A high glycemic status increases the risk for autonomic dysfunction and cardiovascular failure. The aim of this study was to investigate time-dependent changes in the autonomic response and cardiovascular dynamics and the association between the level of hemoglobin A1c (HbA1c) and autonomic response during blood volume reduction. The study population consisted of 26 preoperative participants who were scheduled for autologous blood donation (200-400 mL of whole blood) for intraoperative or postoperative use. These participants without circulatory, respiratory, or brain disease and diabetes mellitus were grouped according to their HbA1c levels: < 6.5% (n = 18) and ≥ 6.5% (n = 8). We measured blood pressure (BP) and analyzed heart rate variability (HRV) to quantify cardiac autonomic regulation throughout blood donation. During blood volume reduction, which was about 10% of the circulating blood volume, the BP and heart rate varied within normal ranges in both groups. The high-frequency (HF) component, an index of parasympathetic nerve activity, and the ratio of low-frequency (LF) to HF components (LF/HF), an index of sympathetic nerve activity, significantly decreased and increased with the progression of blood volume reduction, respectively, in the HbA1c < 6.5% group. In contrast, in the HbA1c ≥ 6.5% group, the HF component did not significantly change, and the increase in the LF/HF ratio was delayed. Time-dependent changes in HRV were related to blood volume reduction only in the HbA1c < 6.5% group. Thus, elevated HbA1c levels are associated with the decrease in the autonomic response induced by blood volume reduction.

Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy worldwide for which the radiation exposure is the most influential risk factor. The levels of oxidative stress in PTC are not well characterized on the tissue level. The objective of this study was to evaluate total oxidant status (TOS) and total antioxidant status (TAS) in PTC and benign goiter (BG) tissues and to examine their association with clinicopathological characteristics. Tumor and normal thyroid tissue samples were collected from 59 PTC patients, and goiter tissues were collected from 50 BG patients. TOS and TAS were quantified in the tissue homogenates by spectrophotometric assays. TOS values in tumor tissues did not differ significantly from normal and goiter tissues; however, PTC tissues have significantly higher TAS values than normal and goiter tissues. TOS values correlated with retrosternal growth in BG patients. The significant correlations were found between TOS and TAS values and thyroid function parameters. In 17 PTC patients with multiple tumor foci (multicentric phenotype), TAS values were significantly lower, compared to 42 patients with unicentric PTC. TAS and TOS are the most useful predictors of thyroid capsular invasion by PTC. The age, sex, body mass index, smoking, familial history of thyroid disease and nodule size did not influence TOS and TAS in PTC or BG patients. In conclusion, we show the profiles of TOS and TAS in PTC and BG tissues. Importantly, PTC tissues possess increased antioxidant capacity. The redox status influences the parameters of the thyroid function and tumor’s biological behavior.

Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first reaction in the mitochondrial fatty acid β-oxidation pathway. VLCAD deficiency is associated with the accumulation of fat in multiple organs and tissues, which results in specific clinical features including cardiomyopathy, cardiomegaly, muscle weakness, and hepatic dysfunction in infants. We speculated that the abnormal fatty acid metabolism in VLCAD-deficient individuals might cause cell necrosis by fatty acid toxicity. The accumulation of fatty acids may activate peroxisome proliferator-activated receptor (PPAR), a master regulator of fatty acid metabolism and a potent nuclear receptor for free fatty acids. We examined six skin fibroblast lines, derived from VLCAD-deficient patients and identified fatty acid accumulation and PPARα activation in these cell lines. We then found that the expression levels of three enzymes involved in fatty acid degradation, including long-chain acyl-CoA synthetase (LACS), were increased in a PPARα-dependent manner. This increased expression of LACS might enhance the fatty acyl-CoA supply to fatty acid degradation and sulfatide synthesis pathways. In fact, the first and last reactions in the sulfatide synthesis pathway are regulated by PPARα. Therefore, we also measured the expression levels of enzymes involved in sulfatide metabolism and the regulation of cellular sulfatide content. The levels of these enzymes and cellular sulfatide content both increased in a PPARα-dependent manner. These results indicate that PPARα activation plays defensive and compensative roles by reducing cellular toxicity associated with fatty acids and sulfuric acid.

Traditional Japanese Kampo medicine has been widely used in clinical practice in Japan. Though it is a compulsory subject in Japanese medical schools, a standard educational program in Kampo medicine does not exist. Tohoku University has incorporated Kampo medicine into clinical education via didactic lectures since 2003; however, student evaluations have been lower for Kampo than for all other clinical specialties. We administered a questionnaire about a Kampo medicine course for fifth-year students from 2009 to 2012 and developed an educational program based on feedback obtained. The questionnaire consisted of nine questions (a clear training plan; opportunities for learning, practice, and patient contact; acquisition of medical knowledge and physical examination; learning professionalism; understanding the specialty; overall assessment) that were rated on a 5-point Likert scale along with open-ended questions about the course’s strengths and weaknesses. The students responded to the questionnaire after clinical practice in Kampo medicine and other clinical specialty courses. Scores for Kampo medicine and the average of other clinical specialties were compared. All 389 students who participated in Kampo clinical practice answered the questionnaire. In 2009, scores for Kampo medicine for nine questions were lower than for the average of the other clinical specialties. After curriculum reformation involving hands-on training in 2012, all scores except “opportunities to learn about clinical cases” and “opportunities to practice involvement” were higher than the average of all other clinical specialties. In conclusion, we have successfully developed a Kampo medicine educational program for our university through this survey study.

Exacerbations of chronic obstructive pulmonary disease (COPD) lead to high morbidity and mortality. Respiratory virus infection is considered as one of the important causes of COPD exacerbations. The aim of this study was to assess the prevalence of respiratory virus infection in COPD exacerbations and to find the factors associated with susceptibility to viral infections. Furthermore, we tried to examine if COPD exacerbations caused by viral infections have more severe clinical outcomes in comparison with those with non-viral causes. We enrolled the patients with acute exacerbations of COPD who were hospitalized in a university hospital, over a 2-year period. Nasopharyngeal swabs were taken and viruses were identified by multiplex polymerase chain reaction. A total of 278 episodes of COPD exacerbations were recorded in 213 patients with COPD (number of females = 73). Among the COPD exacerbations, viral infection was detected in 78 episodes (28.1%) from 67 subjects. The most common virus was rhinovirus (38.8%), followed by respiratory syncytial virus, coronavirus, influenza A, parainfluenza, adenovirus and metapneumovirus. In multivariate regression analysis adjusting for sex, age, BMI, lung function and history of exacerbations, female subjects were found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 2.58, 95%CI 1.25-5.31, P = 0.010). The severity of COPD exacerbations were not different between positive and negative viral detections. In conclusion, the prevalence of viral infection was 28.1% in the hospitalized patients with COPD exacerbations. Moreover, female subjects are at significantly higher risk for viral infections in COPD exacerbations.

Bell’s phenomenon is a physiological phenomenon wherein the eye ball involuntarily rolls upward during eyelid closing. Although this phenomenon occurs in healthy individuals, the neural mechanism related to Bell’s phenomenon has not yet been identified. We aimed to investigate the brain regions relevant to Bell’s phenomenon and volitional eye movement using [¹⁵O] H₂O and positron emission tomography (PET). We measured regional cerebral blood flow (rCBF) in 8 normal subjects under 3 conditions: at rest with eyes closed, during opening and closing of the eyelids in response to sound stimuli (lid opening/closing), and during vertical movement of the eyes with lids closed in response to sound stimuli (volitional eye movement). The supplementary motor area (SMA) proper, right superior temporal gyrus, right insular cortex and left angular gyrus were activated during lid opening/closing. The right frontal eye field (FEF), pre-SMA, left primary motor area, right angular gyrus, and SMA proper were activated during volitional eye movement. The SMA proper was active during both tasks, while the FEF and pre-SMA were active during volitional eye movement, but not during eyelid opening/closing. A comparison of activation during volitional eye movements and lid opening/closing tasks revealed a relative increase in rCBF in the FEF. There were no areas that are activated in relation to Bell’s phenomenon. In conclusion, activation in the FEF mainly occurs during volitional eye movement. Since Bell’s phenomenon is a reflexive eye movement, the FEF is scarcely concerned in Bell’s phenomenon.

Prevention of cervical cancer has been unsuccessful in Japan because of low rates of cancer screening and vaccination. The Vaccine Adverse Review Committee of the Japanese Government investigated 2,475 adverse events and reported 617 (6.9/100,000) severe cases and 176 (2.0/100,000) cases with chronic pain. The proactive recommendation for human papillomavirus (HPV) vaccination has been suspended since June 2013. In this study, we examined vaccination rate and incidence of abnormal cervical cytology in women aged 20 to 24 years attending cancer screening in Miyagi. Among the 3,272 women who underwent a health check in the fiscal year 2014 (April 2014-March 2015), 332 (10.2%) received a HPV vaccination. The HPV vaccination rates were 42.3%, 10%, 17.5%, 3.8% and 4.0% in women aged 20, 21, 22, 23 and 24 years, respectively. The rates of atypical squamous cells of undetermined significance (ASC-US) or worse were 2.41% (8/332) in women with HPV vaccination and 5.03% (148/2,940) in those without HPV vaccination, indicating a significant decrease in vaccinated women (p = 0.03). ASC-US cases were referred to HPV DNA tests. In addition, the rates of high grade squamous intraepithelial lesion (HSIL) or worse were 0.30% (1/332) in women with HPV vaccination and 0.82% (24/2,940) in those without HPV vaccination, showing the marginal decrease in women who were vaccinated (p = 0.3). Thus, this study indicates that HPV vaccination is associated with a reduction in the incidence of cervical abnormalities, suggesting a need for scientific discussion of reinstatement of proactive recommendation for HPV vaccine in Japan.

The taste detection system for oral fatty acid may be related to obesity. In addition, sleep is intrinsically and closely related to food intake and metabolism. However, the association of gustatory salivation with body mass index (BMI), daytime sleepiness, or sleep habits is largely unknown. Therefore, we evaluated the relationship between gustatory salivation and BMI, Epworth sleepiness scale (ESS, a daytime sleepiness scale) or sleep habits among 26 healthy young individuals (20 males and 6 females; mean age: 26.0 ± 4.3 years). We also measured the saliva flow rate (SFR) that was induced by gum-chewing or each of three prototypical tastants (acetic acid, sucrose, and NaCl). Further, the SFR was induced by fatty acid, provided as oleic acid (OA) homogenized in non-fat milk. All participants showed normal rates of salivation during resting and gum-chewing states. The increase in the SFR induced by OA, but not by each of the three tastants, was associated with BMI. Moreover, both daytime sleepiness level and frequency of snoring were associated with the increase in the SFR induced by NaCl. These results suggest that BMI is associated with salivation induced by oral fatty acid exposure. Additionally, the regulatory mechanism for the NaCl-induced salivation reflex may have a relationship with impairments of the respiratory control system that are related to snoring during sleep and lead to daytime sleepiness because of insufficient sleep. Thus, measurement of gustatory salivation might contribute to the evaluation and prevention of obesity and sleep-related breathing disorders.

Neonatal toxic shock syndrome-like exanthematous disease (NTED) is a newly recognized neonatal infectious disease, caused by the superantigen toxic shock syndrome toxin-1 (TSST-1). TSST-1 is mainly produced by methicillin-resistant Staphylococcus aureus, and the immune responses to TSST-1 are known to cause toxic shock syndrome, a life-threatening infectious disease. The clinical symptoms of NTED are skin rash, fever, and thrombocytopenia, but severe thrombocytopenia is rare in term infants with NTED. Although the cause of NTED is the same as that of toxic shock syndrome, the clinical symptoms of NTED are milder than toxic shock syndrome. The mild phenotype of NTED has been explained by selectively elevated serum levels of anti-inflammatory cytokine interleukin (IL)-10, which suppress immune responses to TSST-1. In the present study, we report a term female infant of NTED complicated with hemophagocytic syndrome (HPS). HPS is characterized by systemic inflammation and hemophagocytosis, caused by uncontrolled activation of T cells and macrophages. The serum IL-10 level of the patient at 4 days of age was relatively low (67 pg/mL) for NTED but still higher than normal controls (< 2.0 pg/mL). The patient also showed severe thrombocytopenia. We speculate that the serum IL-10 level of the patient was enough to supress immune responses to TSST-1, thereby resulting in NTED, but not enough to suppress the onset of HPS. This is the first reported case of NTED complicated with HPS. If a physician encounters an NTED patient with severe cytopenia, microscopic examination of peripheral blood smear should be carried out to exclude HPS.

Low birth weight (LBW) has been considered as a risk factor for adult hypertension that is associated with deterioration of autonomic functions and low-grade inflammation. To explore the above effects of LBW, we measured blood pressure (BP) and heart rate variability during postural change from a supine position to a sitting position in 21 healthy Mongolian adults aged 23-34 years: 4 with LBW (birth weight < 2,500 g), 13 with normal birth weight (NBW, 2,500 g ≤ birth weight < 4,000 g), and 4 with high birth weight (HBW, ≥ 4,000 g). Mongolian population is known to have higher prevalence of hypertension. The ratio of low frequency (LF, 0.04-0.15 Hz) to high frequency components (HF, 0.15-0.40 Hz) was used as an index of sympathetic nerve activity, and HF was used as an index of parasympathetic nerve activity. In contrast to the NBW group, the LBW and HBW groups showed no significant increase in heart rate, systolic BP and LF/HF following postural change. We also measured blood cell counts and other blood parameters related to inflammation. After adjusting for age, BMI, sex and family history of hypertension, LBW was retained as an independent predictor only for higher counts of leukocytes (β = −0.51, p < 0.05), basophils (β = −0.62, p < 0.01), eosinophils (β = −0.83, p < 0.001), and platelets (β = −0.61, p < 0.05). We propose that LBW leads to blunted autonomic responses and low-grade inflammation in seemingly healthy Mongolian adults.