ABSTRACT
BACKGROUND: The continuation rates of pharmacotherapy in schizophrenia exhibit variability, a phenomenon influenced by the specific antipsychotic agent prescribed and patient-related factors such as age and duration of illness. In this context, our study aims to elucidate the predictors of medication continuation for asenapine sublingual tablets, characterized by unique formulation properties. METHODS: Our investigation leveraged real-world data collected through post-marketing surveillance in Japan, comprising 3236 cases. Utilizing multivariate logistic regression analysis, we identified patient-related factors associated with medication continuation as the primary outcome measure, subsequently employing survival analysis for further evaluation. Additionally, adverse event occurrence was assessed as a secondary outcome measure. RESULTS: Multivariate logistic regression analysis unveiled significant predictors of asenapine continuation, notably including patient-related factors such as a chlorpromazine equivalent dose exceeding 600 mg/day and an illness duration of 25 years or more. While the overall continuation rate stood at 40.6%, patients exhibiting factors such as a chlorpromazine equivalent dose surpassing 600 mg/day or an illness duration exceeding 25 years demonstrated continuation rates of 46.3% and 47.9%, respectively. Remarkably, patients presenting both factors showcased the highest continuation rate at 52.5%. CONCLUSIONS: Our findings shed light on distinct patient-related predictors of asenapine continuation, deviating from those observed with other antipsychotic medications. This underscores the necessity of recognizing that predictive factors for antipsychotic medication continuation vary across different agents. Moving forward, elucidating these predictive factors for various antipsychotic medications holds paramount importance in schizophrenia treatment, facilitating the delivery of tailored therapeutic interventions for individual patients.
ABSTRACT
ß-Aspartyl compounds, such as ß-aspartyl hydroxamate (serine racemase inhibitor), ß-aspartyl-l-lysine (moisture retention), and ß-aspartyl-l-tryptophan (immunomodulator) are physiologically active compounds. There is limited literature on the development of effective methods of production of ß-aspartyl compounds. In this study, we describe the biochemical characterization of asparagine synthetase (AS) from Streptococcus thermophilus NBRC 13957 (StAS) and the enzymatic synthesis of ß-aspartyl compounds using StAS. Recombinant StAS was expressed in Escherichia coli BL21(DE3) and it displayed activity towards hydroxylamine, methylamine, ethylamine, and ammonia, as acceptors of the ß-aspartyl moiety. StAS exhibited higher activity toward hydroxylamine and ethylamine as acceptor substrates compared with the enzymes from Lactobacillus delbrueckii NBRC 13953, Lactobacillus reuteri NBRC 15892, and E. coli. The coupling of the synthesis of ß-aspartyl compounds by StAS with an ATP-regeneration system using polyphosphate kinase from Deinococcus proteoliticus NBRC 101906 displayed an approximately 2.5-fold increase in the production of ß-aspartylhydroxamate from 1.06 mM to 2.53 mM after a 76-h reaction.
Subject(s)
Aspartate-Ammonia Ligase , Escherichia coli , Recombinant Proteins , Streptococcus thermophilus , Streptococcus thermophilus/enzymology , Streptococcus thermophilus/genetics , Escherichia coli/genetics , Escherichia coli/metabolism , Aspartate-Ammonia Ligase/metabolism , Aspartate-Ammonia Ligase/genetics , Aspartate-Ammonia Ligase/chemistry , Recombinant Proteins/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/chemistry , Aspartic Acid/metabolism , Aspartic Acid/biosynthesis , Substrate Specificity , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/chemistryABSTRACT
Successful implementation of enzymes in practical application hinges on the development of efficient mass production techniques. However, in a heterologous expression system, the protein is often unable to fold correctly and, thus, forms inclusion bodies, resulting in the loss of its original activity. In this study, we present a new and more accurate model for predicting amino acids associated with an increased L-amino acid oxidase (LAO) solubility. Expressing LAO from Rhizoctonia solani in Escherichia coli and combining random mutagenesis and statistical logistic regression, we modified 108 amino acid residues by substituting hydrophobic amino acids with serine and hydrophilic amino acids with alanine. Our results indicated that specific mutations in Euclidean distance, glycine, methionine, and secondary structure increased LAO expression. Furthermore, repeated mutations were performed for LAO based on logistic regression models. The mutated LAO displayed a significantly increased solubility, with the 6-point and 58-point mutants showing a 2.64- and 4.22-fold increase, respectively, compared with WT-LAO. Ultimately, using recombinant LAO in the biotransformation of α-keto acids indicates its great potential as a biocatalyst in industrial production.
Subject(s)
Escherichia coli , L-Amino Acid Oxidase , Solubility , Escherichia coli/genetics , Escherichia coli/metabolism , L-Amino Acid Oxidase/genetics , L-Amino Acid Oxidase/metabolism , L-Amino Acid Oxidase/chemistry , Logistic Models , Rhizoctonia/enzymology , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Recombinant Proteins/chemistryABSTRACT
AIMS: A meta-analysis of short-term studies revealed no significant differences between the doses of asenapine, 10 and 20 mg/day, in the acute treatment of schizophrenia. However, it should be noted that many patients from clinical practice were excluded, and the dose-response to asenapine in a real-world setting is still unclear. Additionally, the dose-response in the maintenance phase is not clear. This study aimed to evaluate the differences in the efficacy of different asenapine doses in patients with maintenance phase of schizophrenia in a real-world setting. METHODS: This study conducted post-marketing surveillance of asenapine in clinical settings in Japan. It followed patients diagnosed with schizophrenia who received asenapine for the first time for a maximum of 52 weeks. These patients were divided into two categories based on their average daily asenapine dosage: ≤10 mg/day and >10 mg/day. Asenapine efficacy was assessed by adjusting for patient demographics using multivariate logistic regression analysis, employing the Clinical Global Impression-Global Improvement (CGI-I) scale, which has seven categories. RESULTS: A total of 2774 patients were included in the analysis. Of these, 1689 and 1085 patients were treated with asenapine ≤10 mg/day and >10 mg/day, respectively. The CGI-I improvement rate was significantly higher in the asenapine >10 group (p = 0.012) after adjusting for patient background factors. CONCLUSION: These results suggest that asenapine doses >10 mg/day may be more effective than 10 mg/day in the treatment of schizophrenia; however, further studies are needed to confirm these findings.
Subject(s)
Antipsychotic Agents , Dibenzocycloheptenes , Schizophrenia , Humans , Schizophrenia/drug therapy , Antipsychotic Agents/adverse effects , Treatment Outcome , Heterocyclic Compounds, 4 or More Rings/adverse effectsABSTRACT
AIM: The combination of locomotive syndrome (LS) and poor sleep quality (PQ) has not yet been shown to result in falls or to affect bone conditions in old age and middle age. [Correction added on 1 December 2023, after first online publication: The preceding sentence has been updated for clarity.] METHODS: This cross-sectional study enrolled 2233 community-dwelling middle-aged to older Japanese women. LS and PSQ were assessed by the stand-up test, two-step test, the 25-question Geriatric Locomotive Function Scale, and the Pittsburgh Sleep Quality Index (PSQI). Participants with both LS 1-3 (any) and a PSQI score ≥6 were classified as belonging to the LS(+)/PSQ(+) group. The incidence of falls in the previous month was collected using a self-administered questionnaire. Bone conditions were evaluated using an ultrasonic bone densitometer. RESULTS: The LS(+)/PSQ(+) group independently had a higher risk of falls after adjusting for confounding factors than the LS(-)/PSQ(-) group using multiple logistic regression analysis (odds ratio 1.92, 95% confidence interval 1.01-3.65, P < 0.05). No relationships between LS(-)/PSQ(+) and LS(+)/PSQ(-) groups and the incidences of fall were observed (P > 0.05). [Correction added on 1 December 2023, after first online publication: The two preceding sentences have been corrected to provide greater clarity.] The LS(+)/PSQ(+) group had lower trabecular bone density and cortical bone thickness than the LS(-)/PSQ(-) group (P < 0.05). CONCLUSION: The combination of LS and PSQ is an independent risk factor of falls, indicating that assessing both LS and PSQ could be useful in detecting middle-aged and older women with low bone density and thickness who fall easily at an early stage. Geriatr Gerontol Int 2023; 23: 912-918.
Subject(s)
Accidental Falls , Sleep Quality , Humans , Female , Middle Aged , Aged , Cross-Sectional Studies , Independent Living , Syndrome , Risk FactorsABSTRACT
OBJECTIVE: Evidence for an association between locomotive syndrome (LS) and depression is lacking in middle-aged women. This study aimed to investigate the relationship between LS severity and depressive symptoms in community-dwelling middle-aged women. METHODS: This cross-sectional study included 1,520 middle-aged women (mean age 52 ± 6 years). LS severity was evaluated using the 25-question Geriatric Locomotive Function Scale (GLFS-25) questionnaire and motor function test. Depressive symptoms were assessed using the Zung self-rating depression scale (SDS). Multiple logistic regression analyses were performed to determine the association between depressive symptoms and LS severity, adjusting for potential confounding factors. RESULTS: LS severity, as evaluated through both questionnaires and motor function tests, was significantly associated with depressive symptoms (SDS ≥ 40 points) in middle-aged women. The relationship between LS and depressive symptoms was only significant when assessed through the GLFS-25 questionnaire rather than the motor function tests. Additionally, a stepwise association was observed between pain severity, as assessed by the GLFS-25, and the prevalence of depressive symptoms. CONCLUSIONS: LS severity is significantly associated with depressive symptoms in community-dwelling middle-aged women, suggesting the need for additional mental status assessment in participants with LS and concurrent pain.
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BACKGROUND: The present genome-wide association study (GWAS) aimed to reveal the genetic loci associated with folate metabolites as well as to detect related gene-environment interactions in Japanese. METHODS: We conducted the GWAS of plasma homocysteine (Hcy), folic acid (FA), and vitamin B12 (VB12) levels in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study participants who joined from 2005 to 2012, and also estimated gene-environment interactions. In the replication phase, we used data from the Yakumo Study conducted in 2009. In the discovery phase, data of 2,263 participants from four independent study sites of the J-MICC Study were analyzed. In the replication phase, data of 573 participants from the Yakumo Study were analyzed. RESULTS: For Hcy, MTHFR locus on chr 1, NOX4 on chr 11, CHMP1A on chr 16, and DPEP1 on chr 16 reached genome-wide significance (P < 5×10-8). MTHFR also associated with FA, and FUT2 on chr 19 associated with VB12. We investigated gene-environment interactions in both studies and found significant interactions between MTHFR C677T and ever drinking, current drinking, and physical activity > 33% on Hcy (ß = 0.039, 0.038 and -0.054, P = 0.018, 0.021 and < 0.001, respectively) and the interaction of MTHFR C677T with ever drinking on FA (ß = 0.033, P = 0.048). CONCLUSIONS: The present GWAS revealed the folate metabolism-associated genetic loci and gene-environment interactions with drinking and physical activity in Japanese, suggesting the possibility of future personalized CVD prevention.
ABSTRACT
The gene encoding γ-glutamyltranspeptidase II (PaGGTII) from Pseudomonas aeruginosa PAO1 was cloned in Escherichia coli. Recombinant PaGGTII showed a weak activity (0.0332 U/mg), and it can be easily inactivated. Multiple alignment of microbial GGTs showed the redundancy of the C-terminal of the small subunit of PaGGTII in length. The truncation of eight amino acid residues at the C-terminal of PaGGTII remarkably improved the activity and stability of the enzyme (PaGGTIIΔ8; 0.388 U/mg). Further truncation at the C-terminal also provided the enzyme relatively higher activity (PaGGTIIΔ9, -Δ10, -Δ11, and -Δ12). Among C-terminal truncated mutants, we focused on PaGGTIIΔ8 and examined the effect of C-terminal amino acid residues on the properties of PaGGTIIΔ8 because the activity of PaGGTII was found to be greatly improved when 8 amino acid residues were truncated. Various mutant enzymes with different C-terminal amino acid residues were constructed. They were expressed in E. coli and purified to homogeneity by ion-exchange chromatography. The properties of PaGGTIIΔ8 and the mutants obtained from mutation at E569 were characterized. Km and kcat of PaGGTIIΔ8 for γ-glutamyl-p-nitroanilide (γ-GpNA) were 8.05 mM and 15.49 s-1, respectively. PaGGTIIΔ8E569Y showed the highest catalytic efficiency for γ-GpNA with a kcat/Km of 12.55 mM-1 s-1. Mg2+, Ca2+, and Mn2+ exhibited positive effects on the catalytic activity for PaGGTIIΔ8 and its ten E569 mutants.
Subject(s)
Escherichia coli , Pseudomonas aeruginosa , Escherichia coli/metabolism , Amino Acid Sequence , gamma-Glutamyltransferase/genetics , gamma-Glutamyltransferase/chemistry , gamma-Glutamyltransferase/metabolism , Amino AcidsABSTRACT
BACKGROUND: Previous cohort studies have yielded contradictory findings regarding the associations of dietary carbohydrate and fat intakes with risks of mortality. OBJECTIVES: We examined long-term associations of carbohydrate and fat intakes with mortality. METHODS: In this cohort study, 34,893 men and 46,440 women aged 35-69 y (mean body mass index of 23.7 and 22.2 kg/m2, respectively) were followed up from the baseline survey (2004-2014) to the end of 2017 or 2018. Intakes of carbohydrate, fat, and total energy were estimated using a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for all-cause and cause-specific mortality according to percentage of energy intakes of carbohydrate and fat. RESULTS: During a mean 8.9-y follow-up, we identified 2783 deaths (1838 men and 945 women). Compared with men who consumed 50% to <55% of energy from carbohydrate, those who consumed <40% carbohydrate energy experienced a significantly higher risk of all-cause mortality (the multivariable-adjusted HR: 1.59; 95% CI: 1.19-2.12; P-trend = 0.002). Among women with 5 y or longer of follow-up, women with high-carbohydrate intake recorded a higher risk of all-cause mortality; the multivariable-adjusted HR (95% CI) was 1.71 (0.93-3.13) for ≥65% of energy from carbohydrate compared with that for 50% to <55% (P-trend = 0.005). Men with high fat intake had a higher risk of cancer-related mortality; the multivariable-adjusted HR (95% CI) for ≥35% was 1.79 (1.11-2.90) compared with that for 20% to <25%. Fat intake was marginally inversely associated with risk of all-cause and cancer-related mortality in women (P-trend = 0.054 and 0.058, respectively). CONCLUSIONS: An unfavorable association with mortality is observed for low-carbohydrate intake in men and for high-carbohydrate intake in women. High fat intake can be associated with a lower mortality risk in women among Japanese adults with a relatively high-carbohydrate intake.
Subject(s)
Cardiovascular Diseases , Neoplasms , Adult , Female , Humans , Male , Cardiovascular Diseases/etiology , Cohort Studies , Dietary Carbohydrates , East Asian People , Japan/epidemiology , Prospective Studies , Risk Factors , Middle Aged , AgedABSTRACT
BACKGROUND AND AIM: We investigated whether oral-dental conditions may be associated with the prevalence of irritable bowel syndrome (IBS) in a cross-sectional study in Japan. METHODS: Information on lifestyle and abdominal symptoms was collected, and oral-dental examinations were performed from 2013 to 2017. To investigate the association between oral-dental conditions and IBS, this study used logistic regression analyses adjusted for relevant confounding factors, such as age, sex, BMI, stress, and eating between meals. RESULTS: The prevalence of IBS was 484 (13.4%) among 3626 participants. The mean maximum occlusal force in the IBS group was significantly lower than that in the non-IBS group (0.306 ± 0.192 kN vs. 0.329 ± 0.205 kN, P = 0.014). The maximum occlusal force of the constipation-type IBS was significantly lower than that of other types of IBS without constipation type (0.269 ± 0.164 kN vs. 0.317 ± 0.198 kN, P = 0.010). Compared with those who had high values of maximum occlusal force (â§0.265 kN), those with a low value of maximum occlusal force (<0.265 kN) had a significantly greater risk for IBS (OR, 1.426; 95% CI, 1.135-1.792; P = 0.002), by multivariate analyses, across different categories of oral-dental condition in women, not in men. Women who had lowest third occlusal force (<0.206 kN) had approximately 35% significantly greater odds of having IBS compared with those who had highest third occlusal force (â§0.386 kN). CONCLUSIONS: Results suggest that a reduction in the maximum occlusal force increases the risk of IBS in Japanese women.
Subject(s)
Irritable Bowel Syndrome , Male , Adult , Humans , Female , Irritable Bowel Syndrome/etiology , Irritable Bowel Syndrome/complications , Prevalence , Bite Force , Cross-Sectional Studies , East Asian People , Constipation/etiology , Constipation/complications , Surveys and QuestionnairesABSTRACT
BACKGROUND: The relationship between lifestyle and obesity is a major focus of research. Personalized nutrition, which utilizes evidence from nutrigenomics, such as gene-environment interactions, has been attracting attention in recent years. However, evidence for gene-environment interactions that can inform treatment strategies is lacking, despite some reported interactions involving dietary intake or physical activity. Utilizing gene-lifestyle interactions in practice could aid in optimizing interventions according to genetic risk. METHODS: This study aimed to elucidate the effects of gene-lifestyle interactions on body mass index (BMI). Cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study were used. Interactions between a multi-locus genetic risk score (GRS), calculated from 76 ancestry-specific single nucleotide polymorphisms, and nutritional intake or physical activity were assessed using a linear mixed-effect model. RESULTS: The mean (standard deviation) BMI and GRS for all participants (n = 12,918) were 22.9 (3.0) kg/m2 and -0.07 (0.16), respectively. The correlation between GRS and BMI was r(12,916) = 0.13 (95% confidence interval [CI] 0.11-0.15, P < 0.001). An interaction between GRS and saturated fatty acid intake was observed (ß = -0.11, 95% CI -0.21 to -0.02). An interaction between GRS and n-3 polyunsaturated fatty acids was also observed in the females with normal-weight subgroup (ß = -0.12, 95% CI -0.22 to -0.03). CONCLUSION: Our results provide evidence of an interaction effect between GRS and nutritional intake and physical activity. This gene-lifestyle interaction provides a basis for developing prevention or treatment interventions for obesity according to individual genetic predisposition.
Subject(s)
Genetic Predisposition to Disease , Obesity , Female , Humans , Cross-Sectional Studies , Cohort Studies , Obesity/genetics , Risk Factors , Life Style , Polymorphism, Single Nucleotide , Body Mass IndexABSTRACT
AIMS: The association between dietary patterns and serum low density lipoprotein (LDL) cholesterol would be changing in recent dietary habits in Japan. We investigated the relationship between dietary patterns and serum LDL cholesterol in a large general population. METHODS: From the baseline survey of Japan Multi-Institutional Collaborative Cohort Study between 2005 and 2013, 27,237 participants (13,994 were women) aged 35-69 years were cross-sectionally analyzed. Using a semi-quantitative food frequency questionnaire, five major sex-specific dietary patterns were identified using factor analysis. We assessed serum LDL cholesterol by quintiles of dietary pattern factor score. RESULTS: We identified dietary patterns; "vegetable rich pattern" , "meat and fried food rich pattern" and "high bread and low rice pattern" in women and men; "fish and shellfish rich pattern" and "high confectioneries and low alcohol pattern" in men; "healthy Japanese diet pattern" and "high alcohol and low rice pattern" in women. Serum LDL cholesterol in men was associated with "high bread and low rice pattern" score (Q5 was 4.2 mg/dL higher than Q1, p for trend ï¼0.001) and "high confectioneries and low alcohol pattern" scores (Q5 was 9.5 mg/dL higher than Q1, p for trend ï¼0.001). In women, serum LDL cholesterol was associated with "high bread and low rice pattern" score (Q5 was 7.1 mg/dL higher than Q1, p for trend ï¼0.001). CONCLUSION: Some recent dietary patterns in Japan were associated with serum LDL cholesterol. Serum LDL cholesterol was associated with high bread and low rice pattern in both sex, and high confectioneries and low alcohol pattern in men.
Subject(s)
Cholesterol, LDL , Diet , East Asian People , Female , Humans , Male , Cholesterol, LDL/blood , Cohort Studies , Japan/epidemiologyABSTRACT
The Pseudomonas aeruginosa strain, PAO1, has three putative γ-glutamyltranspeptidase (GGT) genes: ggtI, ggtII, and ggtIII. In this study, the expression of each of these genes in P. aeruginosa PAO1 was analyzed, and the properties of the corresponding GGT proteins were investigated. This is the first report on biochemical characterization of GGT paralogs from Pseudomonas species. The crude extracts prepared from P. aeruginosa PAO1 exhibited hydrolysis and transpeptidation activities of 17.3 and 65.0 mU/mg, respectively, and the transcription of each gene to mRNA was confirmed by RT-PCR. All genes were cloned, and the expression plasmids constructed were introduced into an Escherichia coli expression system. Enzyme activity of the expressed protein of ggtI (PaGGTI) was not detected in the system, while the enzyme activities of the expressed proteins derived from ggtII and ggtIII (PaGGTII and PaGGTIII, respectively) were detected. However, the enzyme activity of PaGGTII was very low and easily decreased. PaGGTII with C-terminal his-tag (PaGGTII25aa) showed increased activity and stability, and the purified enzyme consisted of a large subunit of 40 kDa and a small subunit of 28 kDa. PaGGTIII consisted of a large subunit of 37 kDa and a small subunit of 24 kDa. The maximum hydrolysis and transpeptidation activities of PaGGTII25aa were obtained at 40ºC-50ºC, and the maximum hydrolysis and transpeptidation activities of PaGGTIII were obtained at 50ºC-60ºC. These enzymes retained approximately 80% of their hydrolysis and transpeptidation activities after incubation at 50ºC for 10 min, reflecting good stability. Both PaGGTII25aa and PaGGTIII showed higher activities of hydrolysis and transpeptidation in the alkali range than in the acidic range. However, they were highly stable at a wide pH range (5-10.5).
Subject(s)
Pseudomonas Infections , Pseudomonas aeruginosa , Humans , Pseudomonas aeruginosa/genetics , Pseudomonas , Escherichia coli/geneticsABSTRACT
The high stereo- and substrate specificities of enzymes have been utilized for microdetermination of amino acids. Here, I review the discovery of l-Arg oxidase from Pseudomonas sp. TPU 7192, l-Lys oxidase/decarboxylase from Burkholderia sp. AIU 395, and enzymes showing apparent l-His oxidase activity from Achromobacter sp. TPU 5009. I also discuss screening and uses of the selective enzymes for microdetermination of amino acids. In addition, functional modifications of l-amino acid oxidase/monooxygenase from Pseudomonas sp. AIU 813, l-Trp dehydrogenase from Nostoc punctiforme ATCC 29133, and l-Lys ε-oxidase from Marinomonas mediterranea NBRC 103028 by directed evolution are reviewed. Finally, I review the rational identification of aggregation hotspots based on secondary structure and amino acid hydrophobicity-this process enables the wider use of natural enzymes.
Subject(s)
Amino Acids , Oxidoreductases , Amino Acids/metabolism , Oxidoreductases/metabolism , Lysine/metabolism , L-Amino Acid Oxidase/metabolism , Substrate Specificity , Amino Acid Oxidoreductases/chemistryABSTRACT
BACKGROUND: Little is known about whether insufficient moderate-to-vigorous physical activity (MVPA) and longer sedentary behavior (SB) are independently associated with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), whether they interact with known risk factors for CKD, and the effect of replacing sedentary time with an equivalent duration of physical activity on kidney function. METHODS: We examined the cross-sectional association of MVPA and SB with eGFR and CKD in 66,603 Japanese cohort study in 14 areas from 2004 to 2013. MVPA and SB were estimated using a self-reported questionnaire, and CKD was defined as eGFR <60 mL/min/1.73 m2. Multiple linear regression analyses, logistic regression analyses, and an isotemporal substitution model were applied. RESULTS: After adjusting for potential confounders, higher MVPA and longer SB were independently associated with higher eGFR (P for trend MVPA <0.0001) and lower eGFR (P for trend SB <0.0001), and a lower odds ratio (OR) of CKD (adjusted OR of MVPA ≥20 MET·h/day, 0.76; 95% confidence interval [CI], 0.68-0.85 compared to MVPA <5 MET·h/day) and a higher OR of CKD (adjusted OR of SB ≥16 h/day, 1.81; 95% CI, 1.52-2.15 compared to SB <7 h/day), respectively. The negative association between MVPA and CKD was stronger in men, and significant interactions between sex and MVPA were detected. Replacing 1 hour of SB with 1 hour of physical activity was associated with about 3 to 4% lower OR of CKD. CONCLUSION: These findings indicate that replacing SB with physical activity may benefit kidney function, especially in men, adding to the possible evidence on CKD prevention.
Subject(s)
Exercise , Renal Insufficiency, Chronic , Sedentary Behavior , Humans , Male , Cohort Studies , Cross-Sectional Studies , Exercise/physiology , Japan/epidemiology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/prevention & control , Female , Adult , Middle Aged , Aged , Glomerular Filtration Rate/physiology , Risk FactorsABSTRACT
There are many reports on the risk of falls in older adults but none regarding the risk among middle-aged people. We aimed to determine fall risk factors among middle-aged women. The participants comprised 1421 women aged 40 to 64 years; anthropometric and other measurements were obtained, and lifestyle factors were examined using a self-administered questionnaire. The participants were categorized into two groups (No-fall and Fall/Almost-fall) based on their questionnaire responses. The No-fall and Fall/Almost-fall groups comprised 1114 and 307 participants, respectively. Body mass index, abdominal circumference measurements, and prevalence of dyslipidemia were significantly higher in the Fall/Almost-fall group. Additionally, those in the Fall/Almost-fall group had a shorter two-step test, experienced difficulty performing the 40 cm single-leg sit-to-stand test, and had higher 25-question Geriatric Locomotive Function Scale (GLFS-25) scores than those in the No-fall group. The results of the adjusted logistic regression analysis indicated that physical activity, higher GLFS-25 scores, and sedentary time of more than seven hours were all risk factors for falling or almost falling. Longer sedentary time is a new risk factor for falls among middle-aged women. It is necessary for people to be concerned with their sedentary behavior, such as by reducing or interrupting continuous sedentary time.
ABSTRACT
OBJECTIVE: Findings on the increased mortality risk in individuals with insomnia are inconsistent across studies. Rather than improving insomnia by sleep control, hypnotic use may be one factor in the increased risk of death; however, the effects of hypnotics on mortality remains unclear. This study aimed to examine the association between all-cause mortality and hypnotic use in a large sample, while adjusting for the effects of comorbidities. METHODS: Overall, 92,527 individuals aged 35-69 years were followed up for mortality in the Japan Multi-Institutional Collaborative Cohort Study. Regular use of hypnotics was assessed using a self-administered questionnaire. Since cancer history carries a substantial risk of death and is associated with the treatment of insomnia with hypnotics, participants with a cancer history were excluded. The hazard ratio (HR) and 95% confidence interval (CI) for all-cause mortality related to hypnotic use were estimated using a Cox proportional hazard model with adjustments for covariates including sleeping hours and comorbidities (body mass index, ischemic heart disease, stroke, and diabetes). RESULTS: During the follow-up (mean, 8.4 ± 2.5 years), 1,492 mortalities were recorded, and the prevalence of taking hypnotics was 4.2%. Hypnotic use was associated with significantly greater risk of all-cause mortality, even after adjustment for the covariates (HR, 1.32; 95% CI, 1.07-1.63). The association between hypnotic use and all-cause mortality was robust in males (HR, 1.51; 95% CI, 1.15-1.96), and participants aged <60 years (HR, 1.75; 95% CI, 1.21-2.54). CONCLUSIONS: Our study revealed sex-age specific associations between hypnotic use and all-cause mortality.
Subject(s)
Neoplasms , Sleep Initiation and Maintenance Disorders , Male , Humans , Sleep Initiation and Maintenance Disorders/drug therapy , Cohort Studies , Hypnotics and Sedatives/adverse effects , Japan/epidemiology , Risk Factors , Age FactorsABSTRACT
Genetic factors play a role in individual differences in pain experience. Here, we performed a genome-wide association study (GWAS) to identify novel loci regulating pain processing. We conducted a 2-stage GWAS and the candidate single-nucleotide polymorphisms (SNPs) association study on pain experience using an exploratory cohort of patients with cancer pain. The confirmatory cohort comprised of participants from the general population with and without habitual use of analgesic medication. In the exploratory cohort, we evaluated pain intensity using a numerical rating scale, recorded daily opioid dosages, and calculated pain reduction rate. In the confirmatory cohort, pain experience was defined as habitual nonsteroidal anti-inflammatory drug usage. Using linear regression models, we identified candidate SNP in the exploratory samples, and tested the association between phenotype and experienced pain in the confirmatory samples. We found 1 novel SNP (rs11764598)-located on the gene encoding for pleiotrophin on chromosome 7-that passed the genome-wide suggestive significance at 20% false discovery rate (FDR) correction in the exploratory samples of patients with cancer pain (P = 1.31 × 10-7, FDR = 0.101). We confirmed its significant association with daily analgesic usage in the confirmatory cohort (P = .028), although the minor allele affected pain experience in an opposite manner. We identified a novel genetic variant associated with pain experience. Further studies are required to validate the role of pleiotrophin in pain processing.
Subject(s)
Cancer Pain , Genome-Wide Association Study , Adult , Humans , Analgesics/therapeutic use , Analgesics, Opioid/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Cancer Pain/drug therapy , Carrier Proteins , Case-Control Studies , Cytokines , Japan , Polymorphism, Single NucleotideABSTRACT
BACKGROUND: Mid-regional pro-adrenomedullin (MR-proADM) is a novel biomarker for cognitive decline based on its association with cerebral small vessel disease (SVD). Cerebral microbleeds (MBs) are characteristic of SVD; however, a direct association between MR-proADM and MBs has not been explored. OBJECTIVE: We aimed to examine whether circulating levels of MR-proADM are associated with the identification of MBs by brain magnetic resonance imaging (MRI) and whether this association could be linked with cognitive impairment. METHODS: In total, 214 participants (mean age: 75.9 years) without history of cerebral infarction or dementia were prospectively enrolled. All participants underwent brain MRI, higher cognitive function testing, blood biochemistry evaluation, lifestyle examination, and blood MR-proADM measurement using a time-resolved amplified cryptate emission technology assay. For between-group comparisons, the participants were divided into two groups according to whether their levels of MR-proADM were normal (<â0.65ânmol/L) or high (≥0.65ânmol/L). RESULTS: The mean MR-proADM level was 0.515±0.127ânmol/L. There were significant between-group differences in age, hypertension, and HbA1c levels (pâ<â0.05). In the high MR-proADM group, the MR-proADM level was associated with the identification of MBs on brain MR images and indications of mild cognitive impairment (MCI). In participants with ≥3 MBs and MCI, high MR-proADM levels remained a risk factor after multivariate adjustment (OR: 2.94; pâ<â0.05). CONCLUSION: High levels of MR-proADM may be a surrogate marker for the early detection of cognitive decline associated with the formation of cerebral MBs. This marker would be valuable during routine clinical examinations of geriatric patients.
Subject(s)
Adrenomedullin , Protein Precursors , Aged , Biomarkers , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnostic imaging , Humans , Prognosis , Risk FactorsABSTRACT
BACKGROUND: Bromine compounds are used in several drugs, including over-the-counter drugs. They sometimes cause intoxication known as bromism. Although the acute neurological symptoms and sequelae of bromism vary, few reports have mentioned acute encephalopathy. CASE PRESENTATION: We report two cases of bromisoval-induced bromism with status epilepticus. Presence of pseudohyperchloremia and history of over-the-counter medication use guided the diagnosis. In the acute phase, our patients showed bilateral medial thalamic lesions on magnetic resonance imaging. The imaging findings were similar to those of Wernicke's encephalopathy. Although these findings improved in the chronic phase, neuropsychiatric sequelae, such as confabulation and amnesia, occurred. CONCLUSION: Bromism can cause acute encephalopathy, and it is important to differentiate it from Wernicke-Korsakoff syndrome.