in sedentary and resistance-trained groups. A forward stepwise multiple regression analysis revealed that LV wall thickness and aortic PWV were significantly and independently associated with the MAP response to HUT, explaining ∼41% of its variability (R(2) =0.414, P < 0.001). Likewise, aortic PWV and the corresponding HUT-mediated change in stroke volume were significantly and independently associated with the SBP response to HUT, explaining ∼52% of its variability (R(2) = 0.519, P < 0.0001). Furthermore, the change in stroke volume significantly correlated with LV wall thickness (r = 0.39, P < 0.01). These results indicate that chronic resistance and endurance exercise training differentially affect the BP response to HUT, and that this appears to be associated with training-induced morphological adaptations of the LV and large-conduit arteries.

Purpose: Human hands are excellent in performing sensory and motor function. We have hypothesized that blood flow of the hand is dynamically regulated by sympathetic outflow during concentrated finger perception. To identify this hypothesis, we measured radial blood flow (RBF), radial vascular conductance (RVC), heart rate (HR), and arterial blood pressure (AP) during Braille reading performed under the blind condition in nine healthy subjects. The subjects were instructed to read a flat plate with raised letters (Braille reading) for 30 s by the forefinger, and to touch a blank plate as control for the Braille discrimination procedure., Results: HR and AP slightly increased during Braille reading but remained unchanged during the touching of the blank plate. RBF and RVC were reduced during the Braille character discrimination task (decreased by -46% and -49%, respectively). Furthermore, the changes in RBF and RVC were much greater during the Braille character discrimination task than during the touching of the blank plate (decreased by -20% and -20%, respectively)., Conclusions: These results have suggested that the distribution of blood flow to the hand is modulated via sympathetic nerve activity during concentrated finger perception.

Background: Arterial stiffness is a major contributor to cardiovascular diseases. Because current methods of measuring arterial stiffness are technically demanding, the purpose of this study was to develop a simple method of evaluating arterial stiffness using oscillometric blood pressure measurement., Methods: Blood pressure was conventionally measured in the left upper arm of 173 individuals using an inflatable cuff. Using the time series of occlusive cuff pressure and the amplitudes of pulse oscillations, we calculated local slopes of the curve between the decreasing cuff pressure and corresponding arterial volume. Whole pressure-volume curve was derived from numerical integration of the local slopes. The curve was fitted using an equation and we identified a numerical coefficient of the equation as an index of arterial stiffness (Arterial Pressure-volume Index, API). We also measured brachial-ankle (baPWV) PWV and carotid-femoral (cfPWV) PWV using a vascular testing device and compared the values with API. Furthermore, we assessed carotid arterial compliance using ultrasound images to compare with API., Results: The slope of the calculated pressure-volume curve was steeper for compliant (low baPWV or cfPWV) than stiff (high baPWV or cfPWV) arteries. API was related to baPWV (r = -0.53, P < 0.05), cfPWV (r = -0.49, P < 0.05), and carotid arterial compliance (r = 0.32, P < 0.05). A stepwise multiple regression analysis demonstrated that baPWV and carotid arterial compliance were the independent determinants of API, and that API was the independent determinant of baPWV and carotid arterial compliance., Conclusions: These results suggest that our method can simply and simultaneously evaluate arterial stiffness and blood pressure based on oscillometric measurements of blood pressure.

Background: Pneumothorax in middle-aged and elderly patients has various different features from young patients. We set out to investigate the outcome and usefulness of video-assisted thoracic surgery (VATS) in this group., Patients and Methods: From January 1993 to August 2010, 168 patients underwent a total of 178 thoracoscopic surgeries. There were 160 men and 8 women with mean age of 67 (range, 50 to 85). The average duration of thoracic drainage before surgery was 7.4 days. We excised only responsible lesions as minimum degree of dissection as possible. When patients have intractable air leakage and chest computed tomography (CT) indicates severe pleural adhesions, pleurography should be performed to locate the site of air leakage and determine surgical approaches. One hundred and seventy patients were treated with the lateral approach, while 8 patients were successfully treated with the anterior approach. One hundred and fifty-one patients were treated with VATS alone, and 27 patients were treated with the combination of VATS and small thoracotomy. The duration of chest tube drainage, hospital stay, post-operative complication, outcome and recurrence were assessed., Results: The air leakages stopped and all patients except for 2 patents were discharged without drainage tubes. Postoperative drainage time was 4.5 +/- 3.4 days. Postoperative hospital stay was 9.9 +/- 13.9 days. One patient died caused by perioperative myocardial infarction. Seventeen patients died of other diseases. Seven patients needed local hospital treatments and the recurrence rate was 3.9%., Conclusion: VATS for pneumothorax in patients over 50 years old is very useful by appropriate perioperative managements.

We reported that murine tumor lysate-pulsed dendritic cells (TP-DC) could elicit tumor-specific CD4(+) and CD8(+) T cells in vitro and in vivo. In some limited cases, TP-DC treatments in vivo could also result in regression of established subcutaneous tumors and lung metastases. By gene array analysis, we reported a high level of expression of a novel member of the cell surface class A scavenger receptor family, MARCO, by murine TP-DC compared to unpulsed DC. MARCO is thought to play an important role in the immune response by mediating binding and phagocytosis, but also in the formation of lamellipodia-like structures and dendritic processes. We have now examined the biologic and therapeutic implications of MARCO expressed by TP-DC. In vitro exposure of TP-DC to a monoclonal anti-MARCO antibody resulted in a morphologic change of rounding with disappearance of dendritic-like processes. TP-DC remained viable after anti-MARCO antibody treatment; had little, if any, change in production of IL-10, IL-12p70 and TNF-alpha; but demonstrated enhanced migratory capacity in a microchemotaxis assay. The use of a selective inhibitor showed MARCO expression to be linked to the p38 mitogen-activated protein kinase (MAPK) pathway. In vivo, anti-MARCO antibody treated TP-DC showed better trafficking from the skin injection site to lymph node, enhanced generation of tumor-reactive IFN-gamma producing T cells, and improved therapeutic efficacy against B16 melanoma. These results, coupled with our finding that human monocyte-derived DC also express MARCO, could have important implications to human clinical DC vaccine trials.

BACKGROUND: Augmented central artery wave reflection is a cardiovascular disease risk factor. Augmentation index (AI) obtained from peripheral artery waveforms provides qualitatively similar information to AI from central artery waveforms. Little information is available, however, regarding the influence of racial difference in association between central and peripheral AI. METHODS: We studied 47 White adults (45+/-17 yr, 20 women) and 94 age-matched Asian adults (45+/-14 yr, 42 women). RESULTS: The White group was significantly taller than the Asian group, whereas there were no significant group differences in blood pressure and heart rate. Carotid and radial AI tended to be lower in White compared with Asian adults (P<0.10 for both). Such tendency disappeared when the difference in height was taken into account using ANCOVA (P=0.84 and P=0.77, respectively). Radial AI was strongly and positively correlated with carotid AI in White adults (r=0.75, P<0.0001) as well as in Asian adults (r=0.82, P<0.0001). The slope and intercept of linear regression line between radial and carotid AI of White adults were highly comparable with those of Asian adults. CONCLUSION: AI in the conveniently located peripheral vasculature may provide a surrogate measure of central AI irrespective of difference in race (e.g., Asian vs. White populations).

Sensitivity to 10 anticancer drugs was evaluated in 6 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines. Authenticity of newly established cell lines was confirmed by genomic fingerprinting. The line YCUB-5R established at relapse was more resistant to 4-hydroperoxy-cyclophosphamide, cytarabine, L-asparaginase, topotecan, fludarabine, and etoposide than YCUB-5 from the same patient at diagnosis. Of the drugs tested, etoposide and SN-38 (irinotecan) showed highest efficacy in the panel, with 50% growth inhibition at 0.22-1.8 microg/ml and 0.57-3.6 ng/ml, respectively. This cell line panel offers an in vitro model for the development of new therapies for childhood BCP-ALL.

Background: Regular aerobic exercise improves large artery compliance in middle-aged and older humans. However, the underlying mechanisms are unknown. We tested the hypothesis that the improved central arterial compliance with endurance training is mediated by decreased alpha-adrenergic tone and/or increased endothelial function., Methods: Seven sedentary healthy adults (60+/-3 years) underwent systemic alpha-adrenergic blockade (phentolamine) and nitric oxide synthase (NOS) inhibition using N(G)-monomethyl-L-arginine in sequence before and after a 3-month moderate endurance training (walk/jog, 4-5 days/week). Phentolamine was given first to isolate the contribution of nitric oxide to arterial compliance by minimizing reflex suppression of sympathetic tone resulting from systemic NOS inhibition as well as to assess the alpha-adrenergic receptor-mediated modulation of arterial compliance., Results: Baseline arterial compliance (via simultaneous ultrasound and applanation tonometry on the carotid artery) increased 34+/-12% after exercise training (P<0.01). When alpha-adrenergic blockade was performed, arterial compliance increased 37+/-6% (P<0.01) before the exercise training but did not change significantly after the training. Decreases in arterial compliance from the alpha-adrenergic blockade to the subsequent additional NOS blockade were not different before and after exercise training., Conclusion: Our results suggest that the reduction in alpha-adrenergic receptor-mediated vascular tone contributes to the improved central arterial compliance with endurance training.

Endurance exercise training increases arterial baroreflex sensitivity that corresponds to alteration in vessel wall compliance of the carotid artery in elderly men. Here, we examined whether regular endurance exercise increases arterial baroreflex sensitivity through neural alteration of the baroreflex arc in young men. We assessed arterial baroreflex sensitivity in eight sedentary men (age 24 +/- 1 yr) and nine men trained in endurance exercise (age 23 +/- 1 yr) during phase IV of the Valsalva maneuver [systolic arterial blood pressure (SAP)-R-R interval relationship]. Arterial baroreflex sensitivity was further analyzed by dividing the mechanical component [SAP-end-systolic carotid lumen diameter relationship (ultrasonography)] and the neural component (end-systolic carotid lumen diameter-R-R interval relationship). Carotid arterial compliance was determined using B-mode ultrasound and arterial applanation tonometry on the common carotid artery. Arterial baroreflex sensitivity and its neural component were greater in the exercise-trained group (P < 0.05). In contrast, carotid arterial compliance and the mechanical component of arterial baroreflex sensitivity did not differ between groups. These results suggest that regular endurance exercise in young men increases arterial baroreflex sensitivity through changes in the neural component of the baroreflex arc and not through alterations in vessel wall compliance of the carotid artery.

In men, regular aerobic exercise increases central arterial elasticity, but it is decreased by resistance training. We determined the relation between the type of exercise training and arterial elasticity in healthy young women: 26 healthy young women who were sedentary (CO, n = 9), endurance-trained (ET, n = 9), and resistance-trained (RT, n = 8) groups. We determined the carotid arterial compliance and distensibility coefficient (simultaneous ultrasound and applanation tonometry), VO(2max), and 1RM (bench press and leg extension). The VO(2max) in the ET groups was higher than in the CO and RT groups. Both 1RM were higher in the RT groups than in the CO and ET groups. No significant difference was found in the carotid artery compliance and distensibility coefficient among the ET, RT, and CO groups. These results underscore the difficulty in detecting a change in arterial elasticity in young female athletes using the type of exercise training by which it is shown in young men.

We examined whether a sympathetic cholinergic mechanism contributed to increased blood flow of the exercising muscle at the onset of voluntary static exercise in conscious cats. After six cats were operantly conditioned to perform static bar press exercise with a forelimb while maintaining a sitting posture, a Transonic or pulsed Doppler flow probe was implanted on the brachial artery of the exercising forelimb, and catheters were inserted into the left carotid artery and jugular vein. After the baseline brachial blood flow and vascular conductance decreased and became stable in progress of postoperative recovery, the static exercise experiments were started. Brachial blood flow and vascular conductance began to increase simultaneously with the onset of exercise. Their initial increases reached 52 +/- 8% and 40 +/- 6% at 3 s from the exercise onset, respectively. Both a sympathetic ganglionic blocker (hexamethonium bromide) and atropine sulfate or methyl nitrate blunted the increase in brachial vascular conductance at the onset of static exercise, whereas an inhibitor of nitric oxide synthesis (N(omega)-nitro-l-arginine methyl ester) did not alter the increase in brachial vascular resistance. Brachial blood flow and vascular conductance increased during natural grooming behavior with the forelimb in which the flow probe was implanted, whereas they decreased during grooming with the opposite forelimb and during eating behavior. Thus it is likely that the sympathetic cholinergic mechanism is capable of evoking muscle vasodilatation at the onset of voluntary static exercise in conscious cats.

Endurance training improves endothelium-dependent vasodilation, yet it does not increase basal blood flow in the legs. We determined the effects of a 3-mo aerobic exercise intervention on basal leg blood flow and alpha-adrenergic vasoconstriction and nitric oxide (NO) release in seven apparently healthy middle-aged and older adults (60 +/- 3 yr). Basal femoral artery blood flow (via Doppler ultrasound) (pretraining: 354 +/- 29; posttraining: 335 +/- 34 ml/min) and vascular conductance did not change significantly with the exercise training. Before the exercise intervention, femoral artery blood flow increased 32 +/- 16% with systemic alpha-adrenergic blockade (with phentolamine) (P < 0.05), and the addition of nitric oxide synthase (NOS) inhibition using N(G)-monomethyl-L-arginine (L-NMMA) did not affect femoral artery blood flow. After training was completed, femoral artery blood flow increased 47 +/- 7% with alpha-adrenergic blockade (P < 0.01) and then decreased 18 +/- 7% with the subsequent administration of L-NMMA (P < 0.05). Leg vascular conductance showed a greater alpha-adrenergic blockade-induced vasodilation (+1.7 +/- 0.5 to +3.0 +/- 0.5 units, P < 0.05) as well as NOS inhibition-induced vasoconstriction (-0.8 +/- 0.4 to -2.7 +/- 0.7 units, P < 0.05) after the exercise intervention. Resting plasma norepinephrine concentration significantly increased after the training. These results suggest that regular aerobic exercise training enhances NO bioavailability in middle-aged and older adults and that basal limb blood flow does not change with exercise training because of the contrasting influences of sympathetic nervous system activity and endothelium-derived vasodilation on the vasculature.

Stiffening of large elastic arteries impairs the buffering function of the arterial system and contributes to cardiovascular disease. The aim of this study was to determine whether endothelium-derived nitric oxide (NO) modulates the stiffness of large elastic arteries in humans. Seven apparently healthy adults (60+/-3 years, 2 males and 5 females) underwent systemic alpha-adrenergic blockade (phentolamine) and systemic NO synthase inhibition using NG-monomethyl-L-arginine (L-NMMA) in sequence. Phentolamine was given first to isolate contribution of NO to arterial stiffness by preventing reflex changes in sympathetic tone that result from systemic NO synthase inhibition, and also to compare arterial stiffness at a similar mean arterial pressure. Mean arterial blood pressure decreased (p<0.05) after phentolamine infusion but returned to baseline levels after L-NMMA infusion. The carotid beta-stiffness index (via simultaneous ultrasound and applanation tonometry on the common carotid artery) did not change after the restraint of systemic alpha-adrenergic nerve activity (9.8+/-1.2 vs. 9.1+/-1.1 U) but increased (p<0.05) after NO synthase inhibition (12.6+/-2.0 U). These results suggest that NO appears to modulate central arterial stiffness in humans.

Objective: Increased aortic and carotid arterial augmentation index (AI) has been directly linked with cardiovascular disease risk, mortality and morbidity. The aim of this study was to examine whether AI obtained directly from radial artery pressure waveforms (radial AI) can provide information comparable with carotid arterial AI measurements., Methods: In a cross-sectional study of 204 apparently healthy subjects (88 men and 116 women) aged 19-76 years (51 +/- 15 years, mean +/- SD), carotid AI [(second peak carotid systolic pressure - first peak carotid systolic pressure)/carotid pulse pressure*100] and radial AI [(second peak radial systolic pressure - diastolic pressure)/(first peak radial systolic pressure - diastolic pressure)*100] were measured using applanation tonometry., Results: Radial AI was strongly correlated with carotid AI (r = 0.86, P < 0.0001, SD of difference 10.0%), although radial AI was consistently approximately 66% higher than carotid AI. In 16 apparently healthy young adults (11 men and five women, aged 23 +/- 3 years) handgrip exercise was immediately followed by post-exercise muscle ischaemia (PEMI) to compare changes in carotid and radial AI during increased sympathetic nervous activity. PEMI caused parallel increases in carotid and radial AI (26 and 19%). Accordingly, changes in radial AI with PEMI were strongly correlated with corresponding changes in carotid AI (r = 0.86, P < 0.0001, SD of difference 7.3%)., Conclusion: These results suggest that AI obtained directly from radial arterial pressure waveforms could provide equivalent information to carotid arterial AI, and has potential as a surrogate marker of cardiovascular disease.

We demonstrate a scalable architecture for a high-power, high-brightness, solid-state laser based on coherent combinations of master oscillator power amplifier chains. A common master oscillator injects a sequence of multikilowatt Nd:YAG zigzag slab amplifiers. Adaptive optics correct the wavefront of each amplified beamlet. The beamlets are tiled side by side and actively phase locked to form a single output beam. The laser produces 19 kW with beam quality <2x diffraction limited. To the best of our knowledge, this is the brightest cw solid-state laser demonstrated to date.

Background: Human interferon-gamma (hIFN-gamma) is produced by lymphocytes and has a variety of biological properties. Measurement of hIFN-gamma is widely used for various immunological responses for allergic or autoimmune diseases. Enzyme-linked immunosorbent assay (ELISA) is an established immunoassay used to quantify cellular metabolites or cytokines. ELISA requires many incubation and wash steps and is not practically suitable for screening large numbers of samples., Methods: We have developed a fluorescence-linked immunosorbent assay (FLISA) method for the detection of hIFN-gamma. We measured the 50% inhibitory concentration (IC50) value of the hIFN-gamma production by interleukin (IL)-18 binding protein and anti-IL-18 monoclonal antibody. The IC50 described by FLISA was compared with that by ELISA., Results: We developed a new system for measuring hIFN-gamma using Allophycocyanine (APC) fluorescent protein and compared it with the previous method using Cy5.5. The proposed FLISA had a smaller coefficient of variation than ELISA, and the means of coefficient of variation using the same samples measured by ELISA and FLISA were, respectively, 11.1% and 3.8%, suggesting that the edge effect often giving non-specific results may be smaller in FLISA than in ELISA., Conclusions: The improved FLISA system proposed is ideally suited for efficient measurements of hIFN-gamma. This homogeneous and multiplex method will be a powerful tool for high throughput screening for drug discovery research.

We have reported that baroreflex bradycardia by stimulation of the aortic depressor nerve is blunted at the onset of voluntary static exercise in conscious cats. Central command may contribute to the blunted bradycardia, because the most blunted bradycardia occurs immediately before exercise or when a forelimb is extended before force development. However, it remained unknown whether the blunted bradycardia is due to either reduced sensitivity of the baroreflex stimulus-response curve or resetting of the curve toward a higher blood pressure. To determine this, we examined the stimulus-response relationship between systolic (SAP) or mean arterial pressure (MAP) and heart rate (HR) at the onset of and during the later period of static exercise in seven cats (n = 348 trials) by changing arterial pressure with infusion of nitroprusside and phenylephrine or norepinephrine. The slope of the MAP-HR curve decreased at the onset of exercise to 48% of the preexercise value (2.9 +/- 0.4 beats x min(-1) x mmHg(-1)); the slope of the SAP-HR curve decreased to 59%. The threshold blood pressures of the stimulus-response curves, at which HR started to fall due to arterial baroreflex, were not affected. In contrast, the slopes of the stimulus-response curves during the later period of exercise returned near the preexercise levels, whereas the threshold blood pressures elevated 6-8 mmHg. The maximal plateau level of HR was not different before and during static exercise, denying an upward shift of the baroreflex stimulus-response curves. Thus central command is likely to attenuate sensitivity of the cardiac component of arterial baroreflex at the onset of voluntary static exercise without shifting the stimulus-response curve.

Aortic pulse wave velocity (PWV) significantly decreased after 16 weeks of moderate-intensity exercise training (walking/jogging) in 17 sedentary middle-aged men, whereas leg PWV did not. These results suggest that in contrast with central arterial stiffness, peripheral arterial stiffness is difficult to change with aerobic exercise training.

A complex balance between extrinsic neural and intrinsic mechanisms is responsible for regulating atrioventricular (AV) conduction. We hypothesized that atrial excitation interval is shortened during dynamic exercise by extrinsic cardiac autonomic activity and that if AV conduction time responds inversely to fluctuation in atrial rhythm, ventricular excitation interval will be maintained at the predetermined cardiac cycle length. To examine such inverse relationship between PP interval and the subsequent change in PR interval (DeltaPR), we analyzed the beat-to-beat changes in PP, PR, and RR intervals during stair-stepping exercise for 10 min in 11 sedentary and 9 trained subjects. In the sedentary group, the average PR interval significantly shortened during exercise, in parallel with the reduction in the average PP and RR intervals. The variance of PP and RR intervals was also significantly decreased during exercise. The reduction in the variance of RR interval was, however, much greater than that of PP interval, implying that AV conduction time changes inversely to fluctuation in atrial excitation rhythm. Indeed, the variance of PR interval was augmented during exercise and there was a clear inverse relationship between PP and DeltaPR intervals. Although trained subjects were characterized by their lower heart rate response during dynamic exercise, the responses in the variability of PP, PR, and RR intervals were fundamentally identical with those in sedentary subjects. We conclude that the AV nodal mechanism that operates at a higher level of heart rate during dynamic exercise may cancel fluctuation in atrial excitation interval and keep ventricular excitation rhythm at the predetermined cardiac cycle length.

The purpose of the present study was 1) to investigate whether an increase in heart rate (HR) at the onset of voluntary static arm exercise in tetraplegic subjects was similar to that of normal subjects and 2) to identify how the cardiovascular adaptation during static exercise was disturbed by sympathetic decentralization. Mean arterial blood pressure (MAP) and HR were noninvasively recorded during static arm exercise at 35% of maximal voluntary contraction in six tetraplegic subjects who had complete cervical spinal cord injury (C(6)-C(7)). Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were estimated by using a Modelflow method simulating aortic input impedance from arterial blood pressure waveform. In tetraplegic subjects, the increase in HR at the onset of static exercise was blunted compared with age-matched control subjects, whereas the peak increase in HR at the end of exercise was similar between the two groups. CO increased during exercise with no or slight decrease in SV. MAP increased approximately one-third above the control pressor response but TPR did not rise at all throughout static exercise, indicating that the slight pressor response is determined by the increase in CO. We conclude that the cardiovascular adaptation during voluntary static arm exercise in tetraplegic subjects is mainly accomplished by increasing cardiac pump output according to the tachycardia, which is controlled by cardiac vagal outflow, and that sympathetic decentralization causes both absent peripheral vasoconstriction and a decreased capacity to increase HR, especially at the onset of exercise.

Animals decerebrated at the precollicular-premammillary body level exhibit spontaneous locomotion without any artificial stimulation. Our laboratory reported that the cardiovascular and autonomic responses at the onset of spontaneous locomotor events are evoked by central command, generated from the caudal diencephalon and the brain stem (Matsukawa K, Murata J, and Wada T. Am J Physiol Heart Circ Physiol 275: H1115-H1121, 1998). In this study, we examined whether central command and/or a reflex resulting from muscle afferents modulates arterial baroreflex function using a decerebrate cat model. The baroreflex was evoked by stimulating the aortic depressor nerve (ADN) at the onset of spontaneous muscle contraction (to test the possible influence of central command) and during electrically evoked contraction or passive stretch (to test the possible influence of the muscle reflex). When the ADN was stimulated at rest, heart rate and arterial blood pressure decreased by 40 +/- 2 beats/min and 11 +/- 1 mmHg, respectively. The baroreflex bradycardia was attenuated to 55 +/- 4% at the onset of spontaneous contraction. The attenuating effect on the baroreflex bradycardia was not observed at the onset and middle of electrically evoked contraction or passive stretch. The depressor response to ADN stimulation was identical among resting and any muscle interventions. The inhibition of the baroreflex bradycardia during spontaneous contraction was seen after beta-adrenergic blockade but abolished by muscarinic blockade, suggesting that the bradycardia is mainly evoked through cardiac vagal outflow. We conclude that central command, produced within the caudal diencephalon and the brain stem, selectively inhibits the cardiac component, but not the vasomotor component, of the aortic baroreflex at the onset of spontaneous exercise.

To investigate whether the Model-flow method, by simulating the aortic input impedance model from a noninvasive monitoring of arterial blood pressure, reflected a reliable measure of cardiac output (CO) during postural change and whole-body exercise occurring in daily life, we compared the Modelflow-estimated CO with a simultaneous reference determined by the pulse dye-densitometry. Nine healthy volunteers performed postural change from supine to upright and dynamic stepping exercise. The Modelflow-estimated CO decreased to 4.8 +/- 0.5 l/min, from 5.8 +/- 0.6 l/min, during the postural change and increased to 12.8 +/- 1.3 l/min during a stepping exercise, returning to 5.1 +/- 0.4 l/min at 5 min after exercise. When comparing the pooled data of CO during resting and following exercise between the Modelflow and pulse dye-densitometry, we found that the average CO did not differ between the two estimates and that there was a significant correlation between them; the slope of the linear regression line corresponded to approximately 1.0. Although such linear relationship was also observed in an individual subject, the slope of the regression line varied from 0.737 to 1.588 among the subjects. The calibration of the Modelflow-estimated CO with the dye-densitometry value at supine or upright improved a correlation between the two estimates. Thus it is likely that the noninvasive Modelflow simulation from arterial blood pressure can provide a reliable estimation of group-average cardiac output during postural change and stepping exercise occurring in daily life. It will be recommended for a more accurate estimation of cardiac output in a given subject to calibrate the Modelflow data with an independent measure.

To examine whether the central characteristics of the aortic baroreflex alter from moment to moment during static exercise, we identified the dynamic changes in the sizes of the bradycardia and depressor response evoked by stimulation of the aortic depressor nerve (ADN). Three conscious cats were trained to voluntarily extend the right forelimb and press a bar for 31 +/- 1 s with a peak force of 337 +/- 22 g while maintaining a sitting posture. The ADN stimulation-induced bradycardia was attenuated at the initial period of exercise (up to 8 s from the exercise onset) to 62 +/- 5% of the preexercise bradycardia and remained blunted until the end of exercise. The most blunted bradycardia was observed immediately before or when the forelimb was extended before force development. The baroreflex-induced bradycardia was suppressed again at cessation of exercise when the forelimb was retracted and recovered within a few seconds. In contrast, static exercise did not affect the ADN stimulation-induced depressor response. The ADN stimulation-induced bradycardia was also blunted at the beginning of naturally occurring body movement such as spontaneous postural change or grooming behavior. Thus it is likely that the central characteristics of the aortic baroreflex dynamically change from moment to moment during voluntary static exercise and during natural body movement and that particularly a central inhibition of the cardiac component of the aortic baroreflex is induced by central command at the onset of static exercise, whereas the central property of the vasomotor component of the baroreflex is preserved.