Active use of local exercise facilities can improve physical performance of community-dwelling older adults.

[Purpose] In this study, we investigated the effects of local exercise facility use on physical function of Japanese community-dwelling older adults. [Participants and Methods] We analyzed data obtained from a cohort project initiated in 1991. The study included approximately 4,800 individuals from suburban areas of central Japan; we investigated 322 older individuals residing in Municipality A, who underwent physical fitness assessments in 2018 and 2019. We recorded participants' exercise facility use frequency and physical performance, based on handgrip strength, open-eye single-leg standing, timed up-and-go, and walking speed tests. [Results] Baseline values in the open-eye single-leg standing test were significantly higher in the no-use than in the low- and high-use groups. Follow-up assessments revealed that grip strength was significantly higher in the high-use than in the no- and low-use groups. [Conclusion] Active use of exercise facilities was positively correlated with maintenance and improvement in physical fitness among participants, which highlights the benefits of easily accessible exercise facilities in maintaining long-term physical function. Future studies should focus on functions that extend beyond physical fitness to develop effective support programs that address the evolving health needs of the aging population.

Perfusion with carbon monoxide does not affect extracellular glutamate in dialysates of the hippocampus of freely moving mice.

Carbon monoxide (CO) produces several neurological effects, including cognitive, mood, and behavioral disturbance. Glutamate is thought to play a particularly important role in learning and memory. Thus, the present study was aimed at investigating the local effect of CO on the glutamate level in the hippocampus of mice using in vivo reverse microdialysis. Mice were perfused with Ringer's solution (control) or CO (60-125 µM) in Ringer's solution into the hippocampus via microdialysis probe. Dialysate samples were collected every 20 min, and then analyzed with high-performance liquid chromatography coupled to an electrochemical detector. The result revealed that the perfusion with CO had no significant effect on glutamate levels (p = 0.316) as compared to the control group. This finding does not support a local CO rise as the cause of the increased glutamate level in the hippocampus of mice.

An autopsy case of death by combined use of benzodiazepines and diphenidine.

We present an autopsy case involving benzodiazepines and diphenidine. Quantitative toxicological analysis showed concentrations of 7-aminoflunitrazepam (a flunitrazepam metabolite), 7-aminonimetazepam (a nimetazepam metabolite), chlorpheniramine and diphenidine in femoral blood of 0.086 µg/ml, 0.027 µg/ml, 0.066 µg/ml, and 0.073 µg/ml, respectively. Death was attributed to combined toxicity due to the influence of multiple drug interactions.

Ethanol and Acetaldehyde After Intraperitoneal Administration to Aldh2-Knockout Mice-Reflection in Blood and Brain Levels.

This paper reports, for the first time, on the analysis of ethanol (EtOH) and acetaldehyde (AcH) concentrations in the blood and brains of Aldh2-knockout (Aldh2-KO) and C57B6/6J (WT) mice. Animals were administrated EtOH (1.0, 2.0 or 4.0 g/kg) or 4-methylpyrazole (4-MP, 82 mg/kg) plus AcH (50, 100 or 200 mg/kg) intraperitoneally. During the blood tests, samples from the orbital sinus of the eye were collected. During the brain tests, dialysates were collected every 5 min (equal to a 15 µl sample) from the striatum using in vivo brain microdialysis. Samples were collected at 5, 10, 15, 20, 25, 30 and 60 min intervals post-EtOH and -AcH injection, and then analyzed by head-space GC. In the EtOH groups, high AcH levels were found in the blood and brains of Aldh2-KO mice, while only small traces of AcH were seen in the blood and brains of WT mice. No significant differences in EtOH levels were observed between the WT and the Aldh2-KO mice for either the EtOH dose. EtOH concentrations in the brain were comparable to the EtOH concentrations in the blood, but the AcH concentrations in the brain were four to five times lower compared to the AcH concentrations in the blood. In the AcH groups, high AcH levels were found in both WT and Aldh2-KO mice. Levels reached a sharp peak at 5 min and then quickly declined for 60 min. Brain AcH concentrations were almost equal to the concentrations found in the blood, where the AcH concentrations were approximately two times higher in the Aldh2-KO mice than in the WT mice, both in the blood and the brain. Our results suggest that systemic EtOH and AcH administration can cause a greater increase in AcH accumulation in the blood and brains of Aldh2-KO mice, where EtOH concentrations in the Aldh2-KO mice were comparable to the EtOH concentrations in the WT mice. Furthermore, detection of EtOH and AcH in the blood and brain was found to be dose-dependent in both genotypes.

Search and removal of radioactive seeds: another application of postmortem computed tomography prior to autopsy.

We herein introduce 3 cases illustrating a new application for pre-autopsy postmortem computed tomography (PMCT). In all 3 cases, there was insufficient background information about the victims provided to the forensic pathologists' department. PMCT showed metallic particles in the prostate gland, an indication of metallic seeds containing radioactive isotopes. In 2 of 3 cases, migrated seeds were also detected by CT imaging in the lungs and the heart. Also in 2 of 3 cases, authorities reinvestigated the victim's history before autopsy was completed, which resulted in following appropriate procedure for dealing with the seeds. Although all 3 cadavers were cremated after autopsy, the International Commission on Radiological Protection (ICRP) discourages cremation for deaths soon after radioactive seeds implantation to prevent air pollution by radioactive isotopes in the ash. Our opinion from the present cases is that pre-autopsy PMCT can be recommended for use by forensic pathologists and guidelines for investigating deaths after permanent brachytherapy should include how to deal with cadavers when medical history is limited.

A case of expressive-vocal amusia in a right-handed patient with left hemispheric cerebral infarction.

A 53-year-old right-handed woman had an extensive lesion in the left hemisphere due to an infarction caused by vasospasm secondary to subarachnoid bleeding. She exhibited persistent expressive-vocal amusia with no symptoms of aphasia. Evaluation of the patient's musical competence using the Montreal Battery for Evaluation of Amusia, rhythm reproduction tests, acoustic analysis of pitch upon singing familiar music, Japanese standard language tests, and other detailed clinical examinations revealed that her amusia was more dominantly related to pitch production. The intactness of her speech provided strong evidence that the right hemisphere played a major role in her linguistic processing. Data from functional magnetic resonance imaging while she was singing a familiar song, a scale, and reciting lyrics indicated that perilesional residual activation in the left hemisphere was associated with poor pitch production, while right hemispheric activation was involved in linguistic processing. The localization of infarction more anterior to the left Sylvian fissure might be related to the dominant deficits in expressive aspects of the singing of the patient. Compromised motor programming producing a single tone may have made a major contribution to her poor singing. Imperfect auditory feedback due to borderline perceptual ability or improper audio-motor associations might also have played a role.

Investigation of optimal display size for viewing T1-weighted MR images of the brain using a digital contrast-detail phantom.

We clarified the relationship between the display size of MRI images and observer performance using a digital contrast-detail (d-CD) phantom. The d-CD phantom was developed using Microsoft Visual Basic 2010 Express. It had a 512 × 512 matrix in size and a total of 100 holes, whose diameter increased stepwise from 4 to 40 pixels with a 4-pixel interval in the vertical direction; the contrast varied stepwise in the horizontal direction. The digital driving level (DDL) of the back-ground, the width of the DDL, and the contrast were adjustable. These parameters were determined on the basis of the actual T1-weighted magnetic resonance (MR) images of the brain. In this study, the DDL, width, and contrast were set to 85, 20, and 1, respectively. The observer performance study was performed for three different display sizes (30 cm × 30 cm as the enlarged size, 16 cm × 16 cm as the original size, and 10 cm × 10 cm as the reduced size) using a 2-megapixel color liquid crystal display monitor, and it was analyzed using Friedman and Wilcoxon statistical tests. The observer performances for the original display (p < 0.01) and the reduced display sizes (p < 0.01) were superior to that observed for the enlarged size, whereas there was no significant difference between the original display and reduced display sizes (p = 0.31). Evaluation with the digital phantom simulating MR imaging also revealed that the original and reduced display sizes were superior to the enlarged display size in observer performance. The d-CD phantom enables a short-term evaluation of observer performance and is useful in analyzing relation-ship between display size and observer performance.

Correlation between suicide and meteorological parameters.

OBJECTIVE: The aim of this study was to investigate the link between suicide and meteorological parameters in the 23 wards of Tokyo, Japan. MATERIALS AND METHODS: Monthly data (from January 2008 to December 2012) of suicide stratified by the type of suicide, i.e. hanging, drowning and jumping, were obtained from the Tokyo Medical Examiner's Office official web site. Monthly meteorological parameters (atmospheric pressure, air temperature, humidity and daylight hours) in the 23 wards of Tokyo were also used for the required period. The effects of meteorological parameters on suicide were explored. RESULTS: The number of suicides was 110.4±14.7 (80-149) for men and 55.6±9.1 (41-87) for women in the 23 wards of Tokyo, Japan. The mean air temperature was 16.6°C±7.7 °C (4.8-29.6 °C). The number of suicides by drowning for men was significantly and positively correlated with air temperature, and weakly and positively correlated with humidity. In addition, the number of suicides by drowning for men was significantly and negatively correlated with atmospheric pressure. CONCLUSIONS: The number of suicides by drowning was associated with meteorological parameters, especially in men, in the 23 wards of Tokyo, Japan.

A color test for the convenient identification of an ingested surface activating agent.

Color tests are easy, simple and inexpensive methods for the qualitative identification of chemicals. A color test was applied to the stomach contents of a forensic autopsy case. The result of the test, using bromophenol blue reagent, indicated the ingestion of a commercial cleaning product containing a cationic surface activating agent. Our findings suggest that forensic investigators should consider the additives used in commercial chemical products, such as surface activating agents, when determining the cause of death.

A fatal case of poisoning with ethanol and psychotropic drugs with putrefactive changes.

We present a fatal case involving poisoning with paroxetine, flunitrazepam, and ethanol, with putrefactive changes. Quantitative toxicological analysis showed that the concentrations of paroxetine and 7-aminoflunitrazepam, a metabolite of flunitrazepam, in the femoral blood were 0.28 µg/ml and 0.17 µg/ml, respectively. We also detected an ethanol level of 2.90 mg/ml and an n-propanol level of 0.10 mg/ml. We concluded that the cause of death was due to the interaction of paroxetine, flunitrazepam, and ethanol. The effects of putrefactive changes should be considered during forensic toxicological evaluation.

Efficient and versatile transformation systems in entomopathogenic fungus Lecanicillium species.

Lack of genetic tools in entomopathogenic fungi, especially those for targeted homologous recombination, hindered the advance in this field. To facilitate the genetic study, we constructed a transformation system in entomopathogenic fungus Lecanicillium sp. strain HF627 using the uridine auxotrophic pyrG mutant strain as host and endogenous pyrG as marker. pUC19 harboring endogenous pyrG successfully restored the uridine auxotrophy of the host strain, and the integration of the vector DNA was confirmed by Southern hybridization. An autonomously replicating vector harboring an AMA1 sequence was constructed and applied to the constructed transformation system, which improved the transformation efficiency 16.7-fold. Southern hybridization revealed replication of the AMA1-harboring vector with an average copy number of 2.4. A ku80 knock-out strain was created to improve the efficiency of gene targeting. Deletion of the pyrG locus, which is homologous to the marker gene, from the ku80 knock-out strain achieved a targeting efficiency of 62.5 % against both trp1 and his3; the levels of these genes were 3.2- and 5-fold higher, respectively, than the ku80-intact strain. With the pyrG-deleted and ku80-inactivated strain constructed in this study, transformation and targeted homologous recombination were highly enhanced, by which genetic analysis in Lecanicillium spp. will be performed quickly and efficiently.

Identification of a gene cluster responsible for the biosynthesis of cyclic lipopeptide verlamelin.

Only limited studies are available on the molecular-level biosynthesis of cyclic lipopeptides (cyclic and hybrid molecules consisting of peptide and fatty acid moieties) in filamentous fungi. Here, we identified and characterized biosynthetic genes of the cyclic lipopeptides, known as verlamelins. Only four genes, coding for non-ribosomal peptide synthetase (NRPS), fatty acid hydroxylase, thioesterase, and AMP-dependent ligase, were found to be involved in verlamelin biosynthesis by the analysis of corresponding gene knockouts. Surprisingly, no gene(s) coding for fatty acid synthase or polyketide synthase was present in the cluster, while verlamelin A/B contained a 5-hydroxytetradecanoic acid moiety. Precursor feeding experiment indicated that both fatty acid hydroxylase and thioesterase are involved to supply 5-hydroxytetradecanoic acid. The results suggested that 5-hydroxytetradecanoic acid was supplied from primary metabolism via fatty acid hydroxylase and loaded onto NRPS. Elongation of the peptide and final cyclization were accomplished by NRPS. The knowledge obtained through this study should provide new insight into fungal lipopeptide biosynthesis.

Lower air temperature is associated with ambulance transports and death in Takamatsu area, Japan.

OBJECTIVE: The aim of this study was to investigate the linkage among ambulance transports, the number of death and air temperature in Takamatsu area, Japan. METHODS: Monthly data of ambulance transports (total and acute disease) and the number of death from 2004 to 2012 were obtained from Fire Department Service in Takamatsu and Takamatsu city official website, Japan. Climate parameters for required period were also obtained from Japan Meteorological Agency. Population data in Takamatsu area were also used to adjust ambulance transports and the number of death. The linkage among ambulance transports, the number of death and climate parameters was evaluated by ecological analysis. RESULTS: Total ambulance transports (/a hundred thousand people/day) and ambulance transports due to acute disease (/a hundred thousand people/day) were 12.3 ± 0.9 and 6.8 ± 0.7, respectively. The number of death (/a hundred thousand people/day) was 2.5 ± 0.4. By quadratic curve, ambulance transports due to acute disease and the number of death were significantly correlated with the parameters of air temperature. However, the number of death was the highest in January and the lowest in August. CONCLUSION: Although higher air temperature was only associated with higher ambulance transports, lower air temperature was associated with both higher ambulance transports and the number death in Takamatsu area, Japan.

Senility deaths in aged societies: The case of Japan.

Senility is now the third largest cause of death in Japan, comprising 11.4% of the total number of deaths in 2022. Although senility deaths were common in the period before the Second World War, they declined sharply from 1950 to 2000 and then increased up to the present. The recent increase is more than what we could expect from an increasing number of very old persons or the increasing number of deaths at facilities. The senility death description in the death certificate is becoming poorer, with 93.8% of them only with a single entry of "senility". If other diseases are mentioned, those are again vague diseases or conditions. Senility, dementia and Alzheimer's disease, sequelae of cerebrovascular disease, and heart failure are the largest causes of death in which senility is mentioned in the death certificate. The period from senility onset to death is often described within a few months, but it varies. In some cases, the deceased's age was written out of a conviction that the ageing process starts from birth. As senility is perceived differently among the certifying doctors, a standardised protocol to certify the senility death is needed. On the other hand, senility death is the preferred cause of death and many people do not wish to receive invasive medical examinations before dying peacefully. Together with other causes of death related to frailty, there would be a need to capture senility as a proper cause of death, not just as a garbage code, in the aged, low-mortality population.

Kerosene condenses in the trachea following inhalation.

PURPOSE: We have investigated the absorption dynamics of petroleum fuel components from the analytical results of autopsy samples. METHODS: Post-mortem samples of the severely burned case, including femoral blood, intratracheal contents (mucus) and intratracheal gas-phase samples were collected, and analysed by gas chromatography-mass spectrometer with head-space solid-phase microextraction. RESULTS: The composition of flammable substances in the tracheal gas phase differed slightly from that in mucus. CONCLUSION: High-boiling point components are retained in the trachea, whereas relatively lower-boiling point components are detected predominantly in the tracheal gas phase and blood.

An autopsy case of intoxication caused by drug interaction with multiple psychotropic drugs, fluvoxamine, levomepromazine, and trihexyphenidyl.

A case of death due to combined use of multiple drugs is reported, and the pharmacokinetic interactions are discussed. A woman in her thirties was found dead in her home. A medico-legal autopsy found no findings suggestive of injury or natural disease. Toxicological analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) identified a toxic level of fluvoxamine (0.947 µg/mL), and concentrations greater than the therapeutic levels of levomepromazine (0.238 µg/mL) and trihexyphenidyl (0.225 µg/mL) were present, while bromazepam, haloperidol, sulpiride, and 7-aminoflunitrazepam were within or below their therapeutic ranges. Fluvoxamine is mainly metabolized by cytochrome P450 2D6 (CYP2D6), and levomepromazine is a potent CYP2D6 inhibitor. A high concentration of levomepromazine may increase the blood fluvoxamine level. Since the combined use of levomepromazine and fluvoxamine induces seizures, it may have been involved in causing the subject's death. In addition, combined use of trihexyphenidyl may potentiate anticholinergic effects of fluvoxamine overdose, including convulsions and coma. It was concluded that the cause of the subject's death was the interaction of multiple drugs.

20/(fasting C-peptide × fasting plasma glucose) is a simple and effective index of insulin resistance in patients with type 2 diabetes mellitus: a preliminary report.

BACKGROUND: We developed a simple and new insulin resistance index derived from a glucose clamp and a meal tolerance test (MTT) in Japanese patients with type 2 diabetes mellitus. METHODS: Fifteen patients [mean age: 53 years, fasting plasma glucose (FPG) 7.7 mmol/L, HbA1c 7.1% (54 mmol/mol), body mass index 26.8 kg/m(2)] underwent a MTT and a glucose clamp. Participants were given a test meal (450 kcal). Plasma glucose and insulin were measured at 0 (fasting), 30, 60, 120, and 180 min. Serum C-peptide immunoreactivity (CPR) was measured at 0 (fasting; F-CPR) and 120 min. Homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity indices (ISI) were calculated from the MTT results. The glucose infusion rate (GIR) was measured during hyperinsulinemic-euglycemic glucose clamps. RESULTS: The mean GIR in all patients was 5.8 mg·kg(-1)·min(-1). The index 20/(F-CPR × FPG) was correlated strongly with GIR (r = 0.83, P < 0.0005). HOMA-IR (r = -0.74, P < 0.005) and ISI (r = 0.66, P < 0.01) were also correlated with GIR. In 10 patients with mild insulin resistance (GIR 5.0-10.0 mg·kg(-1)·min(-1)), 20/(F-CPR × FPG) was very strongly correlated with GIR (r = 0.90, P < 0.0005), but not with HOMA-IR and ISI (r = -0.49, P = 0.15; r = 0.20, P = 0.56, respectively). In patients with mild insulin resistance, plasma adiponectin (r = 0.65, P < 0.05), but not BMI or waist circumstance, was correlated with GIR. CONCLUSIONS: 20/(F-CPR × FPG) is a simple and effective index of insulin resistance, and performs better than HOMA-IR and ISI in Japanese patients with type 2 diabetes mellitus. Our results suggest that 20/(F-CPR × FPG) is a more effective index than HOMA-IR in Japanese patients with mild insulin resistance.

Interactions in ion pairs of protic ionic liquids: comparison with aprotic ionic liquids.

The stabilization energies for the formation (E(form)) of 11 ion pairs of protic and aprotic ionic liquids were studied by MP2/6-311G** level ab initio calculations to elucidate the difference between the interactions of ions in protic ionic liquids and those in aprotic ionic liquids. The interactions in the ion pairs of protic ionic liquids (diethylmethylammonium [dema] and dimethylpropylammonium [dmpa] based ionic liquids) are stronger than those of aprotic ionic liquids (ethyltrimethylammonium [etma] based ionic liquids). The E(form) for the [dema][CF3SO3] and [dmpa][CF3SO3] complexes (-95.6 and -96.4 kcal/mol, respectively) are significantly larger (more negative) than that for the [etma][CF3SO3] complex (-81.0 kcal/mol). The same trend was observed for the calculations of ion pairs of the three cations with the Cl(-), BF4(-), TFSA(-) anions. The anion has contact with the N-H bond of the dema(+) or dmpa(+) cations in the most stable geometries of the dema(+) and dmpa(+) complexes. The optimized geometries, in which the anions locate on the counter side of the cations, are 11.0-18.0 kcal/mol less stable, which shows that the interactions in the ions pairs of protic ionic liquids have strong directionality. The E(form) for the less stable geometries for the dema(+) and dmpa(+) complexes are close to those for the most stable etma(+) complexes. The electrostatic interaction, which is the major source of the attraction in the ion pairs, is responsible for the directionality of the interactions and determining the magnitude of the interaction energy. Molecular dynamic simulations of the [dema][TFSA] and [dmpa][TFSA] ionic liquids show that the N-H bonds of the cations have contact with the negatively charged (oxygen and nitrogen) atoms of TFSA(-) anion, while the strong directionality of the interactions was not suggested from the simulation of the [etma][CF3SO3] ionic liquid.

Low-dose nicotine facilitates spatial memory in ApoE-knockout mice in the radial arm maze.

Here, we investigated the effects of nicotine on spatial memory in ApoE-knockout (ApoE-KO) and wild-type (WT) mice in a radial arm maze. Training occurred on three consecutive days and the test was performed on day 4, with one trial per day. Then on day 4, animals were administered nicotine (0.1, 0.25, 0.5, and 1.0 mg/kg) or the antagonist of nicotinic receptors (nAChRs) mecamylamine (MEC 2 mg/kg) alone or together with 0.1 mg/kg nicotine. The number of errors in the first eight choices was recorded. The results were that 0.1 mg/kg nicotine decreased errors in ApoE-KO mice, while 0.1 and 0.25 mg/kg nicotine reduced errors in WT mice, indicating that lower doses of nicotine elicit a memory improvement. In contrast, 1.0 mg/kg nicotine increased errors in WT mice, but not in ApoE-KO mice. MEC alone had no noticeable effect on errors in either strain of mice. However, co-administration of 0.1 mg/kg nicotine and MEC increased errors and reduced the effects of nicotine in WT mice, but not in ApoE-KO mice. Our study found a biphasic effect of nicotine in WT mice: it improves spatial memory at lower doses and impairs it at a higher dose. In ApoE-KO mice, nicotine improves memory at a low dose and has no effect at a higher dose, suggesting that the ApoE deficiency may influence the efficacy of nicotine. Moreover, a reversal of nicotinic effects with MEC was seen in WT mice, indicating the likelihood of the involvement of nAChRs in the spatial-memory response to nicotine.

Xylene; a useful marker for agricultural products ingestion.

Here we report about a case of malathion (an organophosphate insecticide) ingestion. Headspace analysis of stomach content provided useful information for screening of toxic chemicals. We should pay attention to solvents used in commercial industrial products.