Comprehensive Bee Pathogen Screening in Belgium Reveals Crithidia mellificae as a New Contributory Factor to Winter Mortality

Since the last decade, unusually high honey bee colony losses have been reported mainly in North-America and Europe. Here, we report on a comprehensive bee pathogen screening in Belgium covering 363 bee colonies that were screened for 18 known disease-causing pathogens and correlate their incidence in summer with subsequent winter mortality. Our analyses demonstrate that, in addition to Varroa destructor, the presence of the trypanosomatid parasite Crithidia mellificae and the microsporidian parasite Nosema ceranae in summer are also predictive markers of winter mortality, with a negative synergy being observed between the two in terms of their effects on colony mortality. Furthermore, we document the first occurrence of a parasitizing phorid fly in Europe, identify a new fourth strain of Lake Sinai Virus (LSV), and confirm the presence of other little reported pathogens such as Apicystis bombi, Aphid Lethal Paralysis Virus (ALPV), Spiroplasma apis, Spiroplasma melliferum and Varroa destructor Macula-like Virus (VdMLV). Finally, we provide evidence that ALPV and VdMLV replicate in honey bees and show that viruses of the LSV complex and Black Queen Cell Virus tend to non-randomly co-occur together. We also noticed a significant correlation between the number of pathogen species and colony losses. Overall, our results contribute significantly to our understanding of honey bee diseases and the likely causes of their current decline in Europe.     

Metabolomic Analysis Identifies Lactate as an Important Pathogenic Factor in Diabetes-associated Cognitive Decline Rats

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Highlights

• •Quantitative metabolomics identified elevated lactate levels in diabetic brains.
• •Levels and enzymatic activity of LDH-A were also found significantly up-regulated.
• •GPR81 dependent PKA-CREB regulated cognition decline in the diabetic rats.
• •Mechanistic insights into role of lactate in diabetes-associated cognitive decline.

     

Preoperative Plasma Fibrinogen Level Represents an Independent Prognostic Factor in a Chinese Cohort of Patients with Upper Tract Urothelial Carcinoma

Background

Increased plasma fibrinogen is thought to contribute to tumor progression and metastasis. The association of plasma fibrinogen with clinicopathological characteristics, and the optimal cutoff with an ideal predictive value has not been fully determined in patients with upper tract urothelial carcinoma (UTUC). We aimed to investigate the clinical significance of this parameter in a Chinese cohort of patients with UTUC.

Methods

A retrospective study was conducted to analyze the clinical data of 184 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). An optimal cutoff was set for further analysis according to validated web-based software. The associations of plasma fibrinogen with clinicopathological characteristics and survival were assessed. Multivariate analyses were performed to determine the independent prognostic factors.

Results

Elevated plasma fibrinogen was significantly associated with tumor necrosis, lymph node involvement, and a higher preoperative CKD stage, pathological tumor stage and grade (all P < 0.05). Kaplan-Meier analysis showed that plasma fibrinogen ≥ 3.54 g/L predicted a poorer overall and cancer-specific survival than < 3.54 g/L (P < 0.001 for both). Multivariate analyses revealed that elevated preoperative plasma fibrinogen was an independent negative prognostic factor for overall survival (HR = 2.026; 95% CI: 1.226–3.349; P = 0.006) and cancer-specific survival (HR = 1.886; 95% CI: 1.019–3.490; P = 0.043).

Conclusions

Increased plasma fibrinogen was an independent prognostic risk factor for poor outcomes in UTUC. This parameter may serve as an effective biomarker with easy accessibility for evaluating prognosis for patients with UTUC.     

急性心力衰竭患者就诊时血压心率及血浆BNP水平与心功能的关系分析

目的:探讨急性心力衰竭(AHF)患者就诊时血压心率及血浆脑钠肽(BNP)水平与心功能的关系。方法:选取2013年4月-2014年12月于本院治疗的AHF患者134例,于就诊时测量患者血压、心率、BNP及心脏超声相关指标,分析血压心率及血浆BNP水平与心功能的关系。结果:就诊时SBP水平与左心室舒张末期直径及每搏输出量呈现正相关性(r=0.134、0.238,均P0.05);心率与每搏输出量、左室缩短率以及射血分数呈现负相关性(r=-0.177,-0.231,-0.197,均P0.05);BNP水平与左心室舒张末直径成正相关性,与左室缩短率以及射血分数呈负相关性(r=0.150、-0.247、-0.271,均P0.05)。结论:血压、心率以及BNP是临床诊断、评估AHF的重要指标。     

The Prognostic Value of Plasma Soluble ST2 in Hospitalized Chinese Patients with Heart Failure

Background

sST2 has been shown to be a risk predictor in heart failure (HF). Our aim was to explore the characteristics and prognostic value of soluble ST2 (sST2) in hospitalized Chinese patients with HF.

Methods and Results

We consecutively enrolled 1528 hospitalized patients with HF. Receiver operating characteristic (ROC) and multivariable Cox proportional hazards analysis were used to assess the prognostic values of sST2. Adverse events were defined as all-cause death and cardiac transplantation. During a median follow-up of 19.1 months, 325 patients experienced adverse events. Compared with patients free of events, sST2 concentrations were significantly higher in patients with events (P<0.001). Univariable and multivariable Cox regression analyses showed sST2 concentrations were significantly associated with adverse events (per 1 log unit, adjusted hazard ratio 1.52, 95% confidence interval: 1.30 to 1.78, P<0.001). An sST2 concentration in the highest quartiles (>55.6 ng/mL) independently predicted events in comparison to the lowest quartile (≤25.2 ng/mL) when adjusted by multivariable model. In ROC analysis, the area under the curve for sST2 was not different from that for NT-proBNP in short and longer term. Over time, sST2 also improved discrimination and reclassification of risk beyond NT-proBNP.

Conclusions

sST2 is a strong independent risk predictor in Chinese patients hospitalized with HF and can significantly provide additional prognostic value to NT-proBNP in risk prediction.     

Prognostic Value of the Interaction between Galectin-3 and Antigen Carbohydrate 125 in Acute Heart Failure

Aims

Galectin-3 (Gal-3) and carbohydrate antigen 125 (CA125) have emerged as robust prognostic biomarkers in heart failure. Experimental data have also suggested a potential molecular interaction between CA125 and Gal-3; however, the biological and clinical relevance of this interaction is still uncertain. We sought to evaluate, in patients admitted for acute heart failure, the association between plasma Gal-3 with all-cause mortality and the risk for rehospitalizations among high and low levels of CA125.

Methods and Results

We included 264 consecutive patients admitted for acute heart failure to the Cardiology Department in a third-level center. Both biomarkers were measured on admission. Negative binomial and Cox regression models were used to evaluate the prognostic effect of the interaction between Gal-3 and CA125 (dichotomized by its median) with hospital readmission and all-cause mortality, respectively. During a median follow-up of 2 years (IQR = 1-2.8), 108 (40.9%) patients deaths and 365 rehospitalizations in 171 (69.5%) patients were registered. In a multivariable setting, the effect of Gal-3 on mortality and rehospitalization was differentially mediated by CA125 (p = 0.007 and p<0.001, respectively). Indeed, in patients with CA125 above median (>67 U/ml), values across the continuum of Gal-3 showed a positive and almost linear relationship with either the risk of death or rehospitalization. Conversely, when CA125 was below median (≤67 U/ml), Gal-3 lacked any prognostic effect on both endpoints.

Conclusion

In patients with acute heart failure, Gal-3 was strongly associated with higher risk of long-term mortality and repeated rehospitalizations, but only in those patients exhibiting higher values of CA125 (above 67 U/ml).     

Ratio of Metastatic to Examined Lymph Nodes,a Helpful Staging System and Independent Prognostic Factor of Esophagogastric Junction Cancer

Background

The incidence of the esophagogastric junction cancer is growing rapidly. The purpose of this study is to clarify the outcome of the ratio between metastatic and examined lymph nodes in esophagogastric junction cancer patients with or without 7 examined lymph nodes.

Methods

A total of 3,481 patients who underwent operation are identified from the Surveillance, Epidemiology, and End Results database. Different lymph nodes resected groups are analyzed to test the lymph nodes ratio factor.

Results

There are 2522 patients with 7 or more lymph nodes resected and 959 patients with less than 7 lymph nodes resected. Lymph nodes ratio and lymph node involvement are independent prognostic factors. But the lymph nodes ratio categories have a better prognostic value than the lymph node involvement categories. Compared with lymph node involvement categories, lymph nodes ratio categories represent patients with more homogeneous overall survival rate.

Conclusions

This study defines that the lymph nodes ratio is an independent prognostic factor for esophagogastric junction cancer. The lymph nodes ratio can prevent stage migration and may be a helpful system to predict the prognosis of esophagogastric junction cancer patients.     

急性毛细支气管炎并心衰患儿血小板活化因子，血小板源生长因子的表达及临床意义

目的：探讨血小板活化因子（PAF）、肿瘤坏死因子-α（TNF-α）及血小板源生长因子（PDGF）水平变化在毛细支气管炎并急性心衰的变化,探讨它们在该病的发病中的作用。方法：58例心衰组患儿分别于治疗前和临床症状消失后采用双抗体夹心ABC．ELISA法检测PAF、TNF-α及PDGF血清含量,设正常对照组40例比较。结果：心衰组PAF治疗前为370．57±23．6ng／L,明显高于对照组的56．78±19．6ng／L,组间比较差异具有非常显著性意义（t=15．95,P〈0．001）;治疗后恢复至49．63±14．5ng／L,与正常对照差异不明显;治疗前后比较,差异具有非常显著性意义（t=3．70,P〈0．001）。TNF-α治疗前为457．4±40．5ng／L,明显高于对照组的148．8±21．6ng／L,组间比较差异具有显著性意义（t=2．135,P〈0．05）;治疗后恢复至162．6±37．61ng／L,与正常对照差异不明显;治疗前后比较,差异具有非常显著性意义（t=7．25,P〈0．01）。PDGF治疗前为596．23±199．43）ng／L,较对照组259．76±69．58ng／L增高,组间比较,差异具有非常显著性意义（t=-25．52,P〈0．01）;治疗后降为272．83±116．96ng／L,较治疗前明显恢复,组间比较差异均具有显著性意义（t=7．66,P〈0．01）。结论：结果表明,PAF、TNF-α、PDGF作为炎症介质不仅参与心衰的发病过程,还提示细胞外基质的异常在心衰发病学中的重要地位。     

急性毛细支气管炎并心衰患儿血小板活化因子,血小板源生长因子的表达及临床意义

目的:探讨血小板活化因子(PAF)、肿瘤坏死因子-α(TNF-α)及血小板源生长因子(PDGF)水平变化在毛细支气管炎并急性心衰的变化,探讨它们在该病的发病中的作用方法:58例心衰组患儿分别于治疗前和临床症状消失后采用双抗体夹心ABC-ELISA法检测PAF、TNF-α及PDGF血清含量,设正常对照组40例比较。结果:心衰组PAF治疗前为370.57±23.6ng/L,明显高于对照组的56.78±19.6ng/L,组间比较差异具有非常显著性意义(t=15.95,P<0.001);治疗后恢复至49.63±14.5 ng/L,与正常对照差异不明显;治疗前后比较,差异具有非常显著性意义(t=3.70,P<0.001)TNF-α治疗前为457.4±40.5 ng/L,明显高于对照组的148.8±21.6ng/L,组间比较差异具有显著性意义(t=2.135,P<0.05);治疗后恢复至162.6±37.61ng/L,与正常对照差异不明显;治疗前后比较,差异具有非常显著性意义(t=7.25,P<0.01)。PDGF治疗前为596.23±199.43)ng/L,较对照组259.76±69.58ng/L增高,组间比较,差异具有非常显著性意义(t=25.52,P<0.01);治疗后降为272.83±116.96ng/L,较治疗前明显恢复,组间比较差异均具有显著性意义(t=7.66,P<0.01)结论:结果表明,PAF、TNF-α、PDGF作为炎症介质不仅参与心衰的发病过程,还提示细胞外基质的异常在心衰发病学中的重要地位     

Forced Desynchrony Reveals Independent Contributions of Suprachiasmatic Oscillators to the Daily Plasma Corticosterone Rhythm in Male Rats

The suprachiasmatic nucleus (SCN) is required for the daily rhythm of plasma glucocorticoids; however, the independent contributions from oscillators within the different subregions of the SCN to the glucocorticoid rhythm remain unclear. Here, we use genetically and neurologically intact, forced desynchronized rats to test the hypothesis that the daily rhythm of the glucocorticoid, corticosterone, is regulated by both light responsive and light-dissociated circadian oscillators in the ventrolateral (vl-) and dorsomedial (dm-) SCN, respectively. We show that when the vlSCN and dmSCN are in maximum phase misalignment, the peak of the plasma corticosterone rhythm is shifted and the amplitude reduced; whereas, the peak of the plasma adrenocorticotropic hormone (ACTH) rhythm is also reduced, the phase is dissociated from that of the corticosterone rhythm. These data support previous studies suggesting an ACTH-independent pathway contributes to the corticosterone rhythm. To determine if either SCN subregion independently regulates corticosterone through the sympathetic nervous system, we compared unilateral adrenalectomized, desynchronized rats that had undergone either transection of the thoracic splanchnic nerve or sham transection to the remaining adrenal. Splanchnicectomy reduced and phase advanced the peak of both the corticosterone and ACTH rhythms. These data suggest that both the vlSCN and dmSCN contribute to the corticosterone rhythm by both reducing plasma ACTH and differentially regulating plasma corticosterone through an ACTH- and sympathetic nervous system-independent pathway.     

慢性阻塞性肺疾病合并心力衰竭患者的预后影响因素分析

目的:探讨慢性阻塞性肺疾病合并心力衰竭患者的预后影响因素。方法:选取我院自2007年12月-2012年12月收住入院的慢性阻塞性肺疾病患者352例,其中合并心力衰竭患者124例,随访1年两组的结局事件发生率及相关预后。结果:年龄、糖尿病、脑卒中病史、肿瘤、合并CHF均为COPD患者死亡的危险因素(P0.05)。与未合并CHF组比较,合并CHF组患者的死亡、因COPD再次入院、脑梗死或心肌梗死的危险性增高(P0.05)。结论:CHF是COPD的常见合并症,是COPD患者死亡或相关心血管疾病的危险因素,临床需密切关注。     

Prognostic Implication of Physical Signs of Congestion in Acute Heart Failure Patients and Its Association with Steady-State Biomarker Levels

Background

Congestive physical findings such as pulmonary rales and third heart sound (S3) are hallmarks of acute heart failure (AHF). However, their role in outcome prediction remains unclear. We sought to investigate the association between congestive physical findings upon admission, steady-state biomarkers at the time of discharge, and long-term outcomes in AHF patients.

Methods

We analyzed the data of 133 consecutive AHF patients with an established diagnosis of ischemic or non-ischemic (dilated or hypertrophic) cardiomyopathy, admitted to a single-center university hospital between 2006 and 2010. The treating physician prospectively recorded major symptoms and congestive physical findings of AHF: paroxysmal nocturnal dyspnea, orthopnea, pulmonary rales, jugular venous distension (JVD), S3, and edema. The primary endpoint was defined as rehospitalization for HF.

Results

Majority (63.9%) of the patients had non-ischemic etiology and, at the time of admission, S3 was seen in 69.9% of the patients, JVD in 54.1%, and pulmonary rales in 43.6%. The mean follow-up period was 726 ± 31days. Patients with pulmonary rales (p < 0.001) and S3 (p  =  0.011) had worse readmission rates than those without these findings; the presence of these findings was also associated with elevated troponin T (TnT) levels at the time of discharge (odds ratio [OR] 2.8; p  =  0.02 and OR 2.6; p  =  0.05, respectively).

Conclusion

Pulmonary rales and S3 were associated with inferior readmission rates and elevated TnT levels on discharge. The worsening of the readmission rate owing to congestive physical findings may be a consequence of on-going myocardial injury.     

Drought as an Inciting Mortality Factor in Scots Pine Stands of the Valais, Switzerland

During the 20th century, high mortality rates of Scots pine (Pinus silvestris L.) have been observed over large areas in the Rhône valley (Valais, Switzerland) and in other dry valleys of the European Alps. In this study, we evaluated drought as a possible inciting factor of Scots pine decline in the Valais. Averaged tree-ring widths, standardized tree-ring series, and estimated annual mortality risks were related to a drought index. Correlations between drought indices and standardized tree-ring series from 11 sites showed a moderate association. Several drought years and drought periods could be detected since 1864 that coincided with decreased growth. Although single, extreme drought years had generally a short-term, reversible effect on tree growth, multi-year drought initiated prolonged growth decreases that increased a tree’s long-term risk of death. Tree death occurred generally several years or even decades after the drought. In conclusion, drought has a limiting effect on tree growth and acts as a bottleneck event in triggering Scots pine decline in the Valais.     

非ST段抬高急性冠脉综合征患者心衰程度与血浆IL-15水平的相关性研究

目的:分析非ST段抬高急性冠脉综合征(NSTE-ACS)患者心衰程度与血浆IL-15水平的相关性及其临床意义。方法:选择NSTE-ACS不伴心衰及NSTE-ACS伴心衰住院患者154例,对照组为冠脉造影排除冠心病诊断者20例。冠脉造影前,采用ELISA法测定和比较各组的血浆IL-15水平,通过pearson相关检验分析血浆IL-15水平与NSTE-ACS患者心衰程度的相关性;散点图及拟合曲线观察血浆IL-15水平与NSTE-ACS患者心衰程度的关系;多元线性回归对差异变量进行调整,进一步明确血浆IL-15水平与NSTE-ACS患者心衰程度的关系。结果:NSTE-ACS不伴心衰组和NSTE-ACS伴心衰组患者的血清IL-15水平均显著高于正常对照组(P0.01);且NSTE-ACS伴心衰组的患者血清IL-15水平较NSTE-ACS不伴心衰组患者显著升高,差异具有显著统计学意义(P0.01)。Pearson检验结果显示血浆IL-15水平与EF值呈负相关(r=-0.775),与血清BNP水平呈正相关(r=0.474);散点图显示IL-15能与EF值线性拟合,呈负相关;散点图显示IL-15与血清BNP水平线性拟合,呈正相关;多元线性回归调整差异变量,明确IL-15与EF值(β=-0.295)呈显著相关。结论:NSTE-ACS患者的血浆IL-15水平与其心衰严重程度呈正相关。     

The Prognostic Importance of Changes in Renal Function during Treatment for Acute Heart Failure Depends on Admission Renal Function

Background

Worsening and improving renal function during acute heart failure have been associated with adverse outcomes but few studies have considered the admission level of renal function upon which these changes are superimposed.

Objectives

The objective of this study was to evaluate definitions that incorporate both admission renal function and change in renal function.

Methods

696 patients with acute heart failure with calculable eGFR were classified by admission renal function (Reduced [R, eGFR<45 ml/min] or Preserved [P, eGFR≥45 ml/min]) and change over hospital admission (worsening [WRF]: eGFR ≥20% decline; stable [SRF]; and improving [IRF]: eGFR ≥20% increase). The primary outcome was all-cause mortality. The prevalence of Pres and Red renal function was 47.8% and 52.2%. The frequency of R-WRF, R-SRF, and R-IRF was 11.4%, 28.7%, and 12.1%, respectively; the incidence of P-WRF, P-SRF, and P-IRF was 5.7%, 35.3%, and 6.8%, respectively. Survival was shorter for patients with R-WRF compared to R-IRF (median survival times 13.9 months (95%CI 7.7–24.9) and 32.5 months (95%CI 18.8–56.1), respectively), resulting in an acceleration factor of 2.3 (p = 0.016). Thus, an increase compared with a decrease in renal function was associated with greater than two times longer survival among patients with Reduced renal function.     

The Prognostic Value of Plasma Galectin-3 in Chronic Heart Failure Patients Is Maintained when Treated with Mineralocorticoid Receptor Antagonists

Objective

Galectin-3 (Gal-3) is considered as a myocardial fibrosis biomarker with prognostic value in heart failure (HF). Since aldosterone is a neurohormone with established fibrotic properties, we aimed to investigate if mineralocorticoid receptor antagonists (MRAs) would modulate the prognostic value of Gal-3.

Methods

The IBLOMAVED cohort comprised 427 eligible chronic HF patients (CHF) with echocardiography and heart failure biomarkers assessments (BNP). After propensity score matching CHF patients for cardiovascular risk factors, to form balanced groups, Gal-3 levels were measured at baseline in plasma from patients treated with MRAs (MRA-Plus, n=101) or not (MRA-Neg, n=101). The primary end point was all-cause mortality with a follow-up of 3 years.

Results

Gal-3 in plasma from these patients were similar with median values of 14.0 ng/mL [IQR, 9.9–19.3] and 14.4 ng/mL [IQR, 12.3–19.8] (P = 0.132) in MRA-Neg and MRA-Plus, respectively. Patients with Gal-3 ≤17.8 ng/mL had an HR of 1 (reference group) and 1.5 [0.4–5.7] in MRA-Neg and MRA-Plus, respectively (p=0.509). Patients with Gal-3 ≥ 17.8 ng/mL had an HR of 7.4 [2.2–24.6] and 9.0 [2.9–27.8] in MRA-Plus and MRA-Neg, respectively (p=0.539) and a median survival time of 2.4 years [95%CI,1.8–2.4]. Multivariate Cox proportional hazard analysis confirmed that MRA and the interaction term between MRA treatment and Gal-3 >17.8 ng/mL were not factors associated with survival.

Conclusions

MRA treatment did not impair the prognostic value of Gal-3 assessed with a 17.8 ng/mL cut off. Gal-3 levels maintained its strong prognostic value in CHF also in patients treated with MRAs. The significance of the observed lack of an interaction between Gal-3 and treatment effect of MRAs remains to be elucidated.     

Detrended Fluctuation Analysis of Heart Rate Dynamics Is an Important Prognostic Factor in Patients with End-Stage Renal Disease Receiving Peritoneal Dialysis

Background and Objectives

Patients with severe kidney function impairment often have autonomic dysfunction, which could be evaluated noninvasively by heart rate variability (HRV) analysis. Nonlinear HRV parameters such as detrended fluctuation analysis (DFA) has been demonstrated to be an important outcome predictor in patients with cardiovascular diseases. Whether cardiac autonomic dysfunction measured by DFA is also a useful prognostic factor in patients with end-stage renal disease (ESRD) receiving peritoneal dialysis (PD) remains unclear. The purpose of the present study was designed to test the hypothesis.

Materials and Methods

Patients with ESRD receiving PD were included for the study. Twenty-four hour Holter monitor was obtained from each patient together with other important traditional prognostic makers such as underlying diseases, left ventricular ejection fraction (LVEF) and serum biochemistry profiles. Short-term (DFAα1) and long-term (DFAα2) DFA as well as other linear HRV parameters were calculated.

Results

A total of 132 patients (62 men, 72 women) with a mean age of 53.7±12.5 years were recruited from July 2007 to March 2009. During a median follow-up period of around 34 months, eight cardiac and six non-cardiac deaths were observed. Competing risk analysis demonstrated that decreased DFAα1 was a strong prognostic predictor for increased cardiac and total mortality. ROC analysis showed that the AUC of DFAα1 (<0.95) to predict mortality was 0.761 (95% confidence interval (CI). = 0.617–0.905). DFAα1≧ 0.95 was associated with lower cardiac mortality (Hazard ratio (HR) 0.062, 95% CI = 0.007–0.571, P = 0.014) and total mortality (HR = 0.109, 95% CI = 0.033–0.362, P = 0.0003).

Conclusion

Cardiac autonomic dysfunction evaluated by DFAα1 is an independent predictor for cardiac and total mortality in patients with ESRD receiving PD.