The Influence of Socioeconomic Factors on Health Parameters in Overweight and Obese Adults

The prevalence of being overweight and of obesity is increasing worldwide, and is associated with a high risk to health. Therefore, the aim of our study was to investigate whether normal weight, overweight and obese subjects of low, middle or high socioeconomic status (SES) differ with regard to their health behavior, health, quality of life, and the use of medical care. Data from the Austrian Health Interview Survey (ATHIS) 2006/07, comprising 3 groups of 1,077 individuals, each of whom were normal weight, overweight, or obese, respectively, and matched according to their age, sex and SES, were analyzed concerning health outcomes. The results show that subjects with a low SES differ significantly from those of high SES in terms of their health behavior, self-perceived health, levels of impairment, chronic conditions, quality of life, and health care. Additionally, obesity in adults is associated with sub-optimal dietary practices and worse health, poorer quality of life and medical care than normal weight and overweight individuals. A significant interaction between the weight class and SES was found concerning physical exercise, impairment due to health problems and chronic diseases. A low SES has a strong negative impact on health, especially in obese individuals. Therefore a continuous target group-oriented, non-discriminatory public health program is required, prioritizing obese subjects with low SES.     

A Single Nucleotide Polymorphism within the Interferon Gamma Receptor 2 Gene Perfectly Coincides with Polledness in Holstein Cattle

Polledness is a high impact trait in modern milk and beef production to meet the demands of animal welfare and work safety. Previous studies have mapped the polled-locus to the proximal region of the bovine chromosome 1 (BTA1) and narrowed it down to approximately 1 Mb. Sequencing of the positional candidate genes within the 1 Mb polled region and whole genome sequencing of Holsteins revealed a single nucleotide polymorphism (SNP) AC000158: g.1390292G>A within intron 3 of the interferon gamma receptor 2 gene (IFNGR2) in perfect co-segregation with polledness in Holsteins. This complete association was validated in 443 animals of the same breed. This SNP allows reliable genotyping of horned, heterozygous and homozygous polled Holsteins, even in animals that could not be resolved using the previously published haplotype for Holstein.     

Concomitant Tumor Expression of EGFR and TATI/SPINK1 Associates with Better Prognosis in Colorectal Cancer

Background

Epidermal growth factor receptor (EGFR) activation plays a role in colorectal cancer (CRC) carcinogenesis, and anti-EGFR drugs are used in treatment of advanced CRC. One of the EGFR ligands is tumor-associated trypsinogen inhibitor TATI, also called serine protease inhibitor Kazal type1 (SPINK 1), which we recently showed to be an independent prognostic marker in CRC.

Methods

We studied the prognostic value of immunohistochemical expression of EGFR and concomitant expression of EGFR and TATI/SPINK1 in a series of 619 colorectal cancer patients.

Results

Of the samples, 92% were positive for EGFR. EGFR+/TATI+ was seen in 62.8%, EGFR+/TATI− in 29.5%, EGFR−/TATI+ in 4.9%, and EGFR−/TATI− in 2.7% of patients. EGFR expression correlated with WHO grade (p = 0.040). In univariate analysis, EGFR expression correlated with favourable survival (p = 0.006). EGFR+/TATI+ patients showed better survival than did those with other combinations (p<0.001). In multivariate analysis, EGFR+/TATI+ was an independent prognostic factor of favourable prognosis (p<0.001).

Conclusion

Concomitant positivity of EGFR and TATI/SPINK1 predicts favourable prognosis in CRC.     

Common and Rare EGFR and KRAS Mutations in a Dutch Non-Small-Cell Lung Cancer Population and Their Clinical Outcome

Introduction

In randomly assigned studies with EGFR TKI only a minor proportion of patients with NSCLC have genetically profiled biopsies. Guidelines provide evidence to perform EGFR and KRAS mutation analysis in non-squamous NSCLC. We explored tumor biopsy quality offered for mutation testing, different mutations distribution, and outcome with EGFR TKI.

Patient and Methods

Clinical data from 8 regional hospitals were studied for patient and tumor characteristics, treatment and overall survival. Biopsies sent to the central laboratory were evaluated for DNA quality and subsequently analyzed for mutations in exons 18–21 of EGFR and exon 2 of KRAS by bidirectional sequence analysis.

Results

Tumors from 442 subsequent patients were analyzed. For 74 patients (17%) tumors were unsuitable for mutation analysis. Thirty-eight patients (10.9%) had EGFR mutations with 79% known activating mutations. One hundred eight patients (30%) had functional KRAS mutations. The mutation spectrum was comparable to the Cosmic database. Following treatment in the first or second line with EGFR TKI median overall survival for patients with EGFR (n = 14), KRAS (n = 14) mutations and wild type EGFR/KRAS (n = 31) was not reached, 20 and 9 months, respectively.

Conclusion

One out of every 6 tumor samples was inadequate for mutation analysis. Patients with EGFR activating mutations treated with EGFR-TKI have the longest survival.     

CD4+NKG2D+ T Cells Exhibit Enhanced Migratory and Encephalitogenic Properties in Neuroinflammation

Migration of encephalitogenic CD4⁺ T lymphocytes across the blood-brain barrier is an essential step in the pathogenesis of multiple sclerosis (MS). We here demonstrate that expression of the co-stimulatory receptor NKG2D defines a subpopulation of CD4⁺ T cells with elevated levels of markers for migration, activation, and cytolytic capacity especially when derived from MS patients. Furthermore, CD4⁺NKG2D⁺ cells produce high levels of proinflammatory IFN-γ and IL-17 upon stimulation. NKG2D promotes the capacity of CD4⁺NKG2D⁺ cells to migrate across endothelial cells in an in vitro model of the blood-brain barrier. CD4⁺NKG2D⁺ T cells are enriched in the cerebrospinal fluid of MS patients, and a significant number of CD4⁺ T cells in MS lesions coexpress NKG2D. We further elucidated the role of CD4⁺NKG2D⁺ T cells in the mouse system. NKG2D blockade restricted central nervous system migration of T lymphocytes in vivo, leading to a significant decrease in the clinical and pathologic severity of experimental autoimmune encephalomyelitis, an animal model of MS. Blockade of NKG2D reduced killing of cultivated mouse oligodendrocytes by activated CD4⁺ T cells. Taken together, we identify CD4⁺NKG2D⁺ cells as a subpopulation of T helper cells with enhanced migratory, encephalitogenic and cytotoxic properties involved in inflammatory CNS lesion development.     

Potential of autochthonous fungal strains isolated from contaminated soils for degradation of polychlorinated biphenyls

Up to now, most studies on polychlorinated biphenyl (PCB) bioremediation have examined the ability of model fungal strains to biodegrade PCBs. Yet, there is limited information concerning the potential of autochthonous filamentous fungal strains in the biodegradation of PCBs and their possible use in the environmental technologies. In this study, we investigated the capacity of autochthonous fungal strains in the biodegradation of PCBs by isolating 24 taxa from former industrial sites highly contaminated by PCBs. Microscopic and molecular analyses using the internal transcribed spacer (ITS) region revealed that the fungal strains belonged to the phyla Ascomycota (19 strains) and Zygomycota (five strains). The chromatography gas analysis revealed evidence of degradation of seven PCB congeners. With the exception of Circinella muscae which presented no degradation potential, the other fungal strains exhibited a rate of biodegradation ranging from 29 to 85 % after 7 d of incubation in liquid medium. Among these strains, Doratomyces nanus, Doratomyces purpureofuscus, Doratomyces verrucisporus, Myceliophthora thermophila, Phoma eupyrena, and Thermoascus crustaceus showed remarkable degradation ability (>70 %) regardless of the number of chlorine substituents on the biphenyl nucleus and a high tolerance towards PCBs. To our knowledge, this is the first study that demonstrates the ability of PCB degradation by these species and indicates the potential effectiveness of some autochthonous fungal strains in bioremediation systems.     

Measles Outbreak in South Africa: Epidemiology of Laboratory-Confirmed Measles Cases and Assessment of Intervention, 2009–2011

Background

Since 1995, measles vaccination at nine and 18 months has been routine in South Africa; however, coverage seldom reached >95%. We describe the epidemiology of laboratory-confirmed measles case-patients and assess the impact of the nationwide mass vaccination campaign during the 2009 to 2011 measles outbreak in South Africa.

Methods

Serum specimens collected from patients with suspected-measles were tested for measles-specific IgM antibodies using an enzyme-linked immunosorbent assay and genotypes of a subset were determined. To estimate the impact of the nationwide mass vaccination campaign, we compared incidence in the seven months pre- (1 September 2009–11 April 2010) and seven months post-vaccination campaign (24 May 2010–31 December 2010) periods in seven provinces of South Africa.

Results

A total of 18,431 laboratory-confirmed measles case-patients were reported from all nine provinces of South Africa (cumulative incidence 37 per 100,000 population). The highest cumulative incidence per 100,000 population was in children aged <1 year (603), distributed as follows: <6 months (302/100,000), 6 to 8 months (1083/100,000) and 9 to 11 months (724/100,000). Forty eight percent of case-patients were ≥5 years (cumulative incidence 54/100,000). Cumulative incidence decreased with increasing age to 2/100,000 in persons ≥40 years. A single strain of measles virus (genotype B3) circulated throughout the outbreak. Prior to the vaccination campaign, cumulative incidence in the targeted vs. non-targeted age group was 5.9-fold higher, decreasing to 1.7 fold following the campaign (P<0.001) and an estimated 1,380 laboratory-confirmed measles case-patients were prevented.

Conclusion

We observed a reduction in measles incidence following the nationwide mass vaccination campaign even though it was conducted approximately one year after the outbreak started. A booster dose at school entry may be of value given the high incidence in persons >5 years.     

Differential Effects of Drug Interventions and Dietary Lifestyle in Developing Type 2 Diabetes and Complications: A Systems Biology Analysis in LDLr?/? Mice

Excess caloric intake leads to metabolic overload and is associated with development of type 2 diabetes (T2DM). Current disease management concentrates on risk factors of the disease such as blood glucose, however with limited success. We hypothesize that normalizing blood glucose levels by itself is insufficient to reduce the development of T2DM and complications, and that removal of the metabolic overload with dietary interventions may be more efficacious. We explored the efficacy and systems effects of pharmaceutical interventions versus dietary lifestyle intervention (DLI) in developing T2DM and complications. To mimic the situation in humans, high fat diet (HFD)-fed LDLr−/− mice with already established disease phenotype were treated with ten different drugs mixed into HFD or subjected to DLI (switch to low-fat chow), for 7 weeks. Interventions were compared to untreated reference mice kept on HFD or chow only. Although most of the drugs improved HFD-induced hyperglycemia, drugs only partially affected other risk factors and also had limited effect on disease progression towards microalbuminuria, hepatosteatosis and atherosclerosis. By contrast, DLI normalized T2DM risk factors, fully reversed hepatosteatosis and microalbuminuria, and tended to attenuate atherogenesis. The comprehensive beneficial effect of DLI was reflected by normalized metabolite profiles in plasma and liver. Analysis of disease pathways in liver confirmed reversion of the metabolic distortions with DLI. This study demonstrates that the pathogenesis of T2DM towards complications is reversible with DLI and highlights the differential effects of current pharmacotherapies and their limitation to resolve the disease.     

Predicting AD Conversion: Comparison between Prodromal AD Guidelines and Computer Assisted PredictAD Tool

Purpose

To compare the accuracies of predicting AD conversion by using a decision support system (PredictAD tool) and current research criteria of prodromal AD as identified by combinations of episodic memory impairment of hippocampal type and visual assessment of medial temporal lobe atrophy (MTA) on MRI and CSF biomarkers.

Methods

Altogether 391 MCI cases (158 AD converters) were selected from the ADNI cohort. All the cases had baseline cognitive tests, MRI and/or CSF levels of Aβ1–42 and Tau. Using baseline data, the status of MCI patients (AD or MCI) three years later was predicted using current diagnostic research guidelines and the PredictAD software tool designed for supporting clinical diagnostics. The data used were 1) clinical criteria for episodic memory loss of the hippocampal type, 2) visual MTA, 3) positive CSF markers, 4) their combinations, and 5) when the PredictAD tool was applied, automatically computed MRI measures were used instead of the visual MTA results. The accuracies of diagnosis were evaluated with the diagnosis made 3 years later.

Results

The PredictAD tool achieved the overall accuracy of 72% (sensitivity 73%, specificity 71%) in predicting the AD diagnosis. The corresponding number for a clinician’s prediction with the assistance of the PredictAD tool was 71% (sensitivity 75%, specificity 68%). Diagnosis with the PredictAD tool was significantly better than diagnosis by biomarkers alone or the combinations of clinical diagnosis of hippocampal pattern for the memory loss and biomarkers (p≤0.037).

Conclusion

With the assistance of PredictAD tool, the clinician can predict AD conversion more accurately than the current diagnostic criteria.