Maturation of odour identification ability and related factors in children.

BACKGROUND: Olfaction plays an important role in our daily and social lives, both as adults and as children. This study assessed whether the ability to identify odours increases with age, as well as the ability in various age groups and the factors involved. METHODS: The survey was performed in 2017 on 697 Japanese children (366 girls and 331 boys) aged 6â€"18 years who lived in Tsunan, Niigata Prefecture, Japan by using the 'Open Essence', a card-type odour identification test. We collected information regarding age, sex, and physical characteristic. We also inquired whether participants had siblings or if members of the family smoked, and whether they had conversations about odour at home. Statistical analysis was performed to evaluate the factors affecting odour identification abilities. RESULTS: The results showed that the odour identification abilities of children increase with age, and children who have daily conversations about odours at home have better odour identification abilities. CONCLUSIONS: Odour identification ability increases with age. In addition, our findings suggest that conversation may positively affect odour identification. Hence, it is important for children to be exposed to an environment where they develop an interest in smells for better growth of their olfactory identification ability.

Perinatal nicotine exposure suppresses PPARγ epigenetically in lung alveolar interstitial fibroblasts.

Due to the active inhibition of the adipogenic programming, the default destiny of the developing lung mesenchyme is to acquire a myogenic phenotype. We have previously shown that perinatal nicotine exposure, by down-regulating PPARγ expression, accentuates this property, culminating in myogenic pulmonary phenotype, though the underlying mechanisms remained incompletely understood. We hypothesized that nicotine-induced PPARγ down-regulation is mediated by PPARγ promoter methylation, controlled by DNA methyltransferase 1 (DNMT1) and methyl CpG binding protein 2 (MeCP2), two known key regulators of DNA methylation. Using cultured alveolar interstitial fibroblasts and an in vivo perinatal nicotine exposure rat model, we found that PPARγ promoter methylation is strongly correlated with inhibition of PPARγ expression in the presence of nicotine. Methylation inhibitor 5-aza-2'-deoxycytidine restored the nicotine-induced down-regulation of PPARγ expression and the activation of its downstream myogenic marker fibronectin. With nicotine exposure, a specific region of PPARγ promoter was significantly enriched with antibodies against chromatin repressive markers H3K9me3 and H3K27me3, dose-dependently. Similar data were observed with antibodies against DNA methylation regulatory factors DNMT1 and MeCP2. The knock down of DNMT1 and MeCP2 abolished nicotine-mediated increases in DNMT1 and MeCP2 protein levels, and PPARγ promoter methylation, restoring nicotine-induced down regulation of PPARγ and upregulation of the myogenic protein, fibronectin. The nicotine-induced alterations in DNA methylation modulators DNMT1 and MeCP2, PPARγ promoter methylation, and its down-stream targets, were also validated in perinatally nicotine exposed rat lung tissue. These data provide novel mechanistic insights into nicotine-induced epigenetic silencing of PPARγ that could be exploited to design novel targeted molecular interventions against the smoke exposed lung injury in general and perinatal nicotine exposure induced lung damage in particular.

Curcumin protects the developing lung against long-term hyperoxic injury.

Curcumin, a potent anti-inflammatory and antioxidant agent, modulates peroxisome proliferator-activated receptor-γ signaling, a key molecule in the etiology of bronchopulmonary dysplasia (BPD). We have previously shown curcumin's acute protection against neonatal hyperoxia-induced lung injury. However, its longer-term protection against BPD is not known. Hypothesizing that concurrent treatment with curcumin protects the developing lung against hyperoxia-induced lung injury long-term, we determined if curcumin protects against hyperoxic neonatal rat lung injury for the first 5 days of life, as determined at postnatal day (PND) 21. One-day-old rat pups were exposed to either 21 or 95% O2 for 5 days with or without curcumin treatment (5 mg/kg) administered intraperitoneally one time daily, following which the pups grew up to PND21 in room air. At PND21 lung development was determined, including gross and cellular structural and functional effects, and molecular mediators of inflammatory injury. To gain mechanistic insights, embryonic day 19 fetal rat lung fibroblasts were examined for markers of apoptosis and MAP kinase activation following in vitro exposure to hyperoxia for 24 h in the presence or absence of curcumin (5 µM). Curcumin effectively blocked hyperoxia-induced lung injury based on systematic analysis of markers for lung injury (apoptosis, Bcl-2/Bax, collagen III, fibronectin, vimentin, calponin, and elastin-related genes) and lung morphology (radial alveolar count and alveolar septal thickness). Mechanistically, curcumin prevented the hyperoxia-induced increases in cleaved caspase-3 and the phosphorylation of Erk1/2. Molecular effects of curcumin, both structural and cytoprotective, suggest that its actions against hyperoxia-induced lung injury are mediated via Erk1/2 activation and that it is a potential intervention against BPD.

1alpha,25(OH)2D3 and its 3-epimer promote rat lung alveolar epithelial-mesenchymal interactions and inhibit lipofibroblast apoptosis.

Although alveolar wall thinning has been attributed to apoptosis of interstitial lung lipofibroblasts (LFs), the underlying molecular mechanism(s) remains unknown. Although the physiological vitamin D steroid hormone 1alpha,25(OH)(2)D(3) (1,25D) has been suggested as a local paracrine/autocrine effector of fetal lung maturation and is known to affect fibroblast apoptosis, its effects on LF apoptosis are unknown. We determined the role of 1,25D and its metabolite, C-3-epimer (3-epi-1,25D), on LF and alveolar type II (ATII) cell differentiation, proliferation, and apoptosis. Embryonic day 19 Sprague-Dawley fetal rat lung LFs and ATII cells were treated with 1,25D or 3-epi-1,25D (1 x 10(-10) to 1 x 10(-8) M) for 24 h, and cell proliferation, apoptosis, and differentiation were assessed. Both 1,25D and 3-epi-1,25D exhibited dose-dependent increases in expression of the key homeostatic epithelial-mesenchymal differentiation markers, increased LF and ATII cell proliferation, and decreased apoptosis. Furthermore, rat pups administered 1,25D from postnatal days 0 to 14 showed increased expressions of key LF and ATII cell differentiation markers, increased Bcl-2-to-Bax ratio as an index of decreased spontaneous alveolar LF and ATII cell apoptosis, increased alveolar count, and a paradoxical increase in septal thickness. We conclude that spatial- and temporal-specific actions of vitamin D play a critical role in perinatal lung maturation by stimulating key alveolar epithelial-mesenchymal interactions and by modulating LF proliferation/apoptosis. These data not only provide the biological rationale for the presence of an alveolar vitamin D paracrine system, but also provide the first integrated molecular mechanism for increased surfactant synthesis and alveolar septal thinning during perinatal lung maturation.

Analysis of serum FSH bioactivity in a patient with an FSH-secreting pituitary microadenoma and multicystic ovaries: A case report.

FSH-secreting pituitary adenoma (FSHoma) is often associated with increased levels of serum FSH and ovarian hyperstimulation syndrome (OHSS). The OHSS has historically been attributed to elevated FSH production by the FSHoma; however, some FSHoma patients with OHSS have normal serum FSH levels. OHSS may result not from increased FSH levels, but also from increased bioactivity of the FSH derived from the adenoma. To address this, we measured the FSH bioactivity in the serum of a 40-year-old woman with an FSHoma and OHSS, whose FSH levels were normal. Chinese hamster ovary cells stably expressing FSH receptors were prepared and transfected with a cAMP-responsive element-driven luciferase reporter plasmid. Cells were then treated with recombinant human FSH (rhFSH), the patient's sera, or sera from controls, collected at different time points, and subjected to a luciferase assay. Luciferase activity was increased in response to rhFSH in a dose-dependent manner. The responsiveness was further augmented by co-addition of a 3-methyl isobutylxanthine, which improved the sensitivity of our assay. Unexpectedly, the serum FSH bioactivity/immunoactivity ratio of the patient was mostly equal to that of normal subjects. This was confirmed with a granulosa cell aromatase assay. This case report suggests that alternate explanations may exist for the OHSS phenotype seen in some FSHoma patients.

Stress assessment in acute care department nurses by measuring interleukin-8.

BACKGROUND: Cytokines, such as interleukin (IL)-8, have been shown to be related to depressive symptoms or inflammatory diseases and may be useful as stress biomarkers. AIM: This study was to assess whether urinary IL-8 levels were reliable indicators of stress among acute care department (AD) nurses. METHODS: A total of 118 nurses participated in the study. Urinary IL-8 levels of 49 AD nurses were compared with levels of a control group of 69 chronic care department (CD) nurses. RESULTS: The urinary IL-8 levels of AD nurses, who reported a higher level of professional stress, were higher than the levels of CD nurses (P < 0.01). CONCLUSION: Measurement of urinary IL-8 may be an appropriate biomarker for stress assessment in nurses.

Older Adults with Fear of Falling Show Deficits in Motor Imagery of Gait.

OBJECTIVE: Understanding of the underlying mechanisms of Fear of Falling (FoF) could help to expand potential treatments. Given the nature of motor performance, the decline in the planning stage of motor execution may be associated with an expression of FoF. The aim of this study was to assess the planning/prediction accuracy in motor execution in people with FoF using gait-related motor imagery (MI). DESIGN: Cross-sectional case/control study. SETTING: Three health centers in Japan. PARTICIPANTS: Two hundred and eighty-three community-dwelling older adults were recruited and stratified by presence of FoF as FoF group (n=178) or non-FoF group (n=107). MEASUREMENTS: Participants were tested for both imagery and execution tasks of a Timed Up and Go (TUG) test. The participants were first asked to imagine the trial (iTUG) and estimate the time it would take, and then perform the actual trial (aTUG). The difference between iTUG and aTUG (Δ TUG) was calculated. RESULTS: The FoF group was significantly slower in aTUG, but iTUG duration was almost identical between the two groups, resulting in significant overestimation in the FoF group. The adjusted logistic regression analysis showed that increased Δ TUG (i.e., tendency to overestimate) was significantly associated with FoF (OR = 1.05; 95% CI = 1.02-1.10). Low frequency of going outdoors was also associated with FoF (OR 2.95; 95% CI: 1.16-7.44). CONCLUSIONS: Older adults with FoF overestimate their TUG performance, reflecting impairment in motor planning. Overestimation of physical capabilities can be an additional explanation of the high risk of falls in this population.

What factor within the Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) criteria is most strongly correlated with trauma induced DIC? A retrospective study using thromboelastometry in a single center in Japan.

PURPOSE: The diagnostic criteria for disseminated intravascular coagulation (DIC) established by the Japanese Association for Acute Medicine (JAAM) is able to diagnose DIC accurately and promptly. The aim of this retrospective study is to evaluate the degree of association between each parameter of JAAM DIC criteria and the diagnosis of trauma induced DIC (T-DIC) utilizing thromboelastometry (ROTEM). METHODS: Trauma patients transported to our hospital with ROTEM performed in the emergency department between January 2013 and December 2015 were enrolled in this study. We evaluated (1) the characteristics of T-DIC, (2) the relationships between T-DIC and each parameter of the JAAM DIC criteria and (3) the diagnostic accuracies of each parameter for T-DIC by statistical measurement. RESULTS: All 72 patients (21 T-DIC and 51 control) were included in primary analysis. T-DIC was significantly related to younger age, more severe trauma scores, more cases of massive transfusions, and remarkable coagulation abnormality detected by standard coagulation tests. In the cases of T-DIC, ROTEM showed longer clotting time, lower acceleration, lower clot firmness, and inhibited fibrinolysis in EXTEM/INTEM. Within the JAAM DIC score, PT-INR ≥1.2 was the most accurate factor for T-DIC diagnosis; sensitivity 60.0%, specificity 100.0%, and accuracy 88.7%. PT-INR ≥1.2 was statistically correlated with the JAAM DIC score (p < 0.001, r = 0.709). The univariate analysis based on 1.2 of PT-INR indicated statistical differences in most categories of ROTEM, which is similar to analysis performed for the presence and absence of T-DIC. CONCLUSIONS: Among JAAM DIC criteria, the PT-INR ≥1.2 was the most accurate factor for both the diagnosis of T-DIC and the evaluation of its severity.

In vivo conformation of mitochondrial DNA revealed by pulsed-field gel electrophoresis in the true slime mold, Physarum polycephalum.

Pulsed-field gel electrophoresis (PFGE) was used to examine the in vivo and in vitro conformations of Physarum polycephalum mitochondrial DNA (mtDNA). We used plugs containing isolated mitochondria, isolated mitochondrial nucleoids (mt-nuclei), and isolated mtDNA, in addition to whole cells. The mtDNA contained in the myxamoebae, plasmodia, isolated mitochondria, and isolated mt-nuclei was circular, but most of the isolated mtDNA had been site-specifically fragmented and linearized during DNA preparation and storage under low ionic strength conditions. Restriction mapping of Physarum mtDNA by the direct digestion of the isolated mt-nuclei from two different strains, DP89 x AI16 and KM88 x AI16, resulted in the circular form. A linear mitochondrial plasmid, mF, is known to promote mitochondrial fusion and integration of itself into the mtDNA in Physarum. Linearization of mtDNA by the integration of the mF plasmid was demonstrated when we used PFGE to analyze isolated mitochondria from the plasmodial strain DP89 x NG7 carrying the mF plasmid (mF+). The PFGE system can be used not only to determine whether the form of mtDNA is linear or circular but also to analyze the dynamic conformational changes of mtDNA.

Carbon dioxide induced panic attack in panic disorder in Japan.

1. The authors investigated the psychological and biochemical factors associated with challenge by 5% CO2-95% O2 inhalation for 20 min. While fifteen healthy people were used as control, thirteen cases who were diagnosed by DSM-III-R as suffering from panic disorder were used as subjects. CO2 inhalation induced panic in 38% of the panic disorder patients, but did not cause panic in any of the control cases (0%). 2. Acute panic inventory (API), heart rate and breathing rate of the panic group increased significantly after CO2 inhalation compared with the values in the control and non-panic groups. 3. Heart rates and systolic blood pressure were significantly higher those in the panic disorder and non-panic groups than in the control group prior to CO2 inhalation. The cortisol values in the panic and non-panic groups also were significantly higher than those in the control group before and after CO2 inhalation. 4. These results suggest elevated activity of the sympathetic nervous system during panic. The significantly higher heart rate, systolic blood pressure and cortisol values of the panic disorder subjects relative to the control before CO2 inhalation may have been due to circumstantial factors. The present findings of convincing evidence for behavioral, physiological, and biochemical hypersensitivity to CO2 in patients with panic disorders are consistent with a model of interoceptive conditioning in these patients.

Spontaneous passage of a colon cast in the absence of abdominal aneurysm.

The spontaneous passage of colon cast from a 76-year-old Japanese female patient is reported. Macroscopically, the colon case was shaped like the airbladder of a fish. Histopathologically, the cast consisted of degenerated colonal mucosa, including glands. No inflammatory reaction was apparent. The patient lacked any evidence of abdominal aneurysm. Since there have been only five reported cases of colon cast in the literature, and since in all of those association with abdominal aneurysms was always described, the present study represents the first report demonstrating the formation of a colon cast in the absence of associated abdominal aneurysm. However, the patient was found to exhibit several risk factors for ischemic colitis, such as arteriosclerosis on the wall of the abdominal aorta, chronic constipation, and colonic stenosis. Her colonal mucosal surface, indeed, suggested ischemic colitis. This case report, therefore, indicates that ischemic colitis, due to various causes, may be responsible for the formation of colon casts, and that the presence of an abdominal aneurysm is not necessarily a prerequisite for colon cast formation. This report may contribute to a better understanding of the pathogenesis of colon casts.

Sociomedical factors affecting participation in screening program on cerebro- and cardio- vascular disease.

In 1984 the Public Health Bureau of Nagoya City began a new health check-up program to encourage citizens aged 40 years to have a medical examination. The rate of participation was 46.6% greater than that of the previous program; however, at about 16%, it was still low. From the survey in Moriyama Ward following results were suggested. Housewives and female part-time workers who had not had a health examination during the previous year showed participation rates of 32.7% and 42.4%, respectively. It would seem that the low rate of participation in the health examination program conducted in the metropolitan area by the municipal Public Health Bureau is due to the existence of many medical care facilities, and the fact that 64.6% of men and 52.6% of women had undergone a medical examination in the year preceding the program. Total screening rates became 69.7% in males and 66.0% in females. Participation rates of 32.7% and 42.4% were achieved by unemployed women and by women with part-time employment, respectively, who had no experience of screening in the previous year. Total screening rates were 63.7% for the unemployed women and 82.1% for the part-time women.

Autoregulation of the gene for cystathionine gamma-synthase in Arabidopsis: post-transcriptional regulation induced by S-adenosylmethionine.

Cystathionine gamma-synthase (CGS) catalyses the first committed step of methionine biosynthesis in higher plants. CGS is encoded by the CGS1 gene in Arabidopsis. Stability of CGS1 mRNA is down-regulated in response to methionine application and the exon 1-coding region of CGS1 itself is necessary and sufficient for this regulation. mto1 (for methionine overaccumulation) mutants of Arabidopsis, which carry single-amino-acid sequence alterations within CGS1 exon 1, are deficient in this regulation and overaccumulate methionine. Since CGS1 exon 1 acts in cis during this regulation, we have proposed a model that the regulation occurs during translation of CGS1 mRNA when the nascent polypeptide of CGS and its mRNA are in close proximity. In fact, application of the translation inhibitor cycloheximide abolished this regulation in vivo. This model predicts that the regulation can be reproduced in an in vitro translation system. Studies using the in vitro translation system of wheatgerm extract have indicated that S-adenosylmethionine, a direct metabolite of methionine, is the effector of this regulation. A 5'-truncated RNA species, which is a probable degradation intermediate of CGS1 mRNA in vivo, was also detected in vitro, suggesting that the wheatgerm in vitro translation system reflects the in vivo regulation.

Effects of various types of vagotomy on gastrin release and gastric secretion in dogs.

Changes of serum gastrin and acid secretory responses to histamine, feeding and insulin stimulation before and after various types of vagotomy (TV, SV, SPV and SAV) were investigated in Heidenhain pouch dogs. The following results were obtained: (1) The acid secretory response to histamine slightly decreased after various types of vagotomy. (2) The responses of serum gastrin and acid secretion to feeding were elevated after various types of vagotomy. (3) The serum gastrin response to insulin was highly increased after SPV and TV, whereas the response was slightly increased and decreased after SV and SAV, respectively. The acid secretion in response to insulin was increased only after SPV, while it was decreased after the other types of vagotomy. These results led to the condition that there might be no correlation between serum gastrin and acid secretory responses to feeding and insulin after various types of vagotomy.

Prognosis of female patients with pulmonary tuberculosis.

To study the risk of death and causes of death among female patients with tuberculosis (TB), a total of 1,083 female patients who diagnosed as having active pulmonary TB and newly registered into the Nagoya TB registry between 1979-1981 were followed up till the end of 1983. During follow-up period 138 deaths (12.7%) were observed, a significantly higher rate than expected from the general population. Observed deaths (O) from all types of cancer (O/E ratio = 2.5), lung (6.4) and colorectal cancers (5.0), were significantly higher than that which was expected (E). The number of deaths from TB was naturally high (O/E ratio = 40.0, p less than 0.001). Malignant lymphoma and multiple myeloma also showed high relative risk. The smoking rate among the patients was 14%, about the same as with the general population. Excessive high rates of death from lung cancer were observed both among smoking and non-smoking cancer patients. Non-smokers showed a high proportion (60%) of adenocarcinoma. The proportion of the use of antituberculous drugs during the past five years was not different between the lung cancer group and the non-lung cancer group. Patients who died from cirrhosis of the liver showed more frequent use of antituberculous drugs than the others. Factors causing excess incidence of colorectal cancer remain unknown. It was suggested that some immunologic disorders in TB patients may play some role in the development of cancer.

The complete DNA sequence of the mitochondrial genome of Physarum polycephalum.

The complete sequence of the mitochondrial DNA (mtDNA) of the true slime mold Physarun polycephalum has been determined. The mtDNA is a circular 62,862-bp molecule with an A+T content of 74.1%. A search with the program BLAST X identified the protein-coding regions. The mitochondrial genome of P. polycephalum was predicted to contain genes coding for 12 known proteins [for three cytochrome c oxidase subunits, apocytochrome b, two F1Fo-ATPase subunits, five NADH dehydrogenase (nad) subunits, and one ribosomal protein], two rRNA genes, and five tRNA genes. However, the predicted ORFs are not all in the same frame, because mitochondrial RNA in P. polycephalum undergoes RNA editing to produce functional RNAs. The nucleotide sequence of an nad7 cDNA showed that 51 nucleotides were inserted at 46 sites in the mRNA. No guide RNA-like sequences were observed in the mtDNA of P. polycephalum. Comparison with reported Physarum mtDNA sequences suggested that sites of RNA editing vary among strains. In the Physarum mtDNA, 20 ORFs of over 300 nucleotides were found and ORFs 14 19 are transcribed.