Observation of Collective Resonance Modes in a Chiral Spin Soliton Lattice with Tunable Magnon Dispersion.

A chiral spin soliton lattice (CSL), one of the representative systems of a magnetic superstructure, exhibits reconfigurability in periodicity over a macroscopic length scale. Such coherent and tunable characteristics of the CSL lead to an emergence of elementary excitation of the CSL as phononlike modes due to translational symmetry breaking and bring a controllability of the dispersion relation of the CSL phonon. Using a broadband microwave spectroscopy technique, we directly found that higher-order magnetic resonance modes appear in the CSL phase of a chiral helimagnet CrNb_{3}S_{6}, which is ascribed to the CSL phonon response. The resonance frequency of the CSL phonon can be tuned between 16 and 40 GHz in the vicinity of the critical field, where the CSL period alters rapidly. The frequency range of the CSL phonon is expected to extend over 100 GHz as extrapolated on the basis of the theoretical model. The present results indicate that chiral helimagnets could work as materials useful for broadband signal processing in the millimeter-wave band.

Record-high sensitivity compact multi-slot sub-wavelength Bragg grating refractive index sensor on SOI platform.

In this paper, a high sensitivity compact multi-slot sub-wavelength Bragg grating refractive index (RI) sensor was investigated. The structural parameters were optimized for higher sensitivity to RI change of the surrounding medium from viewpoints of a wavelength shift, an extinction ratio and a transmission loss, and a record-high sensitivity was experimentally demonstrated with a compact size. In this sensor, the first side-lobe at the Bragg grating (BG) stop-band end was focused as a sensing peak wavelength for moderate transmission loss and efficient sensing. To realize the compactness, a period count of the BG was kept as small as 20. By increasing the RI of the surrounding medium, the sensing peak shifts toward a longer wavelength side; thus due to the high sharpness and easy tracing of the first side-lobe, the device worked as an efficient RI sensor. The structural optimization was carried out by using 3D finite-difference time-domain (FDTD) simulation approach, and also influences of the structural parameters to sensitivities were discussed. Based on these optimized parameters, the devices were fabricated using the lift-off technique. By exposing the sensor to various liquid samples with different RIs such as pure water, sugar-dissolved water with various concentrations, acetone and isopropyl alcohol (IPA), a record-high sensitivity of 730 nm/RIU was attained for a sensor fabricated on SOI platforms with a length of as small as 9.5 µm and a transmission loss of 3 dB.

NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy.

Genetic abnormalities in mitochondrial complex assembling factors are associated with leukoencephalopathy. We present a 1-year-old girl with consciousness disturbance after a respiratory infection. Brain MRI revealed leukoencephalopathy with bilaterally symmetrical hyperintensity in the substantia nigra, medial thalamic nuclei, and basal nuclei, as well as cavities in the cerebral white matter and corpus callosum. Lactate levels in the spinal fluid were high, while magnetic resonance spectroscopy of the cerebral white matter and basal nuclei showed high peak lactate levels, suggesting mitochondrial dysfunction. The respiratory enzyme activity of complex I was reduced to 17% to 21% in skeletal muscle. Whole exome sequencing identified compound heterozygous variations in NDUFAF3, involved in the assembly of mitochondrial complex I (c.342_343insGTG:p.117Valdup, c.505C > A:p.Pro169Thr). Two-dimensional, blue-native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-PAGE revealed reductions in Q-module (NDUFS2, NDUFS3, and NDUFA9) and P-module (NDUFB10 and NDUFB11) subunits, indicating disruption of mitochondrial complex I assembly. Our report expands the spectrum of clinical phenotypes associated with pathogenic variants of NDUFAF3.

Efficacy and safety of rebamipide liquid for chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II study.

BACKGROUND: Recent preclinical and phase I studies have reported that rebamipide decreased the severity of chemoradiotherapy-induced oral mucositis in patients with oral cancer. This placebo-controlled randomized phase II study assessed the clinical benefit of rebamipide in reducing the incidence of severe chemoradiotherapy-induced oral mucositis in patients with head and neck cancer (HNC). METHODS: Patients aged 20-75 years with HNC who were scheduled to receive chemoradiotherapy were enrolled. Patients were randomized to receive rebamipide 2% liquid, rebamipide 4% liquid, or placebo. The primary endpoint was the incidence of grade ≥ 3 oral mucositis determined by clinical examination and assessed by central review according to the Common Terminology Criteria of Adverse Events version 3.0. Secondary endpoints were the time to onset of grade ≥ 3 oral mucositis and the incidence of functional impairment (grade ≥ 3) based on the evaluation by the Oral Mucositis Evaluation Committee. RESULTS: From April 2014 to August 2015, 97 patients with HNC were enrolled, of whom 94 received treatment. The incidence of grade ≥ 3 oral mucositis was 29% and 25% in the rebamipide 2% and 4% groups, respectively, compared with 39% in the placebo group. The proportion of patients who did not develop grade ≥ 3 oral mucositis by day 50 of treatment was 57.9% in the placebo group, whereas the proportion was 68.0% in the rebamipide 2% group and 71.3% in the rebamipide 4% group. The incidences of adverse events potentially related to the study drug were 16%, 26%, and 13% in the placebo, rebamipide 2%, and rebamipide 4% groups, respectively. There was no significant difference in treatment compliance among the groups. CONCLUSIONS: The present phase II study suggests that mouth washing with rebamipide may be effective and safe for patients with HNC receiving chemoradiotherapy, and 4% liquid is the optimal dose of rebamipide. TRIAL REGISTRATION: ClinicalTrials.gov under the identifier NCT02085460 (the date of trial registration: March 11, 2014).

Genetic analyses of GII.17 norovirus strains in diarrheal disease outbreaks from December 2014 to March 2015 in Japan reveal a novel polymerase sequence and amino acid substitutions in the capsid region.

A novel GII.P17-GII.17 variant norovirus emerged as a major cause of norovirus outbreaks from December 2014 to March 2015 in Japan. Named Hu/GII/JP/2014/GII.P17-GII.17, this variant has a newly identified GII.P17 type RNA-dependent RNA polymerase, while the capsid sequence displays amino acid substitutions around histo-blood group antigen (HBGA) binding sites. Several variants caused by mutations in the capsid region have previously been observed in the GII.4 genotype. Monitoring the GII.17 variant's geographical spread and evolution is important.

Assessment of maxillary sinus fluid volume for postmortem diagnosis of drowning.

INTRODUCTION: Drowning is a comprehensive and exclusive diagnosis at autopsy. Autopsy findings such as pleural effusion and waterlogged lungs contribute to the diagnosis. Herein, we aim to reveal the practical usefulness and postmortem changes of the maxillary sinus fluid volume to diagnose drowning. METHODS: We evaluated 52 drowning and 59 nondrowning cases. The maxillary sinus fluid volume was measured using a computed tomography (CT) scan, and pleural effusion volume and lung weight were manually measured at autopsy. The utility of these three indices for diagnosing drowning and its postmortem changes was evaluated. RESULTS: The maxillary sinus fluid volume was significantly higher in drowning cases than in other external causes and cardiovascular death cases. Receiver operating characteristic curve analysis revealed that a total maxillary sinus fluid volume >1.04 mL more usefully indicated drowning (odds ratio, 8.19) than a total pleural effusion volume >175 mL (odds ratio, 7.23) and a total lung weight >829 g (odds ratio, 2.29). The combination of maxillary sinus fluid volume and pleural effusion volume more effectively predicted drowning than one index alone. Moreover, the maxillary sinus fluid volume was less influenced by the postmortem interval than the other two indices up to a week after death. CONCLUSION: Maxillary sinus fluid volume can be more useful than pleural effusion volume and lung weight with higher sensitivity and odds ratio for diagnosing drowning. IMPLICATIONS FOR PRACTICE: Fluid accumulation in both the maxillary sinuses strongly predicts drowning in the postmortem imaging.

Supramolecular structure of the Salmonella typhimurium type III protein secretion system.

The type III secretion system of Salmonella typhimurium directs the translocation of proteins into host cells. Evolutionarily related to the flagellar assembly machinery, this system is also present in other pathogenic bacteria, but its organization is unknown. Electron microscopy revealed supramolecular structures spanning the inner and outer membranes of flagellated and nonflagellated strains; such structures were not detected in strains carrying null mutations in components of the type III apparatus. Isolated structures were found to contain at least three proteins of this secretion system. Thus, the type III apparatus of S. typhimurium, and presumably other bacteria, exists as a supramolecular structure in the bacterial envelope.

MRI evaluation of body composition changes in wrestlers undergoing rapid weight loss.

PURPOSE: Changes in body composition of college wrestlers undergoing rapid weight reduction were evaluated over time using magnetic resonance imaging (MRI). METHODS: This study evaluated 12 wrestlers (male, 18-22 years of age) who participated in Japan's 2005 intercollegiate wrestling tournament. For this study, MRI (of the right femoral region and the trunk), as well as measurements of body weight, body fat percentage and body water content, were performed 1 month and 1 week prior to the weigh-in, on the day of the weigh-in, on the day of the match (after the match), and 1 week after the weigh-in. A survey of food and fluid intake was also conducted. RESULTS: Several variables were significantly lower on the day of the weigh-in than one month prior: body weight (p<0.01, -7.3% (SD 1.6%)); body fat (p<0.05, -9.3 (5.8)%); body water content (p<0.01, -5.9 (1.6)%); trunk cross-section (p<0.01, -13.2 (4.4)%), including separate measurements of trunk viscera, trunk muscle, and trunk fat; quadriceps muscle; lower subcutaneous; and food intake (p<0.01, 122 (20)). At 1 week after the match, all metrics had recovered to their levels measured 1 month before the weigh-in. Certain variables that were highly sensitive to hydration recovered more rapidly: they had reached their initial levels when measured immediately after the match. CONCLUSION: Rapid weight reduction reduced the wrestlers' cross-sectional areas of muscle and fat tissues, which tended to recover through rehydration after the weigh-in. These results suggest that rapid weight reduction of wrestlers induced changes in different regions of the body.

Increase in prostaglandin E(2) production by interleukin-1beta in arterial smooth muscle cells derived from patients with moyamoya disease.

Moyamoya disease is a progressive cerebrovascular occlusive disease that primarily affects children. The cause is unknown. We examined the production of prostanoids and the expression of cyclooxygenase-2 (COX-2) in cultured arterial smooth muscle cells (SMCs) derived from patients with moyamoya disease. Twelve moyamoya and 8 control cell strains were examined. The steady-state levels of prostanoids in the culture medium did not differ between moyamoya and control SMCs. When the cells were stimulated with interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)) release into the medium was significantly greater from moyamoya SMCs than from control SMCs, whereas the amounts of prostacyclin and thromboxane B(2) did not differ. IL-1beta-induced PGE(2) production by moyamoya SMCs was completely blocked by the addition of indomethacin or NS-398. IL-1beta significantly stimulated cell migration and DNA synthesis in control SMCs but had an inhibitory effect on moyamoya SMCs. The inhibitory effects on the growth and migration of moyamoya SMCs were caused by excessive secretion of PGE(2) and was reversed with indomethacin treatment. Immunofluorescence studies and Western blot analysis showed greater amounts of COX-2 protein expression in IL-1beta-stimulated moyamoya SMCs. These findings suggest that moyamoya SMCs respond to inflammatory stimuli to produce excess amounts of PGE(2) through the activation of COX-2, which increases vascular permeability and decreases vascular tone. This facilitates the exposure of vessels to blood constituents and promotes the development of intimal thickening in moyamoya disease.

Dose-response studies on the carcinogenicity of potassium bromate in F344 rats after long-term oral administration.

Dose-response studies on the carcinogenicity of potassium bromate (KBrO3), a food additive, were undertaken to examine its effects at low doses. A total of 148 6-week-old male inbred F344 rats were divided into 7 groups. They were given KBrO3 orally in their drinking water at doses of 500, 250, 125, 60, 30, 15, and 0 ppm for 104 weeks, at the end of which time all the surviving animals were autopsied and then examined histopathologically. Shortening of the survival times and marked inhibition of body weight increase were observed in a group given 500 ppm KBrO3. The combined incidences of renal adenocarcinomas and adenomas were significantly increased in rats treated with KBrO3 at doses of 500, 250, and 125 ppm in a dose-related manner. The dose-response curve showed a sigmoid appearance. The value for the virtually safe dose (VSD), calculated by the probit model, was 0.950 ppm KBrO3 at a risk level of 10(-6). However, significant increases in the occurrence of dysplastic foci of the kidney were found in groups at doses higher than 30 ppm KBrO3. The VSD value for the dysplastic foci estimated by the gamma-multi-hit model was 0.148 X 10(-3) ppm KBrO3 at a risk level of 10(-6). In a group tested with 500 ppm KBrO3, the combined incidences for follicular adenocarcinomas and adenomas of the thyroid and for mesotheliomas of the peritoneum were shown to be significantly increased.

A comment on the evaluation of equilibrium constants for alpha-tocopherol interactions with fatty acids by absorbance in the ultraviolet region.

This paper comments on the evaluation of Erin and co-workers (Biochim. Biophys. Acta 774 (1984) 96-102) of equilibrium constants for alpha-tocopherol interactions with fatty acids on the basis of the changes of absorbance in a 200 nm ultraviolet region. It is concluded that the ultraviolet method is inadequate because it is affected by absorption in that region of the solvent, ethanol and fatty acids which they used.

3,4-dihydroxystyrene, a novel microbial inhibitor for phenylalanine hydroxylase and other pteridine-dependent monooxygenases.

A new microbial inhibitor for rat-liver phenylalanine hydroxylase (L-phenylalanine, tetrahydropteridine: oxygen oxidoreductase (4-hydroxylating), EC 1.14.16.1) was isolated from a culture medium of Fomes tasmanicus, and its structure was determined as 3,4-dihydroxystyrene. This compound inhibited the enzyme by 50% at a concentration of 5 X 10(-6) M and 5 X 10(-7) M, respectively, without or with preincubation at 25 degrees C for 15 min. Without preincubation, dihydroxystyrene inhibited phenylalanine hydroxylase noncompetitively with phenylalanine and a pteridine cofactor, 6,7-dimethyltetrahydropterin, and uncompetitively with oxygen. A change in kinetic properties of the inhibition was observed when the enzyme was preincubated with dihydroxystyrene; the degree of inhibition was increased, and the purely noncompetitive-type inhibition with phenylalanine changed to a mixed-type inhibition. A study concerning the structure-inhibitory activity relationship using several compounds similar to dihydroxystyrene, indicated that the catechol structure is essential and that the structure of the aliphatic side-chain affects the inhibitory potency. A similar degree of inhibition was observed using 6,7-dimethyl- or 6-methyltetrahydropterin or tetrahydrobiopterin as a cofactor. Dihydroxystyrene also inhibited other pteridine-dependent monooxygenases, tyrosine hydroxylase (EC 1.14.16.2) and tryptophan hydroxylase (EC 1.14.16.4), indicating that dihydroxystyrene is a general inhibitor for pteridine-dependent monooxygenases.

Full-mouth scaling and root planing combined with azithromycin to treat peri-implantitis.

BACKGROUND: Full-mouth scaling and root planing combined with azithromycin is clinically and bacteriologically effective for the treatment of chronic periodontitis. This study aimed to investigate the clinical and bacteriological effects of this combination treatment in patients with peri-implantitis. METHODS: Twenty adult patients with both chronic periodontitis and peri-implantitis were randomly divided into two groups (10: test, 10: control). All patients underwent full-mouth scaling and root planing but the test group received azithromycin for 3 days before the procedure. The probing depth, bleeding on probing, and the gingival index were assessed clinically. Bacterial samples were obtained before treatment at 1 week and 1, 3, 6, 9 and 12 months after treatment. Quantitative and qualitative analyses were performed using the polymerase chain reaction Invader method. RESULTS: All clinical parameters showed better improvement in both periodontitis and peri-implantitis in the test group. Periodontal bacteria were more effectively reduced in the test group, but gradually increased around implants 6 months after treatment and natural teeth 9 months after treatment. CONCLUSIONS: Full-mouth scaling and root planing combined with azithromycin was temporarily useful for the treatment of peri-implantitis. Clinical improvements were maintained for about 9 months but periodontal bacteria increased again 6 months after treatment.

Effect of glucose on somatostatin secretion from isolated pancreatic islets of normal and streptozotocin-diabetic rats.

Pancreatic somatostatin (SRIF) secretion was examined using the RIA described in earlier paper. Ten isolated rat pancreatic islets were incubated for 30 min in 1 ml Krebs-Ringer bicarbonate buffer. Glucose (5.6 mM) caused a small but significant increase of SRIF secretion. The maximal secretion rate was observed at 16.7 mM glucose, and the half-maximal rate was seen at about 9.7 mM. Islets preincubated with 16.7 mM glucose released higher levels of SRIF and insulin during the subsequent incubation with 16.7 mM glucose than did islets preincubated with 2.8 mM glucose. Glucose-induced SRIF secretion was suppressed by epinephrine, but beta-adrenergic stimulation (epinephrine and phentolamine) produced an increase in SRIF secretion. Islets taken from rats 2 days after streptozotocin administration released minimal amounts of insulin. Basal and glucose-induced SRIF secretion from these islets, which had relatively unchanged SRIF contents and D cell numbers, equaled SRIF secretion from control rat islets. Islets taken from rats 6 weeks after streptozotocin administration, however, had increased SRIF content and D cell numbers, and they oversecreted SRIF. We conclude that pancreatic SRIF secretion can be induced by glucose and modulated by catecholamines and preexposure to high glucose, and the duration and severity of diabetes may be an important determinant of the changes in pancreatic D cell structure and function.

Effect of calcium on the secretion of somatostatin and insulin from pancreatic islets.

Calcium ionophore A23187 (20 micrometer) evoked the secretion of somatostatin (SRIF) as well as insulin from isolated rat pancreatic islets in a medium containing a relatively low concentration of calcium (0.9 mM) and a low concentration of glucose (5.5 mM). A high level of extracellular calcium (7.5 mM) also had a stimulatory effect on SRIF and insulin release. On the other hand, in the presence of high glucose (16.7 mM), A23187 had different effects on D and B cells; insulin release was markedly suppressed by A23187, but SRIF secretion was significantly enhanced. A high concentration of glucose (16.7 mM) did not stimulate SRIF secretion at low extracellular calcium concentration (0.25 mM), at which level insulin release is significantly enhanced. These findings indicate that calcium may play an important role in the regulation of the secretion of SRIF as well as insulin and suggest that the B and D cells differ in their sensitivity to the calcium ion.

Changes in pancreatic somatostatin content in spontaneously diabetic mice, as determined by radioimmunoassay and immunohistochemical methods.

A specific RIA for somatostatin (SRIF) was used to determine the SRIF content of the pancreas and hypothalamus in spontaneously diabetic C57BL/KsJ dbdb and C57BL/6J obob mice. In addition, SRIF- and glucagon-containing cells were examined in the pancreatic islets with an immunohistochemical technique. In dbdb mice, immunoassayable pancreatic SRIF content was increased, as was the number of SRIF- or glucagon-containing cells. In obob mice, immunoassayable pancreatic SRIF content was also increased, but no increase was noted in the number of SRIF- or glucagon-containing cells. The hypothalamic SRIF content of either strain was not different from that of controls. These results regarding pancreatic SRIF content were in accord with some but not all previous reports. These differences may be related to the age of the mice or to the conditions in which they were bred. The pancreatic SRIF increase in both dbdb and obob mice may be attributable to hyperglucagonemia, hyperglycemia, or a decrease in insulin action. Further work is necessary to clearly delineate the mechanism.

High-resolution turbo magnetic resonance angiography for diagnosis of Moyamoya disease.

BACKGROUND AND PURPOSE: High-resolution turbo MR angiography with zero-filling interpolation (ZFI) technique is a new vascular imaging method with reduced scan time. The purpose of the present study was to evaluate high-resolution turbo MR angiography for the diagnosis and assessment of moyamoya disease. METHODS: Forty-six patients suspected of having moyamoya disease were examined with high-resolution turbo MR angiography with the ZFI technique, MRI, and conventional angiography. Moyamoya disease was diagnosed in 42 of these patients. Blind, separate interpretation of the images was performed. RESULTS: High-resolution turbo MR angiography and MRI accurately evaluated 349 (95%) and 325 (88%) of 368 arteries, respectively, but the degree of stenosis was overestimated in the other arteries. MR angiography and MRI depicted basal cerebral moyamoya vessels in 82 (98%) and 82 (98%) of 84 hemispheres, respectively. MR angiography also depicted leptomeningeal and transdural collateral vessels in 51 (100%) of 51 hemispheres and in 38 (88%) of 43 hemispheres, respectively. The sensitivity and specificity of high-resolution turbo MR angiography for the diagnosis of moyamoya disease were 98% and 100%, respectively. CONCLUSIONS: High-resolution turbo MR angiography in reduced scan time is highly accurate in the assessment of both steno-occlusive lesions and collateral vessels in moyamoya disease, thus providing a highly accurate (98%) diagnosis and assessment of moyamoya disease.

Urinary excretion of renin and its biochemical properties in dogs.

The amount and biochemical properties of renin excreted by anesthetized dogs were investigated to elucidate the significance of urinary excretion in the metabolism of renin. Mean arterial blood pressure was 127 +/- 4 mm Hg, renal blood flow was 170 +/- 8 ml/min, glomerular filtration rate, 38.6 +/- 2.3 ml/min, and urine flow rate, 0.37 +/- 0.09 ml/min (n = 11). Urinary renin concentration (URC) was 9.2 +/- 2.1 ng angiotensin I (ANG I)/ml X hr (n = 11), as determined by radioimmunoassay for ANG I generated by incubation with semipurified homologous renin substrate. The ANG I-producing activity was inhibited by more than 90% by a specific antibody to dog kidney renin. The renin secretion rate from the left kidney into the renal vein was 76.4 +/- 13.3 ng ANG I/ml X hr per min (n = 11), and the simultaneous urinary excretion rate of renin was 2.3 +/- 0.4 ng ANG I/ml X hr per min (n = 11). Molecular weight of the urinary renin was 40,000 daltons. The pH dependent curves of the angiotensin-forming capacity of renin showed an optimum between pH 5.5 to 6.0, and the estimated Michaelis constant was 0.42 microM. These biochemical parameters were similar to the findings in the case of renin in the plasma and the kidney. Moreover, neither acid nor trypsin treatment altered the renin activity in the urine. Thus, the active form of renin with a molecular weight 40,000 was excreted into the urine in dogs. Urinary excretion of renin was a small percentage of the renin secretion rate, thereby indicating the minor role of urinary excretion in the metabolism of renin.

Aspirin lowers blood pressure in patients with renovascular hypertension.

To clarify the role of renal prostanoid in hyperreninemia and high blood pressure in human renovascular hypertension, we measured prostaglandin E2 and renin activity in renal venous and abdominal aortic plasma before and after the intravenous administration of the cyclooxygenase inhibitor, aspirin DL-lysine. Subjects were six patients with unilateral renovascular hypertension and six with essential hypertension. In patients with renovascular hypertension, prostaglandin E2 concentration in renal venous plasma from the stenotic kidney was 9.25 +/- 1.48 pg/ml, which was significantly higher (p less than 0.01) than the concentration in the renal venous plasma from the normal kidney (4.97 +/- 1.02 pg/ml) or in the aortic plasma (2.59 +/- 0.15 pg/ml). Plasma renin activity was also higher in the renal vein of the stenotic kidney than in the other two sites. The stenotic side/normal side ratio of the renal venous prostaglandin E2 correlated significantly with a renin ratio greater than 1.5 (r = 0.8211, p less than 0.05). Intravenous injection of aspirin DL-lysine (18 mg/kg) 30 minutes later markedly suppressed prostaglandin E2 and renin levels at all sites and clearly lowered arterial blood pressure (mean: from 120 +/- 6 to 110 +/- 5 mm Hg, p less than 0.01). The reduction in blood pressure correlated significantly with the suppression of plasma renin activity in the aorta (p less than 0.05) and in the renal vein of the stenotic kidney (p less than 0.01). Conversely, in patients with essential hypertension, aspirin had little effect on renin levels and increased mean blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Xe-CT in cerebrovascular disease and moyamoya disease.

(1) Negative response to acetazolamide challenge test using Xe-CT is a reliable indicator for identifying the hemodynamic compromise. (2) The hemodynamic compromise may be a cause of TIAs in some patients with chronic cerebrovascular occlusive diseases. (3) The brain suffering from hemodynamic compromise actively works to induce collateral blood channels.