Spontaneously hyperactive MEK-Erk pathway mediates paradoxical facilitation of cell proliferation in mild hypoxia.

BACKGROUND: Oxygen is important for common eukaryotic cells to generate ATP. Pathophysiological conditions such as ischemic diseases cause tissue hypoxia. In addition, oxygen availability in deep tissues is supposed to be far lower than surrounding atmosphere even in healthy animals, and the oxygen partial pressures in most normal tissues are estimated to be around 40-50mmHg, so-called mild hypoxia. Recent studies have demonstrated that mild hypoxia has distinct effects on living cells from severe hypoxia. For instance, mild hypoxia was reported to promote cell reprogramming. Although severe hypoxia is known to inhibit cell proliferation, mild hypoxia has been paradoxically demonstrated to increase cell proliferation. However, it has not been clarified by which molecular mechanisms mild hypoxia evokes the discontinuous increment of cell proliferation. METHODS: We established experimental conditions showing the opposite influences of mild and severe hypoxia on cell proliferation using undifferentiated Caco2 human colon carcinoma cells in order to clarify the underlying molecular mechanism. RESULTS: The basal activity of Erk, which is a typical mediator of mitogenic signals, is spontaneously increased specifically in cells exposed to mild hypoxia, and inhibition of MEK, an upstream kinase of the Erk, completely inhibited the mild hypoxia-induced enhancement of cell proliferation. CONCLUSIONS: Spontaneous hyperactivation of the MEK-Erk pathway by mild hypoxia should be the plausible molecular mechanism of the paradoxical promotion of cell proliferation. GENERAL SIGNIFICANCE: Our findings will provide clues to the molecular basis of mild hypoxia-evoked phenomena such as cell reprogramming.

Anterior Protrusion of Hydroxyapatite Blocks During Vertebroplasty for Thoracic Burst Fractures: A Case Report.

Research on complications necessitating reoperation following vertebroplasty related to hydroxyapatite (HA) blocks is limited. We present the case of a 25-year-old woman who underwent posterior fixation and vertebroplasty using HA blocks for a T12 burst fracture. Postoperative computed tomography revealed anterior protrusion of some blocks, with consequent compression of the descending aorta. We removed the protruded blocks viaa transthoracic approach and observed no aortic injuries. Although HA blocks are considered safe for vertebroplasty, surgeons should be aware of the risk of anterior protrusion and potential aortic injury.

Efficacy of prophylactic treatment with selective serotonin reuptake inhibitors for depression after open-heart surgery.

PURPOSE: The aim of the present study was to evaluate the efficacy of prophylactic treatment with selective serotonin reuptake inhibitors (SSRIs) in female patients at high risk of suffering depression after cardiac surgery. METHODS: Female patients (n = 58; group I) who were over 70 years of age or who had undergone emergency surgery were administered prophylactic treatment with paroxetine immediately after surgery. The hospital mortality and morbidity data of these patients were compared with those of 59 patients (group II) without prophylactic medication. RESULTS: The Center for Epidemiological Studies Depression Scale (CES-D) score at 10 days after surgery was significantly lower in group I (15.2 ± 7.8) than in group II (21.8 ± 7.5, P = 0.0018). The incidence of depression (I: 12.1% vs II: 64.4%, P < 0.0001) and pneumonia (I: 0% vs II: 10.2%, P = 0.0127) were significantly lower in group I than in group II. In addition, the duration of postoperative hospital stay was significantly shorter for group I than for group II (I: 15.9 ± 56.5 vs II: 23.4 ± 20.5 days, P = 0.0102). The hospital mortality rates were similar. CONCLUSION: The quality of life of patients with depression after open-heart surgery is poor. The early administration of prophylactic medication is therefore necessary for those patients at risk for developing depression.

Oral corticosteroid dosage and clinical presentation of psychiatric conditions after steroid use: A consultation-liaison psychiatry service's experience.

AIM: Psychiatric disturbances are the major adverse effects of corticosteroids. There are no consistent conclusions regarding changes in steroid dosage and the incidence of psychiatric conditions, due in part to the lack of consistent evaluation criteria. The purpose of this research was to determine the incidence and dose-dependency of psychiatric conditions as assessed by trained psychiatrists. METHODS: A retrospective chart review was conducted at a university hospital in Japan. We identified inpatients receiving oral prednisolone treatment, who were referred to the consultation-liaison psychiatry team from April 2015 to March 2018. Patients were divided into high-dose (≥0.5 mg/kg/day) and low-dose (<0.5 mg/kg/day) groups. We investigated the associations between steroid dosage and incidence of psychiatric conditions. RESULTS: A total of 93 patients (35 in the high-dose group, 58 in the low-dose group) were included. Various psychiatric conditions, such as insomnia, delirium, depression, and psychosis, occurred during steroid therapy. The most common condition was insomnia (72%). We observed no significant differences in the patient background characteristics and the incidence of most psychiatric conditions between the high-dose and low-dose groups. However, there were more patients with delirium in the low-dose group than in the high-dose group. CONCLUSIONS: Based on the accurate assessment of psychiatric conditions by psychiatrists, our analysis suggests that, among inpatients referred to a consultation-liaison psychiatry team, the incidence of psychiatric conditions, with the exception of delirium, is independent of the dose of oral prednisolone.

Mental health status, shift work, and occupational accidents among hospital nurses in Japan.

A questionnaire survey was conducted with questions from the 12-item General Health Questionnaire, among others, targeting 4,407 nurses in 8 general hospitals in Japan, in the hope of improving the work environment of nurses and to provide data that will allow a discussion of the measures necessary for preventing medical errors, thus improving occupational health. For each type of accident, the percentage of those who had made medical errors was significantly higher for the "mentally in poor health" group than for the "mentally in good health" group (p<0.0001). The percentage of nurses in the "mentally in good health" and "mentally in poor health" groups who had experienced occupational accidents over the past 12 months (i.e., whether they were "with errors" or "without errors") was calculated for each of the following four types of medical accident: (1) drug-administration errors, (2) incorrect operation of medical equipment, (3) errors in patient identification, and (4) needlestick injuries. For each type of accident, the percentage of those who had made medical errors was significantly higher for the "mentally in poor health" group than for the "mentally in good health" group (p<0.0001). Multiple logistic regression analyses revealed significant associations between experience of medical errors in the past 12 months and being mentally in poor health, with night or irregular shift work, and age.

Risk analysis for depression and patient prognosis after open heart surgery.

BACKGROUND: The aim of the present study was to determine the predictors of depression as a complication after open heart surgery and influence of depression on the patients' prognosis. METHODS AND RESULTS: During the last 3 years, 97 patients (21.5%) of the 452 adult patients who had open heart surgery at our institute experienced depression after the operation. Patients who scored over 16 points using a Center for Epidemiological Studies Depression Scale were diagnosed with significant symptoms of depression. Depressed patients (group I, n=97) and non-depressed patients (group II, n=355) in terms of mortality and length of hospital stay were compared. Predictors for depression were identified by logistic regression analysis. The postoperative hospital stay was significantly longer in group I. Hospital mortality was also significantly higher in group I. Female gender (odds ratio (OR): 5.15, p<0.0001), emergency surgery (OR: 4.46, p<0.0001), and being over 70 years of age (OR: 4.67, p<0.0001) were found to be significant predictors for postoperative depression. CONCLUSION: The prognosis for patients who had depression developed after open heart surgery was poor. It might be important to start prophylactic medication as soon as possible after the operation, particularly for patients at risk of having depression.

Excessive daytime sleepiness among the Japanese general population.

BACKGROUND: Excessive daytime sleepiness is one of the principal symptoms of sleep disturbances, and is often associated with serious consequences including traffic and industrial accidents, decreased productivity, and interpersonal problems. However, there are few epidemiologic studies on excessive daytime sleepiness in a large scale sample targeting Japanese general population. METHODS: The survey was performed using a self-administered questionnaire in June 2000, targeting a population randomly selected from among 300 communities throughout Japan. This questionnaire included information about sleep habits and sleep problems. Excessive daytime sleepiness measured according to a question "Do you fall asleep when you must not sleep (for example when you are driving a car)?" RESULTS: A total of 28,714 subjects completed the questionnaire. The prevalence of excessive daytime sleepiness was 2.5% (male=2.8% and female=2.2%). Backward elimination analysis showed that the following were associated with excessive daytime sleepiness: male sex, young age, short sleep duration, subjective insufficient sleep, loss of deep sleep, disagreeable sensations in the legs, interruption of sleep by snoring or dyspnea, and feeling psychological stress. Interruption of sleep by snoring or dyspnea was the strongest associated factor (adjusted odds ratio=2.46, 95% confidence interval=1.76-3.43) of excessive daytime sleepiness. CONCLUSIONS: These results suggest that excessive daytime sleepiness in Japanese is associated with several sleep problems. These findings may be useful in attempts to prevent excessive daytime sleepiness in the general population of Japan.