Immunoblot analysis of the seroreactivity to recombinant Borrelia burgdorferi sensu lato antigens, including VlsE, in the long-term course of treated patients with Erythema migrans

Objective: We evaluated whether immunoblotting is capable of substantiating the posttreatment clinical assessment of patients with erythema migrans ( EM), the hallmark of early Lyme borreliosis. Methods: In 50 patients, seroreactivity to different antigens of Borrelia burgdorferi sensu lato was analyzed by a recombinant immunoblot test (IB) in consecutive serum samples from a minimum follow-up period of 1 year. Antigens in the IgG test were decorin- binding protein A, internal fragment of p41 (p41i), outer surface protein C (OspC), p39, variable major protein-like sequence expressed (VlsE), p58 and p100; those in the IgM test were p41i, OspC and p39. Immune responses were correlated with clinical and treatment-related parameters. Results: Positive IB results were found in 50% before, in 57% directly after therapy and in 44% by the end of the follow-up for the IgG class, and in 36, 43 and 12% for the IgM class. In acute and convalescence phase sera, VlsE was most immunogenic on IgG testing 60 and 70%), and p41i (46 and 57%) and OspC (40 and 57%) for the IgM class. By the end of the follow-up, only the anti-p41i lgM response was significantly decreased to 24%. Conclusions: No correlation was found between IB results and treatment-related parameters. Thus, immunoblotting does not add to the clinical assessment of EM patients after treatment. Copyright (c) 2008 S. Karger AG, Basel

Circulating alpha1-antitrypsin in the general population: Determinants and association with lung function

BACKGROUND: Severe alpha1-antitrypsin (AAT) deficiency associated with low AAT blood concentrations is an established genetic COPD risk factor. Less is known about the respiratory health impact of variation in AAT serum concentrations in the general population. We cross-sectionally investigated correlates of circulating AAT concentrations and its association with FEV1. METHODS: In 5187 adults (2669 females) with high-sensitive c-reactive protein (CRP) levels < or = 10 mg/l from the population-based Swiss SAPALDIA cohort, blood was collected at the time of follow-up examination for measuring serum AAT and CRP. RESULTS: Female gender, hormone intake, systolic blood pressure, age in men and in postmenopausal women, as well as active and passive smoking were positively, whereas alcohol intake and BMI inversely correlated with serum AAT levels, independent of CRP adjustment. We observed an inverse association of AAT with FEV1 in the total study population (p < 0.001), that disappeared after adjustment for CRP (p = 0.28). In addition, the AAT and FEV1 association was modified by gender, menopausal status in women, and smoking. CONCLUSION: The results of this population-based study reflect a complex interrelationship between tobacco exposure, gender related factors, circulating AAT, systemic inflammatory status and lung function

Accuracy of self-reported height measurements in parents and its effect on mid-parental target height calculation

BACKGROUND: Clinical determination of mid-parental height is an important part of the assessment of a child's growth, however our clinical impression has been that parents cannot be relied upon to accurately report their own heights. Therefore, we conducted this study to assess the accuracy of parental height self-reporting and its effect on calculated mid-parental target height for children presenting to a pediatric endocrinology office. METHODS: All parents bringing their children for an initial evaluation to a pediatric endocrinology clinic over a period of nine months were questioned and then measured by a pediatric endocrinologist. Parents were blinded to the study. Mid-parental target heights, based on reported and actual height were compared. RESULTS: There were 241 families: 98 fathers and 217 mothers in our study. Mean measured paternal height was 173.2 cm, self reported 174.9 cm (p < 0.0001), partner reported 177 cm (p = 0.0004). Only 50% of fathers and 58% of mothers reported their height within ± 2 cm of their measured height, while 15% of fathers and 12% of mothers were inaccurate by more than 4 cm. Mean measured maternal height was 160.6 cm, self-reported 161.1 cm (NS), partner reported 161.7 cm (NS). Inaccuracy of height self-report had a small but significant effect on the mean MPTH (0.4 cm, p = 0.045). Analysis showed that only 70% of MPTH calculated by reported heights fell within ± 2 cm of MPTH calculated using measured heights, 24% being in ± 2–4 cm range, and 6% were inaccurate by more than 4 cm. CONCLUSION: There is a significant difference in paternal measured versus reported heights with an overall trend for fathers to overestimate their own height. A large subset of parents makes a substantial error in their height self-report, which leads to erroneous MPTH. Inaccuracy is even greater when one parent reports the other parent's height. When a child's growth is in question, measured rather than reported parental heights should be obtained

Validation of ACG Case-mix for equitable resource allocation in Swedish primary health care

<p>Abstract</p> <p>Background</p> <p>Adequate resource allocation is an important factor to ensure equity in health care. Previous reimbursement models have been based on age, gender and socioeconomic factors. An explanatory model based on individual need of primary health care (PHC) has not yet been used in Sweden to allocate resources. The aim of this study was to examine to what extent the ACG case-mix system could explain concurrent costs in Swedish PHC.</p> <p>Methods</p> <p>Diagnoses were obtained from electronic PHC records of inhabitants in Blekinge County (approx. 150,000) listed with public PHC (approx. 120,000) for three consecutive years, 2004-2006. The inhabitants were then classified into six different resource utilization bands (RUB) using the ACG case-mix system. The mean costs for primary health care were calculated for each RUB and year. Using linear regression models and log-cost as dependent variable the adjusted R²was calculated in the unadjusted model (gender) and in consecutive models where age, listing with specific PHC and RUB were added. In an additional model the ACG groups were added.</p> <p>Results</p> <p>Gender, age and listing with specific PHC explained 14.48-14.88% of the variance in individual costs for PHC. By also adding information on level of co-morbidity, as measured by the ACG case-mix system, to specific PHC the adjusted R²increased to 60.89-63.41%.</p> <p>Conclusion</p> <p>The ACG case-mix system explains patient costs in primary care to a high degree. Age and gender are important explanatory factors, but most of the variance in concurrent patient costs was explained by the ACG case-mix system.</p

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

Quantifying morbidities by Adjusted Clinical Group system for a Taiwan population: A nationwide analysis

<p>Abstract</p> <p>Background</p> <p>The Adjusted Clinical Group (ACG) system has been used in measuring an individual's and a population's morbidities. Although all required inputs for running the ACG system are readily available, patients' morbidities and their associations to health care utilizations have been rarely studied in Taiwan. Therefore, the objective of this study was using the ACG system to quantify morbidities for Taiwanese population and to examine their relationship to ambulatory utilizations and costs.</p> <p>Methods</p> <p>This secondary analysis examined claims data for ambulatory services provided to 2.71 million representative Taiwanese in 2002 and 2003. People were grouped by the ACG system according to age, gender, and all ambulatory diagnosis codes in a given year. The software collapses the full set of ACGs into six morbidity categories (Non-users, Healthy, Low-morbidity, Moderate-, High- and Very-high) termed Resource Utilization Bands (RUBs). Each ACG was assigned a relative weight (RW), which was calculated as the ratio of mean ambulatory cost for each ACG to that for the overall. The distribution of morbidities was compared between years 2002 and 2003. The consistency of the distributions of visits, costs, and RWs of each ACG were examined for a two-year period. The relationship between people's morbidities and their ambulatory utilizations and costs was assessed.</p> <p>Results</p> <p>Ninety-eight percent of the subjects were correctly assigned to ACGs. Except for non-users (7.9 ~ 8.3%), most subjects were assigned to ACGs of acute and minor diseases and ACGs of moderate-to-high-morbid chronic diseases. The distributions of ACG-based morbidities were highly consistent (r = 0.949, <it>p < 0.001</it>) between 2002 and 2003. The ACG-specific visits (r = 0.955, <it>p < 0.001</it>), costs (r = 0.966, <it>p < 0.001</it>) and RWs (r = 0.991, <it>p < 0.001</it>) were correlated across two years. People grouped to the high-morbid ACGs had more visits and costs than those grouped to the low-morbid ACGs. Forty-six percent of the total ambulatory costs were spent by eighteen percent of the population, who were grouped to the High- and Very-high-morbidity RUBs.</p> <p>Conclusion</p> <p>This study demonstrated the feasibility, validity, and reliability of using the ACG system to measure morbidities in a Taiwan population and to explain their associations with ambulatory utilizations and costs for the whole country.</p