Retraction: Transcriptome analysis reveals a role for the endothelial ANP-GC-A signaling in interfering with pre-metastatic niche formation by solid cancers.

[This retracts the article DOI: 10.18632/oncotarget.18032.].

Changes in cognitive function in patients with intractable dizziness following vestibular rehabilitation.

The purpose of the present study was to investigate changes in cognitive functions, including visuospatial ability, attention, and executive function in patients with intractable dizziness following vestibular rehabilitation. The correlations between improvements in cognitive function and dizziness-related variables and emotional distress were also explored. During hospitalization for 5 days, participants were trained on a vestibular rehabilitation program. Participants completed questionnaires including the Dizziness Handicap Inventory (DHI), Hospital Anxiety and Depression Scale (HADS), and Trail Making Test (TMT), which were used to assess cognitive function. The center of gravity fluctuation measurement and timed up and go test (TUG), which were objective dizziness severity indexes, were performed before, 1 month after, and 4 months after hospitalization. Following vestibular rehabilitation, participants exhibited a significant improvement in the TMT, DHI, HADS, and TUG scores. Correlation analysis between the variables at each time point indicated that TMT scores positively correlated with TUG at baseline. The correlation between changes observed in the TUG and TMT scores was not significant. The degree of improvement of the TUG score did not bear a linear relationship with that of the TMT scores. However, these correlation results were not completely consistent with those in the multiply imputed dataset.

Psychiatric disorders in patients with intractable dizziness in the department of otolaryngology.

OBJECTIVE: Vertigo and dizziness are often not fully explained by organic illnesses, but instead may be related to psychiatric disorders. It is important to determine the types of psychiatric comorbidities that are frequent in cases of intractable dizziness. METHOD: The study subjects were 90 patients who had experienced intractable dizziness for more than three months and were referred to a psychiatrist when their symptoms could not be fully explained based on their physical illness. The patients' final diagnosis and questionnaire (DHI,SDS and STAI) scores were evaluated. RESULTS: Seventy percent (63/90) of patients with intractable dizziness had been diagnosed as having psychiatric conditions by the study psychiatrists. The most common diagnosis was unspecified depressive disorder. CONCLUSIONS: Psychiatric comorbidities seem to be more prevalent in certain subgroups of organic dizziness. We found a higher rate of depressive disorders in the sequelae of sudden deafness and migraine-related dizziness.

Transcriptome analysis reveals a role for the endothelial ANP-GC-A signaling in interfering with pre-metastatic niche formation by solid cancers.

Cancer establishes a microenvironment called the pre-metastatic niche in distant organs where disseminated cancer cells can efficiently metastasize. Pre-metastatic niche formation requires various genetic factors. Previous studies suggest that inhibiting a single niche-factor is insufficient to completely block pre-metastatic niche formation especially in human patients. Here we show that the atrial natriuretic peptide (ANP), an endogenous hormone produced by the heart, inhibits pre-metastatic niche formation and metastasis of murine solid cancer models when pharmacologically supplied in vivo. On the basis of a wealth of comprehensive RNA-seq data, we demonstrated that ANP globally suppressed expression of cancer-induced genes including known niche-factors in the lung. The lungs of mice overexpressing GC-A, a receptor for ANP in endothelial cells, were conferred resistance against pre-metastatic niche formation. Importantly, neither ANP administration nor GC-A overexpression had a detrimental effect on lung gene expression in a cancer-free condition. The current study establishes endothelial ANP-GC-A signaling as a therapeutic target to control the pre-metastatic niche.

Remote reprogramming of hepatic circadian transcriptome by breast cancer.

Cancers adversely affect organismal physiology. To date, the genes within a patient responsible for systemically spreading cancer-induced physiological disruption remain elusive. To identify host genes responsible for transmitting disruptive, cancer-driven signals, we thoroughly analyzed the transcriptome of a suite of host organs from mice bearing 4T1 breast cancer, and discovered complexly rewired patterns of circadian gene expression in the liver. Our data revealed that 7 core clock transcription factors, represented by Rev-erba and Rorg, exhibited abnormal daily expression rhythm in the liver of 4T1-bearing mice. Accordingly, expression patterns of specific set of downstream circadian genes were compromised. Osgin1, a marker for oxidative stress, was an example. Specific downstream genes, including E2f8, a transcriptional repressor that controls cellular polyploidy, displayed a striking pattern of disruption, "day-night reversal." Meanwhile, we found that the liver of 4T1-bearing mice suffered from increased oxidative stress. The tetraploid hepatocytes population was concomitantly increased in 4T1-bearing mice, which has not been previously appreciated as a cancer-induced phenotype. In summary, the current study provides a comprehensive characterization of the 4T1-affected hepatic circadian transcriptome that possibly underlies cancer-induced physiological alteration in the liver.

Is the Headache in Patients with Vestibular Migraine Attenuated by Vestibular Rehabilitation?

BACKGROUND: Vestibular rehabilitation is the most effective treatment for dizziness due to vestibular dysfunction. Given the biological relationship between vestibular symptoms and headache, headache in patients with vestibular migraine (VM) could be improved by vestibular rehabilitation that leads to the improvement of dizziness. This study aimed to compare the effects of vestibular rehabilitation on headache and other outcomes relating to dizziness, and the psychological factors in patients with VM patients, patients with dizziness and tension-type headache, and patients without headache. METHODS: Our participants included 251 patients with dizziness comprising 28 patients with VM, 79 patients with tension-type headache, and 144 patients without headache. Participants were hospitalized for 5 days and taught to conduct a vestibular rehabilitation program. They were assessed using the Dizziness Handicap Inventory (DHI), Headache Impact Test (HIT-6), Hospital Anxiety and Depression Scale (HADS), and Somatosensory Catastrophizing Scale (SSCS) and underwent center of gravity fluctuation measurement as an objective dizziness severity index before, 1 month after, and 4 months after their hospitalization. RESULTS: The VM and tension-type headache groups demonstrated a significant improvement in the HIT-6 score with improvement of the DHI, HADS, SSCS, and a part of the objective dizziness index that also shown in patients without headache following vestibular rehabilitation. The change in HIT-6 during rehabilitation in the VM group was positively correlated with changes in the DHI and anxiety in the HADS. Changes in the HIT-6 in tension-type headache group positively correlated with changes in anxiety and SSCS. CONCLUSION: Vestibular rehabilitation contributed to improvement of headache both in patients with VM and patients with dizziness and tension-type headache, in addition to improvement of dizziness and psychological factors. Improvement in dizziness following vestibular rehabilitation could be associated with the improvement of headache more prominently in VM compared with comorbid tension-type headache.

Effects of vestibular rehabilitation combined with transcranial cerebellar direct current stimulation in patients with chronic dizziness: An exploratory study.

BACKGROUND: Vestibular rehabilitation is useful to alleviate chronic dizziness in patients with vestibular dysfunction. It aims to induce neuronal plasticity in the central nervous system (especially in the cerebellum) to promote vestibular compensation. Transcranial cerebellar direct current stimulation (tcDCS) reportedly enhances cerebellar function. OBJECTIVE/HYPOTHESIS: We investigated whether vestibular rehabilitation partially combined with tcDCS is superior to the use of rehabilitation alone for the alleviation of dizziness. METHODS: Patients with chronic dizziness due to vestibular dysfunction received rehabilitation concurrently with either 20-min tcDCS or sham stimulation for 5 days. Pre- and post-intervention (at 1 month) dizziness handicap inventory (DHI) scores and psychometric and motor parameters were compared. RESULTS: Sixteen patients completed the study. DHI scores in the tcDCS group showed significant improvement over those in the sham group (Mann-Whitney U test, p = 0.033). CONCLUSION: Vestibular rehabilitation partially combined with tcDCS appears to be a promising approach.

Analysis of Factors Affecting the Outcomes of In-hospitalized Vestibular Rehabilitation in Patients With Intractable Dizziness.

OBJECTIVE: To analyze somatic and psychological factors affecting the outcomes of in-hospital vestibular rehabilitation in patients with intractable dizziness. MATERIALS AND METHODS: The study involved 138 patients with persistent dizziness caused by peripheral vestibular dysfunction. They were hospitalized and taught to conduct a vestibular rehabilitation program for 30 minutes by themselves three times a day over 5 days. They were then instructed to continue performing the program every day after discharge. Several questionnaires were conducted immediately before, and 1 month after, the treatment. For example, the dizziness handicap inventory (DHI), the somatosensory catastrophizing scale (SSCS), and indexes of depression and anxiety. Posturography was also performed. The main outcome was the difference between the DHI scores before and after rehabilitation. Body sway was objectively evaluated using static posturography. RESULTS: The vestibular rehabilitation significantly improved the DHI score, the SSCS score, depression, and anxiety. Multivariate analysis indicated that the improvement in the DHI score was poorer in patients who showed high SSCS score before intervention. A higher prevalue of the DHI was associated with greater improvements in this perceived handicap after the rehabilitation. Small body sway pre-rehabilitation was related to positive effects on the DHI score in patients with a high prevalue of the DHI. CONCLUSION: The vestibular rehabilitation contributed to the improvement of perceived handicap due to dizziness, catastrophization of bodily sensation, and emotional distress. Patients who catastrophized their bodily sensations before vestibular rehabilitation saw smaller improvements in perceived handicap due to dizziness.

Accuracy analysis of intrahepatic fat density measurements using dual-energy computed tomography: Validation using a test phantom.

BACKGROUND: Currently, no standardized method for measuring intrahepatic fat density via conventional computed tomography (CT) exists. OBJECTIVE: We aim to quantify intrahepatic fat density via material decomposition analysis using rapid kilovolt peak-switching dual-energy (RSDE) CT. METHODS: Homogenized porcine liver and fat (lard) were mixed in various ratios to produce phantoms for fat density verification. The actual fat density was measured on the basis of the phantom volume and weight, and these measurements were used as reference densities. The fat and liver mass attenuation coefficients, which were used as the material basis pairs, were employed in the material decomposition analysis. Then, the measured fat density of each phantom was compared with the reference densities. RESULTS: For fat content differences exceeding 2%, the measured fat density for the phantoms became statistically significant (p < 0.01). The correlation between the reference densities and RSDE-measured fat densities was reasonably high (R > 0.9997); this indicates the validity of this analysis method. CONCLUSIONS: Intrahepatic fat density can be measured using the mass attenuation coefficients of fat and liver in a material decomposition analysis. Given the knowledge of the accuracy and the limitations found in this study, our method can quantitatively evaluate fat density.

The effect of sleep disturbance in patients with chronic dizziness.

CONCLUSIONS: The comorbidity of sleep disturbance with chronic dizziness in women was related to the intensity of distress and interference with their lives due to dizziness, although it was not related to objective variables of dizziness. In addition, the presence of sleep disturbance was associated with severe anxiety and depression, and low health-related quality-of-life (QoL). OBJECTIVES: This study investigated the effect of sleep disturbance in patients with chronic dizziness on symptoms of dizziness, handicaps due to dizziness, health-related QoL, and emotional distress. METHOD: The participants of this study were 252 in-patients with chronic dizziness. Participants completed questionnaires containing the Dizziness Handicap Inventory (DHI, three sub-scales: Physical [DHI-P], Emotional [DHI-E], and Functional [DHI-F] scores), Pittsburgh sleep quality index (PSQI-J), Hospital Anxiety and Depression Scale (HADS), and Medical Outcomes Study 8-items Short Form Health Survey (SF-8, health-related QoL). The participants then underwent gravity center fluctuation measurement as an objective indicator of the severity of dizziness. RESULTS: The prevalence of sleep disturbance (PSQI-J global score ≧6) was 65.1% in these participants. Two-way ANOVA of the DHI scores showed significant interaction between sleep disturbance and sex in DHI total, DHI-E score, and DHI-F score, indicating that these scores were higher in women with sleep disturbance. Regarding DHI-P score, only the main effect of sex was significant (women > men). Sleep disturbance had no significant effect on objective indicators of severity of dizziness. Patients with sleep disturbance had significantly higher HADS scored and a lower SF-8 scored than patients without sleep disturbance.

The effect of vestibular rehabilitation on sleep disturbance in patients with chronic dizziness.

CONCLUSIONS: Improvement in sleep, emotional distress, and health-related quality-of-life (QoL) accompanied the improvement in dizziness symptoms after vestibular rehabilitation. Persistent sleep disturbance could prevent improvements in self-perceived handicap due to chronic dizziness and anxiety. OBJECTIVE: The present study investigated prospectively the effects of intervention for dizziness (vestibular rehabilitation) on sleep disturbance, and the relationship between improvements in dizziness symptoms and improvements in sleep disturbance after the intervention. METHODS: The participants of this study were 127 chronic dizziness inpatients with comorbid sleep disturbance (Pittsburgh sleep quality index [PSQI-J] global score ≥6). Participants completed the Dizziness Handicap Inventory (DHI, three sub-scales: Physical, Emotional, and Functional), PSQI-J, Hospital Anxiety and Depression Scale (HADS), and SF-8 (health-related QoL), and underwent gravity center fluctuation measurement before (time 1) and 1 month after (time 2) an in-hospital rehabilitation program. RESULTS: All measured variables were significantly improved at time 2, compared to time 1. At time 2, 80.31% of patients still reported sleep disturbance. Analysis of covariance showed that chronic dizziness patients with sleep disturbance at time 2 had significantly higher DHI total, DHI-physical, and HADS-anxiety scores at time 2 than patients without sleep disturbance at time 2, after adjusting for these scores at time 1.

A Case of Undiagnosed Sleep Disorder with Hearing Difficulty and Dizziness.

INTRODUCTION: The aim of this case report was to investigate the relationship between sleep disorders and audio vestibular symptoms. CASE REPORT: A case of undiagnosed sleep disorder, presenting as a temporary auditory processing difficulty, is presented. The disorder was initially treated as sudden deafness with dizziness. A 23-year-old male patient complained of acute hearing disturbance despite normal results on pure tone audiometry. The patient was initially administered a steroid injection in the hospital. After treatment, his hearing symptoms improved only slightly and he reported balance difficulty with rightward spontaneous nystagmus. Vestibular rehabilitation was performed. We also suspected that his hearing symptom was due to an auditory processing difficulty. Despite steroid treatment and vestibular rehabilitation, neither of his symptoms improved. We subsequently identified the presence of insomnia. He was prescribed zolpidem 5 mg, which slightly improved his symptoms, and referred to a sleep specialist for further examination. Polysomnography was performed, which identified restless leg syndrome and sleep disturbance with delayed sleep phase syndrome. After pharmacological treatment, his sleep disturbance, hearing difficulty, and balance disorder completely resolved. CONCLUSION: Sleep disorders may provoke reversible auditory processing difficulties. We should carefully evaluate patients for a potentially undiagnosed sleep disorder, even in patients chiefly complaining of intractable sensory dysfunction such as hearing or balance disturbance.

The influence of headaches in patients with chronic dizziness.

CONCLUSION: The frequency of headaches in patients complaining of chronic dizziness is closely related to the severity of the dizziness impairments and mood states, such as anxiety. It is, therefore, important to treat co-morbid headache in patients with chronic dizziness. The severity of the dizziness impairments and other mood states, including anxiety, did not differ between patients with migraine or non-migraine headaches. OBJECTIVES: Patients with chronic dizziness often complain of headaches or general fatigue. This study investigated the influence of the frequency of headaches on dizziness impairments, anxiety, quality-of-life, and other mood states in patients with chronic dizziness. METHOD: The subjects consisted of 100 consecutive patients with intractable dizziness. Several types of questionnaires were used in the investigations. RESULTS: Of the 85 patients, 51 had either type of headache (tension headache, 38; migraine, 13). The total score on the Dizziness Handicap Inventory correlated linearly with general fatigue (R = 0.39, p < 0.001) and headache (R = 0.25, p < 0.05). The patients with any type of headache had a significantly more positive family history of headache (p < 0.05).

FAS/FASL-mediated cell death in the bovine endometrium.

In many mammals, endometrial cells are remodeled by apoptosis and cell proliferation throughout the estrous cycle. Although apoptosis is known to be induced by various factors involving two major apoptotic pathways (the death receptor- and mitochondria-mediated pathways), how it is regulated in the bovine endometrium is unclear. We examined (1) the cyclic expressions of apoptosis-related factors, FAS, DcR3, BCL2 and BAX, in the bovine endometrium and (2) the effect of death ligands on the viability of, and FAS mRNA expression in, cultured bovine endometrial epithelial and stromal cells. FAS expression did not change during the estrous cycle, whereas DcR3 expression was higher at the mid and late luteal stages than at the early luteal and follicular stages. BCL2 expression was higher at the late luteal stage than at the early luteal and follicular stages, and the BAX/BCL2 ratio was higher at the early luteal stage than at the late luteal stage. Treatment or pretreatment with tumor necrosis factor-α (TNF)+interferon γ (IFNG) in combination with FAS ligand significantly reduced the viability of both epithelial and stromal cells. Furthermore, TNF+IFNG treatment significantly increased the expression of FAS mRNA in both types of endometrial cells. The overall results suggest that both extrinsic and intrinsic pathways are involved in remodeling the bovine endometrium throughout the estrous cycle, and that the death ligands produced by immune cells and the endometrium play important roles in inducing cyclic endometrial cell death.

Remodeling of bovine endometrium throughout the estrous cycle.

The mammalian endometrium changes morphologically and functionally throughout the estrous cycle. In some species, endometrial cells also undergo periodic proliferation and degeneration. However, the remodeling of bovine endometrium throughout the estrous cycle remains unclear. In the present study, we examined how the remodeling of bovine endometrium varied through the estrous cycle by measuring the relative rates of cell proliferation and apoptosis. Cells positive for both KI-67 (a proliferation marker) and cleaved caspase-3 (CCP3: an apoptotic cell marker) were immunohistochemically evaluated throughout the estrous cycle in the luminal and glandular epithelia, and the stroma of bovine endometrium. Percentages of KI-67-positive cells tended to be higher at the early luteal and follicular stages than at the mid and late luteal stages in all cell types. Similarly, percentages of CCP3-positive cells were higher at the early luteal stage than at the mid and late luteal stages in the luminal epithelium and stroma. Furthermore, CCP3 expression levels by Western blot analysis agreed with these immunohistological observations. On the other hand, DNA fragmentation was detected in the bovine endometrium without significant differences during the estrous cycle by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Together, these results show that cell proliferation and apoptosis undergo cyclic patterns in the bovine endometrium, and suggest that the bovine endometrium is remodeled in each estrous cycle.

Down-regulation of interferon tau gene transcription with a transcription factor, EOMES.

Interferon tau (IFNT), produced for a short interval during early pregnancy by the ruminant embryonic trophectoderm, is essential for the maintenance of early pregnancy, but the mechanism by which it is transcriptionally regulated has not been fully determined. To identify a transcription factor(s) involved in the down-regulation of IFNT genes, mRNAs for various known transcription factors were investigated by reverse-transcriptase and real-time PCR in conceptus tissues collected on Days 15, 17, and 21, or Days 17, 20, and 22 of ovine or bovine pregnancy, respectively. In particular, the T-box protein eomesodermin (EOMES) exhibited high mRNA expression in Day 17 or 22 ovine or bovine conceptuses. Interaction between EOMES and the identified transcription factors was studied using transient transfection, revealing that ovine/bovine IFNT-reporter transactivation was down-regulated by EOMES. Transcription factor interactions with EOMES were further studied through immunoprecipitation, demonstrating an association between EOMES and cAMP-response element binding protein (CREB)-binding protein (CREBBP). Uterine flushing media collected from cyclic or early pregnancy animals were added to bovine trophoblast CT-1 cells cultured on type-I collagen (monoculture) or bovine uterine epithelial cells (coculture) in an attempt to regulate EOMES expression. In the coculture, but not the monoculture, addition of uterine flushing from Day 17 pregnant animals resulted in increased EOMES expression in CT-1 cells. These results suggest that as conceptuses attach to the uterine epithelium, IFNT gene transcription is down-regulated by an increase in EOMES expression and EOMES-CREBBP binding in the attached trophoblast cells.

A randomized crossover study comparing tafluprost 0.0015% with travoprost 0.004% in patients with normal-tension glaucoma [corrected].

PURPOSE: We compared the intraocular pressure (IOP)-lowering effect of tafluprost 0.0015% once daily with travoprost 0.004% once daily in Japanese patients with normal-tension glaucoma (NTG). METHODS: One hundred sixteen patients with NTG were randomized to use tafluprost 0.0015% or travoprost 0.004% once daily for 12 weeks, followed by a washout period of 4 weeks between switching medications. IOP was measured at baseline and 4, 8, and 12 weeks of each treatment period. RESULTS: Ninety patients completed both treatment periods and had IOP data available for evaluation. In both groups, a significant decrease in IOP was observed for all measurement points compared with baseline values (P < 0.0001). There was no significant difference in IOP at each time point between the two groups. Both drugs were effective (defined as more than 10% IOP reduction) in 39 (43%) of 90 patients; only tafluprost was effective in 26 (29%) patients, and only travoprost was effective in 17 (19%) patients. Eight (9%) patients were nonresponders to both drugs. CONCLUSIONS: Tafluprost and travoprost were equally effective in lowering IOP in patients with normal-tension glaucoma. However, patients with normal-tension glaucoma may vary in response to each medication.

Coculture system that mimics in vivo attachment processes in bovine trophoblast cells.

The establishment of pregnancy requires bidirectional communication between the developing conceptus and the uterine endometrium. The aim of this study was to establish an in vitro coculture system with bovine trophoblast cells and uterine epithelial cells (EECs) that mimics the in vivo attachment process. We previously reported that expression of interferon tau (IFNT), a major secretory product from the trophectoderm, decreases with changes in chromatin structure when the conceptus successfully attaches to the uterine epithelium. Thus, IFNT is a good marker to assess whether attachment has successfully occurred. In this study, bovine trophoblast CT-1 cells were cultured to generate spheroids, which were then placed on type I collagen-coated plates (monoculture) or bovine EECs (coculture) with or without uterine flushings collected from Day 15 cyclic or Days 15, 17, or 19 pregnant animals. In the coculture but not the monoculture, addition of uterine flushings from Day 15 or 17 pregnant animals resulted in decreased IFNT and CDX2 mRNA expression in CT-1 spheroids, accompanied with changes in histone modifications. In monocultured CT-1 spheroids, integrin subunit ITGA8 and ITGB3 mRNAs were minimally expressed but were induced in cocultured CT-1 spheroids with or without uterine flushings. Expression of CDH2, another marker for bovine conceptus attachment to the uterine epithelium, was also induced in the cocultured CT-1 spheroids. These results suggest that this in vitro coculture system could be used to isolate processes essential for conceptus attachment to uterine EECs.

Enhanced hydrogen adsorptivity of single-wall carbon nanotube bundles by one-step c60-pillaring method.

Single-wall carbon nanotube (SWCNT) bundles were pillared by fullerene (C60) by the cosonication of C60 and SWCNT in toluene to utilize the interstitial pores for hydrogen storage. C60-pillared SWCNTs were confirmed by the shift in the X-ray diffraction peak and the expanded hexagonal and distorted tetragonal bundles revealed by high-resolution transmission electron microscopy. The H2 adsorptivity of the C60-pillared SWCNT bundles was twice that of the original SWCNT bundles, indicating a design route for SWCNT hydrogen storage.

Nanoporosities and catalytic activities of Pd-tailored single wall carbon nanohorns.

The nanoporosities and catalytic activities of Pd nanoparticles dispersed on single wall carbon nanohorns (Pd-SWCNHs) and oxidized single wall carbon nanohorns (Pd-ox-SWCNHs) were examined. A transmission electron microscopy (TEM) observation indicated that Pd nanoparticles of 2-3 nm size were highly dispersed on both the SWCNHs. X-ray photoelectron spectra and N2 adsorption isotherms at 77 K illustrated the differences in the deposition process mechanisms of the Pd-SWCNHs and Pd-ox-SWCNHs; the deposition process depended on the surface functional groups. The supercritical H2 adsorption isotherms at 77 K suggested the relationships between the interaction of Pd-SWCNHs and Pd-ox-SWCNHs with H2 and the catalytic activities for a water formation reaction in a gas phase at 273 or 298 K. The catalytic activity measurement and TEM observation of the catalysts after the reactions demonstrated that the Pd-SWCNHs and Pd-ox-SWCNHs are promising catalysts.