Relationship between Psychological Status and Health Behaviors during the Coronavirus Disease Pandemic in Japanese Community-Dwelling Older Adults.

The coronavirus disease (COVID-19) continues to be a widespread pandemic. We investigated the relationship between anxiety/stress and health behaviors during the COVID-19 pandemic in homebound Japanese older adults during January and February 2021. We surveyed 1507 community-dwelling, older Japanese adults using a self-administered questionnaire on primary attributes, including family structure, evaluation of psychological anxiety/stress, and health behaviors. Participants were divided into four anxiety/stress groups based on the frequency of experiencing anxiety/stress, and their association with health behaviors was analyzed using bivariate and multivariate analyses. Responses were received from 469 (31.1%) respondents. In the bivariate analysis, age and family structure were significantly associated with anxiety/stress (p < 0.01). The health behaviors significantly associated with anxiety/stress were walking, balanced eating habits, limited snacking, regular lifestyle, and dental visits. Logistic regression analysis was performed using the variables in the bivariate analysis that showed a significant association with anxiety/stress status as independent variables. Finally, age and dietary habits were significantly associated with anxiety/stress status. No significant associations were found between any other variables. Among older adults living in the rural areas of Japan during the COVID-19 pandemic, anxiety/stress status was significantly associated with age and dietary habits but not with other health behaviors.

Mitochondrial toxins potentiate hydroxyl radical production in rat striatum during carbon monoxide poisoning.

Hydroxyl radical (•OH) production in the rat striatum during carbon monoxide (CO) poisoning, which inhibits complex IV, was enhanced synergistically by malonate, a mitochondrial complex II inhibitor, but not N-methyl-4-phenylpyridinium or NaCN, complex I and IV inhibitors, respectively. No such enhancement appeared in the case of NaCN combined with malonate. Intrastriatal dopamine, which is involved in •OH production by malonate, did not synergistically enhance CO-induced •OH production. Diphenyleneiodonium, a nonselective NADPH oxidase inhibitor, partly suppressed the potentiation of CO-induced •OH production by malonate. Impairment of mitochondrial functions might potentiate oxidative stress and intensify CO toxicity in the brain.

Blockade of the renin-angiotensin system suppresses hydroxyl radical production in the rat striatum during carbon monoxide poisoning.

Oxidative stress has been suggested to play a role in brain damage during carbon monoxide (CO) poisoning. Severe poisoning induced by CO at 3000 ppm, but not 1000 ppm, enhances hydroxyl radical (˙OH) production in the rat striatum, which might be mediated by NADPH oxidase (NOX) activation associated with Ras-related C3 botulinum toxin substrate (Rac) via cAMP signaling pathway activation. CO-induced ˙OH production was suppressed by antagonists of angiotensin II (AngII) type 1 receptor (AT1R) and type 2 receptor (AT2R) but not an antagonist of the Mas receptor. Suppression by an AT1R antagonist was unrelated to peroxisome proliferator-activated receptor γ. Angiotensin-converting enzyme inhibitors also suppressed CO-induced ˙OH production. Intrastriatal AngII at high concentrations enhanced ˙OH production. However, the enhancement of ˙OH production was resistant to inhibitors selective for NOX and Rac and to AT1R and AT2R antagonists. This indicates a different mechanism for ˙OH production induced by AngII than for that induced by CO poisoning. AT1R and AT2R antagonists had no significant effects on CO-induced cAMP production or ˙OH production induced by forskolin, which stimulates cAMP production. These findings suggest that the renin-angiotensin system might be involved in CO-induced ˙OH production in a manner independent of cAMP signaling pathways.

Hydroxyl radical production via NADPH oxidase in rat striatum due to carbon monoxide poisoning.

Severe poisoning induced by carbon monoxide (CO) at 3000 ppm, but not 1000 ppm, enhances hydroxyl radical (OH) production in rat striatum, which is greatly susceptible to inhibitors of NADPH oxidase (NOX), including diphenyleneiodonium (DPI), but not xanthine oxidase. The quantitative real-time PCR confirmed the previous microarray finding that CO at 3000 ppm, but not 1000 ppm, enhanced mRNA expression of dual oxidase 2 (DUOX2), but not DUOX1, in rat striatum, both of which are NOX family members producing reactive oxygen species. However, the protein levels of DUOX2 and DUOX1 were decreased by 3000 ppm CO. The CO-induced OH production was resistant to chelerythrine and SB230580, inhibitors of protein kinase C and p38MAPK, respectively, which are reported to mediate activation of DUOX1 and DUOX2, respectively. Deprivation of Ca2+, which is required for activation of both DUOXs, failed to suppress the CO-induced OH production. The CO-induced OH production was strongly suppressed by EHT1864, an inhibitor of Rac (Ras-related C3 botulinum toxin substrate), which is a factor for activation of NOX1, NOX2 and NOX3 (the role of Rac on Nox3 activation is controversial) as much as that was suppressed by DPI. In addition, EHT1864 in combination with DPI further suppressed the CO-induced OH production. There were no significant changes in the protein levels of NOX1 through NOX4 and Rac1. It is likely that the CO-induced OH production is mediated through the activation of Rac-dependent NOX enzymes, such as Nox1, Nox2, and Nox3.

Gene expression in rat striatum following carbon monoxide poisoning.

Carbon monoxide (CO) poisoning causes brain damage, which is attenuated by treatment with hydrogen [1], [2], a scavenger selective to hydroxyl radical (•OH) [3]. This suggests a role of •OH in brain damage due to CO poisoning. Studies have shown strong enhancement of •OH production in rat striatum by severe CO poisoning with a blood carboxyhemoglobin (COHb) level > 70% due to 3000 ppm CO, but not less severe CO poisoning with a blood COHb level at approximately 50% due to 1000 ppm CO [4]. Interestingly, 5% O2 causes hypoxia comparable with that by 3000 ppm CO and produces much less •OH than 3000 ppm CO does [4]. In addition, cAMP production in parallel with •OH production [5] might contribute to •OH production [6]. It is likely that mechanisms other than hypoxia contribute to brain damage due to CO poisoning [7]. To search for the mechanisms, we examined the effects of 1000 ppm CO, 3000 ppm CO and 5% O2 on gene expression in rat striatum. All array data have been deposited in the Gene Expression Omnibus (GEO) database under accession number GSE94780.

[The association between health-related quality of life and voice as evaluated by an acoustic analysis in elderly Japanese nursing home residents].

PURPOSE: We carried out a cross-sectional study investigating the association between health-related quality of life (HRQOL) and voice, as evaluated by an acoustic analysis, in elderly residents of a nursing home. METHODS: The HRQOL of 61 elderly nursing home residents (mean age: 82.1±8.3 years) was assessed via the SF-8 Health Survey questionnaire, Japanese version (SF-8). The subjects' voices were recorded and analyzed by a voice assessment software program, which calculated the pitch period perturbation quotient (PPQ), amplitude perturbation quotient (APQ), and noise-to-harmonic ratio (NHR). RESULTS: Subjects who scored under the 25th percentile on general health (GH), vitality (VT), or physical summary (PCS) in the SF-8 showed significantly higher PPQ, APQ, and NHR scores in comparison to their counterparts (p<0.05). After adjustment for age, lower GH scores were found to be associated with higher PPQ, APQ, and NHR scores; lower VT scores were associated with higher APQ and NHR scores; and lower PCS scores were associated with higher APQ and NHR scores (p<0.05). CONCLUSION: The results of the acoustic analysis indicated that voice was associated with HRQOL in the elderly nursing home residents of the present study. Among the acoustic parameters that were analyzed, PPQ, APQ, and NHR may be an influential factor that can be used to assess HRQOL, independently of the effects of age, in elderly individuals.

[Relationship between the nutritional status and the oral function among community-dwelling dependent elderly persons].

AIM: We herein examined the relationship between the nutritional status and the oral function among community-dwelling dependent elderly persons. METHODS: The subjects included 218 community-dwelling dependent elderly persons. The data were collected via questionnaires, including information regarding age, sex, the level of care required, nutritional status and swallowing function. We used the Mini Nutritional Assessment-Short Form (MNA-SF) to measure the nutritional status and the Dysphagia Risk Assessment for the Community-dwelling Elderly (DRACE) to evaluate the swallowing function. The tongue pressure and the labial closure force were measured using a tongue pressure measurement system (JMS Co. Ltd., Hiroshima, Japan) and the Lip de Cum (Cosmo-Instruments Co, Ltd, Tokyo, Japan). RESULTS: The mean MNA-SF score was 10.07±2.58. The mean DRACE score was 4.39±3.80. The mean tongue pressure was 23.89±10.61 kPa. The mean labial closure force was 10.17±6.04 N. The results of bivariate regression analyses showed that there was a poor correlation between the MNA-SF and the DRACE, tongue pressure and labial closure force. Furthermore, the multiple regression analysis with the MNA-SF as the dependent variable revealed a correlation between the DRACE and labial closure force (p<0.01, R(2)=0.02). CONCLUSIONS: Our results suggest that the nutritional status is significantly related to the swallowing function and labial closure force among community-dwelling dependent elderly persons.

[Relationship between the swallowing function and the health-related QOL among community-dwelling dependent elderly persons].

AIM: We examined the relationship between the swallowing function and the health-related QOL (quality of life) among community-dwelling dependent elderly persons. METHODS: The subjects included 191 community-dwelling dependent elderly persons. Data were collected via questionnaires, including information regarding age, gender, the level of care required, post-cerebrovascular disease, the health-related QOL and the swallowing function. We used the SF-8 to measure the health-related QOL and the DRACE (Dysphagia Risk Assessment for the Community-dwelling Elderly) to evaluate the swallowing function. RESULTS: The average DRACE score was 4.29±3.81. In addition, the swallowing risk was found to be related to the SF (social functioning) and MH (mental health) subscales of the SF-8. CONCLUSIONS: Our results suggest that the swallowing function is significantly related to the health-related QOL among community-dwelling dependent elderly persons.

Rupture of abdominal aortic aneurysm associated with long-term steroid therapy--a case report.

We report an autopsy case of bronchial asthma patient with a specific abdominal aortic aneurysm. The aneurysm did not show arteriosclerosis, and a specific saccular morphology was noted above the bifurcation. Histologically, necrosis of the media resembling acute aortic dissociation was observed. However, angiitis was ruled out. In addition, the aneurysm showed a cicatrized, old intimal crack in addition to the rupture site, suggesting repeated failures. The long-term steroid therapy-related fragility of the arterial wall may have been involved in the etiology of the aneurysm.

[Relationship between comprehensive quality of life and factors related to chewing and swallowing function among community-dwelling elderly individuals].

AIM: The purpose of the present study was to examine the relationship between comprehensive quality of life (QOL) and some factors regarding chewing and swallowing function among community-dwelling elderly individuals. METHODS: The subjects were 675 independent elderly persons residing in the northern area of Miyazaki Prefecture, and we obtained the self-administered questionnaires from 545 elderly people. We used "active scale for the elderly (ASE)" and "dysphagia risk assessment for the community-dwelling elderly (DRACE)" to evaluate their comprehensive QOL and function of chewing and swallowing, respectively. Furthermore, we examined some factors such as age, gender, subjective satisfaction with diet and verbal communication. RESULTS: The score of ASE showed a significant decline with age (p<0.01) while the DRACE score increased significantly with age (p<0.01). Pearson's correlation coefficients revealed that the ASE score was significantly related to all of the factors regarding regulation of food intake. Partial correlation coefficients adjusted for age also revealed the same tendency. From the multiple regression analysis, subjective satisfaction with verbal communication, DRACE score, age and appetite were extracted as factors influencing ASE score (adjusted R(2)=0.43, p<0.01). CONCLUSION: Among independent elderly persons residing in the community, the comprehensive QOL was significantly related to factors such as subjective satisfaction with verbal communication, dysphagia risk, age, and appetite.

[Oral diadochokinesis among Japanese aged over 55 years: analysis of standard values].

AIM: We investigated oral diadochokinesis (OD) among 212 Japanese aged over 55 years to assess the standard values of articulation ability. METHODS: Each subject repeatedly produced the OD syllables /pa/, /ta/, and /ka/. Subjects were divided into three age-groups (55-64 years, 65-74 years, and over 75 years) and by gender to compare the number of OD syllables per second. We also calculated the lower limit of values that determined the standard range for OD syllables. RESULTS: The number of all OD syllables in the over-75 age-group was significantly lower than in the 55-64 group. The number of OD /pa/ syllables in the over-75 group was significantly lower than in the 65-74 group. The number of OD /ta/ syllables in the 65-74 group was significantly lower than in the 55-64 group. The lower limit of the standard values for OD /pa/, /ta/, and /ka/ was, respectively, as follows: 4.9, 4.7, and 4.5 times in the 55-64 group; 3.8, 4.1, and 3.7 times in the 65-74 group; and 3.8, 3.3, and 2.6 times in the over-75 group. Among women, the number of OD /pa /, /ta/, and /ka/ syllables was significantly lower in the over-75 group than in other age-groups. CONCLUSIONS: We demonstrated that the lower limit of standard OD values is a means of assessing articulation in elderly subjects. We found that OD /ta/ tends to decrease from age 65 years. The decline in articulation ability clearly begins earlier in women than in men.

An autopsy case of bilateral adrenal pheochromocytoma-associated cerebral hemorrhage.

The autopsy findings of a 30-year-old woman who died of cerebral hemorrhage induced by bilateral adrenal pheochromocytoma are presented. The cerebral hemorrhage was shown on the left cerebral hemisphere widely. Her both adrenal glands were severe swelling, and their parenchyma was occupied by a dark red-brown tumorous positive for chromogranin A. The serum catecholamine and their metabolite, vanillylmandelic acid (VMA) levels were markedly high. Furthermore, cardiac hypertrophy and sclerosis of the arteries of various organs had progressed, suggesting an influence of persistent endocrinal hypertension. The measurement of serum VMA level was thought to be valuable for a postmortem diagnosis of pheochromocytoma. Bilateral adrenal pheochromocytoma may have excessively secreted catecholamine and subsequently caused secondary hypertension, leading to cerebral hemorrhage.

[Association between activities of daily living and oral diadochokinesis among Japanese elderly individuals in a nursing home].

AIM: We studied the association between the activities of daily living (ADL) and oral diadochokinesis (OD) among 84 Japanese elderly individuals residing in a nursing home. METHODS: We assessed OD in terms of speech and articulation. Each subject repetitively produced the syllables /pa/, /ta/, /ka/ and the sequence /pataka/. We also evaluated comprehensive ADL (basic, BADL; instrumental, IADL; and communicative, CADL) based on the criteria of the ADL-20 and intellectual ability using the revised Hasegawa Dementia Scale (HDS-R). We classified types of OD into a hypokinesia group (less than 3 times per second for OD /pa//ta//ka/ or less than once per second for OD /pataka/) and a repetition exercise maintenance group (more than 3 times per second for OD /pa//ta/ /ka/ or more than once per second for OD /pataka/). RESULTS: After adjusting for age, sex, and HDS-R score, the ADL-20 total score of the hypokinesia group was significantly lower than that of the maintenance group for OD (/pa/ and /pataka/) (p<0.01). The BADL for mobility (BADLm) score in the hypokinesia group for all OD sections was significantly lower than that in the maintenance group (p<0.05). The BADL for self-care score (BADLs) in the hypokinesia group for OD (/pataka/) was lower than that in the maintenance group (p<0.01). The CADL score in the hypokinesia group for OD (/pa/) was lower than that in the maintenance group (p<0.05). CONCLUSION: A decline in OD may have been associated with a decline in ADL in our subjects, suggesting that the rate of decline in OD may affect overall ADL in elderly individuals.

Peroxynitrite mediates disruption of Ca2+ homeostasis by carbon monoxide via Ca2+ ATPase degradation.

AIM: Sublethal carbon monoxide poisoning causes prolonged neurological damage involving oxidative stress. Given the central role of Ca(2+) homeostasis and its vulnerability to stress, we investigated whether CO disrupts neuronal Ca(2+) homeostasis. RESULTS: Cytosolic Ca(2+) transients evoked by muscarine in SH-SY5Y cells were prolonged by CO (applied via the donor CORM-2), and capacitative Ca(2+) entry (CCE) was dramatically enhanced. Ca(2+) store mobilization by cyclopiazonic acid was similarly augmented, as was the subsequent CCE, and that evoked by thapsigargin. Ca(2+) rises evoked by depolarization were also enhanced by CO, and Ca(2+) levels often did not recover in its presence. CO increased intracellular nitric oxide (NO) and all effects of CO were prevented by inhibiting NO formation. However, NO donors did not mimic the effects of CO. The antioxidant ascorbic acid inhibited effects of CO on Ca(2+) signaling, as did the peroxynitrite scavenger, FeTPPS, and CO increased peroxynitrite formation. Finally, CO caused significant loss of plasma membrane Ca(2+)ATPase (PMCA) protein, detected by Western blot, and this was also observed in brain tissue of rats exposed to CO in vivo. INNOVATION: The cellular basis of CO-induced neurotoxicity is currently unknown. Our findings provide the first data to suggest signaling pathways through which CO causes neurological damage, thereby opening up potential targets for therapeutic intervention. CONCLUSION: CO stimulates formation of NO and reactive oxygen species which, via peroxynitrite formation, inhibit Ca(2+) extrusion via PMCA, leading to disruption of Ca(2+) signaling. We propose this contributes to the neurological damage associated with CO toxicity.

Dual contradictory roles of cAMP signaling pathways in hydroxyl radical production in the rat striatum.

Studies have suggested that cAMP signaling pathways may be associated with the production of reactive oxygen species. In this study, we examined how modifications in cAMP signaling affected the production of hydroxyl radicals in rat striatum using microdialysis to measure extracellular 2,3-dihydroxybenzoic acid (2,3-DHBA), which is a hydroxyl radical adduct of salicylate. Up to 50 nmol of the cell-permeative cAMP mimetic 8-bromo-cAMP (8-Br-cAMP) increased 2,3-DHBA in a dose-dependent manner (there was no additional increase in 2,3-DHBA at 100 nmol). Another cAMP mimetic, dibutyryl cAMP (db-cAMP), caused a nonsignificant increase in 2,3-DHBA at 50 nmol and a significant decrease at 100 nmol. Up to 20 nmol of forskolin, which is a direct activator of adenylyl cyclase, increased 2,3-DHBA, similar to the effect of 8-Br-cAMP; however, forskolin resulted in a much greater increase in 2,3-DHBA. A potent inhibitor of protein kinase A (PKA), H89 (500 µM), potentiated the 8-Br-cAMP- and forskolin-induced increases in 2,3-DHBA and antagonized the inhibitory effect of 100 nmol of db-cAMP. Interestingly, the administration of 100 nmol of 8-bromo-cGMP alone or in combination with H89 had no significant effect on 2,3-DHBA levels. Doses of 100 nmol of a preferential PKA activator (6-phenyl-cAMP) or a preferential PKA inhibitor (8-bromoadenosine-3',5'-cyclic monophosphorothionate, Rp-isomer; Rp-8-Br-cAMPS), which also inhibits the cAMP-mediated activation of Epac (the exchange protein directly activated by cAMP), suppressed or enhanced, respectively, the formation of 2,3-DHBA. Up to 100 nmol of 8-(4-chlorophenylthio)-2'-O-methyladenosine-cAMP, which is a selective activator of Epac, dose-dependently stimulated the formation of 2,3-DHBA. These findings suggest that cAMP signaling plays contradictory roles (stimulation and inhibition) in the production of hydroxyl radicals in rat striatum by differential actions of Epac and PKA. These roles might contribute to the production of hydroxyl radicals concomitant with cAMP in carbon monoxide poisoning, because the formation of 2,3-DHBA was potentiated by the PKA inhibitor H89 and suppressed by Rp-8-Br-cAMPS, which inhibits PKA and Epac.

cAMP production mediated through P2Y(11)-like receptors in rat striatum due to severe, but not moderate, carbon monoxide poisoning.

We examined the effect of carbon monoxide (CO) poisoning on the production of cAMP, an intracellular second messenger, in rat striatum in terms of extracellular cAMP, which is highly correlated with intracellular cAMP, by using microdialysis. Severe poisoning due to 3000ppm CO, but not moderate poisoning due to 1000ppm CO, caused an increase in cAMP, which was susceptible to a voltage-dependent Na(+) channel blocker, tetrodotoxin, and more profound than that under comparable hypoxia caused by 5% O(2). These results were similar to our previous findings on the production of hydroxyl radical ((•)OH), suggesting a close relationship between cAMP and (•)OH production. The increase in cAMP was suppressed by a non-selective purine P2 receptor antagonist, suramin. However, other non-selective P2 receptor antagonists, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and reactive blue 2, exhibited no effect and weak non-significant suppression, respectively. A P2Y(11) receptor antagonist, NF157, dose-dependently suppressed the increase in cAMP, although rats lack the P2Y(11) receptor. These results suggest that a threshold for cAMP production mediated through P2Y(11)-like receptors following depolarization triggered by Na(+) influx exists in rat striatum during CO poisoning, and that the threshold is reached only in cases of severe CO poisoning. It is also likely that the threshold is related to the generation of (•)OH, contributing to the toxicity of CO in the brain.

Existence of a threshold for hydroxyl radical generation independent of hypoxia in rat striatum during carbon monoxide poisoning.

We examined the role of hypoxia in the carbon monoxide (CO)-induced generation of the hydroxyl radical (•OH) in the striatum, which could contribute to brain damage due to CO poisoning. Exposure of free-moving rats to 1,000 and 3,000 ppm CO or 8 and 5% O2 for 40 min caused concentration-dependent hypoxic conditions in terms of carboxyhemoglobin (COHb), deoxyhemoglobin, oxyhemoglobin, and O2 contents in arterial blood. The hypoxic conditions seemed comparable between 3,000 ppm CO and 5% O2, although alterations of pH and partial O2 pressure (PO2) were complex and concentration independent. In the striatum, CO and low O2 decreased tissue PO2 levels in a concentration-dependent and concentration-independent manner, respectively, but levels at the end of exposure were comparable among all groups. This was also the case for the increase in striatal blood flow. Although the increases in extracellular glutamate (excitatory), taurine (inhibitory), and alanine (non-neurotransmitter), in the striatum in response to CO and low O2 were complex, 3,000 ppm CO and 5% O2 had comparable effects. Thus, 3,000 ppm CO and 5% O2 seemed to induce comparable hypoxic conditions. Nevertheless, the former more strongly stimulated (•OH generation in the striatum than the latter. In addition, in contrast to low O2 which caused a concentration-dependent increase in (•OH, 1,000 ppm CO had no effect. The findings suggest that striatal •OH generation due to CO poisoning may be independent of hypoxia per se and that a threshold might exist.

Autopsy and genetic diagnosis of 21-hydroxylase deficiency with bilateral testicular tumors in a case under no medication for over one year.

The autopsy findings of an adult patient with 21-hydroxylase deficiency are presented. Genetic analysis of the 21-hydroxylase gene (CYP21A2) was performed for accurate diagnosis of congenital adrenal hyperplasia (CAH), and bilateral testicular tumors were characterized. We report a 29-year-old Japanese man who was diagnosed with CAH (21-hydroxylase deficiency) in infancy and had continued steroid therapy until the age of 28. However, for more than one year, he had not been treated for CAH and was found dead. In the medico-legal autopsy findings, both adrenal glands were enlarged, and hypertrophy of adrenal cortices and bilateral testicular tumors positive for melan-A were observed. Genomic DNA was prepared from cervical lymph nodes collected during autopsy, and CYP21A2 was PCR amplified and sequenced directly using newly designed primers. From the morphological findings, the bilateral testicular tumors were considered to be adrenogenital syndrome (TTAGS). Through the whole sequence of CYP21A2, the intron 2 splice mutation (656)A to (656)G was found. TTAGS were thought to be adrenal rests enlarged by ACTH stimulus. From the autopsy findings and the result of genetic analysis, he was diagnosed with the salt-wasting form of 21-hydroxylase deficiency and his cause of death was presumed to be heart failure based on abnormal electrolytes.

An autopsy case in which self-bloodletting via a cervical blood access led to a fatal outcome.

A 48-year-old woman was found dead on a chair in her living room. She had received dialysis every day because of chronic renal failure for the past 15 years. On a table beside her, there was a mirror and 10-mL syringe on a napkin. A stopper was out of place in a portion of a three-way blood access tube established in the right cervical region, and blood coagulation was noted in the lumen. There was a bloodstained measuring cup on the floor. Autopsy findings included a large number of shunt traces in the bilateral infraclavicular fossae and upper limbs, as well as the cervical blood access terminal reaching the right atrium via the internal jugular vein to superior vena cava. Various organs showed anemia. Neither a fatal lesion nor injury was noted in the main organs. Therefore, this patient may have committed suicide by self-bloodletting via a cervical blood access.