Elevated Brain-Derived Neurotrophic Factor Levels During Depressive Mixed States.

OBJECTIVE: Neurotrophin-like brain-derived neurotrophic factor (BDNF) and pro-inflammatory cytokines may modulate the pathophysiology of mood disorders. Although several studies show alterations in these biomarkers during the depressive, manic, and euthymic states of mood disorders, evidence is lacking for those in a mixed state. Therefore, this study aimed to investigate the relationship between the depressive mixed state (DMX) and peripheral neurobiological factors. METHODS: We enrolled 136 patients with major depressive episodes. Depressive symptoms were assessed using the Quick Inventory of Depressive Symptomatology Self-Report Japanese version (QIDS-SR-J). The severity of DMX was assessed using the self-administered 12-item questionnaire (DMX-12). Categorical screening as DMX-positive (n=54) was determined by a cutoff score of 13 or more in the specific eight symptoms from the DMX-12; the remaining were DMX-negative (n=82). Serum BDNF, tumor necrosis factor-α, highsensitivity C-reactive protein, and interleukin-6 levels were measured. RESULTS: When comparing biomarkers between the DMX-positive and DMX-negative groups, higher serum BDNF concentration in the DMX-positive group than in the DMX-negative group was the only significant finding (p=0.009). A positive correlation existed between the total score of the eight specific symptoms of DMX-12 and the BDNF concentration (r=0.190, p=0.027). After adjustment for confounders, logistic regression analysis revealed that BDNF (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.00-1.14, p=0.045), bipolar diagnosis (OR=3.43, 95% CI=1.36-8.66, p=0.009), and total QIDS-SR-J score (OR=1.29, 95% CI=1.15-1.43, p<0.001) were significantly associated with DMX positivity. CONCLUSION: BDNF was positively associated with DMX severity, suggesting that higher BDNF concentrations may be involved in the pathophysiology of DMX.

Are Online Simulations for Radiation Emergency Medical Preparedness Less Effective in Teaching Than Face-to-Face Simulations?

OBJECTIVE: The study clarified differences in understanding and satisfaction between face-to-face and online training on radiation emergency medical preparedness (REMP) training. METHODS: The training was held at Hirosaki University between 2018 and 2022, with 46 face-to-face participants and 25 online participants. RESULTS: Face-to-face training was significantly more understandable than online for the use of the Geiger counter (P < 0.05), but the educational effect of virtual reality (VR) was not significantly different from the actual practice. For the team exercise of taking care of the victims, online resulted in a significantly higher understanding (P < 0.05). CONCLUSIONS: Interactive exercises can be done online with equipment sent to learners, and VR is also as effective. The use of videos was more effective for first-timers to learn the practical process from a bird's-eye view, especially for team-based medical procedures.

The association of circulating endocannabinoids with cancer cachexia: A cross-sectional study.

BACKGROUND & AIMS: Endocannabinoids (eCBs) are involved in various physiological functions such as appetite, metabolism, and inflammation. Although deterioration of these functions is often observed in patients with refractory cancer cachexia (RCC), the relationship between circulating eCBs and cancer cachexia remains unknown. This study aimed to evaluate the relationship between circulating levels of eCBs and clinical findings in patients with RCC. METHODS: Circulating N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) levels were measured in 39 patients with RCC (36% females, median age and IQR: 79 and 69-85), and 18 age- and sex-matched controls who received medical therapy for non-communicable diseases, using liquid chromatography with tandem mass spectrometry. In the RCC group, relationships between eCB levels and clinical findings-such as anorexia, awareness of pain, performance status, and survival period-were also examined. As anti-inflammatory drugs can influence the action and metabolism of eCBs, the following two analyses were conducted. In analysis 1, all participants were included, and in analysis 2, participants receiving any anti-inflammatory drugs were excluded. RESULTS: Serum AEA and 2-AG levels were more than twice as high in the RCC group than in those in the control group in both analyses. In analysis 1, only 8% of patients reported normal appetite assessed using the numerical rating scale (NRS), and serum AEA levels were negatively correlated with the NRS scores (R = -0.498, p = 0.001). Serum 2-AG levels were positively correlated with serum triglyceride levels (R = 0.419, p = 0.008). Both AEA and 2-AG levels were positively correlated with serum C-reactive protein (CRP) levels (AEA: R = 0.516, p < 0.001; 2-AG: R = 0.483, p = 0.002). Multiple linear regression analysis in the form of a stepwise procedure was performed; NRS scores and CRP levels showed a significant association with AEA levels (NRS: p = 0.001; CRP: p < 0.001), with an adjusted R2 value of 0.426. Similarly, triglyceride and CRP levels showed a significant association with the log of 2-AG levels (triglycerides: p < 0.001; CRP: p < 0.001), with an adjusted R2 value of 0.442. In analysis 2, serum AEA levels were negatively correlated with the NRS scores (R = -0.757, p < 0.001), whereas serum triglyceride levels were positively correlated with 2-AG levels (R = 0.623, p = 0.010). CONCLUSIONS: Circulating eCB levels were significantly higher in patients with RCC than those in controls. In patients with RCC, circulating AEA may play a role in anorexia, whereas 2-AG may play a role in serum triglyceride levels.

Compensatory Kinetics During the Side-Hop Test in Individuals With Chronic Ankle Instability.

CONTEXT: Individuals with chronic ankle instability (CAI) exhibit altered movement strategies during side-cutting tasks. However, no researchers have assessed how altered movement strategies affect cutting performance. OBJECTIVE: To investigate compensatory strategies in the side-hop test (SHT), with a focus on the entire lower extremity, among individuals with CAI. DESIGN: Cross-sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 40 male soccer players comprising a CAI group (n = 20; age = 20.35 ± 1.15 years, height = 173.95 ± 6.07 cm, mass = 68.09 ± 6.73 kg) and a control group (n = 20; age = 20.45 ± 1.50 years, height = 172.39 ± 4.39 cm, mass = 67.16 ± 4.87 kg). INTERVENTION(S): Participants performed 3 successful SHT trials. MAIN OUTCOME MEASURE(S): We calculated SHT time, torque, and torque power in the ankle, knee, and hip joints during the SHT using motion-capture cameras and force plates. Confidence intervals for each group that did not overlap by >3 points consecutively in the time series data indicated a difference between groups. RESULTS: Compared with the control group, the CAI group showed (1) no delayed SHT time; (2) lower ankle-inversion torque (range = 0.11-0.13 N·m/kg) and higher hip-extension (range = 0.18-0.72 N·m/kg) and -abduction torque (0.26 N·m/kg); (3) less concentric power in ankle dorsiflexion-plantar flexion (0.18 W/kg) and inversion-eversion (0.40 W/kg), more concentric power in hip flexion-extension (0.73 W/kg), and more eccentric power in knee varus-valgus (0.27 W/kg). CONCLUSIONS: Individuals with CAI were likely to rely on hip-joint function to compensate for ankle instability and demonstrated no differences in SHT time compared with the control group. Therefore, the movement strategies of individuals with CAI could differ from those of individuals without CAI, even if SHT time is not different.

Possible Involvement of the Upregulation of ΔNp63 Expression Mediated by HER2-Activated Aryl Hydrocarbon Receptor in Mammosphere Maintenance.

Cancer stem cells (CSCs) contribute to the drug resistance, recurrence, and metastasis of breast cancers. Recently, we demonstrated that HER2 overexpression increases mammosphere formation via the activation of aryl hydrocarbon receptor (AHR). In this study, the objective was to identify the mechanism underlying mammosphere maintenance mediated by HER2 signaling-activated AHR. We compared the chromatin structure of AHR-knockout (AHRKO) HER2-overexpressing MCF-7 (HER2-5) cells with that of wild-type HER2-5 cells; subsequently, we identified TP63, a stemness factor, as a potential target gene of AHR. ΔNp63 mRNA and protein levels were higher in HER2-5 cells than in HER2-5/AHRKO cells. Activation of HER2/HER3 signaling by heregulin treatment increased ΔNp63 mRNA levels, and its induction was decreased by AHR knockdown in HER2-5 cells. The results of the chromatin immunoprecipitation assay revealed an interaction between AHR and the intronic region of TP63, which encodes ΔNp63. A luciferase reporter gene assay with the intronic region of TP63 showed that AHR expression increased reporter activity. Collectively, our findings suggest that HER2-activated AHR upregulates ΔNp63 expression and that this signaling cascade is involved in CSC maintenance in HER2-expressing breast cancers.

Metal Sensing by a Glycine-Histidine Repeat Sequence Regulates the Heme Degradation Activity of PM0042 from Pasteurella multocida.

PM0042 protein from the Gram-negative bacterial pathogen Pasteurella multocida is homologous to the heme-degrading enzyme HutZ belonging to the pyridoxine-5-phosphate oxidase-like family. A characteristic feature of PM0042 is possession of a glycine-histidine (GH) repeat sequence at the C-terminal region. In this study, we examined the heme degradation ability of PM0042, with a particular focus on the role of the GH repeat sequence. PM0042 was expressed in Escherichia coli and successfully purified using a nickel (Ni2+)-affinity column without a histidine tag, suggesting that its GH motif facilitates binding to Ni2+. Reaction with ascorbic acid induced a significant decrease in the Soret band, suggesting the breakage of heme. While a Fe2+-ferrozine complex was not formed upon addition of ferrozine to the solution after the reaction, prior addition of metal ions to fill the metal binding site in the GH repeat sequence led to increased complex formation. In the presence of Fe2+, the heme degradation rate was accelerated ∼threefold, supporting the theory that Fe2+ binds the PM0042 protein (possibly at the GH repeat sequence) and enhances its heme degradation activity. In contrast to HutZ from Vibrio cholerae in which enzymatic activity is regulated by the protonation status of the heme proximal ligand, heme reduction is not the rate-determining step for PM0042. Rather, proton transfer to reduced oxyheme is affected, as established with the H2O/D2O isotope experiment. Based on the collective findings, the GH repeat sequence of PM0042 is proposed to function as a metal sensor that modulates iron uptake via the heme-degrading process in P. multocida.

Clinical Characteristics Associated with the Development of Diabetic Ketoacidosis in Patients with Type 2 Diabetes.

Objective This study analyzed the clinical and laboratory parameters that might influence the clinical outcomes of patients with type 2 diabetes who develop diabetic ketoacidosis (DKA), which has not been well investigated. Methods We reviewed the clinical and laboratory data of 158 patients who were hospitalized due to DKA between January 2006 and June 2019 and compared the data of patients stratified by the type of diabetes. In addition, the patients with type 2 diabetes were subdivided according to age, and their clinical and laboratory findings were evaluated. Results Patients with type 2 diabetes had a longer symptom duration associated with DKA, higher body mass index (BMI), and higher C-peptide levels than those with type 1 diabetes (p<0.05). Among patients with type 2 diabetes, elderly patients (≥65 years old) had a longer duration of diabetes, higher frequency of DKA onset under diabetes treatment, higher effective osmolarity, lower BMI, and lower urinary C-peptide levels than nonelderly patients (<65 years old) (p<0.05). A correlation analysis showed that age was significantly negatively correlated with the index of insulin secretory capacity. Conclusion Patients with DKA and type 2 diabetes had a higher BMI and insulin secretion capacity than those with type 1 diabetes. However, elderly patients with type 2 diabetes, unlike younger patients, were characterized by a lean body, impaired insulin secretion, and more frequent DKA development while undergoing treatment for diabetes.

Training of Medical Responders to Nuclear Disaster: Hybrid Program in the COVID-19 Pandemic.

OBJECTIVE: The spread of COVID-19 has made it difficult to provide training in medical treatment in a radiation disaster. In this study, we will examine the effects and challenges of using a hybrid approach that combines online and face-to-face components. METHODS: A total of 5 face-to face and 25 online medical staff participated in the training program. This program was conducted by using multiple cameras for live coverage, while protective clothing and decontamination kits had been sent in advance to the participants so that they could experience face-to-face and online learning at the same time. RESULTS: Participants reported a high level of satisfaction and achievement with the style of delivery. They also experienced problems such as fatigue due to long hours, and dissatisfaction with the debriefing. CONCLUSIONS: In designing new online training, it is necessary to consider the quantity and content of the program, and to take participant fatigue into consideration.

Sprinting kinematics and inter-limb coordination patterns at varying slope inclinations.

Uphill training is applied to induce specific overload on the musculoskeletal system to improve sprinting mechanics. This study aimed to identify unique kinematic features of uphill sprinting at different slopes and to suggest practical implications based on comparisons we early stance phase. At take-off, steeper slopes induced significantly more extended joint angles and higher ROMs during the late stance phase. Compared with moderate slopes, more anti-phase coordination patterns were detected at steeper slopes. Thus, uphill sprinting at steeper slopes shares essential kinematic features with the early acceleration phase of level sprinting. Moderate inclinations induce biomechanical adaptations similar to those in the late acceleration phase of level sprinting. Hence, the specific transfer of uphill sprinting to acceleration depends on the slope inclinations.

Single-Round DNA Aptamer Selection by Combined Use of Capillary Electrophoresis and Next Generation Sequencing: An Aptaomics Approach for Identifying Unique Functional Protein-Binding DNA Aptamers.

In DNA aptamer selection, existing methods do not discriminate aptamer sequences based on their binding affinity and function and the reproducibility of the selection is often poor, even for the selection of well-known aptamers like those that bind the commonly used model protein thrombin. In the present study, a novel single-round selection method (SR-CE selection) was developed by combining capillary electrophoresis (CE) with next generation sequencing. Using SR-CE selection, a successful semi-quantitative and semi-comprehensive aptamer selection for thrombin was demonstrated with high reproducibility for the first time. Selection rules based on dissociation equilibria and kinetics were devised to obtain families of analogous sequences. Selected sequences of the same family were shown to bind thrombin with high affinity. Furthermore, data acquired from SR-CE selection was mined by creating sub-libraries that were categorized by the functionality of the aptamers (e. g., pre-organized aptamers versus structure-induced aptamers). Using this approach, a novel fluorescent molecular recognition sensor for thrombin with nanomolar detection limits was discovered. Thus, in this proof-of-concept report, we have demonstrated the potential of a "DNA Aptaomics" approach to systematically design functional aptamers as well as to obtain high affinity aptamers.

Lower insulin secretion is associated with hippocampal and parahippocampal gyrus atrophy in elderly patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: We aimed to examine the association between diabetes-related parameters and hippocampal and parahippocampal gyrus atrophy (HPGA) in patients with type 2 diabetes mellitus to elucidate the risk factors for HPGA, which is often accompanied by Alzheimer's disease. MATERIALS AND METHODS: A total of 137 patients aged ≥50 years with type 2 diabetes mellitus (mean age 67.8 ± 9.8 years) underwent brain magnetic resonance imaging scans and comprehensive health examinations. We measured the volume of interest - a portion of the inner temporal lobe that includes the hippocampus, amygdala and entorhinal cortex (frontal part of the parahippocampal gyrus) - using the voxel-based specific regional analysis system for Alzheimer's disease in each patient. The diabetes-related parameters included glycated hemoglobin, fasting plasma glucose, C-peptide (CPR) index (serum CPR / fasting plasma glucose × 100) and duration of diabetes. RESULTS: The mean glycated hemoglobin was 9.3 ± 2.2%, the median CPR index was 1.29 (interquartile range 0.85-1.74) and the median duration of diabetes was 10 years (interquartile range 3-20 years). The severity score of volume of interest atrophy was >1.0 in 36 patients. Using multivariate logistic regression analysis, we found that age (odds ratio 1.09, 95% confidence interval 1.02-1.15) and CPR index (odds ratio 0.451, 95% confidence interval 0.216-0.940) were significantly associated with HPGA. CONCLUSIONS: Lower insulin secretion was significantly associated with HPGA in patients with type 2 diabetes mellitus. The results of this study support the hypothesis that insulin-signaling abnormalities are involved in the pathophysiology of Alzheimer's disease.

Role of conserved arginine in the heme distal site of HutZ from Vibrio cholerae in the heme degradation reaction.

HutZ from Vibrio cholerae is a dimeric enzyme that catalyzes degradation of heme. The highly conserved Arg92 residue in the HutZ family is proposed to interact with an iron-bound water molecule in the distal heme pocket. To clarify the specific role of Arg92 in the heme degradation reaction, the residue was substituted with alanine, leucine, histidine or lysine to modulate electrostatic interactions with iron-bound ligand. All four Arg92 mutants reacted with hydrogen peroxide to form verdoheme, a prominent intermediate in the heme degradation process. However, when ascorbic acid was used as an electron source, iron was not released even at pH 6.0 despite a decrease in the Soret band, indicating that non-enzymatic heme degradation occurred. Comparison of the rates of heme reduction, ligand binding and verdoheme formation suggested that proton transfer to the reduced oxyferrous heme, a potential rate-limiting step of heme degradation in HutZ, is hampered by mutation. In our previous study, we found that the increase in the distance between heme and Trp109 from 16 to 18 Šupon lowering the pH from 8.0 to 6.0 leads to activation of ascorbic acid-assisted heme degradation by HutZ. The distance in Arg92 mutants was >19 Å at pH 6.0, suggesting that subunit-subunit interactions at this pH are not suitable for heme degradation, similar to Asp132 and His63 mutants. These results suggest that interactions of Arg92 with heme-bound ligand induce alterations in the distance between subunits, which plays a key role in controlling the heme degradation activity of HutZ.

Subunit-subunit interactions play a key role in the heme-degradation reaction of HutZ from Vibrio cholerae.

HutZ, a dimeric protein, from Vibrio cholerae is a protein that catalyzes the oxygen-dependent degradation of heme. Interestingly, the ascorbic acid-supported heme-degradation activity of HutZ depends on pH: less than 10% of heme is degraded by HutZ at pH 8.0, but nearly 90% of heme is degraded at pH 6.0. We examined here pH-dependent conformational changes in HutZ using fluorescence spectroscopy. Trp109 is estimated to be located approximately 21 Å from heme and is present in a different subunit containing a heme axial ligand. Thus, we postulated that the distance between heme and Trp109 reflects subunit-subunit orientational changes. On the basis of resonance energy transfer from Trp109 to heme, we estimated the distance between heme and Trp109 to be approximately 17 Å at pH 8.0, while the distance increased by less than 2 Å at pH 6.0. We presumed that such changes led to a decrease in electron donation from the proximal histidine, resulting in enhancement of the heme-degradation activity. To confirm this scenario, we mutated Ala31, located at the dimer interface, to valine to alter the distance through the subunit-subunit interaction. The distance between heme and Trp109 for the A31V mutant was elongated to 24-27 Å. Although resonance Raman spectra and reduction rate of heme suggested that this mutation resulted in diminished electron donation from the heme axial ligand, ascorbic acid-supported heme-degradation activity was not observed. Based on our findings, it can be proposed that the relative positioning of two protomers is important in determining the heme degradation rate by HutZ.

Clinical outcomes of 20 Japanese patients with insulinoma treated with diazoxide.

Diazoxide is recognized as an effective medical treatment for insulinoma. However, due to its adverse effects, such as fluid retention, it is sometimes difficult to employ diazoxide at an effective dose in clinical practice. This study aimed to clarify the clinical factors, which may affect efficacy and safety of the diazoxide treatment. We retrospectively evaluated the medical records of 20 patients with insulinoma including 4 malignant cases. The patients were divided into two groups according to the presence or absence of favorable outcomes or adverse effects, and the clinical features of both groups were compared. Diazoxide was effective and ineffective in each 9 patients, respectively. In other 2 cases, the efficacy could not be determined. In the effective group, all patients had benign insulinoma. Additionally, the tumor size determined by imaging test was tended to smaller than the ineffective group but not statistically significant when malignant cases were excluded (p = 0.065). Fluid retention was observed more frequently in females than in males (p = 0.025). Five patients displayed unacceptable thrombocytopenia within a few weeks after the administration of diazoxide. In these patients, the diazoxide dose was significantly higher than that in the other patients [400 mg/day (250-500 mg/day) vs. 225 mg/day (50-425 mg/day), p = 0.027]. These findings may be informative in determining the indication and dose of diazoxide against insulinoma. In addition, a careful evaluation of platelet count would be required for a few weeks after the initiation of diazoxide treatment.

Evaluation of swelling processes of various natural polymer matrix tablets by X-ray computed tomography and controlled drug release.

BACKGROUND: The swelling properties and the drug-release sustainability of pre-gelatinized starches (𝛼-starch) tablets depend on the polymer characteristics. OBJECTBS: In order to clarify the drug release form, the natural polymers (NPs) were investigated. The relationship between drug release and swelling of natural polymers (NPs), the swelling processes of various starch polymers, were investigated using a drug-release test (DRT) and X-ray computed tomography (XCT). NPs consisting of various starches such as glutinous rice starch (GRS), corn starch (CS), and tapioca starch (TS) were used as additives for sustained drug-release tablets. Tablets consisted of 5% theophylline, 94% 𝛼-starch, and 1% magnesium stearate and were compressed at 6 kN. DRTs were measured in distilled water at 37 °C, and the drug concentrations were measured using UV (271 nm). Swelling ratio (R) profiles of the tablets during DRTs were evaluated based on XCT images. RESULTS: The order of the drug-release rate constant of the tablets was TS < GRS < CS. XCT images of the tablets were measured during the DRTs, and CS, GRS, and TS tablets swelled and showed increased gel-layers, and then finally disintegrated at 6, 9, and 11 h, respectively. CONCLUSION: The relationship between R profile and the % drug release of the tablets differed depending on the kind of NP used.

Complex-amplitude single-pixel imaging.

A single-pixel camera can be represented using complex-amplitude. The complex-amplitude representation of input signals and output signals enables us to perform complex-amplitude imaging of an object, particularly profilometry with reflectance measurements or quantitative phase imaging with transmittance measurements. The complex-amplitude representation of optical coding masks and the coherent addition that is performed by interference can directly represent Hadamard patterns having positive and negative values. Furthermore, the residual area of the mask can be used for a reference beam with phase shifting. Such a complex-amplitude imaging system with a single-beam line structure is highly stabile against external disturbances.

Interleukin-1beta and insulin elicit different neuroendocrine responses to hypoglycemia.

Interleukin (IL)-1beta induces a prolonged hypoglycemia in mice that is not caused by a reduction in food intake and is dissociable from insulin effects. There is a peripheral component in the hypoglycemia that the cytokine induces resulting from an increased glucose uptake, an effect that can be exerted in a paracrine fashion at the site where IL-1 is locally produced. However, the maintenance of hypoglycemia is controlled at brain levels because the blockade of IL-1 receptors in the central nervous system inhibits this effect to a large extent. Furthermore, there is evidence that the cytokine interferes with counter regulation to hypoglycemia. Here we report that administration of IL-1 or long-lasting insulin results in different changes in food intake and in neuroendocrine mechanisms 8 h following induction of the same degree of hypoglycemia (40-45% decrease in glucose blood levels). Insulin, but not IL-1, caused an increase in food intake and an endocrine response that tends to reestablish euglycemia. Conversely, a decrease in noradrenergic and an increase in serotonergic activity in the hypothalamus occur in parallel with a reduction of glucose blood levels only in IL-1-treated mice, effects that can contribute to the maintenance of hypoglycemia. These results are compatible with the proposal that IL-1 acting in the brain can reset glucose homeostasis at a lower level. The biologic significance of this effect is discussed.

Role of substantia innominata in cerebral blood flow autoregulation.

Ascending projections from the substantia innominata (SI) may have an important role in the regulation of cerebral blood flow (CBF). However, several reports have suggested that unilateral lesion of the SI does not affect CBF autoregulation. On the other hand, it is also reported that several cortical and subcortical functions may be regulated not only by ipsilateral SI, but also by contralateral SI. Thus, the objective of this study is to test the hypothesis that bilateral lesions of the SI affect CBF autoregulation. Experiments were performed on anesthetized male Sprague-Dawley rats. Ibotenic acid or physiological saline was microinjected into bilateral SI. Rats were classified into four groups as follows: bilateral SI lesion rats (ibotenic acid was injected bilaterally), left or right SI lesion rats (ibotenic acid was injected into the unilateral SI and saline into the contralateral SI), and control rats (saline was injected bilaterally). Ten days after injection, CBF in the left frontal cortex was measured by laser-Doppler flowmetry during stepwise controlled hemorrhagic hypotension. In bilateral SI lesion rats, CBF was started to decrease significantly at 80 mm Hg (p<0.01). In the other three groups, CBF was well maintained until 50 mm Hg. Changes in CBF through stepwise hypotension in bilateral SI lesion rats were significantly different from the other groups (p<0.01). These results suggest that bilateral SI regulates cortical vasodilator mechanisms during hemorrhagic hypotension. Under unilateral SI lesion, some compensatory effects from the contralateral SI may maintain CBF autoregulation.