Detection of human drowsiness by the vestibulo-ocular reflex compensating for heartbeat-induced head perturbations.

The vestibulo-ocular reflex (VOR) stabilizes vision during head movements by counter-rotating the eyes in the orbits. Although considered one of the simplest reflexes due to its minimal neuronal circuity comprising a 3-neuron arc, previous studies have shown that VOR performance deteriorates in both monkeys and humans when they are drowsy. Given constant head perturbations under dynamic environments, the VOR has been proposed as a viable biomarker for detecting human drowsiness in automobiles and other moving vehicles. However, under stationary environments where exogenous head movements are absent, its applicability has been questioned. In this study, we demonstrate that each heartbeat generates small yet distinctive head movements, and the VOR compensates for these minor head perturbations. Furthermore, we show that the effectiveness of VOR responses varies with the degree of drowsiness, indicating that the VOR can serve as an indicator of drowsiness, even in stationary contexts such as in classrooms and offices.

Learning capabilities to resolve tilt-translation ambiguity in goldfish.

Introduction: Spatial orientation refers to the perception of relative location and self-motion in space. The accurate formation of spatial orientation is essential for animals to survive and interact safely with their environment. The formation of spatial orientation involves the integration of sensory inputs from the vestibular, visual, and proprioceptive systems. Vestibular organs function as specialized head motion sensors, providing information regarding angular velocity and linear acceleration via the semicircular canals and otoliths, respectively. However, because forces arising from the linear acceleration (translation) and inclination relative to the gravitational axis (tilt) are equivalent, they are indistinguishable by accelerometers, including otoliths. This is commonly referred to as the tilt - translation ambiguity, which can occasionally lead to the misinterpretation of translation as a tilt. The major theoretical frameworks addressing this issue have proposed that the interpretation of tilt versus translation may be contingent on an animal's previous experiences of motion. However, empirical confirmation of this hypothesis is lacking. Methods: In this study, we conducted a behavioral experiment using goldfish to investigate how an animal's motion experience influences its interpretation of tilt vs. translation. We examined a reflexive eye movement called the vestibulo-ocular reflex (VOR), which compensatory-rotates the eyes in response to head motion and is known to reflect an animal's three-dimensional head motion estimate. Results: We demonstrated that the VORs of naïve goldfish do not differentiate between translation and tilt at 0.5 Hz. However, following prolonged visual-translation training, which provided appropriate visual stimulation in conjunction with translational head motion, the VORs were capable of distinguishing between the two types of head motion within 3 h. These results were replicated using the Kalman filter model of spatial orientation, which incorporated the variable variance of process noise corresponding to the accumulated motion experience. Discussion: Based on these experimental and computational findings, we discuss the neural mechanism underlying the resolution of tilt-translation ambiguity within a context analogous to, yet distinct from, previous cross-axis VOR adaptations.

Artificial cerebellum on FPGA: realistic real-time cerebellar spiking neural network model capable of real-world adaptive motor control.

The cerebellum plays a central role in motor control and learning. Its neuronal network architecture, firing characteristics of component neurons, and learning rules at their synapses have been well understood in terms of anatomy and physiology. A realistic artificial cerebellum with mimetic network architecture and synaptic plasticity mechanisms may allow us to analyze cerebellar information processing in the real world by applying it to adaptive control of actual machines. Several artificial cerebellums have previously been constructed, but they require high-performance hardware to run in real-time for real-world machine control. Presently, we implemented an artificial cerebellum with the size of 104 spiking neuron models on a field-programmable gate array (FPGA) which is compact, lightweight, portable, and low-power-consumption. In the implementation three novel techniques are employed: (1) 16-bit fixed-point operation and randomized rounding, (2) fully connected spike information transmission, and (3) alternative memory that uses pseudo-random number generators. We demonstrate that the FPGA artificial cerebellum runs in real-time, and its component neuron models behave as those in the corresponding artificial cerebellum configured on a personal computer in Python. We applied the FPGA artificial cerebellum to the adaptive control of a machine in the real world and demonstrated that the artificial cerebellum is capable of adaptively reducing control error after sudden load changes. This is the first implementation and demonstration of a spiking artificial cerebellum on an FPGA applicable to real-world adaptive control. The FPGA artificial cerebellum may provide neuroscientific insights into cerebellar information processing in adaptive motor control and may be applied to various neuro-devices to augment and extend human motor control capabilities.

Human estimates of descending objects' motion are more accurate than those of ascending objects regardless of gravity information.

Humans can accurately estimate and track object motion, even if it accelerates. Research shows that humans exhibit superior estimation and tracking performance for descending (falling) than ascending (rising) objects. Previous studies presented ascending and descending targets along the gravitational and body axes in an upright posture. Thus, it is unclear whether humans rely on congruent information between the direction of the target motion and gravity or the direction of the target motion and longitudinal body axes. Two experiments were conducted to explore these possibilities. In Experiment 1, participants estimated the arrival time at a goal for both upward and downward motion of targets along the longitudinal body axis in the upright (both axes of target motion and gravity congruent) and supine (both axes incongruent) postures. In Experiment 2, smooth pursuit eye movements were assessed while tracking both targets in the same postures. Arrival time estimation and smooth pursuit eye movement performance were consistently more accurate for downward target motion than for upward motion, irrespective of posture. These findings suggest that the visual experience of seeing an object moving along an observer's leg side in everyday life may influence the ability to accurately estimate and track the descending object's motion.

The Effect of Japanese Herbal Medicines (Kampo) Goreisan and Saireito on the Prevention of Recurrent Chronic Subdural Hematoma: A Prospective Randomized Study.

BACKGROUND AND OBJECTIVES: Chronic subdural hematoma (CSDH) sometimes recurs after surgical treatment and requires reoperation. In Japan, Japanese herbal medicines (Kampo), such as Goreisan and Saireito, have been used as adjunctive therapies to prevent the recurrence of CSDH. However, no prospective randomized study has proven the efficacy of Kampo medicine in all patients. To investigate whether Goreisan and Saireito reduce the postoperative recurrence of CSDH in a prospective randomized study. METHODS: Between April 2017 and July 2019, a total of 118 patients who underwent initial burr hole surgery for CSDH were randomly assigned to the following 3 groups: (1) Goreisan for 3 months (Group G), (2) Saireito for 3 months (Group S), and (3) no medication (Group N). The primary end point was symptomatic recurrence within 3 months postoperatively, and the secondary end point was complications associated with the administration of Kampo medicine. RESULTS: Among 118 patients, 114 (Group N, n = 39; Group G, n = 37; and Group S, n = 38) were included in our analysis. In this study, byakujutsu (containing Atractylodes rhizome ) Goreisan and Saireito were used, unlike other prospective randomized studies in which sojutsu (containing Atractylodes lancea rhizome) Goreisan was used. The overall recurrence rate was 11.4% (13/114: 10 for Group N, 2 for Group G, and 1 for Group S). The recurrence rate of Group G was significantly lower than that of Group N (5.4% vs 25.6%; P = .043). The recurrence rate of Group S was also significantly lower than that of Group N (2.6% vs 25.6%; P = .02). No patients developed complications associated with the administration of Kampo medicine. CONCLUSION: This is the first study to show that Kampo medicine reduced the recurrence rate of CSDH in an overall population. This study demonstrated that byakujutsu Goreisan and Saireito may have favorable effects, unlike other studies, because byakujutsu has stronger anti-inflammatory activity than sojutsu.

Electrical stimulation mitigates muscle degradation shift in gene expressions during 12-h mechanical ventilation.

Ventilator-induced diaphragm dysfunction (VIDD), a dysfunction of the diaphragm muscle caused by prolonged mechanical ventilation (MV), is an important factor that hinders successful weaning from ventilation. We evaluated the effects of electrical stimulation of the diaphragm muscle (pulsed current with off-time intervals) on genetic changes during 12 h of MV (E-V12). Rats were divided into four groups: control, 12-h MV, sham operation, and E-V12 groups. Transcriptome analysis using an RNA microarray revealed that 12-h MV caused upregulation of genes promoting muscle atrophy and downregulation of genes facilitating muscle synthesis, suggesting that 12-h MV is a reasonable method for establishing a VIDD rat model. Of the genes upregulated by 12-h MV, 18 genes were not affected by the sham operation but were downregulated by E-V12. These included genes related to catabolic processes, inflammatory cytokines, and skeletal muscle homeostasis. Of the genes downregulated by 12-h MV, 6 genes were not affected by the sham operation but were upregulated by E-V12. These included genes related to oxygen transport and mitochondrial respiration. These results suggested that 12-h MV shifted gene expression in the diaphragm muscle toward muscle degradation and that electrical stimulation counteracted this shift by suppressing catabolic processes and increasing mitochondrial respiration.

Lenvatinib Mitigates Transarterial Embolization-Induced Polarization of Tumor-Associated Macrophages in a Rat Hepatocellular Carcinoma Model.

PURPOSE: To investigate the effect of transarterial embolization (TAE) on macrophage polarization and the modulatory effect of lenvatinib when used in combination with TAE in a rat hepatocellular carcinoma model. MATERIALS AND METHODS: A N1S1-bearing orthotopic rat model was subjected to TAE and administered 5 mg/kg of lenvatinib. CD8+, CD68+, and CD206+ cells were examined in 4 groups: sham (n = 5), lenvatinib (n = 5), TAE (n = 5), and combination of TAE and lenvatinib (n = 5). Transcriptome analysis was performed to assess gene expression related to macrophage polarization in the sham, TAE, and combination groups. An in vitro coculture experiment with bone marrow-derived macrophages was performed to identify lenvatinib target in macrophage polarization. RESULTS: There were no significant differences in the number of CD8+ and CD68+ cells among the 4 groups. Tumor-associated macrophage positivity for CD206 was significantly higher in the TAE group (58.1 ± 20.9) than in the sham (11.2 ± 14.3; P < .001) and combination (27.1 ± 19.7; P = .003) groups. In the transcriptome analysis, compared with the genes in the sham group, 5 macrophage polarization-related genes, including St6gal1, were upregulated by more than 1.5 fold in the TAE group and downregulated by more than 1.5 fold in the combination group. The coculture experiment showed that lenvatinib did not affect macrophages but affected N1S1 cells, leading to macrophage polarization. CONCLUSIONS: TAE-induced M2 macrophage polarization. Lenvatinib administration with TAE could reprogram macrophage polarization, improving tumor immune microenvironment.

Liver regeneration after portal vein embolization: comparison between absolute ethanol and N-butyl-cyanoacrylate in an in vivo rat model.

PURPOSE: To compare the effects of absolute ethanol (ethanol) and N-butyl-cyanoacrylate (NBCA) on non-embolized liver lobe regeneration in a rat model. METHODS: Twenty-seven Sprague-Dawley rats underwent portal vein embolization (PVE) using ethanol:lipiodol, 1:1 (ethanol group, n = 11, 40.74%), NBCA:lipiodol, 1:1 (NBCA group, n = 11, 40.74%), or sham treatment (sham group, n = 5, 18.52%). The non-embolized and embolized lobe-to-whole liver weight ratios 14 days after PVE were compared among the groups (n = 5, 18.52%). The expressions of CD68 and Ki-67 and embolized-lobe necrotic area percentages one day after PVE were compared between the ethanol (n = 3, 11.11%) and NBCA (n = 3, 11.11%) groups. RESULTS: The non-embolized lobe-to-whole liver weight ratio after PVE was significantly higher in the NBCA group (n = 5, 33.33%) than in the ethanol group (n = 5, 33.33%) (84.28% ± 1.53% vs. 76.88% ± 4.12%, P = 0.029). The embolized lobe-to-whole liver weight ratio after PVE was significantly lower in the NBCA group than in the ethanol group (15.72% ± 1.53% vs. 23.12% ± 4.12%, P = 0.029). The proportions of CD68- and Ki-67-positive cells in the non-embolized lobe after PVE were significantly higher in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [60 (48-79) vs. 55 (37-70), P = 0.003; 1 (0-2) vs. 1 (0-2), P = 0.004]. The embolized-lobe necrotic area percentage after PVE was significantly larger in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [29.46 (12.56-83.90%) vs. 16.34 (3.22-32.0%), P < 0.001]. CONCLUSION: PVE with NBCA induced a larger necrotic area in the embolized lobe and promoted greater non-embolized liver lobe regeneration compared with PVE with ethanol.

Emerging order of anomalous eye movements with progressive drowsiness.

It has been widely recognized that human alertness is reflected in the eyes (e.g., when drowsiness, miosis, slow saccades, divergence, less compensatory vestibulo-ocular reflex, and less-accurate optokinetic response and smooth pursuit emerge). Previous studies that discovered these pupil/oculomotor anomalous behaviors along with lowering alertness evaluated only one or a few of them simultaneously, thus their emergence order is yet unknown. Presently, we focused on the following five pupil/oculomotor behaviors that can be evaluated under a natural stationary environment without giving external sensory stimulations: saccades, slow-phase eye movements, vergence, pupil diameter, and blinks. We demonstrate that their anomalous behaviors emerge in the following order: first: frequent saccades; second: slow saccades; third: divergence & miosis, then slow eye movement, while elongated eyelid closure duration emerges randomly in this sequence. These results provide a basis for the oculo-pupillometry-enabling objective monitoring of progressive drowsiness.

Asymmetric posterior reversible encephalopathy syndrome secondary to epilepsy occurring in the chronic phase of subarachnoid hemorrhage.

Background: Posterior reversible encephalopathy syndrome (PRES) is a rare clinical syndrome that refers to a disorder with reversible subcortical vasogenic brain edema involving the parieto-occipital lobe, temporal lobe, basal ganglia, and its surroundings. Radiologically, it is characterized by symmetrical lesions; however, atypical findings have sometimes been reported. Case Description: A 79-year-old woman experienced subarachnoid hemorrhage (SAH) a year and a half previously before this hospitalization. She presented with sudden-onset coma, dacryorrhea, and moderate right hemiparesis and was taken to our hospital. Computed tomography showed no apparent abnormal acute lesions. Electroencephalography confirmed periodic lateralized epileptiform discharges in the left hemisphere. First, based on the findings, she was diagnosed with nonconvulsive status epilepticus and started antiepileptic therapy. Six days after admission, however, multiple asymmetric lesions were confirmed on magnetic resonance imaging. Considering that findings subsequently improved, we finally diagnosed her with asymmetric PRES secondary to epilepsy occurring in the chronic phase of SAH. Aphasia and right hemispatial neglect persisted as sequelae and she was transferred to a rehabilitation hospital with a modified Rankin scale of 3. Conclusion: Excessive elevation of blood flow in the hemisphere is inferred to lead to blood-brain barrier collapse and subsequent asymmetric PRES.

Temporal changes in accommodative responses to periodic visual motion.

When we shift our gaze to stare at objects at various distances, not only eye positions but also lens accommodation changes. Usually, visually induced accommodation responses (AccRes) present longer latency than accompanying eye movements, resulting in a brief period of an unfocused retinal image after each gaze shift. Unfocused periods may be extended further when the eyes are under predictive control in response to a temporally periodic visual stimulus. It has been shown that phase lag of the AccRes shortened when the visual target motion was temporally periodic, contributing to reduction of the unfocused periods. However, how rapidly the phase lag shortening is acquired or how long the shortened phase is maintained has been unknown. Presently, we aimed at clarifying the acquisition and maintenance characteristics of the AccRes adaptation. Experiments employing periodic accommodative stimuli revealed that the phase lag is shortened and the gain is temporarily (for 1.3-4 s) increased as early as in the 2nd cycle of the stimulation. Moreover, we show that the adapted AccRes persist for at least 0.25 s in addition to the latency (0.35 s) in the dark after removing periodic visual stimulation. These results add new insights into the temporal characteristics of AccRes adaptation and its maintenance that would play an important role in our daily visual experiences.

The influence of stimulus and behavioral histories on predictive control of smooth pursuit eye movements.

The smooth pursuit system has the ability to perform predictive feedforward control of eye movements. This study attempted to examine how stimulus and behavioral histories of past trials affect the control of predictive pursuit of target motion with randomized velocities. We used sequential ramp stimuli where the rightward velocity was fixed at 16 deg/s while the leftward velocity was either fixed (predictable) at one of seven velocities (4, 8, 12, 16, 20, 24, or 28 deg/s) or randomized (unpredictable). As a result, predictive pursuit responses were observed not only in the predictable condition but also in the unpredictable condition. Linear mixed-effects (LME) models showed that both stimulus and behavioral histories of the previous two or three trials influenced the predictive pursuit responses in the unpredictable condition. Intriguingly, the goodness of fit of the LME model was improved when both historical effects were fitted simultaneously rather than when each type of historical data was fitted alone. Our results suggest that predictive pursuit systems allow us to track randomized target motion using weighted averaging of the information of target velocity (stimulus) and motor output (behavior) in past time sequences.

Effects of smooth pursuit and second-order stimuli on visual motion prediction.

The purpose of this study was to determine whether smooth pursuit eye movements affect visual motion prediction using a time-to-contact task where observers anticipate the exact instant that a partially occluded target would coincide with a stationary object. Moreover, we attempted to clarify the influence of second-order motion on visual motion prediction during smooth pursuit. One target object moved to another stationary object (6 deg apart) at constant velocity of 3, 4, and 5 deg/s, and then the two objects disappeared 500 ms after the onset of target motion. The observers estimated the moment the moving object would overlap the stationary object and pressed a button. For the pursuit condition, both a Gaussian window and a random dots texture moved in the same direction at the same speed for the first-order motion, whereas a Gaussian window moved over a static background composed of random dots texture for the second-order motion. The results showed that the constant error of the time-to-contact shifted to a later response for the pursuit condition compared to the fixation condition, regardless of the object velocity. In addition, during smooth pursuit, the constant error for the second-order motion shifted to an earlier response compared to the first-order motion when the object velocity was 3 deg/s, whereas no significant difference was found at 4 and 5 deg/s. Therefore, our results suggest that visual motion prediction using a time-to-contact task is affected by both eye movements and motion configuration such as second-order motion.

Cerebellar Roles in Frequency Competitive Motor Learning of the Vestibulo-ocular Reflex.

Biological motions commonly contain multiple frequency components in which each fundamental has to be adjusted by motor learning to acquire a new motor skill or maintain acquired skills. At times during this motor performance one frequency component needs to be enhanced (gain-up) while another is suppressed (gain-down). This pattern of simultaneous gain-up and -down adjustments at different frequencies is called frequency competitive motor learning. Currently we investigated cerebellar roles in this behavior utilizing the goldfish vestibulo-ocular reflex (VOR). Previously, VOR motor learning was shown in primates to be frequency selective and exhibit frequency competitive motor learning. Here we demonstrate that the goldfish VOR performs frequency competitive motor learning when high and low frequency components are trained to gain-up and gain-down, respectively. However, when the two frequency components were trained in the opposite directions only gain-up component was observed. We also found that cerebellectomy precluded any frequency competitive VOR motor learning. Complementary single unit recordings from vestibulo-cerebellar Purkinje cells revealed changes in firing modulation along with gain-down learning, but not with gain-up learning irrespective of frequency. These results demonstrate that the cerebellum is required for all frequency competitive VOR motor learning and Purkinje cell activity therein is well correlated with all gain-down behaviors independent of frequency. However, frequency competitive gain-up learning requires intact, recursive brainstem/cerebellar pathways. Collectively these findings support the idea that VOR gain-up and gain-down learning utilize separate brainstem/cerebellar circuitry that, in turn, clearly underlies the unique ability of the oculomotor system to deal with multiple frequency components.

Hepatic Artery Embolization Enhances Expression of Programmed Cell Death 1 Ligand 1 in an Orthotopic Rat Hepatocellular Carcinoma Model: In Vivo and in Vitro Experimentation.

PURPOSE: To evaluate the effects of hepatic artery embolization (HAE) on the expression of programmed cell death 1 ligand 1 (PD-L1) in an orthotopic rat hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS: A rat HCC model was established in Sprague-Dawley rats with the RH7777 cell line. Six animals each were assigned to receive HAE or sham treatment. Liver tissues were harvested 24 h after the procedure. Immunohistochemistry (IHC) was used to compare expression of PD-L1 and hypoxia-inducible factor (HIF)-1α in the intratumoral and peritumoral regions and normal liver tissue. In vitro cell culture study was performed for 24 h under normoxic and hypoxic conditions, and protein expression of PD-L1 and HIF-1α and the effects of HIF-1α inhibitors were assessed. RESULTS: IHC showed that PD-L1- and HIF-1α-positive areas were significantly larger in the HAE group vs the sham group in intratumoral (P = .006 and P < .001, respectively) and peritumoral regions (both P < .001). The expression of PD-L1 positively correlated with HIF-1α expression in the intratumoral region (r2 = 0.551; P < .001). In vitro cell culture study revealed that protein expression of PD-L1 and HIF-1α were significantly higher when cells were incubated under hypoxic vs normoxic conditions (P = .028 and P = .010, respectively). PD-L1 expression was suppressed significantly when the HIF-1α inhibitor rapamycin was added to the culture medium (P = .024). CONCLUSIONS: HAE enhances intratumoral and peritumoral PD-L1 expression in a rat HCC model. The HIF-1α pathway is a possible mechanism underlying increased intratumoral PD-L1 expression after HAE.

Velocity storage mechanism drives a cerebellar clock for predictive eye velocity control.

Predictive motor control is ubiquitously employed in animal kingdom to achieve rapid and precise motor action. In most vertebrates large, moving visual scenes induce an optokinetic response (OKR) control of eye movements to stabilize vision. In goldfish, the OKR was found to be predictive after a prolonged exposure to temporally periodic visual motion. A recent study showed the cerebellum necessary to acquire this predictive OKR (pOKR), but it remained unclear as to whether the cerebellum alone was sufficient. Herein we examined different fish species known to share the basic architecture of cerebellar neuronal circuitry for their ability to acquire pOKR. Carps were shown to acquire pOKR like goldfish while zebrafish and medaka did not, demonstrating the cerebellum alone not to be sufficient. Interestingly, those fish that acquired pOKR were found to exhibit long-lasting optokinetic after nystagmus (OKAN) as opposed to those that didn't. To directly manipulate OKAN vestibular-neurectomy was performed in goldfish that severely shortened OKAN, but pOKR was acquired comparable to normal animals. These results suggest that the neuronal circuitry producing OKAN, known as the velocity storage mechanism (VSM), is required to acquire pOKR irrespective of OKAN duration. Taken together, we conclude that pOKR is acquired through recurrent cerebellum-brainstem parallel loops in which the cerebellum adjusts VSM signal flow and, in turn, receives appropriately timed eye velocity information to clock visual world motion.

Hepatic Artery Embolization Induces the Local Overexpression of Transforming Growth Factor ß1 in a Rat Hepatoma Model.

INTRODUCTION: The underlying mechanism involved in the recurrence of hepatoma after hepatic arterial embolization (HAE) is not adequately examined. An immunosuppressive cytokine, transforming growth factor ß1 (TGF-ß1), can lead to tumor progression and is affected by hypoxia in various cancers. The study aimed to assess the effect of HAE on the expression of TGF-ß1 in a rat hepatoma model. METHODS: Sprague-Dawley rats bearing N1S1 hepatoma cells underwent HAE (HAE group, n = 5) or sham treatment (sham group, n = 4). The animals were euthanized at 48 h, and liver tissues were harvested. Immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR) were performed to compare the expression of TGF-ß1 and hypoxia-inducible factor 1α (HIF-1α) between the HAE and sham groups. In vitro experiments with the N1S1 cell line were also performed under normoxic (21% O2) or hypoxic (1% O2) conditions for 48 h, and the expression of TGF-ß1 and HIF-1α was assessed with western blotting and enzyme-linked immunosorbent assay. Statistical data comparisons were performed by Student t test. RESULTS: IHC showed that both the TGF-ß1-positive and HIF-1α-positive tumor peripheral areas were larger in the HAE group (6.59 ± 2.49 and 10.26 ± 4.14%; p < 0.001, respectively) than in the sham group (0.34 ± 0.41 and 0.40 ± 0.84% respectively). Similarly, qPCR showed that the mRNA expression levels of TGF-ß1 and HIF-1α were higher (1.95 ± 0.38-fold and 1.62 ± 0.37-fold; p < 0.001 and p = 0.002, respectively) in the HAE group than those in the sham group. TGF-ß1 expression was suppressed when HIF-1α inhibitors were added (p = 0.001), and HIF-1α expression was upregulated when exogenous TGF-ß1 was added (p = 0.033) in N1S1 cells. CONCLUSION: HAE enhanced local TGF-ß1 expression in a rat hepatoma model. In vitro experiments suggest that HAE-induced hypoxic stress may trigger the interdependent expression of TGF-ß1 and HIF-1α.

Vestibulo-ocular reflex characteristics during unidirectional translational whole-body vibration without head restriction.

The vestibulo-ocular reflex (VOR) plays a crucial role in ocular stability. However, VOR characteristics under realistic whole-body vibration conditions, particularly without head restriction, remain unclear. The aim of this study was to characterise the VOR over a wide range of whole-body vibration frequencies (0.7-10 Hz), such as occur when driving a car. Eye and head movements were measured in response to unidirectional translational whole-body vibration that resembled actual vehicle vibrations. The VOR was then modelled by regressing eye velocity data on multiple head movement components. Results showed that the VOR was explained by angular velocity, linear acceleration, and linear jerk components of the head movements. Because the VOR in response to head linear-jerk components disrupted ocular stability in the current experimental setup, our results suggest that degraded vision in whole-body vibratory environments might be partially attributable to jerky head movements. Practitioner summary: The vestibulo-ocular reflex (VOR) during unidirectional translational whole-body vibration without head restriction was modelled using multiple head movement components, with the aim of characterising the VOR. Results showed that the VOR was explained by angular velocity, linear acceleration, and linear jerk components of head movements.

TRPM8 channel is involved in the ventilatory response to CO2 mediating hypercapnic Ca2+ responses.

The role of TRP channels in the ventilatory response to CO2 was investigated in vivo. To this end, the respiration of unrestrained adult TRPM8-, TRPV1- and TRPV4-channel knockout mice was measured using whole-body plethysmography. Under control conditions and hyperoxic hypercapnia, no difference in respiratory parameters was observed between adult wild-type mice and TRPV1- and TRPV4-channel knockout mice. However, TRPM8-channel knockout mice showed decreased tidal volume under both hypercapnia and resting conditions. In addition, the expression of TRPM8, TRPV1 and TRPV4 mRNAs was detected in EGFP-positive glial cells in the medulla of GFAP promoter-EGFP transgenic mice by real-time PCR. Furthermore, we measured intracellular Ca2+ responses of TRPM8-overexpressing HEK-293 cells to hypercapnic acidosis. Subpopulations of cells that exhibited hypercapnic acidosis-induced Ca2+ response also responded to the application of menthol. These results suggest that TRPM8 partially mediates the ventilatory response to CO2 via changes in intracellular Ca2+ and is a chemosensing protein that may be involved in detecting endogenous CO2 production.

Investigation of the characteristics of headache due to unruptured intracranial vertebral artery dissection.

BACKGROUND AND PURPOSE: It is sometimes difficult to diagnose intracranial vertebral artery dissection in patients with headache as the only symptom. Knowledge of the characteristics of the headache would facilitate the diagnosis. In this study, we aimed to clarify the characteristics of intracranial vertebral artery dissection-related headache using our original self-administered questionnaire. METHODS: Via the questionnaire, we ascertained headache characteristics and investigated whether they differed between two types of unruptured intracranial vertebral artery dissection, headache type and ischemic type, based on analysis of the responses. Then, we tried to validate the consistency of commonly used criteria for intracranial artery dissection by comparing them with our results. RESULTS: Thirty-seven patients were analyzed. Our results identified the following seven headache characteristics in patients with intracranial vertebral artery dissection: (i) occurring in the occipitonuchal region (89%); (ii) unilateral (81%); (iii) pulsatile (70%); (iv) of acute onset (70%); (v) severe (73%); (vi) without nausea or vomiting (73%); and (vii) with concomitant clinical symptoms unrelated to ischemia (81%). Comparison of headache characteristics between the two types of intracranial vertebral artery dissection headache showed that the pain was significantly more severe in headache type than ischemic type intracranial vertebral artery dissection ( p = 0.01). Concomitant clinical symptoms occurred significantly more often in ischemic type than headache type intracranial vertebral artery dissection ( p = 0.03). Our results generally satisfied the established headache diagnostic criteria. CONCLUSION: The pain characteristics of headache type and ischemic type intracranial vertebral artery dissection shown in our study may facilitate its diagnosis.