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Pathology of infectious diseases: what does the future hold?

Fri, 09/15/2017 - 14:18
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Pathology of infectious diseases: what does the future hold?

Virchows Arch. 2017 May;470(5):483-492

Authors: Hofman P, Lucas S, Jouvion G, Tauziède-Espariat A, Chrétien F, Cathomas G

Abstract
The demand for expertise in pathology for the diagnosis of infectious diseases (ID) is continually growing, due to an increase in ID in immunocompromised patients and in the (re)-emergence of common and uncommon diseases, including tropical infections and infections with newly identified microbes. The microbiology laboratory plays a crucial role in diagnosing infections, identifying the responsible infectious agents and establishing sensitivity of pathogens to drug therapy. Pathology, however, is the only way to correlate the presence of an infectious agent with the reaction it evokes at cell and tissue level. For pathologists working in the field of ID pathology, it is essential to dispose of competence in cell and tissue pathology as well as in microbiology. Expertise in ID includes understanding of taxonomy and classification of pathogens as well as morphological criteria supporting their identification. Moreover, ID pathologists must master the methods used to detect pathogens in fixed cell and tissue samples, notably immunohistochemistry, in situ hybridization and the polymerase chain reaction. Paradoxically, the increasing frequency of lesions caused by pathogens and diagnosed in a pathology laboratory appears to be paralleled by a gradual loss of expertise of pathologists in the field of infectious and tropical diseases. We contend that this may be due at least in part to the continuously increasing number of samples of tumor tissue pathologists deal with and the rapidly expanding number of tissue based biomarkers with predictive value for new anti-cancer therapies. In this review, we highlight current and future issues pertaining to ID pathology, in order to increase awareness of its importance for surgical and molecular pathology. The intention is to contribute to the development of best practice in ID pathology.

PMID: 28188440 [PubMed - indexed for MEDLINE]

Selected gene polymorphisms effect on skin and hair pigmentation in Polish children at the prepubertal age.

Fri, 09/15/2017 - 14:18
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Selected gene polymorphisms effect on skin and hair pigmentation in Polish children at the prepubertal age.

Anthropol Anz. 2016 Nov 01;73(4):283-293

Authors: Sitek A, Rosset I, Żądzińska E, Siewierska-Górska A, Pietrowska E, Strapagiel D

Abstract
SUMMARY: Background: Human pigmentation, similarly as many other biological features, changes in the course of post-natal ontogenesis, while in case of hair, pigmentation changes are more distinctive than in the skin or the iris. It is therefore extremely important to identify the genes, involved in the constitution of human pigmentation features at various stages of ontogenesis. Results of this type of analyses are of high practical significance in forensic study because they enable to create mathematical tools, allowing for prediction of the pigmentation phenotype, based on DNA studies. Aim: The objective of the investigation was finding out whether the genes, associated with pigmentation of adult subjects, differentiated in any way the newly forming pigmentation phenotype in Polish prepubertal children. Material and methods: The study encompassed Polish children, aged 7 to 10 years, without any abnormalities in skin or hair pigmentation. A total of 245 children were examined. Constitutive skin pigmentation according to skin melanin index (SMI) was evaluated, using a dermaspectrometer, and classified into three groups based on the reference values of 25 and 75 percentile for Polish children. Hair colors were evaluated by means of the descriptive Fischer-Saller scale and classified by a division of color variants (as accepted in that scale) (light blonde, blonde, dark blonde, brown and dark brown). In saliva samples, collected from the children, five (5) single nucleotide polymorphisms were identified: SNPs: rs1800401 (OCA2-15q11.2-q12), rs35264875 (TPCN2-11q13.3), rs16891982 (SLC45A2-5p13.2), rs12913832 (HERC2-15q13) and rs1805007 (MC1R-16q24.3). An association between each allele of verified genotype and skin and hair color phenotypes was assessed, using the z-statistic and associated p-value. The quality of classifiers was evaluated by 10-fold stratified cross-validation and was characterized by the area under the receiver operating characteristic curve (AUC). Results: Light skin pigmentation phenotype (SMI<25 percentile) was associated with rs1805007 (MC1R) (allelic OR=3.95; 95% Cl:1.20-12.99; p=0.0235), while the dark shade of the skin (SMI>75 percentile) with rs16891982 (SLC45A2) (allelic OR =14.37; 95% Cl: 1.78-115.88; p=0.0123). The probability of dark hair (brown and dark brown) in childhood was increased by T rs12913832 allele (HERC2) (OR=3.63); 95% Cl: 2.25-5.85; p < 0.0001) and dependent on it - rs1800401 (OCA2) (OR=6.31; 95% Cl: 1.74-22.91; p=0.0051). Other SNPs were not significantly associated with skin and hair color but improved prediction of these features. Conclusions: From the five gene polymorphisms analysed in Polish children the strongest correlation with hair color has the rs12913832 (HERC2) and with skin color - rs16891982 (SLC45A2). Therefore, the above-mentioned polymorphisms may be used as components of potential models, used to predict pigmentation features in European origin children in prepubertal age. To improve predictive value of the potential scoring model for hair color, the following should be additionally included: rs1800401 (OCA2), rs35264875 (TPCN2) and rs1805007 (MC1R), while for skin color: rs12913832 (HERC2) and rs1805007 (MC1R).

PMID: 27534414 [PubMed - indexed for MEDLINE]

The social dimension of biobanking: objectives and challenges.

Thu, 09/14/2017 - 15:50
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The social dimension of biobanking: objectives and challenges.

Life Sci Soc Policy. 2017 Sep 13;13(1):15

Authors: Bryzgalina EV, Alasania KY, Varkhotov TA, Gavrilenko SM, Shkomova EM

Abstract
The present article allows to explore, analyze and reflect on the consequences and problems posed by biobanks and attempts to prove the need of social and humanitarian support in establishing and functioning of biobanks as a new type of scientific institutions. The basis of the article is the latest publications devoted to social and humanitarian aspects of biobanking and Russian experience of the initial formation of this subject domain (before the first professional biobanks were established in Russia in the 2010-s, the only highly specialized collections of bio-samples had been registered). The article marks and classifies different aspects of biobanking that objectively demands the participation of specialists in ethics and social sciences. The cases of biobanking development and risks are estimated; the objective need of applied ethics and social sciences specialists' participation in biobanking is proved.

PMID: 28900884 [PubMed - in process]

Young adulthood and adulthood adiposity in relation to incidence of pancreatic cancer: a prospective study of 0.5 million Chinese adults and a meta-analysis.

Thu, 09/14/2017 - 15:50
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Young adulthood and adulthood adiposity in relation to incidence of pancreatic cancer: a prospective study of 0.5 million Chinese adults and a meta-analysis.

J Epidemiol Community Health. 2017 Sep 12;:

Authors: Pang Y, Holmes MV, Kartsonaki C, Guo Y, Yang L, Bian Z, Chen Y, Bragg F, Iona A, Millwood IY, Chen J, Li L, Chen Z

Abstract
BACKGROUND: Adult adiposity is positively associated with pancreatic cancer in Western populations. Little is known, however, about the association in China where many have lower body mass index (BMI) or about the relevance of young adulthood adiposity for pancreatic cancer in both Western and East Asian populations.
METHODS: The China Kadoorie Biobank (CKB) recruited 512 891 adults aged 30-79 years during 2004-2008, recording 595 incident cases of pancreatic cancer during 8-year follow-up. Cox regression yielded adjusted HRs for pancreatic cancer associated with self-reported young adulthood (mean ~25 years) BMI and with measured adulthood (mean ~52 years) BMI and other adiposity measures (eg, waist circumference (WC)). These were further meta-analysed with published prospective studies.
RESULTS: Overall, the mean BMI (SD) was 21.9 (2.6) at age 25 years and 23.7 (3.3) kg/m(2) at age 52 years. Young adulthood BMI was strongly positively associated with pancreatic cancer in CKB (adjusted HR=1.36, 95% CI 1.16 to 1.61, per 5 kg/m(2) higher BMI) and in meta-analysis of CKB and four other studies (1.18, 1.12 to 1.24). In CKB, there was also a positive association of pancreatic cancer with adulthood BMI (1.11, 0.97 to 1.27, per 5 kg/m(2)), similar in magnitude to that in meta-analyses of East Asian studies using measured BMI (n=2; 1.08, 0.99 to 1.19) and of Western studies (n=25; 1.10, 1.06 to 1.12). Likewise, meta-analysis of four studies, including CKB, showed a positive association of adulthood WC with pancreatic cancer (1.10, 1.06 to 1.14, per 10 cm).
CONCLUSIONS: In both East Asian and Western populations, adiposity was positively associated with risk of pancreatic cancer, with a somewhat stronger association for young than late-life adiposity.

PMID: 28900029 [PubMed - as supplied by publisher]

Amyloid-independent atrophy patterns predict time to progression to dementia in mild cognitive impairment.

Thu, 09/14/2017 - 15:50
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Amyloid-independent atrophy patterns predict time to progression to dementia in mild cognitive impairment.

Alzheimers Res Ther. 2017 Sep 12;9(1):73

Authors: Ten Kate M, Barkhof F, Visser PJ, Teunissen CE, Scheltens P, van der Flier WM, Tijms BM

Abstract
BACKGROUND: Amyloid pathology in subjects with mild cognitive impairment (MCI) is an important risk factor for progression to dementia due to Alzheimer's disease. Predicting the onset of dementia is challenging even in the presence of amyloid, as time to progression varies considerably among patients and depends on the onset of neurodegeneration. Survival analysis can account for variability in time to event, but has not often been applied to MRI measurements beyond singular predefined brain regions such as the hippocampus. Here we used a voxel-wise survival analysis to identify in an unbiased fashion brain regions where decreased gray matter volume is associated with time to dementia, and assessed the effects of amyloid on these associations.
METHODS: We included 276 subjects with MCI (mean age 67 ± 8, 41% female, mean Mini-Mental State Examination 26.6 ± 2.4), baseline 3D T1-weighted structural MRI, baseline cerebrospinal fluid (CSF) biomarkers, and prospective clinical follow-up. We fitted for each voxel a proportional Cox hazards regression model to study whether decreased gray matter volume predicted progression to dementia in the total sample, and stratified for baseline amyloid status.
RESULTS: Dementia at follow-up occurred in 122 (44%) subjects over an average follow-up period of 2.5 ± 1.5 years. Baseline amyloid positivity was associated with progression to dementia (hazard ratio 2.4, p < 0.001). Within amyloid-positive subjects, decreased gray matter volume in the hippocampal, temporal, parietal, and frontal regions was associated with more rapid progression to dementia (median (interquartile range) hazard ratio across significant voxels 1.35 (1.32-1.40)). Repeating the analysis in amyloid-negative subjects revealed similar patterns (median (interquartile range) hazard ratio 1.76 (1.66-1.91)).
CONCLUSIONS: In subjects with MCI, both abnormal amyloid CSF and decreased gray matter volume were associated with future progression to dementia. The spatial pattern of decreased gray matter volume associated with progression to dementia was consistent for amyloid-positive and amyloid-negative subjects.

PMID: 28899429 [PubMed - in process]

Caspase-cleaved keratin-18 fragments increase during alcohol withdrawal and predict liver-related death in patients with alcoholic liver disease.

Thu, 09/14/2017 - 15:50
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Caspase-cleaved keratin-18 fragments increase during alcohol withdrawal and predict liver-related death in patients with alcoholic liver disease.

Hepatology. 2017 Jul;66(1):96-107

Authors: Mueller S, Nahon P, Rausch V, Peccerella T, Silva I, Yagmur E, Straub BK, Lackner C, Seitz HK, Rufat P, Sutton A, Bantel H, Longerich T

Abstract
Noninvasive assessment of disease activity in patients with nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) is still unsettled, but essential for the evaluation of disease progression. We here studied the association of total (M65) and caspase-cleaved (M30) serum keratin-18 fragments (n = 204) with histological parameters (n = 106) in heavy drinkers primarily admitted for alcohol withdrawal before and after alcohol detoxification. An age-, sex-, and fibrosis-stage matched NAFLD cohort (n = 30) was used for comparison. The prognostic value of M30 and M65 levels were assessed in an additional prospectively followed-up cohort of 230 patients with alcoholic cirrhosis (AC) using competing risk analyses. Among the histological parameters, both M30/65 correlated significantly and better than any other serum marker with apoptosis and liver damage, such as ballooning (r = 0.65; P < 0.001), followed by lobular inflammation (0.48; P < 0.001), steatosis (0.46; P < 0.001), but less with fibrosis (0.24; P < 0.001). Area under the receiver operating characteristics curves to detect ballooning, steatosis, or steatohepatitis (SH) were slightly better for M30 (P < 0.005). Optimal M30 cut-off values for mild and severe ballooning were 330 and 420 U/L, and 290 and 330 U/L for SH grades 1 and 2. No significant differences of M30/65 were found between the matched NAFLD and ALD cohort. In contrast to aspartate-amino-transferase and M65, M30 levels increased significantly from 391 to 518 U/L during alcohol detoxification. Moreover, levels of M30 and M65 predicted non-hepatocellular carcinoma liver-related mortality in patients with AC during a mean observation interval of 67.2 months.
CONCLUSION: Our data suggest M30 as highly specific marker of liver apoptosis both in ALD and NAFLD. In addition, hepatocellular apoptosis, as determined by M30 levels, occurs during alcohol withdrawal, and survival data point toward a novel underestimated role of apoptosis in patients with ALD. (Hepatology 2017;66:96-107).

PMID: 28170108 [PubMed - indexed for MEDLINE]

Genetic identification of a common collagen disease in puerto ricans via identity-by-descent mapping in a health system.

Wed, 09/13/2017 - 13:55
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Genetic identification of a common collagen disease in puerto ricans via identity-by-descent mapping in a health system.

Elife. 2017 Sep 12;6:

Authors: Belbin GM, Odgis J, Sorokin EP, Yee MC, Kohli S, Glicksberg BS, Gignoux CR, Wojcik GL, Van Vleck T, Jeff JM, Linderman M, Schurmann C, Ruderfer D, Cai X, Merkelson A, Justice AE, Young KL, Graff M, North KE, Peters U, James R, Hindorff L, Kornreich R, Edelmann L, Gottesman O, Stahl EE, Cho JH, Loos RJ, Bottinger EP, Nadkarni GN, Abul-Husn NS, Kenny EE

Abstract
Achieving confidence in the causality of a disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with both elevated genetic relatedness and extreme short stature. We link the gene, COL27A1, with a little-known genetic disease, previously thought to be rare and recessive. We demonstrate that disease manifests in both heterozygotes and homozygotes, indicating a common collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian disease.

PMID: 28895531 [PubMed - in process]

Will Big Data Close the Missing Heritability Gap?

Wed, 09/13/2017 - 13:55
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Will Big Data Close the Missing Heritability Gap?

Genetics. 2017 Sep 11;:

Authors: Kim H, Grueneberg A, Vazquez AI, Hsu S, de Los Campos G

Abstract
Despite the important discoveries reported by Genome-Wide Association studies, for most traits and diseases the prediction R-squared (R-sq.) achieved with genetic scores remains considerably lower than the trait heritability. Modern biobanks will soon deliver unprecedentedly large biomedical data sets: Will the advent of Big Data close the gap between the trait heritability and the proportion of variance that can be explained by a genomic predictor? We addressed this question using Bayesian methods and a data analysis approach that produces a surface response relating prediction R-sq. with sample size and model complexity (e.g., number of SNPs). We applied the methodology to data from the interim release of the UK Biobank. Focusing on human height as a model trait and using 80,000 records for model training, we achieved a prediction R-sq. in testing (n=22,221) of 0.24 (95% CI: 0.23-0.25). Our estimates show that prediction R-sq. increases with sample size reaching an estimated plateau at values that ranged from 0.1 to 0.37 for models using 500 and 50,000 (GWA-selected) SNPs, respectively. Soon much larger data sets will become available. Using the estimated surface response, we forecast that larger sample sizes will lead to further improvements in prediction R-sq. We conclude that Big Data will lead to a substantial reduction of the gap between trait heritability and the proportion of inter-individual differences that can be explained with a genomic predictor. However, even with the power of Big Data, for complex traits, we anticipate that the gap between prediction R-sq. and trait heritability will not be fully closed.

PMID: 28893854 [PubMed - as supplied by publisher]

The Canadian HIV and aging cohort study - determinants of increased risk of cardio-vascular diseases in HIV-infected individuals: rationale and study protocol.

Wed, 09/13/2017 - 13:55
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The Canadian HIV and aging cohort study - determinants of increased risk of cardio-vascular diseases in HIV-infected individuals: rationale and study protocol.

BMC Infect Dis. 2017 Sep 11;17(1):611

Authors: Durand M, Chartrand-Lefebvre C, Baril JG, Trottier S, Trottier B, Harris M, Walmsley S, Conway B, Wong A, Routy JP, Kovacs C, MacPherson PA, Monteith KM, Mansour S, Thanassoulis G, Abrahamowicz M, Zhu Z, Tsoukas C, Ancuta P, Bernard N, Tremblay CL, investigators of the Canadian HIV and Aging Cohort Study

Abstract
BACKGROUND: With potent antiretroviral drugs, HIV infection is becoming a chronic disease. Emergence of comorbidities, particularly cardiovascular disease (CVD) has become a leading concern for patients living with the infection. We hypothesized that the chronic and persistent inflammation and immune activation associated with HIV disease leads to accelerated aging, characterized by CVD. This will translate into higher incidence rates of CVD in HIV infected participants, when compared to HIV negative participants, after adjustment for traditional CVD risk factors. When characterized further using cardiovascular imaging, biomarkers, immunological and genetic profiles, CVD associated with HIV will show different characteristics compared to CVD in HIV-negative individuals.
METHODS/DESIGN: The Canadian HIV and Aging cohort is a prospective, controlled cohort study funded by the Canadian Institutes of Health Research. It will recruit patients living with HIV who are aged 40 years or older or have lived with HIV for 15 years or more. A control population, frequency matched for age, sex, and smoking status, will be recruited from the general population. Patients will attend study visits at baseline, year 1, 2, 5 and 8. At each study visit, data on complete medical and pharmaceutical history will be captured, along with anthropometric measures, a complete physical examination, routine blood tests and electrocardiogram. Consenting participants will also contribute blood samples to a research biobank. The primary outcome is incidence of a composite of: myocardial infarction, coronary revascularization, stroke, hospitalization for angina or congestive heart failure, revascularization or amputation for peripheral artery disease, or cardiovascular death. Preplanned secondary outcomes are all-cause mortality, incidence of the metabolic syndrome, incidence of type 2 diabetes, incidence of renal failure, incidence of abnormal bone mineral density and body fat distribution. Patients participating to the cohort will be eligible to be enrolled in four pre-planned sub-studies of cardiovascular imaging, glucose metabolism, immunological and genetic risk profile.
DISCUSSION: The Canadian HIV and Aging Cohort will provide insights on pathophysiological pathways leading to premature CVD for patients living with HIV.

PMID: 28893184 [PubMed - in process]

Adapted Morris Water Maze protocol to prevent interference from confounding motor deficits on cognitive functioning.

Tue, 09/12/2017 - 12:34

Adapted Morris Water Maze protocol to prevent interference from confounding motor deficits on cognitive functioning.

Somatosens Mot Res. 2017 Sep 10;:1-7

Authors: De Coninck M, Van Dam D, Van Ginneken C, De Deyn PP

Abstract
Purpose/aim of the study: Cognitive functioning in the Morris Water Maze (MWM) is assumed to be reflected by path length. In this study, the interference of motor deficits, as a confounding factor on cognitive functioning, was assessed by means of a lateralization study with hemicerebellectomized (HCX) mice. This model is characterized by motor deficits restricted to the lesion side, allowing comparison within the model itself (left vs. right), rather than the effect of the manipulation on this measure (experimental vs. control).
MATERIALS AND METHODS: Spatial learning was assessed after left or right hemicerebellectomy in adult mice by means of two MWM designs in which the location of the starting positions was altered for one condition in the adapted (Adap) MWM experiment, hypothesizing that motor impairments ipsilateral to the lesion side result in a difference in path length.
RESULTS: When the starting positions were equal for both conditions in the traditional (Trad) MWM experiment, path length during the acquisition phase and spatial memory were more affected for the left HCX, while these effects disappeared after mirroring the starting positions in the Adap MWM, implying that motor phenotype and corresponding increase in task difficulty are responsible for the contradictory results in the Trad MWM experiment.
CONCLUSION: The differences found in the latter experiment were circumvented in the adapted MWM protocol, and therefore, excluding the motor deficit as a confounding factor on cognitive MWM parameters.

PMID: 28891404 [PubMed - as supplied by publisher]

The association between scabies and myasthenia gravis: A nationwide population-based cohort study.

Tue, 09/12/2017 - 12:34
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The association between scabies and myasthenia gravis: A nationwide population-based cohort study.

J Clin Neurosci. 2017 Sep 07;:

Authors: Hsu RJ, Lin CY, Chang FW, Huang CF, Chuang HC, Liu JM

Abstract
Scabies is an infectious inflammatory pruritic skin disease. Cytokine-mediated inflammatory processes contribute to the pathologic mechanism in scabies. Myasthenia gravis (MG) is also an autoimmune disease that is mediated by cytokines. The study aimed to investigate the association between scabies and myasthenia gravis. We conducted a nationwide population-based cohort study utilized data from the National Health Insurance Research Database (NHIRD) of Taiwan. Patients with scabies (n=5429) and control subjects without scabies (n=20,176) were enrolled. We tracked the subjects in both groups for a 7-year period to identify new onset MG. Cox regression analysis was performed to calculate the hazard ratio (HR) for MG. A total of 25,605 patients were enrolled in the study, including 5429 patients in the scabies group and 20,176 in the control group. There were 40 (0.7%) patients from the scabies group and 84 (0.4%) subjects from the control group who were newly diagnosed with MG during the 7-year follow-up period. The scabies patients had a significantly increased risk of MG, with an adjusted HR of 1.27 (95% confidence interval [CI] 1.01-1.89). As such, prompt diagnosis and treatment of scabies may decrease the risk of subsequent MG.

PMID: 28890037 [PubMed - as supplied by publisher]

Exploring the nature of prediagnostic blood transcriptome markers of chronic lymphocytic leukemia by assessing their overlap with the transcriptome at the clinical stage.

Tue, 09/12/2017 - 12:34
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Exploring the nature of prediagnostic blood transcriptome markers of chronic lymphocytic leukemia by assessing their overlap with the transcriptome at the clinical stage.

BMC Genomics. 2017 Mar 20;18(1):239

Authors: Vlaanderen J, Leenders M, Chadeau-Hyam M, Portengen L, Kyrtopoulos SA, Bergdahl IA, Johansson AS, Hebels DD, de Kok TM, Vineis P, Vermeulen RC

Abstract
BACKGROUND: We recently identified 700 genes whose expression levels were predictive of chronic lymphocytic leukemia (CLL) in a genome-wide gene expression analysis of prediagnostic blood from future cases and matched controls. We hypothesized that a large fraction of these markers were likely related to early disease manifestations. Here we aim to gain a better understanding of the natural history of the identified markers by comparing results from our prediagnostic analysis, the only prediagnostic analysis to date, to results obtained from a meta-analysis of a series of publically available transcriptomics profiles obtained in incident CLL cases and controls.
RESULTS: We observed considerable overlap between the results from our prediagnostic study and the clinical CLL signals (p-value for overlap Bonferroni significant markers 0.01; p-value for overlap nominal significant markers < 2.20e-16). We observed similar patterns with time to diagnosis and similar functional annotations for the markers that were identified in both settings compared to the markers that were only identified in the prediagnostic study. These results suggest that both gene sets operate in similar pathways.
CONCLUSION: An overlap exists between expression levels of genes predictive of CLL identified in prediagnostic blood and expression levels of genes associated to CLL at the clinical stage. Our analysis provides insight in a set of genes for which expression levels can be used to follow the time-course of the disease; providing an opportunity to study CLL progression in more detail in future studies.

PMID: 28320322 [PubMed - indexed for MEDLINE]

Detection of human antibodies binding with smooth and rough LPSs from Proteus mirabilis O3 strains S1959, R110, R45.

Mon, 09/11/2017 - 13:39

Detection of human antibodies binding with smooth and rough LPSs from Proteus mirabilis O3 strains S1959, R110, R45.

Antonie Van Leeuwenhoek. 2017 Sep 09;:

Authors: Gleńska-Olender J, Durlik K, Konieczna I, Kowalska P, Gawęda J, Kaca W

Abstract
Bacteria of the genus Proteus of the family Enterobacteriaceae are facultative human pathogens responsible mainly for urinary tract and wound infections, bacteremia and the development of rheumatoid arthritis (RA). We have analyzed and compared by ELISA the titer of antibodies in plasmas of healthy individuals and in sera of rheumatoid arthritis patients recognizing a potential host cross-reactive epitope (lysine-galacturonic acid epitopes) present in Proteus lipopolysaccharide (LPS). In our experiments LPSs isolated from two mutants of smooth Proteus mirabilis 1959 (O3), i.e. strains R110 and R45, were used. R110 (Ra type mutant) is lacking the O-specific polysaccharide, but possesses a complete core oligosaccharide, while R45 (Re type) has a reduced core oligosaccharide and contains two 3-deoxy-D-manno-oct-2-ulosonic acid residues and one of 4-amino-4-deoxy-L-arabinopyranose residues. Titer of P. mirabilis S1959 LPS-specific-antibodies increased with the age of blood donors. RA and blood donors' sera contained antibodies against S and Ra and Re type of P. mirabilis O3 LPSs. Antibodies recognizing lysine-galacturonic acid epitopes of O3 LPS were detected by ELISA in some plasmas of healthy individuals and sera of rheumatoid arthritis patients. RA patients antibodies reacting with P. mirabilis S1959 S and R LPSs may indicate a potential role of anti-LPS antibodies in molecular mimicry in RA diseases.

PMID: 28889208 [PubMed - as supplied by publisher]

Tissue alkalosis in cold-ischemia time.

Sat, 09/09/2017 - 13:09

Tissue alkalosis in cold-ischemia time.

Sci Rep. 2017 Sep 07;7(1):10867

Authors: Denninghoff V, Olivieri EHR, Fresno C, Uceda A, Mota L, Suenaga AP, Carraro DM, Martins VR, Avagnina A, Soares FA, Campos AHJFM

Abstract
The control of pre-analytical-factors in human biospecimens collected for health research is currently required. Only two previous reports using post-mortem brain samples have tried to address the impact of cold-ischemia on tissue pH. Here we report pH variations according to time (third-order polynomial model) in mice for liver, kidney and lung samples. Tissue alkalosis in cold-ischemia time may be an underlying mechanism of gene expression changes. Therefore, tissue-pH regulation after organ removal may minimize biological stress in human tissue samples.

PMID: 28883635 [PubMed - in process]

Proof-of-Concept Integration of Heterogeneous Biobank IT Infrastructures into a Hybrid Biobanking Network.

Sat, 09/09/2017 - 13:09

Proof-of-Concept Integration of Heterogeneous Biobank IT Infrastructures into a Hybrid Biobanking Network.

Stud Health Technol Inform. 2017;243:100-104

Authors: Mate S, Kadioglu D, Majeed RW, Stöhr MR, Folz M, Vormstein P, Storf H, Brucker DP, Keune D, Zerbe N, Hummel M, Senghas K, Prokosch HU, Lablans M

Abstract
Cross-institutional biobank networks hold the promise of supporting medicine by enabling the exchange of associated samples for research purposes. Various initiatives, such as BBMRI-ERIC and German Biobank Node (GBN), aim to interconnect biobanks for enabling the compilation of joint biomaterial collections. However, building software platforms to facilitate such collaboration is challenging due to the heterogeneity of existing biobank IT infrastructures and the necessary efforts for installing and maintaining additional software components. As a remedy, this paper presents the concept of a hybrid network for interconnecting already existing software components commonly found in biobanks and a proof-of-concept implementation of two prototypes involving four biobanks of the German Biobank Node. Here we demonstrate the successful bridging of two IT systems found in many German biobanks - Samply and i2b2.

PMID: 28883179 [PubMed - in process]

A Decentralized IT Architecture for Locating and Negotiating Access to Biobank Samples.

Sat, 09/09/2017 - 13:09

A Decentralized IT Architecture for Locating and Negotiating Access to Biobank Samples.

Stud Health Technol Inform. 2017;243:75-79

Authors: Proynova R, Alexandre D, Lablans M, Van Enckevort D, Mate S, Eklund N, Silander K, Hummel M, Holub P, Ückert F

Abstract
There is a need among researchers for the easy discoverability of biobank samples. Currently, there is no uniform way for finding samples and negotiate access. Instead, researchers have to communicate with each biobank separately. We present the architecture for the BBMRI-CS IT platform, whose goal is to facilitate sample location and access. We chose a decentral approach, which allows for strong data protection and provides the high flexibility needed in the highly heterogeneous landscape of European biobanks. This is the first implementation of a decentral search in the biobank field. With the addition of a Negotiator component, it also allows for easy communication and a follow-through of the lengthy approval process for accessing samples.

PMID: 28883174 [PubMed - in process]

On-The-Fly Query Translation Between i2b2 and Samply in the German Biobank Node (GBN) Prototypes.

Sat, 09/09/2017 - 13:09

On-The-Fly Query Translation Between i2b2 and Samply in the German Biobank Node (GBN) Prototypes.

Stud Health Technol Inform. 2017;243:42-46

Authors: Mate S, Vormstein P, Kadioglu D, Majeed RW, Lablans M, Prokosch HU, Storf H

Abstract
Information retrieval is a major challenge in medical informatics. Various research projects have worked on this task in recent years on an institutional level by developing tools to integrate and retrieve information. However, when it comes down to querying such data across institutions, the challenge persists due to the high heterogeneity of data and differences in software systems. The German Biobank Node (GBN) project faced this challenge when trying to interconnect four biobanks to enable distributed queries for biospecimens. All biobanks had already established integrated data repositories, and some of them were already part of research networks. Instead of developing another software platform, GBN decided to form a bridge between these. This paper describes and discusses a core component from the GBN project, the OmniQuery library, which was implemented to enable on-the-fly query translation between heterogeneous research infrastructures.

PMID: 28883167 [PubMed - in process]

High Levels of (Un)Switched Memory B Cells Are Associated With Better Outcome in Patients With Advanced Atherosclerotic Disease.

Sat, 09/09/2017 - 13:09

High Levels of (Un)Switched Memory B Cells Are Associated With Better Outcome in Patients With Advanced Atherosclerotic Disease.

J Am Heart Assoc. 2017 Sep 07;6(9):

Authors: Meeuwsen JAL, van Duijvenvoorde A, Gohar A, Kozma MO, van de Weg SM, Gijsberts CM, Haitjema S, Björkbacka H, Fredrikson GN, de Borst GJ, den Ruijter HM, Pasterkamp G, Binder CJ, Hoefer IE, de Jager SCA

Abstract
BACKGROUND: Atherosclerosis is an inflammatory lipid disorder and the main underlying pathology of acute ischemic events. Despite a vast amount of data from murine atherosclerosis models, evidence of B-cell involvement in human atherosclerotic disease is limited. We therefore investigated the association of circulating B-cell subtypes with the occurrence of secondary cardiovascular events in advanced atherosclerotic disease.
METHODS AND RESULTS: This cohort study consists of 168 patients who were included in the Athero-Express biobank between 2009 and 2011. Before surgery, peripheral blood mononuclear cells were isolated and stored in liquid nitrogen. After gentle thawing of the peripheral blood mononuclear cells, different B-cell subtypes including naïve, (un)switched memory, and CD27(+)CD43(+) B1-like B cells, were analyzed by flow cytometry. Univariable and multivariable Cox proportional hazard models were used to analyze associations between B-cell subtypes, circulating antibodies and secondary cardiovascular manifestations during the 3-year follow-up period. Mean age was 70.1±9.6 years, males represented 62.8% of the population, and 54 patients had secondary manifestations during follow-up. High numbers of unswitched memory cells were protective against secondary outcome (hazard ratio, 0.30 [95% CI, 0.13-0.69]; P<0.01). Similar results were obtained for the switched memory cells that also showed to be protective against secondary outcome (hazard ratio, 0.33 [95% CI, 0.14-0.77]; P=0.01).
CONCLUSIONS: A high number of (un)switched memory B cells is associated with better outcome following carotid artery endarterectomy. These findings suggest a potential role for B-cell subsets in prediction and prevention of secondary cardiovascular events in patients with atherosclerosis.

PMID: 28882820 [PubMed - in process]

New variants near RHOJ and C2, HLA-DRA region and susceptibility to endometriosis in the Polish population-The genome-wide association study.

Fri, 09/08/2017 - 12:19

New variants near RHOJ and C2, HLA-DRA region and susceptibility to endometriosis in the Polish population-The genome-wide association study.

Eur J Obstet Gynecol Reprod Biol. 2017 Sep 01;217:106-112

Authors: Sobalska-Kwapis M, Smolarz B, Słomka M, Szaflik T, Kępka E, Kulig B, Siewierska-Górska A, Polak G, Romanowicz H, Strapagiel D, Szyłło K

Abstract
OBJECTIVE: Endometriosis is a common gynaecological disease, associated with severe pelvic pain and reduced fertility; however, molecular mechanisms remain largely unknown. Genome-wide association studies (GWAS) are able to identify genetic loci, which can play significant role during endometriosis development.
AIM: The study aimed at localisation of new genes and chromosomal loci, the nucleotide variants of which determine the level of susceptibility to endometriosis.
STUDY DESIGN: Blood samples from 171 patients with endometriosis were used as material for studies. The patients were recruited to the study at the Department of Operative Gynaecology of the Institute of the Polish Mother's Memorial Hospital in Lodz. A control group (n=2934) came from the POPULOUS collection registered at Biobank Lab, Department of Molecular Biophysics, University of Lodz. DNA of the patients with endometriosis was compared with DNA of women free from that disease, the comparison being supported by GWAS.
RESULTS: Genome-wide significant correlation was identified between one new, not previously described, single nucleotide polymorphism (SNP), rs10129516, localised on chromosome 14 in intergenic region between PARP1P2 and RHOJ genes (p=1.44×10(-10), OR=3.104, 95% CI=2.329-4.136) and endometriosis. We have also identified significant association with endometriosis of 18 SNPs localised on chromosome 6 in position range 31883957 - 32681631 (C2 and HLA-DRA genes region) with the lowest observed p value for rs644045 in C2 gene (p=2.04×10(-8), OR=1.955, 95% CI=1.541-2.480).
CONCLUSION: Reported GWAS identified the novel loci associated with endometriosis in Polish women, not previously reported. The most interesting observation shown in our study are regions associated with susceptibility to endometriosis of loci located near C2, HLA-DRA and RHOJ genes.
RESULTS: of that study did not correspond to previously published data about polymorphism in that regions and further evaluations are necessary in groups with higher numbers of patients to explain whether the above-mentioned genetic variant may be the risk factor for pathogenesis of endometriosis.

PMID: 28881265 [PubMed - as supplied by publisher]

How Sensitive Is Genetic Data?

Fri, 09/08/2017 - 12:19

How Sensitive Is Genetic Data?

Biopreserv Biobank. 2017 Sep 07;:

Authors: Sariyar M, Suhr S, Schlünder I

Abstract
The rising demand to use genetic data for research goes hand in hand with an increased awareness of privacy issues related to its use. Using human genetic data in a legally compliant way requires an examination of the legal basis as well as an assessment of potential disclosure risks. Focusing on the relevant legal framework in the European Union, we discuss open questions and uncertainties around the handling of genetic data in research, which can result in the introduction of unnecessary hurdles for data sharing. First, we discuss defining features and relative disclosure risks of some DNA-related biomarkers, distinguishing between the risk for disclosure of (1) the identity of an individual, (2) information about an individual's health and behavior, including previously unknown phenotypes, and (3) information about an individual's blood relatives. Second, we discuss the European legal framework applicable to the use of DNA-related biomarkers in research, the implications of including both inherited and acquired traits in the legal definition, as well as the issue of "genetic exceptionalism"-the notion that genetic information has inherent characteristics that require different considerations than other health and medical information. Finally, by mapping the legal to specific technical definitions, we draw some initial conclusions concerning how sensitive different types of "genetic data" may actually be. We argue that whole genome sequences may justifiably be considered "exceptional" and require special protection, whereas other genetic data that do not fulfill the same criteria should be treated in a similar manner to other clinical data. This kind of differentiation should be reflected by the law and/or other governance frameworks as well as agreed Codes of Conduct when using the term "genetic data."

PMID: 28880588 [PubMed - as supplied by publisher]