Self-reported domain-specific and accelerometer-based physical activity and sedentary behaviour in relation to psychological distress among an urban Asian population.

BACKGROUND: The interpretation of previous studies on the association of physical activity and sedentary behaviour with psychological health is limited by the use of mostly self-reported physical activity and sedentary behaviour, and a focus on Western populations. We aimed to explore the association of self-reported and devise-based measures of physical activity and sedentary behaviour domains on psychological distress in an urban multi-ethnic Asian population. METHODS: From a population-based cross-sectional study of adults aged 18-79 years, data were used from an overall sample (n = 2653) with complete self-reported total physical activity/sedentary behaviour and domain-specific physical activity data, and a subsample (n = 703) with self-reported domain-specific sedentary behaviour and accelerometry data. Physical activity and sedentary behaviour data were collected using the Global Physical Activity Questionnaire (GPAQ), a domain-specific sedentary behaviour questionnaire and accelerometers. The Kessler Screening Scale (K6) and General Health Questionnaire (GHQ-12) were used to assess psychological distress. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals, adjusted for socio-demographic and lifestyle characteristics. RESULTS: The sample comprised 45.0% men (median age = 45.0 years). The prevalence of psychological distress based on the K6 and GHQ-12 was 8.4% and 21.7%, respectively. In the adjusted model, higher levels of self-reported moderate-to-vigorous physical activity (MVPA) were associated with significantly higher odds for K6 (OR = 1.47 [1.03-2.10]; p-trend = 0.03) but not GHQ-12 (OR = 0.97 [0.77-1.23]; p-trend = 0.79), when comparing the highest with the lowest tertile. Accelerometry-assessed MVPA was not significantly associated with K6 (p-trend = 0.50) nor GHQ-12 (p-trend = 0.74). The highest tertile of leisure-time physical activity, but not work- or transport-domain activity, was associated with less psychological distress using K6 (OR = 0.65 [0.43-0.97]; p-trend = 0.02) and GHQ-12 (OR = 0.72 [0.55-0.93]; p-trend = 0.01). Self-reported sedentary behaviour was not associated with K6 (p-trend = 0.90) and GHQ-12 (p-trend = 0.33). The highest tertile of accelerometry-assessed sedentary behaviour was associated with significantly higher odds for K6 (OR = 1.93 [1.00-3.75]; p-trend = 0.04), but not GHQ-12 (OR = 1.34 [0.86-2.08]; p-trend = 0.18). CONCLUSIONS: Higher levels of leisure-time physical activity and lower levels of accelerometer-based sedentary behaviour were associated with lower psychological distress. This study underscores the importance of assessing accelerometer-based and domain-specific activity in relation to mental health, instead of solely focusing on total volume of activity.

A systematic review and meta-analysis of workplace intervention strategies to reduce sedentary time in white-collar workers.

Prolonged sedentary behaviour has been associated with various detrimental health risks. Workplace sitting is particularly important, providing it occupies majority of total daily sedentary behaviour among desk-based employees. The aim of this systematic review and meta-analysis was to examine the effectiveness of workplace interventions overall, and according to different intervention strategies (educational/behavioural, environmental and multi-component interventions) for reducing sitting among white-collar working adults. Articles published through December 2015 were identified in five online databases and manual searches. Twenty-six controlled intervention studies published between 2003 and 2015 of 4568 working adults were included. All 26 studies were presented qualitatively, and 21 studies with a control group without any intervention were included in the meta-analysis. The pooled intervention effect showed a significant workplace sitting reduction of -39.6 min/8-h workday (95% confidence interval [CI]: -51.7, -27.5), favouring the intervention group. Multi-component interventions reported the greatest workplace sitting reduction (-88.8 min/8-h workday; 95% CI: -132.7, -44.9), followed by environmental (-72.8 min/8-h workday; 95% CI: -104.9, -40.6) and educational/behavioural strategies -15.5 min/8-h workday (95% CI:-22.9,-8.2). Our study found consistent evidence for intervention effectiveness in reducing workplace sitting, particularly for multi-component and environmental strategies. Methodologically rigorous studies using standardized and objectively determined outcomes are warranted. © 2016 World Obesity.

Do workplace physical activity interventions improve mental health outcomes?

BACKGROUND: Mental health is an important issue in the working population. Interventions to improve mental health have included physical activity. AIMS: To review evidence for the effectiveness of workplace physical activity interventions on mental health outcomes. METHODS: A literature search was conducted for studies published between 1990 and August 2013. Inclusion criteria were physical activity trials, working populations and mental health outcomes. Study quality was assessed using the Jadad scale. RESULTS: Of 3684 unique articles identified, 17 met all selection criteria, including 13 randomized controlled trials, 2 comparison trials and 2 controlled trials. Studies were grouped into two key intervention areas: physical activity and yoga exercise. Of eight high-quality trials, two provided strong evidence for a reduction in anxiety, one reported moderate evidence for an improvement in depression symptoms and one provided limited evidence on relieving stress. The remaining trials did not provide evidence on improved mental well-being. CONCLUSIONS: Workplace physical activity and yoga programmes are associated with a significant reduction in depressive symptoms and anxiety, respectively. Their impact on stress relief is less conclusive.

The role of the c-Jun N-terminal kinase 2-α-isoform in non-small cell lung carcinoma tumorigenesis.

The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase family and have been implicated in tumorigenesis. One isoform in particular, JNK2α, has been shown to be frequently activated in primary brain tumors, to enhance several tumorigenic phenotypes and to increase tumor formation in mice. As JNK is frequently activated in non-small cell lung carcinoma (NSCLC), we investigated the role of the JNK2α isoform in NSCLC formation by examining its expression in primary tumors and by modulating its expression in cultured cell lines. We discovered that 60% of the tested primary NSCLC tumors had three-fold higher JNK2 protein and two- to three-fold higher JNK2α mRNA expression than normal lung control tissue. To determine the importance of JNK2α in NSCLC progression, we reduced JNK2α expression in multiple NSCLC cell lines using short hairpin RNA. Cell lines deficient in JNK2α had decreased cellular growth and anchorage-independent growth, and the tumors were four-fold smaller in mass. To elucidate the mechanism by which JNK2α induces NSCLC growth, we analyzed the JNK substrate, signal transducer and activator of transcription 3 (STAT3). Our data demonstrates for the first time that JNK2α can regulate the transcriptional activity of STAT3 by phosphorylating the Ser727 residue, thereby regulating the expression of oncogenic genes, such as c-Myc. Furthermore, reintroduction of JNK2α2 or STAT3 restored the tumorigenicity of the NSCLC cells, demonstrating that JNK2α is important for NSCLC progression. Our studies reveal a novel mechanism in which phosphorylation of STAT3 is mediated by a constitutively active JNK2 isoform, JNK2α.

Mycophenolate mofetil use is associated with decreased risk of late acute rejection in adult liver transplant recipients.

Mycophenolate mofetil (MMF) used in a triple-drug regimen has been shown to decrease acute rejection rates, compared to a double-drug regimen. The impact of MMF on late acute rejection (LAR) episodes has not been well described. To investigate the risk of LAR (rejection > or = 6 months post-transplantation) data from the Scientific Registry of Transplant Recipients (SRTR) were used. We studied adult primary liver transplant recipients transplanted between June 1, 1995, and April 30, 2004, with hepatitis C virus (HCV) (n = 3356), hepatitis B virus (HBV) (n = 550) or a nonviral (n = 5740) primary cause of liver disease who were recorded as receiving continuous 3-(MMF + Tacro + steroids) versus 2-drug (Tacro + steroids) therapy for at least 6 months immediately post transplantation. Kaplan-Meier analysis showed significantly lower LAR rates 4 years post-transplant in 3- versus 2-drug HCV, HBV and nonviral disease patients. Multivariate regression confirmed 3- versus 2-drug therapy to be associated with a decreased risk of LAR. Late graft survival was significantly lower at 4 years post-transplant for patients with LAR 6-12 months post-transplantation versus patients with early rejection (78.0% vs. 87.0%, p < 0.001) and no rejection (88.1%, p < 0.001). Three-drug versus 2-drug therapy for a minimum of 6 months may offer a better treatment strategy to avoid the consequences and expense of LAR episodes.

Addition of MMF to dual immunosuppression does not increase the risk of malignant short-term death after liver transplantation.

Immunosuppression is often incriminated for the increased risk of post-transplant malignancies. To examine whether triple- (MMF+Tacro+CS) versus dual-drug therapy (Tacro+CS) is associated with an increased incidence of malignancy, or death due to malignancy, data from a large registry of liver transplant recipients were analyzed. Data from adult primary liver recipients reported to the Scientific Registry of Transplant Recipients between June 1, 1995, and April 30, 2004, and recorded at transplant on triple-drug (n = 9180) or dual-drug (n = 10 099) therapy were included. Kaplan-Meier survival analysis showed no significant differences in death due to malignancy 4 years post-transplantation between the treatment groups. Multivariable analysis using Cox proportional hazard models confirmed no differences in risk of death due to malignancy between the groups (HR: 0.83, p = 0.107). Incidence of any post-transplant malignancy was also not significantly different. Older recipient age and cause of liver disease were significantly associated with an increased risk of malignancy-related death. These data utilizing relatively short follow-up suggest the addition of MMF to Tacro+CS at transplant is not associated with death due to malignancy, at least in the short term. Individual recipient factors appear to be important risk factors for malignancy-related death; elucidating these risk factors can assist in identifying who should be monitored most aggressively for post-transplant malignancies.

Daclizumab is associated with decreased rejection and improved patient survival in renal transplant recipients.

The present study investigated the safety of induction therapy with daclizumab (compared with no induction treatment), in adult renal transplant patients reported to the Scientific Registry of Transplant Recipients (SRTR) database between January 1, 1998 and July 27, 2003. Patients who were discharged from the hospital on mycophenolate mofetil, azathioprine, or sirolimus were divided into two groups: induction treatment with daclizumab (n = 8203) and no induction treatment (n = 25,368). Patient survival, death due to infection and death due to malignancy were evaluated at 1 and 3 yr post-transplantation. Rejection and graft survival were also examined. Kaplan-Meier and Cox regression models were used to evaluate outcomes. No significant differences were found between patients treated with daclizumab compared with patients who received no induction therapy for death due to infection or malignancy at 1 and 3 yr post-transplantation. Patients treated with daclizumab (compared with no induction treatment) had statistically significantly better survival rates at 1 (96.9% vs. 96.2%, p = 0.003) and 3 yr (92.4% vs. 91.4%, p = 0.004) although absolute differences were minimal. This was confirmed in the multivariable Cox regression analysis for patient death at 1 (HR = 0.77, p < 0.001) and 3 yr (HR = 0.83, p = 0.001) post-transplantation. Patients treated with daclizumab compared to no induction had lower rejection rates at 1 (13.1% vs. 17.3%, p < 0.001) and 3 yr post-transplantation (16.7% vs. 21.3%, p < 0.001). Cox regression confirmed a decreased risk for rejection at 1 (HR = 0.74, p < 0.001) and 3 yr (HR = 0.75, p < 0.001). Treatment with daclizumab was associated with reduced risk for graft loss at 1 (HR = 0.82, p < 0.001) and 3 years (HR = 0.86, p < 0.001). In conclusion, daclizumab was associated with a significantly reduced risk for rejection and graft loss compared with no induction treatment, and improved patient survival. In addition, daclizumab was not associated with an increase in risk of death due to infection or malignancy, when compared with no induction therapy. These findings demonstrate the short and long-term safety and efficacy of daclizumab in patients transplanted between January 1998 and July 2003.

Daclizumab is associated with decreased rejection and no increased mortality in cardiac transplant patients receiving MMF, cyclosporine, and corticosteroids.

BACKGROUND: Sparse published data exist on outcomes in daclizumab-treated cardiac transplant patients. One trial observed an increased mortality risk 6 and 12 months posttransplant in patients receiving daclizumab plus mycophenolate mofetil (MMF), cyclosporine, and steroids. This study further investigates the safety profile of daclizumab with this same immunosuppressive regimen from a large registry. METHODS: Data obtained at hospital discharge on all adult cardiac transplants performed in the USA between January 1998 and October 2003 for patients receiving MMF plus cyclosporine and steroids were accessed from the Scientific Registry of Transplant Recipients. Patients were selected based on induction treatment: daclizumab (n = 684) or no induction (n = 2525). Outcomes were evaluated at 6 months, 12 months, and 3 years posttransplant. Univariate Kaplan-Meier and multivariate Cox models were used to evaluate the effect of treatment on outcomes. Patient survival and infectious death were the primary endpoints. Secondary endpoints included rejection within the first year posttransplant (acute rejection; AR) and total rejection episodes over time. The two treatment groups shared similar demographics and transplant procedure details. RESULTS: Daclizumab (vs no induction) patients had no increased risk of patient death nor infectious death. Daclizumab patients had a lower incidence of AR at 6 months (P = .005) and 12 months (P < .001); the adjusted risk for AR at 12 months (hazards ratio [HR] = 0.77; P = .89) and over 3 years (HR 0.83, P = .006) was also lower in daclizumab-treated patients. CONCLUSIONS: In cardiac transplant patients, daclizumab (vs no induction) does not result in increased mortality or infectious death, and is associated with a lower incidence of AR.

Cloning and expression of a novel nuclear matrix-associated protein that is regulated during the retinoic acid-induced neuronal differentiation.

Retinoic acid (RA), a derivative of vitamin A, is essential for the normal patterning and neurogenesis during development. RA treatment induces growth arrest and terminal differentiation of a human embryonal carcinoma cell line (NT2) into postmitotic central nervous system neurons. Using RNA fingerprinting by arbitrarily primed polymerase chain reaction, we identified a novel serine/threonine-rich protein, RA-regulated nuclear matrix-associated protein (Ramp), that was down-regulated during the RA-induced differentiation of NT2 cells. Prominent mRNA expression of ramp could be detected in adult placenta and testis as well as in all human fetal tissues examined. The genomic clone of ramp has been mapped to the telomere of chromosome arm 1q, corresponding to band 1q32.1-32.2. Associated with the nuclear matrix of NT2 cells, Ramp translocates from the interphase nucleus to the metaphase cytoplasm during mitosis. During the late stage of cytokinesis, Ramp concentrates at the midzone of the dividing daughter cells. The transcript expression of ramp is closely correlated with the cell proliferation rate of NT2 cells. Moreover, overexpression of Ramp induces a transient increase in the proliferation rate of NT2 cells. Taken together, our data suggest that Ramp plays a role in the proliferation of the human embryonal carcinoma cells.

Xenopus muscle-specific kinase: molecular cloning and prominent expression in neural tissues during early embryonic development.

A muscle-specific receptor tyrosine kinase, designated MuSK, mediates agrin-induced aggregation of acetylcholine receptors at the vertebrate neuromuscular junction. cDNAs encoding Xenopus MuSK were isolated from embryonic cDNA libraries. The full-length MuSK cDNA encodes for a polypeptide of 948 amino acids and possesses the features unique to mammalian MuSK, including four Ig-like domains, C6 box, transmembrane region and an intracellular tyrosine kinase domain. Interestingly, Xenopus MuSK also contains a kringle domain similar to that previously reported for Torpedo MuSK. The overall amino acid sequence identity of Xenopus MuSK with mammalian MuSK is approximately 65%. Northern blot analysis demonstrated the presence of three MuSK transcripts (approximately 1 kb, approximately 3 kb and approximately 7 kb) which were differentially expressed during development. The expression of the approximately 7 kb MuSK transcript remained as the predominant species in adult tissues, e.g. skeletal muscle, spleen and lung. Immunocytochemical analysis with a MuSK-specific antibody revealed that Xenopus MuSK was colocalized with AChRs at neuromuscular junctions as well as in spontaneous acetylcholine receptor hot spots of cultured muscle cells. In situ hybridization revealed prominent expression of MuSK transcripts in neural tissues and myotomal muscle during the period of neurulation and synaptogenesis. The MuSK transcript detected at abundant levels in the central nervous system (CNS) was localized to the brain, spinal cord and eye vesicles during early embryonic development. In addition, the MuSK protein in the developing eye was found to be prominently expressed during embryonic stages of 32 and 35. These findings raise an intriguing possibility that, in addition to the known function in the formation of the neuromuscular junctions, MuSK may be involved in neural development.

Identification of candidate genes induced by retinoic acid in embryonal carcinoma cells.

Retinoic acid (RA) induced the terminal differentiation of a human embryonal carcinoma cell line (NT2/D1) into several morphologically distinct cell types, including the postmitotic CNS neurons. Although RA has been suggested to play an important role in brain development, little is known about the molecular mechanism by which RA induces neuronal differentiation. In the present study, RNA fingerprinting by arbitrarily primed PCR (RAP-PCR) was used to identify the transcripts in NT2/D1 cells that were differentially regulated by RA. Northern blot analysis of the differentially amplified PCR fragments revealed 11 genes that were regulated by RA. Of these, seven were up-regulated and four were down-regulated along the course of RA treatment. More importantly, four of the RA-regulated genes that were identified in the present study are novel. Our findings suggested that there are a number of RA-regulated genes that have yet to be identified. RAP-PCR provides a useful tool for studying the patterns of transcript expression during the course of RA treatment and allows the cloning of novel genes involved in the process of neuronal differentiation. Furthermore, it provides a basis for the selection of genes that are involved in the RA-induced signaling pathway in the human CNS.

Induction of trk receptors by retinoic acid in a human embryonal carcinoma cell line.

Retinoic acid induced the differentiation of human embryonal carcinoma cells (NT2/D1) into several morphologically distinct cell types, including those resembling terminally differentiated postmitotic CNS neurones. The mechanism by which retinoic acid influences the process of neuronal differentiation in the CNS, however, remains unknown. In the present study, we have examined the ability of retinoic acid to induce the expression of the receptors that mediate the actions of the neurotrophins, using reverse transcription-polymerase chain reaction and Northern blot analysis. Our study demonstrated that the expression of mRNAs for three human trk receptors was significantly induced after treatment with retinoic acid. These findings suggest that the actions of retinoic acid on neuronal differentiation in the human CNS may potentially be mediated by the neurotrophins.

Kinetic studies on the reduction of iron(III)deuteroporphyrin--human serum albumin complex with dithionite ion.

The effects of human serum albumin (HSA) on the rate of dithionite reduction of iron(III)deuteroporphyrin (iron(III)Dp) have been investigated in order to further characterize the porphyrin binding site and the changes manifested in this site under various conditions. These studies were performed under pseudo-first-order conditions, and in the presence of carbon monoxide as a "trapping agent" for the reduced iron(II)porphyrin. The rate of reduction of the free iron(III)Dp in phosphate buffer at pH 7.4 follows second-order kinetics with a rate constant (4.2 X 10(9) M-1 s-1) suggestive of a diffusion-controlled process. A six-orders of magnitude decrease in the rate of reduction was observed with iron(III)Dp was complexed with HSA. This result is consistent with HSA-bound porphyrin being less accessible to the aqueous environment. Additional studies demonstrated that both pH and anions induce various alterations in the complex that are reflected in the rate of reduction of iron(III)porphyrin.

Effects of anions on the ligand-linked subunit assembly of human hemoglobin: the mutual effects of Cl- and EDTA.

We have studied the mutual effects of chloride ion and EDTA on the dimer-tetramer assembly of human deoxyhemoglobin and oxyhemoglobin. It is found that these two anions have similar but interdependent effects. In low C1- (.01 M) increasing concentrations of EDTA are found to decrease both forward and reverse rate constants for deoxyhemoglobin, whereas no effect is observed at 0.1 M C1-. These results suggest that binding of anions at the alpha 1 beta 2 intersubunit contact may stabilize both the dimeric and tetrameric forms of the deoxy molecule, thus inhibiting both the dissociation and reassociation reactions. The overall effects of EDTA and low C1- on the dimer-tetramer equilibrium constants are found to be distinctly different in deoxy and oxyhemoglobins with a major effect on the oxy form. These findings establish validity of the results from previous thermodynamic studies carried out in approximately physiological C1- concentrations along with the small amounts of EDTA which are used to minimize artifacts of oxidation. As observed for deoxyhemoglobin, it is found that in 0.1 M C1- ion there is no further effect of EDTA on the oxyhemoglobin dimer-tetramer equilibrium.

Mutual effects of protons, NaCl, and oxygen on the dimer-tetramer assembly of human hemoglobin. The dimer Bohr effect.

The dimer-tetramer equilibrium constants of human oxyhemoglobin (4K2) and deoxyhemoglobin (0K2) have been determined at 21.5 degrees C as a function of pH and chloride concentration. In buffers containing 0.1 M NaCl, 1 mM EDTA, the apparent numbers of protons released upon assembly of dimers into tetramers were determined from the pH dependencies of 4K2 and 0K2. At pH 7.4, the assembly of unliganded tetramers is accompanied by the absorption of 0.9 +/- 0.1 mol of H+. For assenbly of oxyhemoglobin, there are 0.8 +/- 0.1 mol of H+ released per mol of tetramer formed. From these results and the value of 2.1 mol of H+/402 for the tetramer Bohr effect, a Bohr effect for dimers is determined as 0.2 +/- .08 mol of H+ released upon binding 2 mol of 02. Thus, the dimer Bohr effect is approximately 20% as large as the tetramer Bohr effect. At pH 7.4, the value of 0K2 is insensitive to [Cl-], whereas 4K2 varies inversely with [Cl-]. At pH 8.95, both 4K2 and 0K2 decrease with increasing [Cl-]. These and previous results indicate that salt bridges are not the dominant energetic factor in stabilizing the deoxy quaternary structure of hemoglobin. In buffer conditions of 0.1 M Tris-HCl, 0.1 M NaCl, 1 mM EDTA, pH 7.4, we estimate 1.8 mol of Cl- bound upon dissociation of 1 mol of oxy tetramers into oxy dimers, whereas the deoxy molecules dissociate without any change in bound chloride. From the [Cl-] dependence of oxygenation curves, we estimate 1.8 mol of [Cl-] released upon binding 4 mol of O2 to tetramers. Thus, oxygenation of dimers at pH 7.4 apparently involves no change in bound chloride.

Effect of polyanions on the kinetics of the reaction of apohemoglobin with carbonmonoxy heme.

The reaction of apohemoglobin with carbonmonoxy heme and with carbonmonoxy heme dimethyl ester was investigated in the presence and absence of inositol hexaphosphate. The binding stoichiometry of both heme derivatives to apohemoglobin was not affected by the presence of the polyphosphate, while, in both cases, the overall rate of recombination was substantially decreased. The absence of the negatively charged carboxyl groups in the dimethyl ester derivative of the heme indicated that the effect of inositol hexaphosphate on the reaction of apohemoglobin with heme was not due to electrostatic repulsions and resulted from conformational changes occurring upon the interaction of apohemoglobin with inositol hexaphosphate. Qualitative treatment of the kinetic data suggests that these conformational changes destabilize the intermediates of the reaction by increasing their redissociation into the original components. Also, benzenehexacarboxylate produced conformational changes in apohemoglobin and decreased its rate of reaction with carbonmonoxy heme, proving the aspecificity of the interaction of apohemoglobin with polyanions.

Interaction of human apohemoglobin with inositol hexaphosphate.

Experiments of sedimentation velocity and equilibrium indicate that in the presence of inositol hexaphosphate the degree of polymerization of apohemoglobin is shifted in favor of the formation of tetramers, with a maximum effect when the concentration of the polyphosphate is 1 mM. Above this concentration, a redissociation of the system into dimers is promoted. This phenomenon is probably due to the binding of inositol hexaphosphate to apohemoglobin with a stoichiometry higher than 1 mol of polyphosphate/4 subunits. The optical rotatory dispersion spectrum of apohemoglobin is also modified by its interaction with inositol hexaphosphate suggesting a small increase in the helical content of the protein. Measurements of circular dichroism in the near-UV region of the spectrum indicate that the environment of the aromatic chromophores of the protein such as tyrosine, phenyalanine, and tryptophan is not affected by the interaction. The presence of inositol hexaphosphate decreases the rate of reaction of the beta-93 cysteinyl residues of apohemoglobin with both p-mercuribenzoate and N-ethylmaleimide, suggesting a conformational change of the protein also at the level of its tertiary structure.