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To explore whether and how group cognitive-behavioural therapy (GCBT) plus medication differs from medication alone for the treatment of generalised anxiety disorder (GAD).
Hundred and seventy patients were randomly assigned to the GCBT plus duloxetine (n=89) or duloxetine group (n=81). The primary outcomes were Hamilton Anxiety Scale (HAMA) response and remission rates. The explorative secondary measures included score reductions from baseline in the HAMA total, psychic, and somatic anxiety subscales (HAMA-PA, HAMA-SA), the Hamilton Depression Scale, the Severity Subscale of Clinical Global Impression Scale, Global Assessment of Functioning, and the 12-item Short-Form Health Survey. Assessments were conducted at baseline, 4-week, 8-week, and 3-month follow-up.
At 4 weeks, HAMA response (GCBT group 57.0% vs. control group 24.4%, p=0.000, Cohen’s d=0.90) and remission rates (GCBT group 21.5% vs. control group 6.2%, p=0.004; d=0.51), and most secondary outcomes (all p<0.05, d=0.36−0.77) showed that the combined therapy was superior. At 8 weeks, all the primary and secondary significant differences found at 4 weeks were maintained with smaller effect sizes (p<0.05, d=0.32−0.48). At 3-month follow-up, the combined therapy was only significantly superior in the HAMA total (p<0.045, d=0.43) and HAMA-PA score reductions (p<0.001, d=0.77). Logistic regression showed superiority of the combined therapy for HAMA response rates [odds ratio (OR)=2.12, 95% confidence interval (CI) 1.02−4.42, p=0.04] and remission rates (OR=2.80, 95% CI 1.27−6.16, p=0.01).
Compared with duloxetine alone, GCBT plus duloxetine showed significant treatment response for GAD over a shorter period of time, particularly for psychic anxiety symptoms, which may suggest that GCBT was effective in changing cognitive style.
Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.
We hypothesize that the tumor necrosis factor-α (TNF-α) may play a role in disturbing the effect of selective serotonin reuptake inhibitor (SSRI) on the striatal connectivity in patients with major depressive disorder (MDD).
We performed a longitudinal observation by combining resting-state functional magnetic resonance imaging (rs-fMRI) and biochemical analyses to identify the abnormal striatal connectivity in MDD patients, and to evaluate the effect of TNF-α level on these abnormal connectivities during SSRI treatment. Eighty-five rs-fMRI scans were collected from 25 MDD patients and 35 healthy controls, and the scans were repeated for all the patients before and after a 6-week SSRI treatment. Whole-brain voxel-wise functional connectivity (FC) was calculated by correlating the rs-fMRI time courses between each voxel and the striatal seeds (i.e. spherical regions placed at the striatums). The level of TNF-α in serum was evaluated by Milliplex assay. Factorial analysis was performed to assess the interaction effects of ‘TNF-α × treatment’ in the regions with between-group FC difference.
Compared with controls, MDD patients showed significantly higher striatal FC in the medial prefrontal cortex (MPFC) and bilateral middle/superior temporal cortices before SSRI treatment (p < 0.001, uncorrected). Moreover, a significant interaction effect of ‘TNF-α × treatment’ was found in MPFC-striatum FC in MDD patients (p = 0.002), and the significance remained after adjusted for age, gender, head motion, and episode of disease.
These findings provide evidence that treatment-related brain connectivity change is dependent on the TNF-α level in MDD patients, and the MPFC-striatum connectivities possibly serve as an important target in the brain.
Effective perioperative hand antisepsis is crucial for the safety of patients and medical staff in surgical rooms. The antimicrobial effectiveness of different antiseptic methods, including conventional hand scrubs and waterless hand rubs, has not been well evaluated.
DESIGN, SETTING, AND PARTICIPANTS
A randomized controlled trial was conducted to investigate the effectiveness of the 3 antiseptic methods among surgical staff of Taipei Medical University—Shuang Ho Hospital. For each method used, a group of 80 participants was enrolled.
Surgical hand cleansing with conventional 10% povidone–iodine scrub, conventional 4% chlorhexidine scrub, or waterless hand rub (1% chlorhexidine gluconate and 61% ethyl alcohol).
Colony-forming unit (CFU) counts were collected using the hand imprinting method before and after disinfection and after surgery. After surgical hand disinfection, the mean CFU counts of the conventional chlorhexidine (0.5±0.2, P<0.01) and waterless hand rub groups (1.4±0.7, P<0.05) were significantly lower than that of the conventional povidone group (4.3±1.3). No significant difference was observed in the mean CFU count among the groups after surgery. Similar results were obtained when preexisting differences before disinfection were considered in the analysis of covariance. Furthermore, multivariate regression indicated that the antiseptic method (P=.0036), but not other variables, predicted the mean CFU count.
Conventional chlorhexidine scrub and waterless hand rub were superior to a conventional povidone–iodine product in bacterial inhibition. We recommend using conventional chlorhexidine scrub as a standard method for perioperative hand antisepsis. Waterless hand rub may be used if the higher cost is affordable.
We aimed to clarify whether invasive dental treatment is associated with increased risk of prosthetic joint infection (PJI) and whether prophylactic antibiotics may lower the infection risk remain unclear.
Retrospective cohort study.
All Taiwanese residents (N=255,568) who underwent total knee or hip arthroplasty between January 1, 1997, and November 30, 2009, were screened.
The dental cohort consisted of 57,066 patients who received dental treatment and were individually matched 1:1 with the nondental cohort by age, sex, propensity score, and index date. The dental cohort was further divided by the use or nonuse of prophylactic antibiotics. The antibiotic and nonantibiotic subcohorts comprised 6,513 matched pairs.
PJI occurred in 328 patients (0.57%) in the dental subcohort and 348 patients (0.61%) in the nondental subcohort, with no between-cohort difference in the 1-year cumulative incidence (0.6% in both, P=.3). Multivariate-adjusted Cox regression revealed no association between dental procedures and PJI. Furthermore, PJI occurred in 13 patients (0.2%) in the antibiotic subcohort and 12 patients (0.18%) in the nonantibiotic subcohorts (P=.8). Multivariate-adjusted analyses confirmed that there was no association between the incidence of PJI and prophylactic antibiotics.
The risk of PJI is not increased following dental procedure in patients with hip or knee replacement and is unaffected by antibiotic prophylaxis.
Cancer patients with depression or anxiety have poor survival, and the interaction between mental and physical problems in older patients may exacerbate this problem. K-ras oncogene (KRAS) mutation may play a role in the development of psychosocial distress and may be associated with poor survival of metastatic colorectal cancer (mCRC) patients. This study investigated the association between KRAS gene mutations and psychosocial morbidity to explore the possible cancer/psychosis relationship in older mCRC patients.
In this study, 62 newly diagnosed mCRC patients were recruited and completed the Hospital Anxiety and Depression Scale (HADS). Demographic data were also collected, and clinicopathological data were retrieved from medical records. KRAS mutations were assessed via PCR analysis of tissue specimens from the patients.
The results showed that 28 of the 62 participants (45.2%) had positive screens for possible depression, and 45 of the 62 participants (72.6%) had positive screens for anxiety. The KRAS mutation rate was 40.3% (25/62), and 19 of the 25 patients with KRAS mutations (76.0%) had probable depression, whereas only 24.3% of the patients with wild-type KRAS were probably depressed (p < 0.05). The KRAS mutation was associated with higher HADS depression scores, independent of gender and performance status (p < 0.05), but not with higher HADS anxiety or total scores.
KRAS mutations were associated with depression severity and higher rates of probable depression in older mCRC patients. Depression should be assessed and treated as early as possible in older mCRC patients with the KRAS mutation. Further studies are needed to verify our current findings using a larger sample size.
The long-term outcome of never-treated patients with schizophrenia is
To compare the 14-year outcomes of never-treated and treated patients
with schizophrenia and to establish predictors for never being
All participants with schizophrenia (n = 510) in Xinjin,
Chengdu, China were identified in an epidemiological investigation of 123
572 people and followed up from 1994 to 2008.
The results showed that there were 30.6%, 25.0% and 20.4% of patients who
received no antipsychotic medication in 1994, 2004 and 2008 respectively.
Compared with treated patients, those who were never treated in 2008 were
significantly older, had significantly fewer family members, had higher
rates of homelessness, death from other causes, being unmarried, living
alone, being without a caregiver and poor family attitudes. Partial and
complete remission in treated patients (57.3%) was significantly higher
than that in the never-treated group (29.8%). Predictors of being in the
never-treated group in 2008 encompassed baseline never-treated status,
being without a caregiver and poor mental health status in 1994.
Many patients with schizophrenia still do not receive antipsychotic
medication in rural areas of China. The 14-year follow-up showed that
outcomes for the untreated group were worse. Community-based mental
healthcare, health insurance and family intervention are crucial for
earlier diagnosis, treatment and rehabilitation in the community.
Obesity and hyperlipidaemia increase the risk of CVD. Some strains of probiotics have been suggested to have potential applications in cardiovascular health by lowering serum LDL-cholesterol. In this work, high-fat diet-induced hyperlipidaemia in hamsters was treated with different doses (5×108 and 2·5×109 cells/kg per d) of heat-killed Lactobacillus reuteri GMNL-263 (Lr263) by oral gavage for 8 weeks. The serum lipid profile analysis showed that LDL-cholesterol and plasma malondialdehyde (P-MDA) were reduced in the GMNL-263 5×108 cells/kg per d treatment group. Total cholesterol and P-MDA were reduced in the GMNL-263 2·5×109 cells/kg per d treatment group. In terms of heart function, the GMNL-263 2·5×109 cells/kg per d treatments improved the ejection fraction from 85·71 to 91·81 % and fractional shortening from 46·93 to 57·92 % in the high-fat diet-fed hamster hearts. Moreover, the GMNL-263-treated, high-fat diet-fed hamster hearts exhibited reduced Fas-induced myocardial apoptosis and a reactivated IGF1R/PI3K/Akt cell survival pathway. Interestingly, the GMNL-263 treatments also enhanced the heat-shock protein 27 expression in a dose-dependent manner, but the mechanism for this increase remains unclear. In conclusion, supplementary heat-killed L. reuteri GMNL-263 can slightly reduce serum cholesterol. The anti-hyperlipidaemia effects of GMNL-263 may reactivate the IGF1R/PI3K/Akt cell survival pathway and reduce Fas-induced myocardial apoptosis in high-fat diet-fed hamster hearts.
Salivary α-amylase (sAA) is responsible for the ‘pre-digestion’ of starch in the oral cavity and accounts for up to 50 % of salivary protein in human saliva. An accumulating body of literature suggests that sAA is of nutritional importance; however, it is still not clear how sAA is related to individual's nutritional status. Although copy number variations (CNV) of the salivary amylase gene (AMY1) are associated with variation in sAA levels, a significant amount of sAA variation is not explained by AMY1 CNV. To measure sAA responses to gustatory stimulation with citric acid, we used sAA ratio (the ratio of stimulated sAA levels to those of resting sAA) and investigated acute sAA responses to citric acid in children with normal (Normal-BMI, n 22) and low (Low-BMI, n 21) BMI. The AMY1 gene copy number was determined by quantitative PCR. We, for the first time, demonstrated attenuated acute sAA responses (decreased sAA ratio) to gustatory stimulation in Low-BMI (thinness grade 3) children compared with the Normal-BMI children, which suggest that sAA responses to gustatory stimulation may be of nutritional importance. However, child's nutritional status was not directly related to their resting or stimulated sAA levels, and it was not associated with AMY1 gene copy number. Finally, AMY1 CNV might influence, but did not eventually determine, sAA levels in children.
The present study aimed to compare the effects of a general dietary intervention and an intervention with low glycaemic load (GL) on glycaemic control, blood lipid metabolism and pregnancy outcomes in women with gestational diabetes mellitus.
Participants were randomly assigned to two groups, receiving either an individualized general dietary intervention (Control group) or an intensive low-GL intervention (Low-GL group) every two weeks, from 24–26 weeks of gestation to delivery.
The Center of Maternal Primary Care in Guangdong General Hospital, China.
Ninety-five women with gestational diabetes mellitus were enrolled from June 2008 to July 2009.
After the intervention, both groups significantly decreased their dietary intakes of energy, fat and carbohydrate. The Low-GL group had significantly lower values for GL (122 v. 136) and glycaemic index (50 v. 54) but greater dietary fibre intake (33 v. 29 g/d) than did the Control group (all P<0·01). Significantly greater decreases in fasting plasma glucose (−0·33 v. −0·02 mmol/l, P<0·01) and 2 h postprandial glucose (−2·98 v. −2·51 mmol/l, P<0·01), significantly lower increases in total cholesterol (0·12 v. 0·23 mmol/l) and TAG (0·41 v. 0·56 mmol/l) and a significantly lower decrease in HDL cholesterol (−0·01 v. −0·11 mmol/l) were also observed in the Low-GL group compared with the Control group (all P<0·05). There were no significant differences in body weight gain, birth weight or other maternal–fetal perinatal outcomes between the two groups.
The low-GL targeted dietary intervention outperformed the general dietary intervention in glycaemic control and the improvement of blood lipid levels in women with gestational diabetes mellitus.
Neurosyphilis (NS) may present with neuropsychiatric disorders characterized by cognitive impairment, personality disorders, and confusion, among others. Very few studies have focused on neuropsychiatric disorders secondary to NS in elderly people.
A retrospective chart review was performed to characterize the psychiatric findings, clinical signs and symptoms, laboratory findings, and brain magnetic resonance imaging results of ten elderly inpatients with NS.
In these ten patients, the most common presenting symptoms included a wide variety of psychiatric manifestations. The serum rapid plasma regain (RPR) and Treponema pallidum particle agglutination assay (TPPA) of the ten patients were positive, with positive CSF TPPA and RPR rates of 100% and 60%, respectively. In addition, 90% of the patients demonstrated abnormal imaging, including cerebral atrophy, infarct ischemic stroke, and hydrocephalus.
Our findings support the importance of serological tests for syphilis as a routine component of the evaluation of patients with clinically evident neurological or psychiatric symptoms. If the serology is positive, all of the patients should be examined with a lumbar puncture. Moreover, psychiatric illnesses secondary to NS in the elderly also deserve medical attention.
The present study investigated dietary intake, glucose metabolism and sex hormones in women with polycystic ovary syndrome (PCOS). A total of forty-five women (aged 25–40 years) with PCOS and 161 control women (aged 25–43 years) with non-PCOS-related infertility were recruited. Anthropometry, glucose tolerance and sex hormones were determined and dietary intake was assessed. Women with PCOS had lower serum sex hormone-binding globulin and increased BMI, waist:hip ratio, luteinising hormone, ratio of luteinising hormone:follicle-stimulating hormone, testosterone and free androgen index (FAI). Postprandial glucose, fasting insulin and insulin resistance were elevated in women with PCOS. Women with PCOS had reduced energy and carbohydrate intake but higher fat intake. Serum sex hormone-binding globulin level was negatively associated with BMI in both groups and negatively correlated with macronutrient intake in the PCOS group with hyperandrogenism. However, FAI was positively correlated with BMI, waist circumference and glucose metabolic parameters in both groups. Therefore, women with PCOS consume lower energy and carbohydrate compared with those with non-PCOS-related infertility and macronutrient intake is only negatively associated with serum sex hormone-binding globulin level in the PCOS group with hyperandrogenism.
We have developed a fabrication procedure for growing photonic crystals in the lithographic defined microchannels, which enables easy integration with other planar optical components. This technique is based on the directed evaporation induced self-assembly of nanoparticles in the microchannels. Substrates with pre-patterned microchannels (30-100 μm wide) were dipped into solution of nanoparticles for several days. By controlling the evaporation rate, the meniscus contacting the microchannels will undergo evaporation-induced self-assembly. The capillary forces cause nanospheres to crystallize within the microchannels forming colloidal photonic crystals in the microchannels. Two types of colloidal particles, polystyrene and silica, have been employed to fabricate colloidal photonic crystals in the microchannels. Both types of colloidal particles were found to form large-area well-ordered colloidal single crystals in the microchannels. The optical reflection spectra from the (111) surfaces of the colloidal crystals formed by various sizes of nanoparticles have been measured. And the measured reflection peaks agree with the photonic bandgap calculated by the plane wave expansion method.
Biomaterials such as DNA are currently being explored as potential application in nanotechnology. DNA templates were immobilized on crystal-violet-treated mica by spin coating as a grid-like network. The DNA templates were then activated with PdCl2, followed by reduction with dimethylamine borane (DMAB) to form seeding nanoclusters on the DNA chain. Afterward the DNA chain with deposition of zero-valence Pd nanoclusters was grew in a Co electroless plating bath. SEM/EDS analysis revealed that Co nanoparticles could be assembled on the DNA template to form magnetic nanowires with a diameter of 25nm to 250nm by a conventional electroless plating. Vibrating Sample Magnetometer analysis indicated that Co-DNA nanowires showed a paramagnetic characteristic. Grid-like networks of DNA template were effectively preserved after Co electroless plating. These characteristics indicated that DNA is an ideal template for the production of magnetic nanowires, which could be useful in the development of high-density memory storage or magnetic field sensors.
Our previous studies demonstrated prompt elevation of proteinase activity in mammary secretion of drying-off cows and goats. The current study examined the progressive changes in composition of cow mammary secretion following drying-off and, in parallel, characterized the mode of peptide neogenesis using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and liquid chromatography-electrospray-ionization (LC-ESI) MS/MS. The results show that the percentage of casein of total milk protein at time of drying-off was 76%, which dropped to 41%, 24%, and 16%, respectively, 1, 2, and 3 weeks after drying-off. Levels of β-lactoglobulin and α-lactoalbumin in mammary secretions of drying-off cows decreased prominently while levels of lactoferrin, BSA, and casein derived-proteins increased concomitantly compared with regular milk. A fractionation procedure was applied to remove molecules larger than 10 kDa before MALDI-TOF MS and LC-ESI MS/MS and the results show that the MALDI-TOF MS peptide profile of mammary secretion ranging from m/z 600 to 4000 was apparently modified after drying-off for 1 week, whereas species 1590 m/z and 2460 m/z were most obviously enriched compared with regular milk. LC-ESI MS/MS results were used to map peptide sequence with Mascot search server and under no post translational modification to reduce database size and 202 novel β-casein-derived peptides were successfully identified in mammary secretion after drying-off for 1 week in contrast to regular milk. Accordingly at least 48 additional cleavage positions were assigned on β-casein for mammary secretion. Among the 202 novel peptides, 5 are homologous with confirmed opioid agonists, angiotensin 1-converting enzyme inhibitors, or immuno-modulators. In conclusion, peptides are released in situ from milk proteins within short intervals following drying-off in cows. They might play roles in the transition of mammary glands from lactating to non-lactating. With specified post-translational modifications and focused functional screening, novel peptides are yet to be discovered in dry cow mammary secretion.
Many people with schizophrenia remain untreated in the community.
Long-term mortality and suicidal behaviour among never-treated
individuals with schizophrenia in the community are unknown.
To explore 10-year mortality and suicidal behaviour among never-treated
individuals with schizophrenia.
We used data from a 10-year prospective follow-up study (1994–2004) among
people with schizophrenia in Xinjin County, Chengdu, China.
The mortality rate for never-treated individuals with schizophrenia was
2761 per 100 000 person-years during follow-up. There were no significant
differences of rates of suicide and all-cause mortality between
never-treated and treated individuals. The standardised mortality ratio
(SMR) for never-treated people was 10.4 (95% CI 7.2–15.2) and for treated
individuals 6.5 (95% CI 5.2–8.5). Compared with treated people,
never-treated individuals were more likely to be older, poorer, have a
longer duration of illness, marked symptoms and fewer family members.
The never-treated individuals have similar mortality to and a higher
proportion of marked symptoms than treated people, which may reflect the
poor outcome of the individuals without treatment. The higher rates of
mortality, homelessness and never being treated among people with
schizophrenia in low- and middle-income nations might challenge presumed
wisdom about schizophrenia outcomes in these countries.
Total body fat mass (TBFM) and total body lean mass (TBLM) are the major components of the human body. Although these highly correlated phenotypic traits are frequently used to characterize obesity, the specific shared genetic factors that influence both traits remain largely unknown. Our study was aimed at identifying common quantitative trait loci (QTLs) contributing to both TBFM and TBLM. We performed a whole genome-linkage scan study in a large sample of 3255 subjects from 420 Caucasian pedigrees. Bivariate linkage analysis was carried out in both the entire sample and gender-specific subsamples. Several potentially important genomic regions that may harbour QTLs important for TBFM and TBLM were identified. For example, 20p12-11 achieved a LOD score of 2·04 in the entire sample and, in the male subsample, two genomic regions, 20p12 (LOD=2·08) and 3p26-25 (LOD=1·92), showed suggestive linkage. In addition, two-point linkage analyses for chromosome X showed suggestive linkages on Xp22 in the entire sample (LOD=2·14) and significant linkage on Xp22 in the female subsample (LOD=3·05). Complete pleiotropy was suggested for 20p12 and 3p26-25 in males. Our results suggest that QTLs on chromosomes 20p12, 3p26-25 and Xp22 may jointly influence TBFM and TBLM. Further fine mapping and gene identification studies for these pleiotropic effects are needed.