Time-varying living arrangements and suicide death in the general population sample: 14-year causal survival analysis via pooled logistic regression.

AIMS: While past research suggested that living arrangements are associated with suicide death, no study has examined the impact of sustained living arrangements and the change in living arrangements. Also, previous survival analysis studies only reported a single hazard ratio (HR), whereas the actual HR may change over time. We aimed to address these limitations using causal inference approaches. METHODS: Multi-point data from a general Japanese population sample were used. Participants reported their living arrangements twice within a 5-year time interval. After that, suicide death, non-suicide death and all-cause mortality were evaluated over 14 years. We used inverse probability weighted pooled logistic regression and cumulative incidence curve, evaluating the association of time-varying living arrangements with suicide death. We also studied non-suicide death and all-cause mortality to contextualize the association. Missing data for covariates were handled using random forest imputation. RESULTS: A total of 86,749 participants were analysed, with a mean age (standard deviation) of 51.7 (7.90) at baseline. Of these, 306 died by suicide during the 14-year follow-up. Persistently living alone was associated with an increased risk of suicide death (risk difference [RD]: 1.1%, 95% confidence interval [CI]: 0.3-2.5%; risk ratio [RR]: 4.00, 95% CI: 1.83-7.41), non-suicide death (RD: 7.8%, 95% CI: 5.2-10.5%; RR: 1.56, 95% CI: 1.38-1.74) and all-cause mortality (RD: 8.7%, 95% CI: 6.2-11.3%; RR: 1.60, 95% CI: 1.42-1.79) at the end of the follow-up. The cumulative incidence curve showed that these associations were consistent throughout the follow-up. Across all types of mortality, the increased risk was smaller for those who started to live with someone and those who transitioned to living alone. The results remained robust in sensitivity analyses. CONCLUSIONS: Individuals who persistently live alone have an increased risk of suicide death as well as non-suicide death and all-cause mortality, whereas this impact is weaker for those who change their living arrangements.

Association of Pharmacist-led Deprescribing Intervention with the Functional Recovery in Convalescent Setting.

So far, no studies investigated the association between pharmacist intervention and rehabilitation outcomes. The aim of study was to establish whether the pharmacist-led deprescribing intervention affects rehabilitation outcomes. This retrospective, observational, single-center, cohort study included consecutive geriatric patients (n = 448) with pharmacist-led intervention between 2017 and 2019. Participants were divided based on pharmacist-led deprescribing and non deprescribing interventions during hospitalization. Demographic data, laboratory data, the Functional Independence Measure were (FIM) analyzed between the groups. Multiple linear regression analysis was performed to analyze the relationship between pharmacist-led deprescribing and FIM total gain. The primary outcome was FIM total gain. The rate of pharmacist intervention during the study period was 92.4%. A multiple linear regression analysis of FMI-T gain, adjusting for confounding factors, revealed that the pharmacist-led deprescribing intervention was independently correlated with FMI-T gain. Particularly, the use of dyslipidemia drugs, antipsychotic drugs, hypnotics, and nonsteroidal anti-inflammatory drugs significantly decreased during hospitalization. The pharmacist-led deprescribing intervention was independently and significantly associated with FIM-T gain. The pharmacist-led deprescribing intervention improved functional recovery in a rehabilitation setting.

PCLO rs2522833-mediated gray matter volume reduction in patients with drug-naive, first-episode major depressive disorder.

Major depressive disorder (MDD) has been linked to differences in the volume of certain areas of the brain and to variants in the piccolo presynaptic cytomatrix protein (PCLO), but the relationship between PCLO and brain morphology has not been studied. A single-nucleotide polymorphism (SNP) in PCLO, rs2522833, is thought to affect protein stability and the activity of the hypothalamic-pituitary-adrenal axis. We investigated the relationship between cortical volume and this SNP in first-episode, drug-naive patients with MDD or healthy control subjects. Seventy-eight participants, including 30 patients with MDD and 48 healthy control subjects, were recruited via interview. PCLO rs2522833 genotyping and plasma cortisol assays were performed, and gray matter volume was estimated using structural magnetic resonance images. Among the individuals carrying the C-allele of PCLO rs2522833, the volume of the left temporal pole was significantly smaller in those with MDD than in healthy controls (family-wise error-corrected, P=0.003). No differences were detected in other brain regions. In addition, the C-carriers showed a larger volume reduction in the left temporal pole than those in the individuals with A/A genotype (P=0.0099). Plasma cortisol levels were significantly higher in MDD-affected C-carriers than in the healthy control C-carriers (12.76±6.10 vs 9.31±3.60 nm, P=0.045). We conclude that PCLO SNP rs2522833 is associated with a gray matter volume reduction in the left temporal pole in drug-naive, first-episode patients with MDD carrying the C-allele.

Peracute Bacterial Meningitis due to Infection with Klebsiella pneumoniae in Captive-bred Ruffed Lemurs (Varecia variegate).

We describe the development of neurological signs in four juvenile black-and-white ruffed lemurs (Varecia variegate), housed at a petting zoo in Japan. The clinical course was severe, with three lemurs dying within 1 day of the appearance of clinical signs. The other lemur was treated and survived. Pathological analyses demonstrated meningitis and the presence of gram-negative bacilli in the cerebrum, cerebellum, palatine tonsil and liver. Klebsiella pneumoniae was isolated from the brain of all of the dead lemurs. Multilocus sequence typing analysis showed that all the isolates were sequence type 86 (ST86). To our knowledge, this is the first determination of K. pneumoniae infection in ruffed lemurs of this genus. K. pneumoniae infection may represent a risk to lemurs and people who come into contact with infected animals.

CMAP decrement as a potential diagnostic marker for ALS.

OBJECTIVE: We previously reported that decrement of compound muscle action potential (CMAP) by repetitive nerve stimulation (RNS) was greater in the median nerves than in the ulnar nerves of patients with amyotrophic lateral sclerosis (ALS). The aim of this study was to evaluate whether CMAP decrement by RNS is a feasible marker for the differentiation of ALS from other diseases. MATERIALS & METHODS: We performed RNS in the median and ulnar nerves of 51 patients with ALS and 40 patients with other diseases. RESULTS: The CMAP decrement was significantly greater in the median nerves of patients with ALS, compared to the disease control patients. In the median nerves of patients with ALS, CMAP decrement was significantly greater in the cervical region-onset group than in the other region-onset group. CONCLUSIONS: The finding of CMAP decrement in the median nerves can be useful for differentiating ALS patients with cervical region onset from other controls with active neuropathic diseases.

Increased protein and mRNA expression of resistin after dexamethasone administration.

Synthetic glucocorticoids such as dexamethasone are widely used to treat a variety of inflammatory and autoimmune conditions, but they may induce adverse events including hyperglycemia. To shed light on the effect and action mechanism of dexamethasone, we examined the alterations of gene expression levels caused by dexamethasone.Microarray analysis was performed on whole blood collected from 24 physically healthy subjects at baseline and after dexamethasone administration. The expression levels of resistin mRNA were found to be significantly increased after the dexamethasone administration. In a separate sample of 12 subjects, we examined plasma resistin protein levels and found that they were increased after dexamethasone administration. Furthermore, the plasma mRNA and protein levels of resistin were significantly higher in individuals who carried the A allele of RETN single nucleotide polymorphism rs3219175 than in those who did not carry the allele. There was no significant interaction between the genotype and dexamethasone administration. No significant correlation was found between plasma levels of cortisol and resistin. Consistent with previous studies, the genotype of RETN rs3219175 was a strong determinant of resistin levels. The present study showed that oral administration of dexamethasone increases the protein and mRNA levels of resistin irrespective of the rs3219175 genotype.

Promotion of apoptosis and cytochrome c depletion by a low-temperature environment in hindlimb-unloading rats.

OBJECTIVE: This study aimed to clarify the influence of a low-temperature environment on muscle atrophy and apoptosis. METHODS: Wistar rats were divided into four groups: two groups of hindlimb-unloading rats maintained in a normal (25°C, HU) or low-temperature (10°C, HU+LT) environment for 3 weeks and two corresponding control groups (CON; normal temperature, CON+LT; low-temperature). RESULTS: The soleus muscle wet weight and muscle-to-body mass ratio were lower in the experimental groups than in the control groups. The cross-sectional areas of myofibers in the HU+LT and HU groups were significantly decreased than those in the CON and CON+LT groups. Ubiquitin ladder levels from soleus muscle lysates were significantly increased in the HU+LT group. Caspase-3-activated myofibers were observed only in the HU+LT group. Decreased cytochrome c levels were present in these caspase-3-activated myofibers. Meanwhile, cytochrome c levels were increased significantly in CON+LT rats but unchanged in HU+LT rats. CONCLUSION: Our results suggest that apoptosis caused by hindlimb unloading at low temperatures is associated with a lack of cytochrome c in myofibers. This indicates that long-term hindlimb unloading at low temperatures did not suppress muscle atrophy. We conclude that low-temperature stimulation should not be used as a long-term treatment for preventing disuse atrophy.

Moderating effect of schizotypy on the relationship between smoking and neurocognition.

PURPOSE: Smoking rates in schizotypic individuals are shown to be elevated, as in patients with schizophrenia, although findings on the association of smoking with different symptomatology of schizotypy have been mixed. Moreover, possible moderating effects of schizotypy on the relationship between smoking and cognition have not been well documented. SUBJECTS AND METHODS: The Schizotypal Personality Questionnaire (SPQ) and the full version of the Wechsler Memory Scale-Revised (WMS-R) were administered to 501 healthy adults. Subjects were divided into smokers (n=85) and non-smokers (n=416) based on the presence/absence of current smoking. RESULTS: The analysis of covariance (ANCOVA) on the three factor scores as well as the total score of the SPQ, controlling for age and gender, revealed that cognitive-perceptual factor was significantly associated with an increased rate of smoking (P=0.048). The ANCOVA on the WMS-R indices, with smoking group as a fixed factor and age, gender and total SPQ score as covariates, revealed that the schizotypy-by-smoking interaction was significant for attention/working memory (P=0.029). DISCUSSION AND CONCLUSION: Positive schizotypy may be associated with more smoking. Schizotypy and smoking could interact with each other to negatively affect attention/working memory.

13C-phenylalanine breath test detects altered phenylalanine kinetics in schizophrenia patients.

Phenylalanine is an essential amino acid required for the synthesis of catecholamines including dopamine. Altered levels of phenylalanine and its metabolites in blood and cerebrospinal fluid have been reported in schizophrenia patients. This study attempted to examine for the first time whether phenylalanine kinetics is altered in schizophrenia using L-[1-(13)C]phenylalanine breath test ((13)C-PBT). The subjects were 20 chronically medicated schizophrenia patients (DSM-IV) and the same number of age- and sex-matched controls. (13)C-phenylalanine (99 atom% (13)C; 100 mg) was administered orally and the breath (13)CO(2) /(12)CO(2) ratio was monitored for 120 min. The possible effect of antipsychotic medication (risperidone (RPD) or haloperidol (HPD) treatment for 21 days) on (13)C-PBT was examined in rats. Body weight (BW), age and diagnostic status were significant predictors of the area under the curve of the time course of Δ(13)CO(2) (‰) and the cumulative recovery rate (CRR) at 120 min. A repeated measures analysis of covariance controlled for age and BW revealed that the patterns of CRR change over time differed between the patients and controls and that Δ(13)CO(2) was lower in the patients than in the controls at all sampling time points during the 120 min test, with an overall significant difference between the two groups. Chronic administration of RPD or HPD had no significant effect on (13)C-PBT indices in rats. Our results suggest that (13)C-PBT is a novel laboratory test that can detect altered phenylalanine kinetics in chronic schizophrenia patients. Animal experiments suggest that the observed changes are unlikely to be attributable to antipsychotic medication.

Pharmacotherapeutic determinants for QTc interval prolongation in Japanese patients with mood disorder.

An increased incidence of sudden death has been observed among patients treated with antidepressants. A prolonged QTc interval is a known prognostic factor for fatal arrhythmia, and several studies have shown that the use of antidepressants can cause a prolonged QTc interval. However, few studies, especially in Japan, have compared the effects of multiple drugs on QTc interval or examined dose relationships in a clinical setting.We compared the effects of antidepressants on QT interval, corrected to QTc by Bazett's formula, in 729 Japanese patients who were diagnosed with mood disorder.Using stepwise multiple linear regression analysis, we found that the use of tricyclic antidepressants (P<0.01) and concomitant use of antipsychotics (P<0.05), as well as advanced age and being female (known factors for prolonged QTc interval; both P<0.01), significantly prolonged the QTc interval. Analysis of individual antidepressants also revealed that the use of clomipramine (P<0.01) and amitriptyline (P<0.05) significantly prolonged the QTc interval.Our results reveal that tricyclic antidepressants, especially clomipramine and amitriptyline, confer a risk of prolonged QTc interval in a dose-dependent manner. The selective serotonin reuptake inhibitors investigated (fluvoxamine, paroxetine, sertraline) were not indicated as risk factors for QTc prolongation.

Purulent meningoventriculitis caused by Streptococcus equi subspecies zooepidemicus in a snow leopard (Panthera uncia).

Streptococcus equi subspecies zooepidemicus (SEZ) is a zoonotic pathogen that causes respiratory tract infections in man and animals. SEZ infections are very rare in felids. This report describes purulent meningoventriculitis caused by SEZ in an approximately 16-year-old male snow leopard (Panthera uncia). The animal exhibited neurological signs and died 1 month after their onset. On necropsy examination, the surface blood vessels of the brain were swollen and there was an increased volume and turbidity of cerebrospinal fluid (CSF). Microscopically, suppurative inflammation accompanied by gram-positive cocci was observed in the meninges and near the ventricles. SEZ was isolated from the brain tissue and CSF. This is the first report of infection with SEZ in a felid other than a domestic cat. This animal had not had direct contact with horses, but it had been fed horse flesh that may have been the source of infection.

Glutamatergic changes in the cerebral white matter associated with schizophrenic exacerbation.

OBJECTIVE: Glutamatergic dysfunction in the brain has been implicated in the pathophysiology of schizophrenia. This study was aimed to examine several brain chemical mediators, including Glx (glutamate + glutamine), using (1)H magnetic resonance spectroscopy (MRS) in medicated patients with schizophrenia, with and without psychotic exacerbation. METHOD: (1)H MRS was acquired in 24 patients with schizophrenia, with psychotic exacerbation; 22 patients without exacerbation; and 27 age- and sex-matched healthy volunteers. The levels of metabolites were measured in the left frontal and inferior parietal white matter and compared across the three groups. RESULTS: The Glx level was significantly elevated in the left inferior parietal white matter in the patients with psychotic exacerbation in comparison with that in the healthy volunteers and the patients without exacerbation (P < 0.05). We also detected that there was a significant correlation between Positive and Negative Syndrome Scale-positive scale and Glx level in the left parietal white matter (r = 0.51, P < 0.001). CONCLUSION: Higher than normal Glx levels indicate glutamatergic overactivity in the left inferior parietal white matter with schizophrenic exacerbation, a finding that is in accordance with the glutamatergic hypothesis in schizophrenia. The Glx level measured by (1)H MRS could be a biomarker for exacerbation in schizophrenia.

Reduction of Alzheimer's disease amyloid-ß in plasma by hemodialysis and its relation to cognitive functions.

BACKGROUND/AIMS: Rapid removal of plasma amyloid-ß (Aß) by blood purification may serve as a peripheral Aß sink from the brain for Alzheimer's disease therapy. We investigated the reduction of plasma Aß during hemodialysis and cognitive states. METHODS: Aß concentrations and Mini-Mental State Examinations (MMSE) were investigated in 37 hemodialysis patients (68.9 ± 4.1 years). RESULTS: The dialyzers effectively removed Aß(1-40) and Aß(1-42), 63.9 ± 14.4 and 51.6 ± 17.0% at 4 h dialysis, resulting in the reduction of Aßs in whole-body circulation by 51.1 ± 8.9 and 32.7 ± 12.0%, respectively. Although the plasma Aßs before dialysis (750.8 ± 171.3 pg/ml for Aß(1-40)) were higher than those reported for Alzheimer's disease patients, the cognitive states of hemodialysis patients were relatively normal, especially of longer dialysis vintages. CONCLUSIONS: Dialyzers effectively reduced Aßs in whole-body circulation. Repeated rapid decrease of plasma Aßs might maintain cognitive state.

Comparison of brain N-acetylaspartate levels and serum brain-derived neurotrophic factor (BDNF) levels between patients with first-episode schizophrenia psychosis and healthy controls.

BACKGROUND: N-acetylaspartate (NAA) levels and serum brain-derived neurotrophic factor (BDNF) levels in patients with first-episode schizophrenia psychosis and age- and sex-matched healthy control subjects were investigated. In addition, plasma levels of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were compared between the two groups. METHOD: Eighteen patients (nine males, nine females; age range: 13-52 years) were enrolled in the study, and 18 volunteers (nine males, nine females; age range: 15-49 years) with no current or past psychiatric history were also studied by magnetic resonance spectroscopy (MRS) as sex- and age-matched controls. RESULTS: Levels of NAA/Cr in the left basal ganglia (p=0.0065) and parieto-occipital lobe (p=0.00498), but not in the frontal lobe, were significantly lower in patients with first-episode schizophrenia psychosis than in control subjects. No difference was observed between the serum BDNF levels of patients with first-episode schizophrenia psychosis and control subjects. In regard to the plasma levels of catecholamine metabolites, plasma MHPG, but not HVA, was significantly lower in the patients with first-episode psychosis than in control subjects. In addition, a significantly positive correlation was observed between the levels of NAA/Cr of the left basal ganglia and plasma MHPG in all subjects. CONCLUSION: These results suggest that brain NAA levels in the left basal ganglia and plasma MHPG levels were significantly reduced at the first episode of schizophrenia psychosis, indicating that neurodegeneration via noradrenergic neurons might be associated with the initial progression of the disease.

Expression of ADAMTS4 in Ewing's sarcoma.

Ewing's sarcoma (EWS) is a malignant bone tumor that frequently occurs in teenagers. Genetic mutations which cause EWS have been investigated, and the most frequent one proved to be a fusion gene between EWS gene of chromosome 22 and the FLI1 gene of chromosome 11. However, a limited numbers of useful biological markers for diagnosis of EWS are available. In this study, we identified ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs) as a possible tumor marker for EWS using the retrovirus-mediated signal sequence trap method. ADAMTS4 is a secreted protein of 837 amino acids with a predicted molecular mass of 98-100 kDa. It is a member of metalloprotease family, is expressed mainly in cartilage and brain, and regulates the degradation of aggrecans. ADAMTS4 has been suggested to be involved in arthritic diseases and gliomas. Herein, we show that ADAMTS4 mRNA was expressed in all primary EWS samples and all EWS-derived cell lines examined, while its expression was detected only in small subpopulations of other solid tumors. Furthermore, ADAMTS4 expression was found to be regulated by EWS-FLI1 fusion gene-dependent manner. We also demonstrated that ADAMTS4 protein was highly expressed in tumor samples of the patients with EWS by using immunohistochemistry. These results suggest that ADAMTS4 is a novel tumor marker for EWS.

Identification of QTLs that control clubroot resistance in Brassica oleracea and comparative analysis of clubroot resistance genes between B. rapa and B. oleracea.

To perform comparative studies of CR (clubroot resistance) loci in Brassica oleracea and Brassica rapa and to develop marker-assisted selection in B. oleracea, we constructed a B. oleracea map, including specific markers linked to CR genes of B. rapa. We also analyzed CR-QTLs using the mean phenotypes of F(3) progenies from the cross of a resistant double-haploid line (Anju) with a susceptible double-haploid line (GC). In the nine linkage groups obtained (O1-O9), the major QTL, pb-Bo(Anju)1, was derived from Anju with a maximum LOD score (13.7) in O2. The QTL (LOD 5.1) located in O5, pb-Bo(GC)1, was derived from the susceptible GC. Other QTLs with smaller effects were found in O2, O3, and O7. Based on common markers, it was possible to compare our finding CR-QTLs with the B. oleracea CR loci reported by previous authors; pb-Bo(GC)1 may be identical to the CR-QTL reported previously or a different member contained in the same CR gene cluster. In total, the markers linked to seven B. rapa CR genes were mapped on the B. oleracea map. Based on the mapping position and markers of the CR genes, informative comparative studies of CR loci between B. oleracea and B. rapa were performed. Our map discloses specific primer sequences linked to CR genes and includes public SSR markers that will promote pyramiding CR genes in intra- and inter-specific crosses in Brassica crops. Five genes involved in glucosinolates biosynthesis were also mapped, and GSL-BoELONG and GSL-BoPro were found to be linked to the pb-Bo(Anju)1 and Bo(GC)1 loci, respectively. The linkage drag associated with the CR-QTLs is briefly discussed.

The beneficial effect of propolis on fat accumulation and lipid metabolism in rats fed a high-fat diet.

This study examined whether propolis, which had many biological activities, affected body fat and lipid metabolism. Four-week-old Wistar rats were fed a control or propolis diet for 8 wk. The control group was fed a high-fat diet, the low and the high group were fed a high-fat diet supplemented with 0.5% (w/w) and 0.05% (w/w) propolis, respectively. The weight of total white adipose tissue of the high group was lower than that of the control group. The level of PPARgamma protein in the adipose tissues of the high group was significantly lower than that of the control group. In plasma and the liver, the high group showed a significantly reduced level of cholesterol and triglyceride compared to the control group. The liver PPARalpha protein level of the high group was significantly higher than that of the control group. The liver HMG-CoA reductase protein in the high group was also significantly lower than that in the control group. Results from rats on an olive oil loading test were used to investigate whether propolis inhibited triglyceride absorption. The serum triglyceride level of the group, which received propolis corresponding to the daily dose of the high group, was significantly lower than that of the control group. It is possible that the administration of propolis improves the accumulation of body fat and dyslipidemia via the change of the expression of proteins involved in adipose depot and lipid metabolism.

Effects of alpha-amylase and its inhibitors on acid production from cooked starch by oral streptococci.

This study evaluated acid production from cooked starch by Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinis and Streptococcus mitis, and the effects of alpha-amylase inhibitors (maltotriitol and acarbose) and xylitol on acid production. Streptococcal cell suspensions were anaerobically incubated with various carbohydrates that included cooked potato starch in the presence or absence of alpha-amylase. Subsequently, the fall in pH and the acid production rate at pH 7.0 were measured. In addition, the effects of adding alpha-amylase inhibitors and xylitol to the reaction mixture were evaluated. In the absence of alpha-amylase, both the fall in pH and the acid production rate from cooked starch were small. On the other hand, in the presence of alpha-amylase, the pH fell to 3.9-4.4 and the acid production rate was 0.61-0.92 micromol per optical density unit per min. These values were comparable to those for maltose. When using cooked starch, the fall in pH by S. sanguinis and S. mitis was similar to that by S. mutans and S. sobrinus. For all streptococci, alpha-amylase inhibitors caused a decrease in acid production from cooked starch, although xylitol only decreased acid production by S. mutans and S. sobrinus. These results suggest that cooked starch is potentially acidogenic in the presence of alpha-amylase, which occurs in the oral cavity. In terms of the acidogenic potential of cooked starch, S. sanguinis and S. mitis were comparable to S. mutans and S. sobrinus. Alpha-amylase inhibitors and xylitol might moderate this activity.

Local circular polarization observed in surface vortices of optical near-fields.

We demonstrate local circular polarization in surface vortices of an optical near-field generated by superposing two cross-propagating evanescent waves with transverse electric fields on a planar dielectric surface. The circularly rotating local electric fields are converted into circularly polarized propagating light waves in free space via a near-field interaction with a sub-wavelength size local probe. The results show that optical near-fields generated under the influence of a material environment with local rotational symmetry carry angular pseudo-momentum with respect to the symmetry axis. The local circular polarization is of fundamental significance in spin-related and magneto-optical phenomena in nanophotonics.