The Impact of Frailty Status on Pulmonary Function and Mortality in Older Patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVES: We aimed to evaluate the effect of frailty on lung function and disease outcomes in older adults with chronic obstructive pulmonary disease (COPD). DESIGN: Retrospective observational cohort. SETTING AND PARTICIPANTS: At baseline, comprehensive geriatric assessment and pulmonary function tests were extracted from the case management care system of the geriatric department of a tertiary medical center. MEASUREMENTS: Frailty was assessed by the modified Rockwood frailty index. Kaplan-Meier survival and Cox proportional hazard analyses were used to analyze the primary outcome. Both the Friedman test and generalized estimating equations were used to evaluate the rate of decline in lung function. RESULTS: Among 151 enrolled older patients, comprising 69 non-COPD and 82 COPD subjects, the mean age was 80.9±8.3 years. After a median follow-up of 2.87 years, the serial forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), and forced expiratory flow at 25-75% of FVC (FEF25-75%) showed significantly different slope changes between older COPD patients with and without frailty. The mortality hazard ratio (HR) was 2.53 for COPD without frailty and 3.62 for COPD with frailty, versus those without COPD. Among COPD patients, the factors most strongly associated with mortality were timed up-and-go, activities of daily living (ADLs), instrumental ADLs, FEV1/FVC, and serum HCO3-. After adjustment for potential confounders, ADLs and FEV1/FVC remained independent mortality predictors. CONCLUSION: Among older patients with COPD, frailty was common and associated with pulmonary function decline, and mortality risk was higher in frail than in non-frail subjects.

The unfolded protein response modulates the autophagy-mediated egg production in the mosquito Aedes aegypti.

Mosquitoes must feed on vertebrate blood for egg development. As a consequence, some mosquito species are vectors for pathogens that cause devastating diseases in humans. Hence, understanding the mechanisms that control egg developmental cycles is important for developing novel approaches for the control of mosquito-borne diseases. The unfolded protein response (UPR) is a cellular stress response related to endoplasmic reticulum (ER) stress. The UPR is activated in response to an accumulation of unfolded or misfolded proteins in the ER. Massive proteins have been shown to be produced during egg development, and it is obvious that unfolded or misfolded proteins may arise during vitellogenesis. It has been shown that autophagy in the mosquito fat body plays a central role in the progression of gonadotrophic cycles in the mosquito Aedes aegypti. However, the molecular mechanisms underlying the induction of UPR and the correlation between UPR and autophagy remain unclear. Here, we demonstrate that autophagy is activated during vitellogenesis and that the activation of autophagy is correlated with the UPR. We also show that the expressions of UPR and autophagy can be induced in an in vitro fat body culture system through an amino acid treatment. In addition, the expressions of UPR, autophagy-specific markers and vitellogenin were also induced during dithiothreitol treatment. Interestingly, the silencing of UPR-related genes significantly reduced the expression of autophagy-specific markers and inhibited mosquito fecundity. Taken together, we conclude that autophagy-mediated egg production in the mosquito A. aegypti is regulated by UPR.

Do stillbirth, miscarriage, and termination of pregnancy increase risks of attempted and completed suicide within a year? A population-based nested case-control study.

OBJECTIVE: To investigate the risks of attempted and completed suicide in women who experienced a stillbirth, miscarriage, or termination of pregnancy within 1 year postnatally and compare this risk with that in women who experienced a live birth. DESIGN: A nested case-control study. SETTING: Linking three nationwide population-based data sets in Taiwan: the National Health Insurance Research Database, the National Birth Registry and the National Death Registry. SAMPLE: In all, 485 and 350 cases of attempted and completed suicide, respectively, were identified during 2001-11; for each case, ten controls were randomly selected and matched to the cases according to the age and year of delivery. METHODS: Conditional logistic regression. MAIN OUTCOME MEASURES: Attempted and completed suicidal statuses were determined. RESULTS: The rates of attempted suicide increased in the women who experienced fetal loss. The risk of completed suicide was higher in women who experienced a stillbirth [adjusted odds ratio (aOR) 5.2; 95% CI 1.77-15.32], miscarriage (aOR 3.81; 95% CI 2.81-5.15), or termination of pregnancy (aOR 3.12; 95% CI 1.77-5.5) than in those who had a live birth. Furthermore, the risk of attempted suicide was significantly higher in women who experienced a miscarriage (aOR 2.1; 95% CI 1.66-2.65) or termination of pregnancy (aOR 2.5; 95% CI 1.63-3.82). In addition to marital and educational statuses, psychological illness increased the risk of suicidal behaviour. CONCLUSIONS: The risk of suicide might increase in women who experience fetal loss within 1 year postnatally. Healthcare professionals and family members should enhance their sensitivity to care for possible mental distress, particularly for women who have experienced a stillbirth. TWEETABLE ABSTRACT: Suicide risk increased in women who had a stillbirth, miscarriage, or termination of pregnancy within 1 year postnatally.

Dramatic band gap reduction incurred by dopant coordination rearrangement in Co-doped nanocrystals of CeO2.

A dramatic band gap narrowing of 1.61 eV has been observed in Co-doped nanocrystals of CeO2 (ceria), as a result of thermal annealing, without changing the ceria crystal structure and the Co concentration. As demonstrated by x-ray absorption fine structures, thermal annealing incurs an oxygen coordination rearrangement around Co atoms from an octahedral coordination to a square-planar coordination. First principle calculation using density functional theory reveals two stable oxygen coordination types surrounding Co, consistent with the experimental observation. The band gap values calculated for the two stable coordination types differ dramatically, reproducing the experimentally observed band gap narrowing. These prominent effects due to local structure rearrangement around dopant atoms can lead to unprecedented methods for band gap engineering in doped nanocrystal oxides.

Serum adipokine levels in renal transplant recipients.

BACKGROUND: Metabolic syndrome (MS) is a common complication in renal transplant (RTx) recipients. This study aimed to explore the alterations and interrelationship of various adipokines in RTx recipients with and without MS. METHODS: RTx recipients followed at our hospital were randomly selected for the cross-sectional study of MS. The modified Adult Treatment Panel III criteria adopted for Asian populations were used to define MS. Overnight fasting blood samples were obtained for determination of adipokines, including adiponectin, leptin, resistin, and visfatin. Univariate and multivariate logistic regressions were performed to determine parameters that were associated with serum adipokine levels. Pearson correlation analysis was performed between adipokines. RESULTS: A total of 280 RTx recipients were enrolled for the study. Seventy-three cases (26.1%) fulfilled the criteria of MS. A significantly higher serum leptin level was found in MS patients (16.61 ± 13.90 vs 8.00 ± 7.42 µg/mL; P < .0001). There was no significant difference in serum levels of adiponectin, resistin, and visfatin between the 2 groups. Serum adiponectin level was positively correlated with serum resistin (r = 0.422; P < .0001) and visfatin levels (r = 0.224; P < .0001). Serum resistin level was positively correlated with serum visfatin level. All but serum visfatin level were negatively correlated with estimated glomerular filtration rate. Univariate logistic regression revealed the following variables to be associated with serum leptin level: metabolic syndrome, sex, body weight, waist circumference, body mass index (BMI), hypertension, serum creatinine, fasting blood sugar, HbA1c, serum triglyceride, and uric acid. Multivariate analysis revealed that sex, body weight, BMI, and serum creatinine were associated with serum leptin level. CONCLUSIONS: Compared with RTx recipients without MS, patients with MS were associated with significantly higher serum leptin levels and similar adiponectin, resistin, and visfatin levels. A close interrelationship was also found in the serum levels of these adipokines.

Changing pattern of mortality in renal transplant recipients: a single-center, 30-year experience.

INTRODUCTION: Patient survival among kidney transplant (KTx) recipients has improved remarkably in the past decades. The most common causes of death are cardiovascular disease in the West; in Taiwan, the answer remains uncertain. METHODS: From 1983 to 2012, KTx patients who underwent transplantation and were followed at our hospital were recruited for the study. For comparison, patients were stratified according to the transplant time as group 1, 1983-1989 (the initial era); group 2, 1990-1998 (the cyclosporine era); and group 3, 1999-2012 (the modern era, in which tacrolimus and mycophenolate mofetil were available). RESULTS: A total of 520 KTx patients (male:female ratio of 285:235) were performed in our hospital during the study period. A progressive improvement in patient survival rates (P < .0001) was noted among the 3 groups. At a mean follow-up duration of 9.55 ± 8.20 years, 83 recipients had died. Overall, the most common cause of death was infection (44.6%), followed by cardiovascular disease (21.7%), malignancy (12.0%), and hepatic failure (10.8%). Infection was the main cause of death in groups 1 and 2 (44.1% and 52.6%, respectively) but not in Group 3 (18.2%), although this trend did not reach statistical significance. Death owing to cardiovascular diseases became the most common cause of death (27.3%) in the modern era (group 3). CONCLUSION: The pattern of mortality among Taiwanese KTx patients has changed over the past 30 years. Infection is no longer the commonest cause of death.

Hyperuricemia predicts kidney disease progression after acute allograft dysfunction.

BACKGROUND: Hyperuricemia is associated with the development of new cardiovascular events and chronic allograft nephropathy in patients with decreased allograft function. This study investigates whether hyperuricemia in kidney transplant recipients should be considered as an independent predictor of kidney disease progression after acute allograft dysfunction. METHODS: Between September 1, 2010, and December 31, 2012, 124 patients who underwent kidney graft biopsy for acute allograft dysfunction were enrolled. Participants were divided into 2 groups: A hyperuricemic group (n = 57) and a normouricemic group (n = 67). The mean serum uric acid (UA) level was obtained by averaging all measurements, once per month for 3 months, before the study began. Clinical and laboratory data were collected. We investigated the role of hyperuricemia on the composite end point (CEP) of doubling of serum creatinine and graft failure by using Cox regression and Kaplan-Meier plots. RESULTS: Over a mean follow-up of 14.27 months, the hyperuricemic group had a poor cumulative survival and easily reached the CEP of doubling of serum creatinine and graft failure (P = .025) with a first-year cumulative incidence of 29.84% and a second-year cumulative incidence of 35.09%. Cox regression models revealed that age at biopsy (unadjusted hazard ratio [HR], 1.03; 95% CI, 1.00-1.06), hyperuricemia (HR, 2.24; 95% CI, 1.13-4.46), and interstitial fibrosis and tubular atrophy (IF/TA), including <25% of parenchyma affected (HR, 3.71; 95% CI, 1.34-10.31) and ≥ 25% of parenchyma affected (HR, 5.10; 95% CI, 1.83-14.19), were highly associated with poor outcome. After adjusting different variables, hyperuricemia and IF/TA were still significant. CONCLUSION: Persistently high serum UA and IF/TA both contribute to the risk of kidney disease progression after acute allograft dysfunction.

Uric acid is highly associated with kidney allograft survival in a time-varying analysis.

BACKGROUND: Hyperuricemia may be associated with the development of new cardiovascular events and graft loss in renal transplant recipients. This study was conducted to clarify whether hyperuricemia is a persistently independent predictor of long-term graft survival and patient outcome. METHODS: Renal allograft recipients (n = 880) who underwent transplantation from December 1999 to March 2013 were included. Participants were divided into 2 groups: a hyperuricemic group (n = 389) and a normouricemic group (n = 491). The mean serum uric acid (UA) level was obtained by averaging all measurements, once per month for 3 months, before the study began. Clinical and laboratory data were collected. We investigated the role of hyperuricemia in the primary endpoint of graft failure by using time-varying analysis and Kaplan-Meier plots. All-cause mortality in renal transplant recipients was also surveyed. RESULTS: During a mean follow-up of 43.3 ± 26.3 months, the major predisposing factors in the 389 patients with hyperuricemia were male predominance (62.98%), high entry serum UA (7.70; range 6.70-8.80 mg/dL), more hypertension (92.29%), previous hemodialysis mode (29.56%), hepatitis C infection (24.42%), more frequent use of UA-lowering agents (43.44%), and use of more drugs for inducing high serum UA (17.74%). After 12 months, the hyperuricemic group had persistently high serum UA (7.66 ± 2.00 vs 6.17 ± 1.60 mg/dL, P < .001) and poor renal function (serum creatinine 2.96 ± 3.20 vs 1.61 ± 1.96 mg/dL, P < .001) compared with the normouricemic group. Survival analysis showed the hyperuricemic group had poorer graft survival (60.47%) than the normouricemic group (75.82%, P = .0069) after 13-year follow-up. However, there was no difference in all-cause mortality between the 2 groups. CONCLUSION: Persistently high serum UA seems to be implicated in elevation of serum creatinine, which could increase the risk for allograft dysfunction.

Short-term prospective study of metabolic syndrome in renal transplant recipients.

BACKGROUND: Metabolic syndrome (MS) may affect patient and graft survival in renal transplant recipients. However, the evolution of MS during prospective follow-up remains uncertain. METHODS: Renal transplant patients were recruited for a study of MS in 2010 and then prospectively followed for 2 years. The modified Adult Treatment Panel III criteria adopted for Asian populations were used to define MS. RESULTS: A total of 302 cases (male:female = 154:148) with a mean duration of 10.5 ± 5.7 years after transplantation were enrolled. At initiation, 71 cases (23.5%) fulfilled the criteria of MS. At the end of follow-up, 11 cases had died and 21 had graft failure. Nine cases had insufficient data for reclassification. The remaining 261 cases completed a 2-year follow-up, and the prevalence of MS was 26.1% at the end of study. Of these, 7.79% (18 cases) of patients without MS had developed new-onset MS. Conversely, 16.9% (12 cases) with MS were free from MS at the end of study (P = .362). Patients with MS were associated with older age (57.1 ± 10.4 vs 52.6 ± 12.4 y; P = .006), more chronic allograft nephropathy (17.4% vs 7.1%; P = .01), proteinuria (22.5% vs 10.8%; P = .012), and use of more antihypertensive agents (1.49 ± 0.86 vs 0.80 ± 0.98; P < .0001). There was no significant change in serum creatinine in each subgroup. CONCLUSIONS: The status of MS in renal transplant patients is dynamic. MS patients were associated with more chronic allograft nephropathy and proteinuria.

Gene polymorphisms are associated with posttransplantation diabetes mellitus among Taiwanese renal transplant recipients.

BACKGROUND: Genetic variations may affect posttransplantation metabolic syndrome and diabetes mellitus (PTDM), which is associated with greater morbidity and progressive impairment of both patient and graft survivals. The aim of this study was to evaluate several candidate gene polymorphisms for their association with the risk of developing PTDM. METHODS: In April 1999, we enrolled 278 renal transplant participants, including 251 subjects free of diabetes and 27 with PTDM. We studied several candidate gene polymorphisms associated with diabetes: 4G/5G polymorphism of plasminogen activator inhibitor 1 (PAI-1) at -675; C/T polymorphism of interleukin-1beta (IL-1ß) at -511; G/C polymorphism of IL-6 at 174; polymorphic XbaI of Glucose transporter 1 (GLUT1); and C/T polymorphism of methylenetetrahydrofolate redutase (MTHFR) at 677. RESULTS: The PTDM group had an older mean age (47.6 ± 9.8 years), greater predominance of men (77.8%), higher number of chronic diseases (CDN ≥2, 96.3%), and more patients using tacrolimus-based immunosuppression (44.4%; P < .05). Using model A, a simple logistic regression, we observed that patients with the IL-6 G/G genotype experienced a lower risk of developing PTDM (odds ratio [OR], 0.08; 95% confidence interval [CI] 0.01-0.86), and multiple logistic regression models B and C, after adjusting for different variables, confirmed this observation (model B: OR, 0.05; 95% CI, 0.00-0.66). The IL-6 G/G genotype showed a borderline effect in model C (OR, 0.02; 95% CI, 0.00-1.16). There were no significant differences between the 2 groups in genotype variations of PAI-1, IL-1ß, GLUT-1, and MTHFR. CONCLUSIONS: The G/G genotype of IL-6 may play an important role to lower the risk for PTDM development.

Dynamics of gas-phase trichloramine (NCl3) in chlorinated, indoor swimming pool facilities.

UNLABELLED: Trichloramine (NCl(3)) is recognized as an irritant of the human respiratory system and other tissues. Processes that lead to volatilization from the liquid phase allow for human exposure to gas-phase NCl(3) in swimming pool settings. The dynamics of these processes are not well defined. A N,N-diethyl-p-phenylenediamine/potassium iodide (DPD/KI)-based wet-chemistry method for measuring gas-phase NCl(3) concentration was verified and applied in chlorinated, indoor swimming pool facilities. Other gas-phase oxidants in the air of indoor pools provided interference of 15% or less. The DPD/KI method was applied for the measurement of gas-phase NCl(3) in four chlorinated, indoor swimming pool facilities. All results showed a correlation between bather loading and gas-phase NCl(3) concentration. The nature of swimmer activities also influenced air quality, presumably because of the effects of these activities on mixing near the gas-liquid interface. PRACTICAL IMPLICATIONS: The activities of swimmers promote transfer of volatile compounds from water to the surrounding air. For chlorinated, indoor pool facilities, this can lead to exposure to gas-phase chemicals that can cause irritation of the respiratory system and other tissues. The focus of this study was on NCl(3), a common disinfection by-product (DBP) in chlorinated pools. However, the conditions that promote NCl(3) transfer are likely to promote transfer of other volatile chemicals from water to air. As such, it is possible that other DBPs formed in pools may also contribute to diminished air quality.

Malignant lymphoma of the kidney mimicking rapid progressive glomerulonephritis.

Primary renal lymphoma (PRL) is rare and often presents as rapidly progressive renal failure. Most cases of PRL are large-cell lymphomas of B-cell lineage. Herein, we report a 75-year-old female patient with infiltrative CD20 (+) B-cell lymphoma who underwent 4 consecutive courses of chemotherapy with R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) and after 12 sessions became free from hemodialysis in good general condition. Her serum creatinine level gradually decreased to 4.1 mg/dl with adequate urine output. Unfortunately, a relapse of CD20 (-) lymphoma developed rapidly involving other organs. She died with severe hospital-acquired pneumonia and febrile neutropenia after the last chemotherapy with R-MINE almost 1 year after onset of symptoms. We conclude that renal biopsy enables prompt diagnosis in rapidly progressive renal failure and immunophenotyping and also staging workup of the lymphoma in case of positive biopsy. Though rituximab improved response rate of PRL, it reduced expression of CD20. This may relate to frequent relapse/resistance after rituximab therapy and poor long-term patient survival.

Diffraction-enhanced beam-focusing for X-rays in curved multi-plate crystal cavity.

Unusual x-ray focusing effect is reported for parabolic curved multi-plate x-ray crystal cavities of silicon consisting of compound refractive lenses (CRL). The transmitted beam of the (12 4 0) back reflection near 14.4388 keV from these monolithic silicon crystal devices exhibits extraordinary focusing enhancement, such that the focal length is reduced by as much as 18% for 2-beam and 56% for 24-beam diffraction from the curved crystal cavity. This effect is attributed to the presence of the involved Bragg diffractions, in which the wavevector of the transmitted beam is bent further when traversing several curved crystal surfaces.

Methods for accelerating nitrate reduction using zerovalent iron at near-neutral pH: effects of H2-reducing pretreatment and copper deposition.

Both surface treatments, H2-reducing pretreatment at 400 degrees C and the deposition of copper as a catalyst, were attempted to enhance the removal of nitrate (40 (mg N) L(-1)) using zerovalent iron in a HEPES buffered solution at a pH of between 6.5 and 7.5. After the iron surface was pretreated with hydrogen gas, the removal of the passive oxide layers that covered the iron was indicated by the decline in the oxygen fraction (energy dispersive X-ray analysis) and the overlap of the cyclic polarization curves. The reaction rate was doubled, and the lag of the early period disappeared. Then, the deposition of copper onto freshly pretreated iron promoted nitrate degradation more effectively than that onto a nonpretreated iron surface, because of the high dispersion and small size of the copper particles. An optimum of 0.25-0.5% (w/w) Cu/Fe accelerated the rate by more than six times that of the nonpretreated iron. The aged 0.5% (w/w) Cu/Fe with continual dipping in nitrate solution for 20 days completely restored its reactivity by a regeneration process with H2 reduction. Hence, these two iron surface treatments considerably promoted the removal of nitrate from near-neutral water; the reactivity of Cu/Fe was effectively recovered.

Activation and proliferation signals in primary human T lymphocytes inhibited by ergosterol peroxide isolated from Cordyceps cicadae.

Effects of ergosterol peroxide (C28H44O3; Cpd 6A) from Cordyceps cicadae on phytohemagglutinin (PHA)-stimulated cell proliferation were studied in primary human T cells. The results showed that Cpd 6A suppressed T-cell proliferation for about 24 h after stimulation with PHA. Cell cycle analysis indicated that Cpd 6A arrested the cell cycle progression of activated T cells from the G1 transition to the S phase. To localize the point in the cell cycle where arrest occurred, a set of key regulatory events leading to the G1/S boundary, including the expression of cyclins D2, E, A1, and B1, interleukin (IL)-2, IL-4, interferon-gamma (IFN-gamma), and activating protein-1 (AP-1), was examined. Cpd 6A suppressed, in activated T lymphocytes, the production and mRNA expression of cyclin E, IL-2, IL-4, IL-10, and IFN-gamma in a dose-dependent manner. Expression of AP-1 proteins, consisting of c-Fos and c-Jun, in activated T lymphocytes was decreased by Cpd 6A. The kinetic study indicated that the inhibitory effects of Cpd 6A on IL-2 mRNA expressed in T cells might be related to blocking c-Fos protein synthesis. T-cell proliferation after Cpd 6A treatment was partially restored by addition of IL-2, IL-4, and IFN-gamma. These suppressant effects of Cpd 6A on T-cell proliferation, activated by PHA, appeared to be mediated, at least in part, through the inhibition of early gene transcripts, especially those of cyclin E, IFN-gamma, IL-2, and IL-4, and by arresting cell cycle progression in the cells.

Expression of p16(INK4A) induces dominant suppression of glioblastoma growth in situ through necrosis and cell cycle arrest.

Tumor suppressor genes may represent an important new therapeutic modality in the treatment of human glioblastoma (GBM). p16(INK4A) is a tumor suppressor gene with mutation and/or deletion found in many human tumors, including glioblastomas, melanoma, and leukemias. RT-2 rat GBM cell line was used to investigate if the p16 gene induces dominant suppression of glioblastoma growth. Close to 100% of tumor cells were infected by high titer pCL retrovirus encoding the full-length human p16 cDNA at 5 m.o.i. Infected cells showed a 98% reduction in colony forming assay and a 60% reduction in growth curves in vitro compared to vector control. Exogenous overexpression of p16 induced hypophosphorylation of Rb protein by Western blot analysis. Intracranial injection of p16-infected tumor cells into syngeneic rats resulted in a 95% reduction in tumor volume compared to the controls. Intratumoral injection of p16 retrovirus resulted in tumor necrosis and prominent human p16 transgene expressions. Proliferation marker PCNA was not detected in these human p16-expressed RT-2 tumor cells, suggesting the cells were unable to enter into S phase after p16 expression. In addition, direct repeat intracranial injections of p16 retrovirus prolonged animal survival 3.2-fold compared to the controls (48.4 +/- 13.4 vs 15.0 +/- 2.1 days, p < 0.001). Two out of ten rats were found with dormant tumors at day 60 after p16 retrovirus injection. These results showed that p16 is effective in inhibiting GBM growth in situ. The mechanisms of tumor growth reduction and necrosis in vivo might be due to G1 arrest triggered by p16 expression.

Neuritogenesis, not receptor expression, of NG108-15 cells can be modulated by monosialoganglioside GM1.

In this study, involvement of gangliosides in neurite outgrowth and receptor expression of the neuroblastoma X glioma hybrid NG108-15 cloned cells was investigated. Monosialoganglioside GM1 (100 microM) and disialoganglioside GD1a (100 microM) were applied to the culture medium at different concentrations of fetal bovine serum, 1-10%, with or without addition of dibutyryl adenosine 3',5'-cyclic monophosphate (500 microM). In some experiments, 5 mg/ml of cholera toxin B was added to the media to block endogenous GM1. The results indicated that GM1 had an influence on cell proliferation and neuritogenesis but did not induce muscarinic receptor expression of NG108-15 cells.