Markers of Disease Severity Are Associated with Malnutrition in Parkinson's Disease

Objective

In Parkinson''s disease (PD), commonly reported risk factors for malnutrition in other populations commonly occur. Few studies have explored which of these factors are of particular importance in malnutrition in PD. The aim was to identify the determinants of nutritional status in people with Parkinson''s disease (PWP).

Methods

Community-dwelling PWP (>18 years) were recruited (n = 125; 73M/52F; Mdn 70 years). Self-report assessments included Beck''s Depression Inventory (BDI), Spielberger Trait Anxiety Inventory (STAI), Scales for Outcomes in Parkinson''s disease – Autonomic (SCOPA-AUT), Modified Constipation Assessment Scale (MCAS) and Freezing of Gait Questionnaire (FOG-Q). Information about age, PD duration, medications, co-morbid conditions and living situation was obtained. Addenbrooke''s Cognitive Examination (ACE-R), Unified Parkinson''s Disease Rating Scale (UPDRS) II and UPDRS III were performed. Nutritional status was assessed using the Subjective Global Assessment (SGA) as part of the scored Patient-Generated Subjective Global Assessment (PG-SGA).

Results

Nineteen (15%) were malnourished (SGA-B). Median PG-SGA score was 3. More of the malnourished were elderly (84% vs. 71%) and had more severe disease (H&Y: 21% vs. 5%). UPDRS II and UPDRS III scores and levodopa equivalent daily dose (LEDD)/body weight(mg/kg) were significantly higher in the malnourished (Mdn 18 vs. 15; 20 vs. 15; 10.1 vs. 7.6 respectively). Regression analyses revealed older age at diagnosis, higher LEDD/body weight (mg/kg), greater UPDRS III score, lower STAI score and higher BDI score as significant predictors of malnutrition (SGA-B). Living alone and higher BDI and UPDRS III scores were significant predictors of a higher log-adjusted PG-SGA score.

Conclusions

In this sample of PWP, the rate of malnutrition was higher than that previously reported in the general community. Nutrition screening should occur regularly in those with more severe disease and depression. Community support should be provided to PWP living alone. Dopaminergic medication should be reviewed with body weight changes.     

GM抗原检测对血液病患者侵袭性曲霉病的诊断价值

目的:探讨血清半乳甘露聚糖(GM)抗原检测对于血液病患者侵袭性曲霉病(invasive aspergillosis,IA)的早期诊断和疗效评价的临床意义。方法:选取137例具有侵袭性真菌病IFD高危因素患者的468份血清标本,进行GM试验,检测抗真菌治疗前后GM抗原水平的变化,同时收集患者的临床资料,进行统计学分析,并评价GM检测对于血液病患者IA的诊断价值。结果:以GM检测单次I≥1.0作为阳性界值时,本试验的敏感性、特异性、阳性预测值和阴性预测值分别为90.91%,95.65%95.24%和91.67%,与试剂盒提供的血清GM试验结果的单次I≥1.5的阳性界值相比敏感性明显提高,而特异性无明显降低,因此能够有效区分临床诊断和拟诊两个IA级别。在其他实验室检测和影像学检查的基础上加入GM试验后,IA临床诊断组的人数明显增加。诊断级别与I值总体均数的分布具有相关性,回顾性确诊IA组、回顾性可疑IA组、回顾性排除IA组的I值呈现明显的由高到低的群落分布,且三个诊断级别的I值分布范围的差异有统计学意义。根据阳性界值标准I≥1.0,GM试验阳性早于痰培养阳性平均7.73±8.71 d,也早于CT影像学证据平均6.89±8.02 d。基于GM值阳性时的抢先抗曲霉治疗组的有效率明显提高(P=0.039)。结论:血清GM抗原检测是早期诊断IA的一种有效方法,将单次I≥1.0作为阳性界值具有较好的敏感性和特异性,在阳性检出率和阳性检出时间方面较主要影像学表现和微生物学证据具有一定优势。在高危血液病伴粒细胞缺乏患者中根据GM试验阳性进行抢先抗曲霉治疗,可提高治疗有效率,监测血清GM浓度的动态变化具有评价疗效的重要价值。该研究成果对临床侵袭性曲霉病的诊断和治疗具有一定指导意义。     

Identification of Potential Markers for Cushing Disease

Objective: Cushing disease (CD) causes a wide variety of nonspecific symptoms, which may result in delayed diagnosis. It may be possible to uncover unusual combinations of otherwise common symptoms using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Our aim was to identify and evaluate dyads of clinical symptoms or conditions associated with CD.Methods: We conducted a matched case-control study using a commercial healthcare insurance claims database designed to compare the relative risk (RR) of individual conditions and dyad combinations of conditions among patients with CD versus matched non-CD controls.Results: With expert endocrinologist input, we isolated 10 key conditions (localized adiposity, hirsutism, facial plethora, polycystic ovary syndrome, abnormal weight gain, hypokalemia, deep venous thrombosis, muscle weakness, female balding, osteoporosis) with RRs varying from 5.3 for osteoporosis to 61.0 for hirsutism (and infinite RR for localized adiposity). The RRs of dyads of these conditions ranged from 4.1 for psychiatric disorders/serious infections to 128.0 for hirsutism/fatigue in patients with versus without CD. Construction of uncommon dyads resulted in further increases in RRs beyond single condition analyses; for example, osteoporosis alone had an RR of 5.3, which increased to 8.3 with serious infections and to 52.0 with obesity.Conclusion: This study demonstrated that RR of any one of 10 key conditions selected by expert opinion was ≥5 times greater in CD compared to non-CD, and nearly all dyads had RR≥5. An uncommon dyad of osteoporosis and obesity had an RR of 52.0. If clinicians consider the diagnosis of CD when the highest-risk conditions are seen, identification of this rare disease may improve.Abbreviations:CD = Cushing diseaseCPT = Current Procedural TerminologyCS = Cushing syndromeEMR = electronic medical recordICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical ModificationID = identificationRR = relative risk     

Identification of Neutrophil Activation Markers as Novel Surrogate Markers of CF Lung Disease

Background and aims

Cystic Fibrosis (CF) lung disease is characterized by progressively declining lung function and represents a major factor contributing to the high morbidity and mortality associated with CF. However, apart from spirometry, respiratory disease surrogate markers reliably indicating CF lung disease and the occurrence of pulmonary exacerbations (PEx) are still lacking. Within this study, we aimed to identify new experimental biomarkers for the detection of CF lung disease.

Methods

54 adult and 26 pediatric CF patients were included in the study and serum concentrations of MMP-1, -2, -8, -9, -13, TIMP-1, TIMP-2, YKL-40, hyaluronic acid, procollagen III peptide were quantified by ELISA. CF lung disease was diagnosed by lung function test, PEx was defined based on a clinical scoring established by Rosenfeld in 2001.

Results

Adults and children with moderate to severe CF lung disease exhibited significantly increased serum expression of MMP-8, MMP-9, YKL-40 and TIMP-1. Further, MMP-8, MMP-9 and YKL-40 were significantly increased in adult CF patients suffering from PEx compared to those without clinical signs of respiratory exacerbation. MMP-8, MMP-9, YKL-40, and TIMP-1 serum levels were unaffected by the presence or absence of CF liver disease or pancreatic insufficiency.

Conclusions

MMP-8, MMP-9, and YKL-40 might serve as novel non-invasive biomarkers of CF lung disease and PEx.     

Use of Multiple Genetic Markers in Prediction of Breeding Values

Genotypes at a marker locus give information on transmission of genes from parents to offspring and that information can be used in predicting the individuals' additive genetic value at a linked quantitative trait locus (MQTL). In this paper a recursive method is presented to build the gametic relationship matrix for an autosomal MQTL which requires knowledge on recombination rate between the marker locus and the MQTL linked to it. A method is also presented to obtain the inverse of the gametic relationship matrix. This information can be used in a mixed linear model for simultaneous evaluation of fixed effects, gametic effects at the MQTL and additive genetic effects due to quantitative trait loci unlinked to the marker locus (polygenes). An equivalent model can be written at the animal level using the numerator relationship matrix for the MQTL and a method for obtaining the inverse of this matrix is presented. Information on several unlinked marker loci, each of them linked to a different locus affecting the trait of interest, can be used by including an effect for each MQTL. The number of equations per animal in this case is 2m + 1 where m is the number of MQTL. A method is presented to reduce the number of equations per animal to one by combining information on all MQTL and polygenes into one numerator relationship matrix. It is illustrated how the method can accommodate individuals with partial or no marker information. Numerical examples are given to illustrate the methods presented. Opportunities to use the presented model in constructing genetic maps are discussed.     

Markers of Celiac Disease and Gluten Sensitivity in Children with Autism

Objective

Gastrointestinal symptoms are a common feature in children with autism, drawing attention to a potential association with celiac disease or gluten sensitivity. However, studies to date regarding the immune response to gluten in autism and its association with celiac disease have been inconsistent. The aim of this study was to assess immune reactivity to gluten in pediatric patients diagnosed with autism according to strict criteria and to evaluate the potential link between autism and celiac disease.

Methods

Study participants included children (with or without gastrointestinal symptoms) diagnosed with autism according to both the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI-R) (n = 37), their unaffected siblings (n = 27), and age-matched healthy controls (n = 76). Serum specimens were tested for antibodies to native gliadin, deamidated gliadin, and transglutaminase 2 (TG2). Affected children were genotyped for celiac disease associated HLA-DQ2 and -DQ8 alleles.

Results

Children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls (p<0.01). The IgG levels were also higher compared to the unaffected siblings, but did not reach statistical significance. The IgG anti-gliadin antibody response was significantly greater in the autistic children with gastrointestinal symptoms in comparison to those without them (p<0.01). There was no difference in IgA response to gliadin across groups. The levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between patients and controls. An association between increased anti-gliadin antibody and presence of HLA-DQ2 and/or -DQ8 was not observed.

Conclusions

A subset of children with autism displays increased immune reactivity to gluten, the mechanism of which appears to be distinct from that in celiac disease. The increased anti-gliadin antibody response and its association with GI symptoms points to a potential mechanism involving immunologic and/or intestinal permeability abnormalities in affected children.     

Statin Use and Markers of Immunity in the Doetinchem Cohort Study

It has been suggested that statins can both stimulate and suppress the immune system, and thereby, may influence autoimmune diseases. Therefore, we studied effects of statins on innate and adaptive immunity, and self-tolerance by measuring serological levels of C-reactive protein (CRP), neopterin, immunoglobulin E (IgE) antibodies and the presence of autoantibodies (antinuclear antibodies (ANA) and IgM rheumatoid factor (RF)) in the general population. We conducted a nested case-control study within the population-based Doetinchem cohort. Data from health questionnaires, serological measurements and information on medication from linkage to pharmacy-dispensing records were available. We selected 332 statin users (cases) and 331 non-users (controls), matched by age, sex, date of serum collection, history of cardiovascular diseases, diabetes mellitus type II and stroke. Multivariate regression analyses were performed to estimate effect of statins on the immune system. The median level of CRP in statin users (1.28 mg/L, interquartile range (IQR): 0.59-2.79) was lower than in non-users (1.62 mg/L, IQR: 0.79-3.35), which after adjustment was estimated to be a 28% lower level. We observed an inverse association between duration of statin use and CRP levels. Elevated levels of IgE (>100 IU/mL) were more prevalent in statin users compared to non-users. A trend towards increased levels of IgE antibodies in statin users was observed, whereas no associations were found between statin use and levels of neopterin or the presence of autoantibodies. In this general population sub-sample, we observed an anti-inflammatory effect of statin use and a trend towards an increase of IgE levels, an surrogate marker for Th (helper) 2 responses without a decrease in neopterin levels, a surrogate marker for Th1 response and/or self-tolerance. We postulate that the observed decreased inflammatory response during statin therapy may be important but is insufficient to induce loss of self-tolerance.     

The Use of RAPD Markers to Assess Catfish Hybridization

Taiwan's endemic catfish Clarias fuscus is gradually disappearing from its native habitat, and has been proposed for genebank preservation. Environmental pressures, including exotic species interference and habitat destruction, as well as possible competitive advantages of the hybrids over this species. In order to quickly and effectively provide a reliable DNA fingerprint for the pure strain of C. fuscus we used RAPD markers to assess C. fuscus, C. mossambicus, and C.batrachus. Of the 200 primers screened to prime PCR amplification of DNA from wild-caught C. fuscus, 16 yielded reproducible DNA bands. Unique RAPD markers generated from 3 PCR primers (#211, #245 and #287) are shown to be alleles present in the genomes of C. mossambicus but absent in the genome of C. fuscus. Hybrids of C. fuscus and C. mossambicus, therefore, could possibly be distinguished by the use of these specific molecular markers. Catfish caught from the Mingder Dam were then cautiously removed from the preserved stock because of the appearance of hybrid markers in their genomes.     

Conditional Quadratic Discrimination in the Identification of Biological Markers for Disease Screening

Conditional multivariate normal density functions are used to construct conditional quadratic discriminant functions that adjust for covariate differences between disease groups. An expected actual error rate for the conditional discriminant function is defined. The purpose of this paper is to use the conditional quadratic discriminant function and its misolassification error rate in order to help determine if a set of discriminators is a good biological marker for disease screening. The conditional quadratic discriminant analysis is illustrated using data from two alcoholism classification problems. It is shown how the discriminant functions can identify a set of variables that can be used as biological markers.     

Evaluation of Preoperative Hematologic Markers as Prognostic Factors and Establishment of Novel Risk Stratification in Resected pN0 Non-Small-Cell Lung Cancer

Background

The aims of this study were to investigate whether the preoperative hematologic markers, the neutrophil-lymphocyte ratio (NLR) or the platelet-lymphocyte ratio (PLR) were prognostic indicators and to develop a novel risk stratification model in pN0 non-small-cell lung cancer (NSCLC).

Methods

We performed a retrospective analysis of 400 consecutive pN0 NSCLC patients. Prognostic values were evaluated by Cox proportional hazard model analyses and patients were stratified according to relative risks for patients’ survival.

Results

During the follow-up, 117 patients had cancer recurrence, and 86 patients died. In univariate analysis, age, gender, smoke status and tumor size as well as WBC, NEU, LYM, PLR and NLR were significantly associated with patients’ prognosis. In multivariate analysis, age, tumor size and NLR were independent predictors for patients’ overall survival (P = 0.024, 0.001, and 0.002 respectively). PLR didn’t associated with patients’ survival in multivariate analysis. Patients were stratified into 3 risk groups and the differences among the groups were significant according to disease free survival and overall survival (P = 0.000 and 0.000 respectively).

Conclusions

We confirmed that NLR other than PLR was an independent prognostic factor. Combination of NLR, age and tumor size could stratify pN0 NSCLC patients into 3 risk groups and enabled us to develop a novel risk stratification model.     

Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity

Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005) in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B) were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively). There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.