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2.
Int J Legal Med ; 137(3): 863-873, 2023 May.
Article in English | MEDLINE | ID: mdl-36781444

ABSTRACT

As part of a third-party funded project, expert opinions according to the Istanbul Protocol (IP) standards were compiled in Germany on a larger scale for the first time. The assessment process was initiated for 130 project participants. Statistical analysis on numerous variables was performed to test the impact of the expert opinions, foremost of the forensic medical expert opinions, on the individuals' asylum proceedings. The variables were drawn from forensic medical expert opinions and reports of findings, questionnaires for the study participants' counsellors in the project and a query on the asylum status of the study participants. Regression analysis and bivariate analysis on two dependent variables-subjective impact on the asylum procedure from the counsellors' point of view and objective change in the asylum status-were performed to test for an influence on asylum procedures. No statistically significant results were obtained for the objective change of the study participants' asylum status. For the subjective dependent variable, a positive prediction was possible when simultaneously controlling for the independent variables introduction of a forensic medical expert opinion and highest IP grade; a negative prediction was possible when simultaneously controlling for the independent variables introduction of a forensic medical expert opinion and use of IP grading. Apart from the statistical analysis, a positive effect of the assessment on the psychosocial well-being of the study participants could be demonstrated. The results differed from other European studies which demonstrated a correlation between the objective outcome of an asylum procedure (asylum status) and, for example, specific types of violence or the number of documented injuries. Differences also occurred in the use of the plausibility grades proposed by the IP, which questions their use in cases in which the reported torture happened a relevant time ago. Therefore, compiling individually worded evaluations instead of using the IP grading system-if possible, by an experienced forensic physician-is recommended in this scenario. Still, the assessment of alleged torture experiences should follow the IP guidelines, since psychological assessments are of especially high importance in cases with healed physical injuries and since the results also demonstrated a positive effect on the psychosocial well-being of the study participants.


Subject(s)
Refugees , Torture , Humans , Expert Testimony , Forensic Medicine , Germany
3.
J Dairy Sci ; 105(6): 5206-5220, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35450715

ABSTRACT

As part of the From'MIR project, traits related to the composition and cheese-making properties (CMP) of milk were predicted from 6.6 million mid-infrared spectra taken from 410,622 Montbéliarde cows (19,862 with genotypes). Genome-wide association studies of imputed whole-genome sequences highlighted candidate SNPs that were then added to the EuroG10K BeadChip, which is routinely used in genomic selection. In the present study, we (1) assessed the reliability of single-step genomic BLUP breeding values (ssEBVs) for cheese yields, coagulation traits, and casein and calcium content generated from test-day records of the first 3 lactations, (2) estimated realized genetic trends for these traits over the last decade, and (3) simulated different cheese-making breeding objectives and estimated the responses for CMP as well as for other traits currently selected in the Montbéliarde breed. To estimate the reliability of ssEBVs, the available data were split into 2 independent training and validation sets that respectively contained cows with the oldest and the most recent lactation data. The training set included 155,961 cows (12,850 with genotypes) and was used to predict ssEBVs of 2,125 genotyped cows in the validation set. We first tested 4 models that included either lactation (LACT) or test-day (TD) records from the first (1) or the first 3 (3) lactations, giving equal weight to all 50K SNP effects. Mean reliabilities were 61%, 62%, 63%, and 64% for the LACT1, LACT3, TD1, and TD3 models, respectively. Using the most accurate model (TD3), we then compared the reliabilities of 3 scenarios with: SNPs from the Illumina BovineSNP50 BeadChip only, equally weighted (50K); 50K SNPs plus additional candidate SNPs, equally weighted (50K+); and 50K and candidate SNPs with additional weight given to 7 to 14 candidate SNPs, depending on the trait (CAND). The 50K+ and CAND scenarios led to similar mean reliabilities (67%) and both outperformed the 50K scenario (64%), whereas the CAND scenario generated the less biased ssEBVs. To assess genetic trends, SNP effects were estimated with a single-step GBLUP based on the TD3 model and the 50K scenario applied to the whole population (2.6 million performance records from 190,261 cows and 423,348 animals in the pedigree, of which 21,874 were genotyped) and then applied to 50K genotypes of 21,171 males and 311,761 females. We detected a positive genetic trend for all CMP during the last decade, probably due to selection for an increase in milk protein and fat content in Montbéliarde cows. Finally, we compared the selection responses to 3 different breeding objectives: the current Montbéliarde total merit index (TMI) and 2 alternative scenarios that gave a weight of 70% to TMI and the remaining 30% to either milk casein content (TMI-COMP) or a combination of 3 CMP (TMI-Cheese). The TMI-Cheese scenario yielded the best responses for all the CMP analyzed, whereas values in the TMI-COMP scenario were intermediate, with a slight effect on other traits currently included in TMI. Based on these results, a program of genomic evaluation for CMP predicted from mid-infrared spectra was designed and implemented for the Montbéliarde breed.


Subject(s)
Cheese , Animals , Caseins/genetics , Cattle/genetics , Cytidine Monophosphate , Female , Genome-Wide Association Study/veterinary , Genomics , Genotype , Male , Phenotype , Polymorphism, Single Nucleotide , Reproducibility of Results
4.
Vet Rec ; 188(6): e14, 2021 03.
Article in English | MEDLINE | ID: mdl-33646624

ABSTRACT

BACKGROUND: Even though tumours are considered to occur frequently in pet hamsters, there is only a small number of scientific reports in current literature. METHODS: Pathological reports from 177 hamsters were evaluated. RESULTS: Of these, 78 were male and 75 were female. Median age of affected hamsters was 12 months (range 2-34). Integumental tumours were the most common neoplasms (62%, 109/177). As far as species was known, the number of Syrian hamsters (52%, 30/58) affected by tumours seemed to be lower than the number of affected dwarf hamsters (85%, 47/55). Tumours of the hematopoietic system were the second most frequently neoplasms (17%, 30/177). Relative number of neoplasms of the endocrine system, tumours of the digestive system (1.7%, 3/177) and other tumours (4%, 7/177 each) was low. The majority of integumental tumours were epithelial (66%; 91/126). CONCLUSION: This study aimed to analyze data from veterinary surgeries and pathological institutes about the occurrence of spontaneous tumours in Syrian hamsters and dwarf hamsters to give information about the frequency of tumours, prognosis and survival time. This is the first study about tumours in pet hamsters in Germany so far.


Subject(s)
Neoplasms/veterinary , Pets , Rodent Diseases/epidemiology , Animals , Cricetinae , Female , Germany/epidemiology , Male , Neoplasms/epidemiology , Retrospective Studies
5.
J Dairy Sci ; 103(7): 5992-6002, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32331888

ABSTRACT

Franche-Comté is the primary producing region of Protected Designation of Origin cheeses in France. Normally, mid-infrared (MIR) prediction models for cheese-making property (CMP) traits are developed using individual bovine milks. However, considering the requests of all actors in the dairy sector, the present study aimed to assess the feasibility of MIR spectroscopy to develop CMP equations of Montbéliarde herd and dairy vat milks. For this purpose, 22 CMP traits were analyzed on samples collected in 2016 (half in February-March and half in May-June) from 100 commercial herds and 70 dairy vats (55 cheese dairies) located in Franche-Comté. These characteristics included 11 rennet coagulation traits and 8 lactic acidification traits measured in either soft cheese or pressed cooked cheese conditions and 3 laboratory curd yields. Models of MIR prediction for each of the 22 CMP traits were built using partial least squares regression with external validation by dividing the data set into calibration (70%) and validation (30%) sets. We confirmed that the variability of milk traits depends largely on the production scale and is higher for individual milk than for herd milk and even higher for vat milk. The best prediction models were obtained in herd milk samples for curd yields expressed in dry matter or fresh, with a coefficient of determination (R2) in external validation of 0.78 and 0.77, respectively. As with individual milk, these traits are closely related to the gross composition of the milk and therefore easier to predict by MIR spectroscopy. However, these curd yield traits were poorly predicted (R2 = 0.58) in vat milk samples due to their lower variability. In herd milk samples, prediction models of other CMP traits were poorly accurate except for the ratio of the time to obtain a standard firmness to the rennet coagulation time in soft cheese or pressed cooked cheese conditions, which showed R2 > 0.66 in external validation. Such trait is important in qualifying the behavior of milk during cheese production. Prediction models of other CMP traits for either herd or vat milk samples had poor accuracy, and further work is needed to improve their performance.


Subject(s)
Cattle/physiology , Cheese/analysis , Milk/standards , Spectrophotometry, Infrared/veterinary , Animals , Calibration , Chymosin/analysis , Female , France , Geography , Least-Squares Analysis , Phenotype
6.
J Dairy Sci ; 102(8): 6943-6958, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31178172

ABSTRACT

Assessing the cheese-making properties (CMP) of milks with a rapid and cost-effective method is of particular interest for the Protected Designation of Origin cheese sector. The aims of this study were to evaluate the potential of mid-infrared (MIR) spectra to estimate coagulation and acidification properties, as well as curd yield (CY) traits of Montbéliarde cow milk. Samples from 250 cows were collected in 216 commercial herds in Franche-Comté with the objectives to maximize the genetic diversity as well as the variation in milk composition. All coagulation and CY traits showed high variability (10 to 43%). Reference analyses performed for soft (SC) and pressed cooked (PCC) cheese technology were matched with MIR spectra. Prediction models were built on 446 informative wavelengths not tainted by the water absorbance, using different approaches such as partial least squares (PLS), uninformative variable elimination PLS, random forest PLS, Bayes A, Bayes B, Bayes C, and Bayes RR. We assessed equation performances for a set of 20 CMP traits (coagulation: 5 for SC and 4 for PCC; acidification: 5 for SC and 3 for PCC; laboratory CY: 3) by comparing prediction accuracies based on cross-validation. Overall, variable selection before PLS did not significantly improve the performances of the PLS regression, the prediction differences between Bayesian methods were negligible, and PLS models always outperformed Bayesian models. This was likely a result of the prior use of informative wavelengths of the MIR spectra. The best accuracies were obtained for curd yields expressed in dry matter (CYDM) or fresh (CYFRESH) and for coagulation traits (curd firmness for PCC and SC) using the PLS regression. Prediction models of other CMP traits were moderately to poorly accurate. Whatever the prediction methodology, the best results were always obtained for CY traits, probably because these traits are closely related to milk composition. The CYDM predictions showed coefficient of determination (R2) values up to 0.92 and 0.87, and RSy,x values of 3 and 4% for PLS and Bayes regressions, respectively. Finally, we divided the data set into calibration (2/3) and validation (1/3) sets and developed prediction models in external validation using PLS regression only. In conclusion, we confirmed, in the validation set, an excellent prediction for CYDM [R2 = 0.91, ratio of performance to deviation (RPD) = 3.39] and a very good prediction for CYFRESH (R2 = 0.84, RPD = 2.49), adequate for analytical purposes. We also obtained good results for both PCC and SC curd firmness traits (R2 ≥ 0.70, RPD ≥1.8), which enable quantitative prediction.


Subject(s)
Cattle/metabolism , Cheese/analysis , Milk/chemistry , Animals , Bayes Theorem , Calibration , Female , France , Least-Squares Analysis , Milk/metabolism , Phenotype , Spectrophotometry, Infrared/veterinary
7.
Article in German | MEDLINE | ID: mdl-31013526

ABSTRACT

OBJECTIVE: Retrospective evaluation of the diagnostic value of bacterial culture of nasal mucosal swabs and histopathologic assessment of nasal mucosal biopsies in dogs with nasal discharge. MATERIAL AND METHODS: Medical records of dogs with the predominant clinical sign of nasal discharge that were referred to the ENT Unit of the Small Animal Department between January 2015 and December 2016 were reviewed. RESULTS: Data of 85 dogs were evaluated. On the basis of the results of computed tomography (CT), rhinoscopy, bacterial culture of a nasal mucosal swab and histopathologic examination of nasal mucosal biopsies, dogs were assigned to one of six groups of primary nasal diseases: nasal neoplasia (24/85, 28 %), oronasal defect (22/85, 26 %), idiopathic chronic rhinitis (17/85, 20 %), foreign body (8/85, 10 %), sinonasal aspergillosis (7/85, 8 %) and diseases of the planum nasale (7/85, 8 %). In brachycephalic dogs (14/85, 17 %), oronasal defects (8/14, 57 %) were the most frequent cause of nasal discharge. No cases of a primary bacterial infection of the nasal cavity were observed and, therefore, antibiotic treatment had not been successful. Nevertheless, 72 % of the dogs in this study had received prior antibiotic treatment. Secondary bacterial infec tions diagnosed via nasal mucosal swabs were not diagnostic for the underlying primary nasal diseases. Targeted biopsies of tumors obtained under endoscopic visualization may lead to a definitive diagnosis, whereas biopsies of the nasal mucosa and the type of the inflammatory infiltrate were not diagnostic. CONCLUSIONS: Nasal discharge in dogs is frequently an indicator of an underlying severe primary nasal disease possibly leading to mortality of the affected dogs. Further diagnostics under anesthesia should be performed early in the diagnostic evaluation. Rhinoscopy as the central diagnostic is supported by CT and biopsy. Bacterial culture of the nasal discharge does not provide a diagnosis for the primary nasal disease process. CLINICAL RELEVANCE: Without further diagnostics, antibiotic treatment of dogs presenting with nasal discharge is considered as not appropriate and can be harmful in dogs with nasal tumors or sinonasal aspergillosis. When an intranasal malignant neoplasia is suspected, endoscopic-guided biopsies of the nasal mass should be obtained, because blind nasal biopsies are associated with a high rate of false-negative results.


Subject(s)
Dog Diseases/microbiology , Dog Diseases/pathology , Nasal Mucosa/microbiology , Nasal Mucosa/pathology , Nose Diseases/veterinary , Animals , Aspergillosis/microbiology , Aspergillosis/pathology , Aspergillosis/veterinary , Chronic Disease/veterinary , Dogs , Endoscopy/veterinary , Foreign Bodies/pathology , Foreign Bodies/veterinary , Nose Diseases/microbiology , Nose Diseases/pathology , Nose Neoplasms/pathology , Nose Neoplasms/veterinary , Retrospective Studies , Rhinitis/microbiology , Rhinitis/pathology , Rhinitis/veterinary , Tomography, X-Ray Computed/veterinary
8.
J Dairy Sci ; 101(11): 10076-10081, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30219425

ABSTRACT

In a previous study, we identified candidate causative variants located in 24 functional candidate genes for milk protein and fatty acid composition in Montbéliarde, Normande, and Holstein cows. We designed these variants on the custom part of the EuroG10K BeadChip (Illumina Inc., San Diego, CA), which is routinely used for genomic selection analyses in French dairy cattle. To validate the effects of these candidate variants on milk composition and to estimate their effects on cheesemaking properties, a genome-wide association study was performed on milk protein, fatty acid and mineral composition, as well as on 9 cheesemaking traits (3 laboratory cheese yields, 5 coagulation traits, and milk pH). All the traits were predicted from midinfrared spectra in the Montbéliarde cow population of the Franche-Comté region. A total of 194 candidate variants located in 24 genes and 17 genomic regions were imputed on 19,862 cows with phenotypes and genotyped with either the BovineSNP50 (Illumina Inc.) or the EuroG10K BeadChip. We then tested the effect of each SNP in a mixed linear model including random polygenic effects estimated with a genomic relationship matrix. We confirm here the effects of candidate causative variants located in 17 functional candidate genes on both cheesemaking properties and milk composition traits. In each candidate gene, we identified the most plausible causative variant: 4 are missense in the ALPL, SLC26A4, CSN3, and SCD genes, 7 are located in 5'UTR (AGPAT6), 3' untranslated region (GPT), or upstream (CSN1S1, CSN1S2, PAEP, DGAT1, and PICALM) regions, and 6 are located in introns of the SLC37A1, MGST1, CSN2, BRI3BP, FASN, and ANKH genes.


Subject(s)
Cattle/genetics , Cheese , Genetic Variation/genetics , Milk/chemistry , Animals , Breeding/methods , Chemical Phenomena , Fatty Acids/analysis , Female , Food Handling , France , Genome-Wide Association Study/veterinary , Genotype , Milk Proteins/analysis , Minerals/analysis , Phenotype , Polymorphism, Single Nucleotide/genetics , Selection, Genetic/genetics
9.
J Dairy Sci ; 101(11): 10048-10061, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30197141

ABSTRACT

Cheese-making properties of pressed cooked cheeses (PCC) and soft cheeses (SC) were predicted from mid-infrared (MIR) spectra. The traits that were best predicted by MIR spectra (as determined by comparison with reference measurements) were 3 measures of laboratory cheese yield, 5 coagulation traits, and 1 acidification trait for PCC (initial pH; pH0PPC). Coefficients of determination of these traits ranged between 0.54 and 0.89. These 9 traits as well as milk composition traits (fatty acid, protein, mineral, lactose, and citrate content) were then predicted from 1,100,238 MIR spectra from 126,873 primiparous Montbéliarde cows. Using this data set, we estimated the corresponding genetic parameters of these traits by REML procedures. A univariate or bivariate repeatability animal model was used that included the fixed effects of herd × test day × spectrometer, stage of lactation, and year × month of calving as well as the random additive genetic, permanent environmental, and residual effects. Heritability estimates varied between 0.37 and 0.48 for the 9 cheese-making property traits analyzed. Coagulation traits were the ones with the highest heritability (0.42 to 0.48), whereas cheese yields and pH0 PPC had the lowest heritability (0.37 to 0.39). Strong favorable genetic correlations, with absolute values between 0.64 and 0.97, were found between different measures of cheese yield, between coagulation traits, between cheese yields and coagulation traits, and between coagulation traits measured for PCC and SC. In contrast, the genetic correlations between milk pH0 PPC and CY or coagulation traits were weak (-0.08 to 0.09). The genetic relationships between cheese-making property traits and milk composition were moderate to high. In particular, high levels of proteins, fatty acids, Ca, P, and Mg in milk were associated with better cheese yields and improved coagulation. Proteins in milk were strongly genetically correlated with coagulation traits and, to a lesser extent, with cheese yields, whereas fatty acids in milk were more genetically correlated with cheese yields than with coagulation traits. This study, carried out on a large scale in Montbéliarde cows, shows that MIR predictions of cheese yields and milk coagulation properties are sufficiently accurate to be used for genetic analyses. Cheese-making traits, as predicted from MIR spectra, are moderately heritable and could be integrated into breeding objectives without additional phenotyping cost, thus creating an opportunity for efficient improvement via selection.


Subject(s)
Breeding/methods , Cattle/genetics , Cheese , Milk/chemistry , Spectrophotometry, Infrared/veterinary , Animals , Cheese/analysis , Chemical Phenomena , Fatty Acids/analysis , Female , Food Handling/methods , Lactose/analysis , Milk Proteins/analysis , Pregnancy , Quantitative Trait, Heritable , Spectrophotometry, Infrared/methods
10.
Malays J Pathol ; 38(2): 165-8, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27568675

ABSTRACT

Prostate cancer is one of the most common cancers among men worldwide and in the USA. Most prostate cancer progression either locally invades to seminal vesicles or metastasizes distally to bone. Skin is not a common site of metastasis for the majority of malignancies including prostate cancer. This paper reports two extremely rare cases of prostate carcinoma metastatic to the skin: a 74-year-old man previously treated with radiation for prostate cancer with cutaneous metastases to the shoulder and a 68-year-old man with prostate adenocarcinoma and cutaneous metastases to the groin. Both patients were diagnosed with skin punch biopsy and later confirmed with immunohistochemical staining for PSA and prostate specific acid phosphatase, specific for prostatic carcinoma. Although unusual, development of multiple skin lesions in patients with prostate adenocarcinoma should raise the flags of cutaneous metastases.


Subject(s)
Adenocarcinoma/secondary , Prostatic Neoplasms/pathology , Skin Neoplasms/secondary , Aged , Biomarkers, Tumor/analysis , Humans , Immunohistochemistry , Male
11.
J Math Biol ; 69(3): 687-735, 2014 Sep.
Article in English | MEDLINE | ID: mdl-23918091

ABSTRACT

The time-evolution of continuous-time discrete-state biochemical processes is governed by the Chemical Master Equation (CME), which describes the probability of the molecular counts of each chemical species. As the corresponding number of discrete states is, for most processes, large, a direct numerical simulation of the CME is in general infeasible. In this paper we introduce the method of conditional moments (MCM), a novel approximation method for the solution of the CME. The MCM employs a discrete stochastic description for low-copy number species and a moment-based description for medium/high-copy number species. The moments of the medium/high-copy number species are conditioned on the state of the low abundance species, which allows us to capture complex correlation structures arising, e.g., for multi-attractor and oscillatory systems. We prove that the MCM provides a generalization of previous approximations of the CME based on hybrid modeling and moment-based methods. Furthermore, it improves upon these existing methods, as we illustrate using a model for the dynamics of stochastic single-gene expression. This application example shows that due to the more general structure, the MCM allows for the approximation of multi-modal distributions.


Subject(s)
Biochemistry/methods , Data Interpretation, Statistical , Models, Chemical , Gene Expression , Proteins/genetics , Stochastic Processes
13.
Gut ; 60(1): 34-40, 2011 Jan.
Article in English | MEDLINE | ID: mdl-19926616

ABSTRACT

BACKGROUND: Acute appendicitis is a local intestinal inflammation with unclear origin. The aim was to test whether bacteria in appendicitis differ in composition to bacteria found in caecal biopsies from healthy and disease controls. METHODS AND PATIENTS: We investigated sections of 70 appendices using rRNA-based fluorescence in situ hybridisation. Four hundred caecal biopsies and 400 faecal samples from patients with inflammatory bowel disease and other conditions were used as controls. A set of 73 group-specific bacterial probes was applied for the study. RESULTS: The mucosal surface in catarrhal appendicitis showed characteristic lesions of single epithelial cells filled with a mixed bacterial population ('pinned cells') without ulceration of the surroundings. Bacteria deeply infiltrated the tissue in suppurative appendicitis. Fusobacteria (mainly Fusobacterium nucleatum and necrophorum) were a specific component of these epithelial and submucosal infiltrates in 62% of patients with proven appendicitis. The presence of Fusobacteria in mucosal lesions correlated positively with the severity of the appendicitis and was completely absent in caecal biopsies from healthy and disease controls. Main faecal microbiota represented by Bacteroides, Eubacterium rectale (Clostridium group XIVa), Faecalibacterium prausnitzii groups and Akkermansia muciniphila were inversely related to the severity of the disease. The occurrence of other bacterial groups within mucosal lesions of acute appendicitis was not related to the severity of the appendicitis. No Fusobacteria were found in rectal swabs of patients with acute appendicitis. CONCLUSIONS: Local infection with Fusobacterium nucleatum/necrophorum is responsible for the majority of cases of acute appendicitis.


Subject(s)
Appendicitis/microbiology , Fusobacterium Infections/complications , Fusobacterium necrophorum/isolation & purification , Fusobacterium nucleatum/isolation & purification , Acute Disease , Appendectomy , Appendicitis/pathology , Appendicitis/surgery , Appendix/microbiology , Biopsy , Case-Control Studies , Cecum/microbiology , Cecum/pathology , Feces/microbiology , Fusobacterium Infections/microbiology , Humans , In Situ Hybridization, Fluorescence , Intestinal Mucosa/microbiology
14.
IET Syst Biol ; 4(6): 441-52, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21073242

ABSTRACT

Within systems biology there is an increasing interest in the stochastic behaviour of biochemical reaction networks. An appropriate stochastic description is provided by the chemical master equation, which represents a continuous-time Markov chain (CTMC). The uniformisation technique is an efficient method to compute probability distributions of a CTMC if the number of states is manageable. However, the size of a CTMC that represents a biochemical reaction network is usually far beyond what is feasible. In this study, the authors present an on-the-fly variant of uniformisation, where they improve the original algorithm at the cost of a small approximation error. By means of several examples, the authors show that their approach is particularly well-suited for biochemical reaction networks.


Subject(s)
Algorithms , Biochemical Phenomena , Markov Chains , Systems Biology , Crystallization , Monte Carlo Method , Nucleic Acids
15.
Oncogene ; 29(19): 2795-806, 2010 May 13.
Article in English | MEDLINE | ID: mdl-20190799

ABSTRACT

Nuclear factor-kappaB (NF-kappaB) and p53 critically determine cancer development and progression. Defining the cross talk between these transcription factors can expand our knowledge on molecular mechanisms of tumorigenesis. Here, we show that induction of replicational stress activates NF-kappaB p65 and triggers its interaction with p53 in the nucleus. Experiments with knockout cells show that p65 and p53 are both required for enhanced NF-kappaB activity during S-phase checkpoint activation involving ataxia-telangiectasia mutated and checkpoint kinase-1. Accordingly, the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) also triggers formation of a transcriptionally active complex containing nuclear p65 and p53 on kappaB response elements. Gene expression analyses revealed that, independent of NF-kappaB activation in the cytosol, TNF-induced NF-kappaB-directed gene expression relies on p53. Hence, p53 is unexpectedly necessary for NF-kappaB-mediated gene expression induced by atypical and classical stimuli. Remarkably, data from gain- and loss-of function approaches argue that anti-apoptotic NF-kappaB p65 activity is constitutively evoked by a p53 hot-spot mutant frequently found in tumors. Our observations suggest explanations for the outstanding question why p53 mutations rather than p53 deletions arise in tumors of various origins.


Subject(s)
Transcription Factor RelA/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Apoptosis/drug effects , Ataxia Telangiectasia Mutated Proteins , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Checkpoint Kinase 1 , DNA/genetics , DNA/metabolism , DNA Replication , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Humans , Hydroxyurea/pharmacology , Mice , Mutation , Protein Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , S Phase/drug effects , Signal Transduction/drug effects , Stress, Physiological/genetics , Transcription, Genetic/drug effects , Transcriptional Activation/drug effects , Tumor Necrosis Factor-alpha/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Proteins/metabolism
16.
Genet Mol Res ; 7(2): 509-17, 2008.
Article in English | MEDLINE | ID: mdl-18561384

ABSTRACT

Reproductive failures are still common grounds for complaint by commercial swine producers. Porcine parvovirus (PPV) is associated with different clinical reproductive signs. The aim of the present study was to investigate PPV fetal infection at swine farms having ongoing reproductive performance problems. The presence of virus in fetal tissues was determined by nested-polymerase chain reaction assay directed to the conserved NS1 gene of PPV in aborted fetuses, mummies and stillborns. Fetuses show a high frequency of PPV infection (96.4%; n = 28). In 60.7% of the fetuses, PPV were detected in all tissue samples (lung, heart, thymus, kidney, and spleen). Viral infection differed among fetal tissues, with a higher frequency in the lung and heart (p < 0.05). Fetuses with up to 99 days of gestational age and from younger sows showed a higher frequency of PPV (p < 0.05). No significant difference in the presence of PPV was detected among the three clinical presentations. The results suggest that PPV remains an important pathogenic agent associated with porcine fetal death.


Subject(s)
Parvoviridae Infections/diagnosis , Parvovirus, Porcine/genetics , Swine Diseases/diagnosis , Abortion, Veterinary , Animals , DNA, Viral/genetics , Fetus/virology , Parvoviridae Infections/virology , Parvovirus, Porcine/isolation & purification , Polymerase Chain Reaction , Stillbirth/veterinary , Swine , Swine Diseases/virology
17.
Rev Epidemiol Sante Publique ; 56(2): 87-95, 2008 Apr.
Article in French | MEDLINE | ID: mdl-18472373

ABSTRACT

OBJECTIVES: Our aim was to estimate the number of non-satisfied instutionalization requests for inpatients and to describe the strategies elaborated to compensate for the waiting time. METHODS: This prospective follow-up study concerning all requests for institution admission for inpatients aged 75 years or older hospitalized in acute care and rehabilitation wards. Descriptive data were gathered throughout the social support process conducted during the hospitalization. A three months follow-up was conducted. RESULTS: Among 5200 hospitalizations, a social support process was initiated for 270 patients aged 75 years and over. Two thirds of the sample were women (n=163). Mean age was 82 years. Fifty-two percent of the subjects met the criteria for iso-resource grades (IRG) 1 to 2 and 90% in IRG 1 to 4. The mean length of hospitalized stay (MLOS) was 56.8+/-10.2 days; the MLOS of unjustified stay of 23.5+/-5.6 (n=222). The average time before the social worker was informed of the patient's situation was 13.6+/-2.0 days; in addition, the time required to establish the administrative documents necessary for initiation of the social support progress was 15.0+/-1.8. The principal reasons for social support were physical dependence (77%), mental dependence (60%), insufficient family support (36%) and/or disease progression (21%). At three months, 104 patients were institutionalized, 128 were still on institution waiting list (in hospital: 48%; at home: 16%) and 38 had died (14%). The estimated annual institutional deficit for disabled elderly people was 512 beds. CONCLUSION: In light of demographical perspectives, an overall re-organization of the geriatric network is absolutely necessary. A simple increase in the capacity to fulfil the institutional beds deficit would be insufficient.


Subject(s)
Disabled Persons/statistics & numerical data , Hospital Units , Patient Admission/statistics & numerical data , Aged , Aged, 80 and over , Female , France , Humans , Male , Prospective Studies , Social Work , Waiting Lists
18.
Genet. mol. res. (Online) ; 7(2): 509-517, 2008. tab, ilus
Article in English | LILACS | ID: lil-640987

ABSTRACT

Reproductive failures are still common grounds for complaint by commercial swine producers. Porcine parvovirus (PPV) is associated with different clinical reproductive signs. The aim of the present study was to investigate PPV fetal infection at swine farms having ongoing reproductive performance problems. The presence of virus in fetal tissues was determined by nested-polymerase chain reaction assay directed to the conserved NS1 gene of PPV in aborted fetuses, mummies and stillborns. Fetuses show a high frequency of PPV infection (96.4%; n = 28). In 60.7% of the fetuses, PPV were detected in all tissue samples (lung, heart, thymus, kidney, and spleen). Viral infection differed among fetal tissues, with a higher frequency in the lung and heart (p < 0.05). Fetuses with up to 99 days of gestational age and from younger sows showed a higher frequency of PPV (p < 0.05). No significant difference in the presence of PPV was detected among the three clinical presentations. The results suggest that PPV remains an important pathogenic agent associated with porcine fetal death.


Subject(s)
Animals , Swine Diseases/diagnosis , Parvoviridae Infections/diagnosis , Parvovirus, Porcine/genetics , Abortion, Veterinary , DNA, Viral/genetics , Swine Diseases/virology , Fetus/virology , Parvoviridae Infections/virology , Polymerase Chain Reaction , Parvovirus, Porcine/isolation & purification
19.
Int J Cardiol ; 97(3): 529-34, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15561344

ABSTRACT

OBJECTIVE: Recent studies have shown that immunoadsorption (IA) leads to improvements in left ventricular function and in functional status in selected patients with idiopathic dilated cardiomyopathy (DCM) and circulating autoantibodiesautoantibod. Most of the few studies dealing with this topic describe only short-term results. The aim of this study was to ascertain the prolonged effects of IA over a period of 3 years. MATERIALS AND METHODS: Our study included nine patients with circulating beta1-adrenoreceptor antibodies who suffered from idiopathic DCM (left ventricular ejection fraction <30%). IA was performed using an adsorber against immunoglobulins (Ig Therasorb, Baxter). During therapy and after 3 months, hemodynamic parameters were monitored using a Swan-Ganz thermodilution catheter. All patients were monitored under clinical and echographical examinations over a period of at least 3 years. RESULTS: During IA hemodynamic measurements show increases in both cardiac and stroke volume index (from 2.0 (S.E.M. 0.16) to 3.0 (S.E.M. 0.32) l min(-1) m(-2), and from 26.1 (S.E.M. 2.63) to 38.9 (S.E.M. 3.56) ml/m2, respectively). Hemodynamic stabilization was observed after the following 3 months (CI 2.6 (S.E.M. 0.14) l min(-1) m(-2), SVI 37.9 (S.E.M. 2.14) ml/m2). After 36 months five patients were still alive. Antibody titers increased in patients who deteriorated. The five patients who are still alive show an increase in left ventricular ejection fraction and no significant increase in antibody titers. CONCLUSION: Immunoadsorption may improve short-term hemodynamics as well as long-term follow-up of patients with severe idiopathic dilated cardiomyopathy. Increase in antibody titers is accompanied by deterioration of cardiovascular function.


Subject(s)
Cardiomyopathy, Dilated/etiology , Autoantibodies/blood , Female , Follow-Up Studies , Heart Transplantation/immunology , Humans , Male , Middle Aged , Receptors, Adrenergic, beta/immunology , Stroke Volume/immunology
20.
J Vet Med A Physiol Pathol Clin Med ; 51(4): 203-8, 2004 May.
Article in English | MEDLINE | ID: mdl-15265178

ABSTRACT

The objective of this study was to analyse the heritabilitiy of the lactational incidence of displaced abomasum (DA) and the relationships of DA with milk production traits in German Holstein cows. Data were recorded between February 1999 and January 2000 in cooperation with five veterinary practitioners. Their veterinary practices were located in the northern part of Lower Saxony. The investigation included 160 dairy farms under the official milk-recording scheme with 9,315 cows. The lactational incidence of the left abomasal displacement amounted to 1.21%, and of the right abomasal displacement to 0.41%, respectively. The linear heritability estimates for the lactational incidences of left and right DA were h(2) = 0.05 +/- 0.012 and h(2) = 0.004 +/- 0.005, respectively. Using the Dempster-Lerner-transformation the corresponding heritabilities were h(2) = 0.53 and 0.09, respectively. Milk losses for the lactation when DA was diagnosed were significant and reached 1016 kg milk, 41 kg fat, 36 kg protein and 0.07% protein. Fat content significantly increased by 0.18%. The analysis could not show significant differences between cows diagnosed with DA and cows not diagnosed with DA in the 305-day milk production traits of the lactation preceding the diagnosis of DA. There was also no indication for an unequal distribution of breeding values for milk performance traits between cows with and without DA. The additive genetic correlations between 305-day milk performance and left DA were low. The results indicated that cows with a high milk production and superior breeding values for milk performance were not exposed to an increased risk for DA.


Subject(s)
Abomasum , Cattle Diseases/epidemiology , Lactation/physiology , Milk/physiology , Stomach Diseases/veterinary , Animals , Cattle , Cattle Diseases/etiology , Cattle Diseases/genetics , Cattle Diseases/physiopathology , Dairying , Female , Germany/epidemiology , Incidence , Models, Statistical , Risk Factors , Stomach Diseases/epidemiology
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