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Relatively few studies have explored the differential contributions of the accumulative dosage of psychotropic medications on mortality in patients with schizophrenia.
Methods
We aimed to explore the effects of the exposure dosage of psychotropic medications on mortality during a follow-up period of 5 years with a national cohort of individuals with schizophrenia in 2010. Causes of death were linked through Taiwan's National Mortality Registry. The mean defined daily dose of antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, were calculated and survival analyses were conducted.
Results
A total of 102 964 individuals (54 151 men, 52.59%) with schizophrenia were included. Compared to patients with no exposure to antipsychotics, those with antipsychotic exposure had better survival outcomes, regardless of antipsychotic dosage. Antidepressant exposure, in low and moderate dosage, was associated with decreased all-cause mortality; exposure to mood stabilizers appeared to be associated with an increase in all-cause mortality. Although 89.7% of the patients had been prescribed sedative-hypnotics, exposure to sedative-hypnotics was associated with dose-related increased mortality risk [hazard ratio (HR) in low dose group: 1.16, 95% confidence interval (CI) 1.07–1.27; HR in moderate dose: 1.32, 95% CI 1.21–1.44; HR in high dose: 1.83, 95% CI 1.67–2.01)].
Conclusions
The results indicate that in the treatment of schizophrenia, antipsychotics and antidepressants are associated with lower mortality when using adequate dosages and mood stabilizers and sedative-hypnotics with higher mortality compared with no use. Furthermore, exposure to sedative-hypnotics is associated with a dose-related increased mortality risk which warrants clinical attention and further study.
Given the concerns of health inequality associated with mental illnesses, we aimed to reveal the extent of which general mortality and life expectancy at birth in people with schizophrenia, bipolar disorder and depressive disorder varied in the 2005 and 2010 nationally representative cohorts in Taiwan.
Methods
Two nationally representative samples of individuals with schizophrenia, bipolar disorder and depressive disorder were identified from Taiwan's national health insurance database in 2005 and 2010, respectively, and followed-up for consecutive 3 years. The database was linked to nationwide mortality registry to identify causes and date of death. Age-, gender- and cause-specific mortality rates were generated, with the average follow-up period of each age- and gender-band applied as ‘weighting’ for the calculation of expected number of deaths. Age- and gender-standardised mortality ratios (SMRs) were calculated for these 3-year observation periods with Taiwanese general population in 2011/2012 as the standard population. The SMR calculations were then stratified by natural/unnatural causes and major groups of death. Corresponding life expectancies at birth were also calculated by gender, diagnosis of mental disorders and year of cohorts for further elucidation.
Results
The general differential in mortality rates for people with schizophrenia and bipolar disorder remained wide, revealing an SMR of 3.65 (95% confidence interval (CI): 3.55–3.76) for cohort 2005 and 3.27 (3.18-3.36) for cohort 2010 in schizophrenia, and 2.65 (95% CI: 2.55–2.76) for cohort 2005 and 2.39 (2.31-2.48) for cohort 2010 in bipolar disorder, respectively. The SMRs in people with depression were 1.83 (95% CI: 1.81–1.86) for cohort 2005 and 1.59 (1.57-1.61) for cohort 2010. SMRs due to unnatural causes tended to decrease in people with major mental illnesses over the years, but those due to natural causes remained relatively stable. The life expectancies at birth for schizophrenia, bipolar disorder and depression were all significantly lower than the national norms, specifically showing 14.97–15.50 years of life lost for men and 15.15–15.48 years for women in people with schizophrenia.
Conclusions
Compared to general population, the differential in mortality rates for people with major mental illnesses persisted substantial. The differential in mortality for unnatural causes of death seemed decreasing over the years, but that due to natural causes remained relatively steady. Regardless of gender, people with schizophrenia, bipolar disorder and depression were shown to have shortened life expectancies compared to general population.
The present study investigated the effects of glutamine (GLN) pretreatment on CD4+ T cell polarisation and remote kidney injury in mice with gut-derived polymicrobial sepsis. Mice were randomly assigned to three groups: normal control fed with American Institute of Nutrition (AIN)-93G diet and two sepsis groups provided with either AIN-93G-based diet or identical components, except part of casein was replaced by GLN. Mice were given their respective diets for 2 weeks. Then, mice in the sepsis groups were performed with caecal ligation and puncture and were killed 72 h after the surgery. Blood, spleens and kidneys were collected for further examination. The results showed that sepsis resulted in decreased circulating and splenic total T lymphocyte and CD4+ T cell percentages, whereas IL-4-, and forkhead box p3 (Foxp3)-expressing CD4+ T cells percentages were up-regulated. Compared with the sepsis control group, pretreatment with GLN maintained blood T and CD4+ T cells and reduced percentages of IL-4- and Foxp3-expressing CD4+ T cells. Also, a more pronounced activation and increased anti-apoptotic Bcl-2 gene expression of splenic CD4+ T cells were observed. Concomitant with the decreased plasma IL-6, keratinocyte-derived chemokine (KC) levels, the gene expression of KC, macrophage inflammatory protein-2 and renal injury biomarker kidney injury molecule-1 (Kim-1) were down-regulated when GLN was administered. These findings suggest that antecedent of GLN administration elicit a more balanced blood T helper cell polarisation, sustained T cell populations, prevented splenic CD4+ T cell apoptosis and attenuated kidney injury at late phase of polymicrobial sepsis. GLN may have benefits in subjects at risk of abdominal infection.
This article analyzes America Today, a United States Information Service publication circulated to Southeast Asian Chinese between 1949 and 1952. Although the federal government had no intention of lifting immigration restrictions, the magazine promoted the idea that the United States provided humanitarian assistance and abundant opportunities to Chinese immigrants as well as their American-born Chinese counterparts to achieve upward mobility, form a conjugal family, and enjoy patriarchal authority. The stories demonstrated an attempt to inspire Chinese male readers in Southeast Asia to support the United States and the “free world,” rather than Communism and the People's Republic of China.
Evidence regarding the relationships between the socioeconomic status and
long-term outcomes of individuals with bipolar affective disorder (BPD)
is lacking.
Aims
We aimed to estimate the effects of baseline socioeconomic status on
longitudinal outcomes.
Method
A national cohort of adult participants with newly diagnosed BPD was
identified in 2008. The effects of personal and household socioeconomic
status were explored on outcomes of hospital treatment, mortality and
healthcare costs, over a 3-year follow-up period (2008–2011).
Results
A total of 7987 participants were recruited. The relative risks of
hospital treatment and mortality were found elevated for the ones from
low-income households who also had higher healthcare costs. Low premium
levels did not correlate with future healthcare costs.
Conclusions
Socioeconomic deprivation is associated with poorer outcome and higher
healthcare costs in BPD patients. Special care should be given to those
with lower socioeconomic status to improve outcomes with potential
benefits of cost savings in the following years.
Apathy is a condition characterized by a lack of motivation that manifests in emotional, behavioral, and cognitive domains. Although previous studies have indicated that apathy is associated with frontal lesions, few studies have focused on the different subdomains of apathy, and no in vivo human biochemical data have been obtained to examine the neurochemical changes related to apathy in patients with Alzheimer's disease (AD). Thus, we investigated the frontal neurochemical alterations related to apathy among patients with AD using proton magnetic resonance spectroscopy (1H MRS).
Methods:
Apathy was assessed through the Apathy Evaluation Scale (AES). 1H MRS was performed to measure neurochemical metabolite levels in the anterior cingulate region and right orbitofrontal region. Associations between neurochemical metabolites and the total score and subscores of each domain of the AES were analyzed.
Results:
Altogether, 36 patients completed the study. Patients with lower N-acetylaspartate/creatine ratios (NAA/Cr) in the anterior cingulate region demonstrated higher total apathy scores (β = −0.56, p = 0.003) with adjustments for age, gender, educational level, dementia severity, and depression severity. In a further analysis, a lower NAA/Cr in the anterior cingulate region was associated with all subdomains of apathy, including cognition (β = −0.43, p = 0.028), behavior (β = −0.55, p = 0.002), and emotion (β = −0.50, p = 0.005). No statistically significant associations were discovered in the right orbitofrontal region.
Conclusions:
Our results suggest that apathy, in each of its cognitive, behavioral, or emotional subdomains is associated with brain neurochemical alterations in the anterior cingulate region. Abnormal neuronal integrity over the anterior cingulate cortex may exhibit a central role in causing all aspects of apathy in patients with AD.
To determine the therapeutic effect of levodopa/benserazide and tolcapone on gait in patients with advanced Parkinson's disease.
Methods:
Instrumental gait analysis was performed in 38 out of 40 patients with wearing-off phenomenon during a randomized, double-blind, placebo-controlled trial of tolcapone.
Results:
Gait analysis disclosed a significant improvement by levodopa/benserazide in walking speed, stride length and the range of motion of hip, knee and ankle joints. At the end of the study, both the UPDRS motor scores during off-period and the percentage of off time improved significantly using tolcapone. However, gait analysis could not confirm this improvement. With respect to levodopa/benserazide effect, the reduction in rigidity correlated with improved angular excursion of the ankle, whereas the decreased bradykinesia correlated with improved stride length and angular excursion of the hip and knee joints.
Conclusion:
The results of our gait analysis confirmed that in parkinsonian patients with fluctuating motor symptoms levodopa/benserazide, but not tolcapone, produced a substantial improvement.
Unawareness of deficits is common and is associated with poor outcomes in Alzheimer's disease (AD); however, little is known about correlated neurobiochemical changes.
Methods:
Proton magnetic resonance spectroscopy was used to examine neurobiochemical correlates of unawareness of deficits as assessed by the Dementia Deficit Scale in 36 patients with AD. Magnetic resonance spectroscopy spectra were acquired from the anterior cingulate area and right orbitofrontal area. Concentrations of N-acetyl-aspartate (NAA), total creatine, and other neurometabolites were calculated.
Results:
Nineteen (52.8%) participants had relative unawareness of deficits. This condition was negatively correlated with NAA/creatine in the anterior cingulate area (β = −0.36, p = 0.025) and positively correlated with NAA/creatine in the right orbitofrontal area (β = 0.41, p = 0.009) after controlling for dementia severity.
Conclusions:
These findings suggest unawareness of deficits in AD was associated with the altered neurochemical metabolites in the anterior cingulate area and right orbitofrontal area. However, the two areas might have opposite neuronal functions in unawareness of deficits.
The present study investigated the effect of glutamine (Gln) on dextran sulphate sodium (DSS)-induced changes in the expression of small-intestinal intraepithelial lymphocyte (IEL) γδ-T cells in mice. Mice were randomly assigned to a normal control (NC) group and two DSS-treated groups. The NC group and one of the DSS-treated groups (DSS-C) were fed a common semi-purified diet, while the other DSS-treated group (DSS-G) was fed an identical diet, except that part of casein was replaced by Gln, which provided 25 % of total amino acid nitrogen. After being fed the diets for 10 d, mice in the NC group were given distilled water, while the DSS-treated groups were given distilled water containing 2·5 % DSS for 5 d. At the end of the experiment, the mice were killed. The small-intestinal IEL γδ-T-cell subset was isolated for further analysis. The results indicated that DSS treatment resulted in a lower percentage of small-intestinal IEL γδ-T cells and higher mRNA expressions of interferon-γ, TNF-α, IL-17, complement 5a receptor and keratinocyte growth factor in IEL γδ-T cells. Gln administration increased the proportion of small-intestinal IEL γδ-T cells, and the expression levels of immunomodulatory mediator genes in IEL γδ-T cells were lower in the DSS-treated mice. The histological findings indicated that the immunoreactive intensity of the tight junction protein ZO-1 in the small-intestinal mucosa was higher in the DSS-G group than in the DSS-C group. These results indicate that pretreatment with Gln increases the proportion of small-intestinal IEL γδ-T cells and down-regulates γδ-T-cell-expressed inflammatory mediators, which may consequently ameliorate the severity of DSS-induced small-intestinal epithelial injury.
There are close links among hyperglycaemia, oxidative stress and diabetic complications. Glutamine (GLN) is an amino acid with immunomodulatory properties. The present study investigated the effect of dietary GLN on oxidative stress-relative gene expressions and tissue oxidative damage in diabetes. There were one normal control (NC) and two diabetic groups in the present study. Diabetes was induced by an intraperitoneal injection of nicotinamide followed by streptozotocin (STZ). Rats in the NC group were fed a regular chow diet. In the two diabetic groups, one group (diabetes mellitus, DM) was fed a common semi-purified diet while the other group received a diet in which part of the casein was replaced by GLN (DM-GLN). GLN provided 25 % of total amino acid N. The experimental groups were fed the respective diets for 8 weeks, and then the rats were killed for further analysis. The results showed that blood thioredoxin-interacting protein (Txnip) mRNA expression in the diabetic groups was higher than that in the NC group. Compared with the DM group, the DM-GLN group had lower glutamine fructose-6-phosphate transaminase 1, a receptor of advanced glycation end products, and Txnip gene expressions in blood mononuclear cells. The total antioxidant capacity was lower and antioxidant enzyme activities were altered by the diabetic condition. GLN supplementation increased antioxidant capacity and normalised antioxidant enzyme activities. Also, the renal nitrotyrosine level and Txnip mRNA expression were lower when GLN was administered. These results suggest that dietary GLN supplementation decreases oxidative stress-related gene expression, increases the antioxidant potential and may consequently attenuate renal oxidative damage in rats with STZ-induced diabetes.
Arginine (Arg) is known to possess numerous useful physiological properties and have immunomodulatory effects. In vitro studies reported that Arg inhibits advanced glycation endproduct (AGE) formation; however, the effects of Arg on the receptor of AGE (RAGE) expression in inflammatory conditions are not clear. The present study investigated the effects of dietary Arg supplementation on inflammatory mediator production and RAGE expression in type 2 diabetic rats. There were one normal control (NC) group and two diabetic groups in the present study. Rats in the NC group were fed with a regular chow diet. One diabetic group (DM) was fed a common semi-purified diet while the other diabetic group received a diet in which part of the casein was replaced by Arg (DM-Arg) for 8 weeks. Diabetes was induced by an intraperitoneal injection of nicotinamide followed by streptozotocin. Rats with blood glucose levels exceeding 1800 mg/l were considered diabetic. Blood samples and the liver and lungs of the animals were collected at the end of the study for further analysis. Results showed that plasma glucose and fructosamine contents were significantly higher in the diabetic groups than those in the NC group. The DM group had higher fructosamine and C-reactive protein than the DM-Arg group. Immunohistochemical staining showed that the expressions of RAGE in liver and lung tissues were significantly lower in the DM-Arg group than in the DM group. These results suggest that supplemental dietary Arg can decrease AGE–RAGE interactions and consequently reduce tissue damage in rats with type 2 diabetes.
Although teachers are the key participants in health-promoting schools (HPS) programme delivery, it is still unknown whether teachers are appropriate health information resources and role models for students with respect to healthy diets. The present study aimed to investigate the effects of implementing HPS programmes on teachers’ nutrition knowledge and diets.
Design
One HPS programme aiming at dietary intervention (HP-D) and one HPS not aiming at dietary intervention (HP-ND) were selected, along with two non-health-promoting (NHP) schools matched for school size and urbanization level with the two HPS. All 361 teachers in the four schools were invited to participate, yielding a 78·4 % overall valid response rate. A structured, self-reported questionnaire was administered, with regression models used for statistical analysis.
Results
Teachers in the HP-D group had a mean score of 21·1 on a range of 0–30 for nutrition knowledge, which was significantly higher than the mean scores of 18·5 in the HP-ND group and 19·1 in the NHP group (P < 0·001). Better dietary behaviours were also observed among HP-D teachers. Further, being a ‘health education’ course instructor was associated with significantly higher scores on nutrition knowledge (β = 2·6, P < 0·001) and vegetable and fruit consumption (β = 1·4, P = 0·02) in the HP-D group than in the NHP group. The HP-ND and NHP groups exhibited similar patterns of non-significant differences compared with the HP-D group.
Conclusions
Implementation of a coordinated HPS framework on nutrition and diet was positively correlated with schoolteachers’ nutrition knowledge and dietary intake.
The present study investigated the effect of parenteral glutamine (Gln) supplementation on cellular adhesion molecule expression and release of chemokines responsible for inflammatory cell recruitment in rats undergoing a total gastrectomy. Normal rats with internal jugular catheters were assigned to one control group and two experimental groups and received total parenteral nutrition (TPN). A total gastrectomy was performed in the experimental groups, whereas the control group received a sham operation (Sham). The TPN solutions were isonitrogenous and identical in nutrient composition except that the Sham group and one of the experimental group received conventional (Conv) TPN solution, whereas the other experimental group received 25 % of the amino acid nitrogen as Gln. Half of the rats in each group were killed 1 or 3 d after surgery or the Sham to examine their immune response. The results showed that the surgery produced higher polymorphonuclear leucocyte CD11b/CD18 expressions, and Gln supplementation lowered CD11b/CD18 expressions compared with the Conv group post-operatively. The levels of monocyte chemotactic protein-1 and macrophage inflammatory protein-2 in peritoneal lavage fluid were higher in the Gln group than those in the Conv group 1 d post-operatively; these chemotactic proteins had returned to the levels comparable with those in the Sham group on post-operative day 3. These results suggest that Gln supplementation attenuated polymorphonuclear leucocyte integrin expression. In addition, Gln-enriched parenteral nutrition induced an earlier more intensive and rapid immune response to injury than the Conv parenteral nutrition after a total gastrectomy.
This study investigated the effect of n-3 fatty acids on adhesion molecules and tissue myeloperoxidase (MPO) activity in diabetic mice with sepsis. Diabetes was induced by a streptozotocin injection. Mice with blood glucose levels exceeding 2000 mg/l were considered diabetic. Diabetic mice were assigned to two groups with a medium-fat (10 %, w/w) diet either provided by soyabean oil (SO, n 30) or fish oil (FO, n 30). n-3 fatty acids provided 4·3 % of the total energy and the n-3/n-6 fatty acid ratio was 1:2 in the FO diet. After feeding the respective diet for 3 weeks, all mice had sepsis induced by caecal ligation and puncture (CLP) and were killed at 0, 6 or 24 h after CLP, with ten mice at each time-point. The result showed that compared with the SO group, FO group had lower PGE2 and TNF-α levels in peritoneal lavage fluid after CLP. Lymphocyte CD11a/CD18 expressions were higher at 6 h, whereas the percentage was lower at 24 h in the SO group than in the FO group. Neutrophil CD11b/CD18 expressions were significantly higher in the SO group than in the FO group at 0 h. The FO group had lower organ MPO activities at various time-points after CLP when compared with those of the SO group. The present findings suggest that compared with the diabetic mice fed SO, a low-dose n-3 fatty acid supplementation may attenuate leucocyte adhesion and infiltration into tissues in diabetic mice complicated with sepsis.
This study investigated the effects of fish oil (FO) diet on plasma intercellular adhesion molecule 1 (ICAM-1) levels and leucocyte integrin expression in polymicrobial sepsis. Mice were randomly assigned to a control group and an FO group. The control group was fed a medium-fat diet containing soyabean oil, whereas in the FO group, 70 % of the soyabean oil was replaced by FO for 3 weeks. After that, sepsis was induced by caecal ligation and puncture (CLP) in the experimental groups and mice were killed at 0, 6, 12 and 24 h, respectively, after CLP. Results showed that compared with the control group, plasma ICAM-1 levels were higher in the FO group 6 h after CLP. Intra-lymphocyte interferon-γ expression in the FO group was lower, whereas IL-4 expression was higher than in the control group 12 and 24 h after CLP. The expression of leucocyte integrin was significantly higher in the FO group 12 and 24 h after CLP. The FO group had higher IL-6 levels at 12 h in the lungs, at 6 and 12 h in the kidneys, and at 6, 12 and 24 h in the intestines after CLP. The survival rate did not differ between the two groups after CLP. The present findings suggest that pretreatment with an FO diet enhances adhesion molecule and inflammatory cytokine expressions during sepsis, which might aggravate the inflammatory reaction and increase neutrophil infiltration into tissues. In addition, FO diet promotes the Th2-type response and suppresses cellular immune response in polymicrobial sepsis.
The present study investigated the effect of arginine (Arg)-containing parenteral nutrition on phagocytic activity to elucidate the possible roles of Arg in the secretion of anabolic hormones and N balance in rats undergoing gastrectomy. Rats were divided into two experimental groups and received total parenteral nutrition (TPN). The TPN solutions were isonitrogenous and identical in nutrient compositions except for differences in amino acid content. One group received conventional TPN, the other group replaced 2 % of the total energy as Arg. After receiving TPN for 3 d, one-third of the rats in each experimental group were killed as the baseline group. The remaining rats underwent a partial gastrectomy and were killed 1 or 3 d after surgery. The results showed that there were no differences in N balance, plasma growth hormone and insulin-like growth factor-1 levels between the two groups before or after surgery. The phagocytic activity of peritoneal macrophages was higher in the Arg group than in the control group 1 d after surgery. There were no differences in the phagocytic activities of blood polymorphonuclear neutrophils between the two groups at various time points. TNF-α levels in peritoneal lavage fluid were lower in the Arg group than in the control group on post-operative day 3. These results suggest that parenterally infused Arg enhances phagocytic activity and reduces the production of inflammatory mediators at the site of injury. However, Arg supplementation did not influence the secretion of anabolic hormones nor N balance in rats with a partial gastrectomy.
The present study examined the effect of glutamine (Gln)-enriched diets before sepsis or Gln-containing total parenteral nutrition (TPN) after sepsis, or both, on the phagocytic activity and blood lymphocyte subpopulation in rats with gut-derived sepsis. Rats were assigned to a control group or one of four experimental groups. The control group and groups 1 and 2 were fed a semipurified diet; groups 3 and 4 had part of casein replaced by Gln. After feeding the diets for 10d, sepsis was induced by caecal ligation and puncture (CLP); TPN was maintained for 3d after CLP. The control group and groups 1 and 3 were infused with conventional TPN and groups 2 and 4 were supplemented with Gln in the TPN solution. All rats were killed 3d after CLP or sham operation to examine their immune responses. The results showed that compared with the control group, the phagocytic activities of peritoneal macrophages were enhanced in groups 3 and 4, but not in groups 1 and 2. The proportion of CD3+ cells in group 1 was significantly lower (P<0·05) than that of the control group, whereas no differences were observed among the control and Gln-supplemented groups. The CD4+ cell proportion was significantly lower (P<0·05) in group 1 compared with the control group and groups 3 and 4. These findings suggest that Gln-enriched diets before CLP significantly enhanced peritoneal macrophage phagocytic activity, preserved CD4+ cells and maintained blood total T lymphocytes in gut-derived sepsis. However, parenteral Gln administration after caecal ligation and puncture had no favourable effects on modulating immune response in septic rats.
Pylyshyn's effort in establishing the cognitive
impenetrability of early vision is welcome. However, his view about
the role of attention in early vision seems to be oversimplified. The
allocation of focal attention manifests its effect among multiple
stages in the early vision system, it is not just confined to the
input and the output levels.
The clinical significance in schizophrenia of positive and negative symptoms at discharge was assessed.
Method
Of schizophrenic patients fulfilling DSM–III criteria, 113 were recruited for this study. Personal, social and psychopathological data were collected and all cases were followed up at one and two years after discharge.
Results
The presence of positive symptoms (64 cases), without concomitant negative symptoms, did not predict the follow-up social function and positive symptom score. Conversely, the presence of negative symptoms (31 cases) predicted worse social functioning (P < 0.05 to P < 0.005) and higher positive symptom scores (P < 0.01) at follow-up using MANOVA. Eighteen cases (15.9%) had neither positive nor negative symptoms and had the best clinical outcome.
Conclusions
Negative, but not positive, symptoms assessed at discharge are an important predictor of poor outcome. In addition, negative symptoms may themselves expose a biological vulnerability to the presence of positive symptoms.
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