A seven-nuclear receptor-based prognostic signature in breast cancer.

BACKGROUND: Breast cancer (BRCA) is a malignant cancer that threatened the life of female with unsatisfactory prognosis. The aim of this study was to identify prognostic nuclear receptors (NRs) signature of BRCA. METHODS: BRCA patient samples were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Consensus clustering analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis were performed to evaluate, select NRs as prognostic factors and build Risk Score model. GSEA analysis was explored to check signaling differences between High- and Low-Risk group. Nomogram model basing on age and Risk Score was established to predict the 1-, 3- and 5-year survival. Model performance was assessed by a time-dependent receiver operating characteristic (ROC) curve and calibration plot. CIBERSORT, ESTIMATE and TIMER algorithm were introduced to evaluate the immune landscape. RESULTS: NR3C1, NR4A3, THRA, RXRG, NR2F6, NR1D2 and RORB were optimized as a prognostic signature for BRCA. This seven-NR-based Risk Score could effectively predict overall survival status. The area under the curve (AUC) of 1-, 3- and 5-year overall survival are 0.702, 0.734 and 0.722 in TCGA training cohort, and 0.630, 0.721 and 0.823 in GEO validation cohort, respectively. Calibration plot demonstrated satisfactory agreement between predictive and observed outcomes. Nomogram model worked well on predicting survival probabilities. Multiple cancer-related pathways were highly enriched in High-Risk group. High- and Low-Risk groups showed significant differed immune cell infiltration. There exists an obvious connection between Risk Score and immune checkpoints LAG3, PD1 and TIM3. CONCLUSION: The seven-NR-based Risk Score represents a promising signature for estimating overall survival in patients with BRCA, and is correlated with the immune microenvironment.

Association Analysis Between Polymorphism of Gonadotrophin Releasing Hormone Genes and Growth Traits of Quail (Coturnix Coturnix)

This study investigated SNP mutation sites of Gonadotrophin releasing hormone (GnRH) gene in China yellow quail, Beijing white quail and Korean quail through PCR amplification and DNA sequencing technologies. Moreover, polymorphism of GnRH gene and its association with growth traits of quail were analyzed, aiming to get molecular markers associated to growth traits of quail, which could provide references for breeding of new quail species. According to research results, a total of 14 SNP mutation sites of GnRH were detected in China yellow quail, Beijing white quail and Korean quail, which were C71T, C108T, C168T, C178T, A184G, C206T, A209C, C215T, A252G, A279T, C281T, C293G, C339T and C458T. Except that only 2 genotypes were detected for A209C and C281T in China yellow quail and Beijing white quail, 3 genotypes were detected for all of the remaining 12 SNP mutation sites in three quail species. Of the 14 SNP sites, C71T, A209C, C215T, C281T, C293G, C339T and C458T were significantly associated with body weight (p 0.05), C71T, C108T, C168T, C178T, A184G, C206T, C215T, A252G, C293G, C339T and C458T were significantly associated with shank length (p 0.05), C71T, C215T, C293G and C458T were significantly associated with breastbone length (p 0.05), A209C and C281T were significantly associated with shank circumference (p 0.05).(AU)

Association Analysis Between Polymorphism of Gonadotrophin Releasing Hormone Genes and Growth Traits of Quail (Coturnix Coturnix)

This study investigated SNP mutation sites of Gonadotrophin releasing hormone (GnRH) gene in China yellow quail, Beijing white quail and Korean quail through PCR amplification and DNA sequencing technologies. Moreover, polymorphism of GnRH gene and its association with growth traits of quail were analyzed, aiming to get molecular markers associated to growth traits of quail, which could provide references for breeding of new quail species. According to research results, a total of 14 SNP mutation sites of GnRH were detected in China yellow quail, Beijing white quail and Korean quail, which were C71T, C108T, C168T, C178T, A184G, C206T, A209C, C215T, A252G, A279T, C281T, C293G, C339T and C458T. Except that only 2 genotypes were detected for A209C and C281T in China yellow quail and Beijing white quail, 3 genotypes were detected for all of the remaining 12 SNP mutation sites in three quail species. Of the 14 SNP sites, C71T, A209C, C215T, C281T, C293G, C339T and C458T were significantly associated with body weight (p 0.05), C71T, C108T, C168T, C178T, A184G, C206T, C215T, A252G, C293G, C339T and C458T were significantly associated with shank length (p 0.05), C71T, C215T, C293G and C458T were significantly associated with breastbone length (p 0.05), A209C and C281T were significantly associated with shank circumference (p 0.05).

Effect of Bifidobacterium infantis NLS super strain in symptomatic coeliac disease patients on long-term gluten-free diet - an exploratory study.

Bifidobacterium infantis NLS super strain (B. infantis NLS-SS) was previously shown to alleviate gastrointestinal symptoms in newly diagnosed coeliac disease (CD) patients consuming gluten. A high proportion of patients following a gluten-free diet experiences symptoms despite dietary compliance. The role of B. infantis in persistently symptomatic CD patients has not been explored. The aim of the study was to evaluate the effect of B. infantis NLS-SS on persistent gastrointestinal symptoms in patients with CD following a long-term GFD. We conducted a randomised, cross-over, double-blind, placebo-controlled trial in symptomatic adult CD patients on a GFD for at least two years. After one-week run-in, patients were randomised to B. infantis NLS-SS or placebo for 3 weeks with cross-over after a 2-week wash-out period. We estimated changes (Δ) in celiac symptom index (CSI) before and after treatment. Stool samples were collected for faecal microbiota analysis (16S rRNA sequencing). Gluten immunogenic peptide (GIP) excretion in stool and urine samples was measured at each study period. Eighteen patients were enrolled; six patients were excluded due violations in protocol. For patients with the highest clinical burden, CD symptoms were lower in probiotic than in placebo treatment (P=0.046). B. infantis and placebo treated groups had different microbiota profiles as assessed by beta diversity clustering. In probiotic treated groups, we observed an increase in abundance of B. infantis. Treatment with B. infantis was associated with decreased abundance of Ruminococcus sp. and Bifidobacterium adolescentis. GIP excretion in stools and urine was similar at each treatment period. There were no differences in adverse effects between the two groups. B. infantis NLS-SS improves specific CD symptoms in a subset of highly symptomatic treated patients (GFD). This is associated with a shift in stool microbiota profile. Larger studies are needed to confirm these findings. ClinicalTrials.gov: NCT03271138.

Tissue distribution and early developmental expression patterns of aldolase A, B, and C in grass carp Ctenopharyngodon idellus.

Aldolase is a key enzyme involved in glycolysis, gluconeogenesis, and the pentose phosphate pathway. To establish the expression patterns of all three aldolase isozyme genes in different tissues and during early embryogenesis in lower vertebrates, as well as to explore the functional differences between these three isozymes, the grass carp was selected as a model owing to its relatively high glucose-metabolizing capability. Based on the cDNA sequences of the aldolase A, B, and C genes, the expression patterns of these three isozymes were analyzed in different tissues and during early embryogenesis using quantitative real-time polymerase chain reaction (qRT-PCR). Sequence analysis of cDNAs indicated that aldolase A, B, and C (GenBank accession numbers: KM192250, KM192251, and KM192252) consist of 364, 364, and 363 amino acids, respectively. The qRT-PCR results showed that the expression levels of aldolase A, B, and C were highest in the muscle, liver, and brain, respectively. Aldolase A and C exhibited similar expression patterns during embryogenesis, with high levels observed in unfertilized and fertilized eggs and at the blastocyst stage, followed by a decline and then increase after organogenesis. In contrast, aldolase B transcript was not detected during the unfertilized egg stage, and appeared only from gastrulation; the expression increased markedly during the feeding period (72 h after hatching), at which point the level was higher than those of aldolase A and C. These data suggest that the glucose content of grass carp starter feed should be adjusted according to the metabolic activity of aldolase B.

Effect of Shenqin biochemical extract on hypoxia-inducible factor-1α expression in ultraviolet B-irradiated HaCaT cells.

Hypoxia-inducible factor-1α (HIF-1α) is considered the main transcriptional regulator of the hypoxia-specific cellular and developmental response. This study was performed to investigate the effect of Shenqin biochemical extract (SQBE) on HIF-1α expression in ultraviolet B (UVB)-irradiated HaCaT cells and the possible action mechanisms of SQBE against UVB-induced skin cancer. HaCaT cells in logarithmic growth phase were seeded in Dulbecco's modified Eagle's medium with 10% fetal bovine serum, and conventionally cultured at 37°C with 5% CO2. Cells were divided into control group (administered the same amounts of dimethyl sulfoxide), SQBE1 group (12.5 µg/mL SQBE), SQBE2 group (25.0 µg/mL SQBE), and SQBE3 group (50.0 µg/mL SQBE). Four hours post administration, the control and treatment groups were irradiated with UVB (0, 20, 40, and 60 mJ/cm2). After 24 h, cell survival rate was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression levels of HIF-1α mRNA and protein were detected by polymerase chain reaction and western blotting, respectively. SQBE-treated, UVB-irradiated cells had improved survival rates. This increase was most significant in SQBE3 group (P < 0.01), which also had effectively reduced expression of intracellular HIF-1α mRNA and protein. Hence, SQBE had a protective effect on UVB-irradiated HaCaT cells and inhibited the UVB irradiation-induced expression of HIF-1α. This indicates that SQBE could prevent the occurrence of UVB radiation-induced skin cancer.

Study on the morphological development of quail embryos

In this study, the SWKQ series microcomputer automatic incubator was used to study the growth and development of quail in the embryonic stage. Results showed that the embryo shape of became gradually defined as embryo aged. On day 6, the head and body of quail were clearly differentiated, the legs became longer and the wings appeared. At 7 embryo age, the entire embryo of quail was very clear, and the beak has formed. During 3 to 9 days of age, quail embryos length increased quickly, showing a linearly upward trend. At 9 day old, quail embryos length reached 2.2 cm. The regression equation of embryo length to day old was curve regression, giving as following: y=-0.464+0.325x-0.004x2, y: embryo length, x: the age of the embryo.(AU)

Study on the morphological development of quail embryos

In this study, the SWKQ series microcomputer automatic incubator was used to study the growth and development of quail in the embryonic stage. Results showed that the embryo shape of became gradually defined as embryo aged. On day 6, the head and body of quail were clearly differentiated, the legs became longer and the wings appeared. At 7 embryo age, the entire embryo of quail was very clear, and the beak has formed. During 3 to 9 days of age, quail embryos length increased quickly, showing a linearly upward trend. At 9 day old, quail embryos length reached 2.2 cm. The regression equation of embryo length to day old was curve regression, giving as following: y=-0.464+0.325x-0.004x2, y: embryo length, x: the age of the embryo.

Microsatellite analysis of genetic diversity in quail populations from China

Polymorphism of three quail communities was analyzed by using 12 microsatellite markers in this paper, aiming to provide scientific references for the evaluation, protection and utilization of quail genetic resources in China. Results demonstrated that the number of observed alleles by 12 microsatellite markers ranges between 4~7. The average polymorphism information contents (PIC) of the Chinese yellow quail, the Chinese black quail and the Korean quail, as detected by 12 microsatellite markers, are 0.6853, 0.6401 and 0.6565,respectively, and average heterozygosity values are 0.7333, 0.6957 and 0.7111, respectively. This indicates that the Chinese yellow quail has the richest genetic polymorphism. According to cluster analysis, the Chinese black quail and the Korean quail have the smallest genetic distance (0.0628), which reflects that they have the closest genetic relationship. The genetic distance between the Chinese yellow quail and the Korean quail is 0.0951. Therefore, the Chinese black quail and the Korean quail are clustered together firstly, and then the Chinese yellow quail.(AU)

Microsatellite analysis of genetic diversity in quail populations from China

Polymorphism of three quail communities was analyzed by using 12 microsatellite markers in this paper, aiming to provide scientific references for the evaluation, protection and utilization of quail genetic resources in China. Results demonstrated that the number of observed alleles by 12 microsatellite markers ranges between 4~7. The average polymorphism information contents (PIC) of the Chinese yellow quail, the Chinese black quail and the Korean quail, as detected by 12 microsatellite markers, are 0.6853, 0.6401 and 0.6565,respectively, and average heterozygosity values are 0.7333, 0.6957 and 0.7111, respectively. This indicates that the Chinese yellow quail has the richest genetic polymorphism. According to cluster analysis, the Chinese black quail and the Korean quail have the smallest genetic distance (0.0628), which reflects that they have the closest genetic relationship. The genetic distance between the Chinese yellow quail and the Korean quail is 0.0951. Therefore, the Chinese black quail and the Korean quail are clustered together firstly, and then the Chinese yellow quail.

Development and application of Est-Ssr markers in quails

Aiming at accelerating the application of molecular markers in the genetic improvement of quails, six EST-SSR markers were successfully developed using a bioinformatics method. Polymorphisms of three quail populations (Chinese yellow quail, China black quail and Korean quail) were detected. The results showed that there were 2-6 alleles in six EST-SSR markers. Mean polymorphism information contents of Chinese yellow quails, Chinese black quails and Korean quails were determined as 0.5451, 0.4962 and 0.4937, respectively. Average heterozygosity valuesof 0.6134, 0.5759 and 0.5613 were calculated. Among the six EST-SSR markers, three were highly polymorphic, and the other three were moderately polymorphic. The newly-developed six EST-SSR markers may be used to determine the genetic diversity of quails. The six EST-SSR markers identified were related to carbohydrate metabolism and melanin synthesis, but their specific mechanisms need to be further analyzed.(AU)

Development and application of Est-Ssr markers in quails

Aiming at accelerating the application of molecular markers in the genetic improvement of quails, six EST-SSR markers were successfully developed using a bioinformatics method. Polymorphisms of three quail populations (Chinese yellow quail, China black quail and Korean quail) were detected. The results showed that there were 2-6 alleles in six EST-SSR markers. Mean polymorphism information contents of Chinese yellow quails, Chinese black quails and Korean quails were determined as 0.5451, 0.4962 and 0.4937, respectively. Average heterozygosity valuesof 0.6134, 0.5759 and 0.5613 were calculated. Among the six EST-SSR markers, three were highly polymorphic, and the other three were moderately polymorphic. The newly-developed six EST-SSR markers may be used to determine the genetic diversity of quails. The six EST-SSR markers identified were related to carbohydrate metabolism and melanin synthesis, but their specific mechanisms need to be further analyzed.

[Body profile and physical and cognitive function by age in ambulatory elderly women from the city of Córdoba]. / Perfil corporal y función física y cognitiva según edad en mujeres mayores ambulatorias de la ciudad de Córdoba.

UNLABELLED: Aging produces body changes such as redistribution of fat and loss of muscle mass and strength, predisposing to fragility, functional impairment and disability. OBJECTIVE: To analyze the relationship between body profile and physical and cognitive function by age in in ambulatory elderly women from the city of Córdoba. METHODS: 178 healthy older women (OW) ≥60 years free living were evaluated attending centers of retirees and day homes in the city of Córdoba. We evaluated body profile from: skeletal muscle mass index (SMMI), relative body adiposity (RBA) -dual X-ray absorptiometry- and muscle strength (MS) -dynamometry-. Categories: normal/(N) sarcopenia/(SP), obesity/(OB), sarcopenic obesity/(SO); Physical function: with/without physical limitation (PL); cognitive function: with/without cognitive impairment (CI). INSTRUMENTS: Lunar Prodigy Densitometer and Smedley dynamometer, Lawton and Brody and Minimental Examination of Folstein scales. RESULTS: SO prevailed and increased with age, contrary to OB. Most of the OW did not PL or CI. Only 2.25% had low SMMI and 48.3% dynapenia. 76.97% had elevated RBA. The SP - obese or not - had greater PL and CI. CI frequency doubled to PL (15.17% versus 6.74%). We found negative correlations and significant associations between age and MS (r= -0.279; p=0.0001), physical function (r=-0.164; p=0.0283) and cognitive function (r=-0.028; p=0.0002). CONCLUSIONS: In this group of healthy OW the dynapenia was responsible for the observed SP, not low SMMI. The OW with SP had more PL and CI, and increased with age.

El envejecimiento produce cambios corporales como redistribución de la grasa y pérdida de la masa y fuerza muscular, predisponiendo a fragilidad, deterioro funcional y discapacidad. Objetivo: Analizar la relación entre perfil corporal y función física y cognitiva según edad en mujeres mayores de la ciudad de Córdoba. Material y Métodos: Se valoraron 178 Mujeres Mayores (MM) sanas ambulatorias ≥60 años que asisten a Centros de Jubilados y Hogares de Día de Córdoba capital. Se evaluó Perfil Corporal a partir de: índice de masa muscular esquelética (IMME), adiposidad corporal relativa (ACR) -absorciometría dual de rayos X- y fuerza muscular (FM) ­dinamometría-. Categorías: Normal/(N) Sarcopenia/(SP), Obesidad/(OB), Obesidad Sarcopénica/(OB/SP); Función Física: con/sin limitación física (LF); y Función Cognitiva: con/sin deterioro cognitivo (DC). Instrumentos: Densitómetro Lunar Prodigy y dinamómetro Smedley, Escalas de Lawton y Brody y Minimental Examination de Folstein. Resultados: La OB/SP predominó y se incrementó con la edad; contrario a la OB. La mayoría de las MM no presentó LF ni DC. Sólo 2,25% tuvo IMME bajo y 48,3% dinapemia. El 76,97% tenía ACR elevada. Las SP ­obesas o no- presentaron mayor LF y DC. La frecuencia de DC duplicó a la de LF (15,17% versus 6,74%). Se hallaron correlaciones negativas y asociaciones significativas entre edad y FM (r= -0,279; p=0,0001), FF (r= -0,164; p=0,0283) y FC (r= -0,028; p=0,0002). Conclusiones: En este grupo de MM sanas la dinapenia fue responsable de la SP observada, no el IMME bajo. Las ancianas SP tuvieron mayor LF y DC, y aumentaron con la edad.

Genetic polymorphisms of the BMAP-28 and MASP-2 genes and their correlation with the somatic cell score in Chinese Holstein cattle.

DNA sequencing, nested polymerase chain reaction (PCR), and PCR-restriction fragment length polymorphism were used to investigate mutations in the coding regions of the bovine myeloid antimicrobial peptide-28 (BMAP-28) and mannan-binding lectin-associated serine protease-2 (MASP-2) genes in 249 Chinese Holstein dairy cows. The associations between the polymorphisms and somatic cell score (SCS) were analyzed to determine the potential of these genes as genetic markers for breeding mastitis-resistant dairy cattle. The results revealed a C-86G synonymous mutation in the BMAP-28 gene that caused no alteration in the amino acid sequence. G553A mutation was found in the MASP-2 gene that led to the substitution of glycine with serine. The chi-square test showed that the G553A mutation was in Hardy-Weinberg equilibrium in the Chinese Holstein dairy cows, whereas the C-86G mutation was not. The variance analysis of the influence of group loci and different genotypes on the SCS showed that the SCS of genotype CC was significantly lower than those of genotypes CG and GG (P < 0.05) of the C-86G mutation, and that the SCS of genotype GG was significantly lower than those of genotypes GA and AA (P < 0.05) of the G553A mutation. Genotype combination analysis showed that the combination of the BMAP-28 genotype CC and the MASP-2 genotype GG was the best one, in which the SCS was significantly lower than those in the other combinations. Thus, this combination might be useful as a molecular and genetic marker of mastitis in Chinese Holstein dairy cows.

Transcriptome analysis of the grass carp (Ctenopharyngodon idella) using 454 pyrosequencing methodology for gene and marker discovery.

Total RNA isolated from the brain, muscle, liver, gonad, and intestinal tissues of grass carp was pooled to construct cDNA libraries. Using 454 pyrosequencing, a total of 738,604 high-quality reads were generated from the normalized cDNAs of the pooled individuals. Clustering and assembly of these reads produced a set of 37,086 all-unigene sequences after BLAST. Of these, 24,010 (64.74%) were annotated in the National Center for Biotechnology Information database, and 3715 simple sequence repeats and 2008 single nucleotide polymorphisms were identified in this EST dataset as potential molecular markers. This study provides new data for functional genomic and biological research on grass carp. The markers identified in this study will enrich the currently used molecular markers and facilitate marker-assisted selection in grass carp-breeding programs. These results also demonstrate that transcriptomic analysis based on 454 sequencing is a powerful tool for gene discovery and molecular marker development in non-model species.

IL-15 controls T cell functions through its influence on CD30 and OX40 antigens in Celiac Disease.

AIM: To evaluate the ability of interleukin (IL)-15 to control T cell functions through its influence on CD30 and OX40 expressing cells in Celiac Disease (CD). In peripheral blood (PB), by examining the expression of OX40 in conventional effectors cells and T cells with a phenotypic specialization of regulatory cells [CD4+CD25high forkhead box protein 3 (Foxp3)+], and the co stimulation of IFN-γ and IL-4 production within CD30 and OX40 positive subsets of T cells. At the duodenal mucosa, by assessing the expression of CD30 and OX40 in intraepithelial (IE) and lamina propria (LP) lymphocytes (IEL, LPL). PATIENTS AND METHODS: PB and duodenal mucosal biopsies were obtained from 38 patients with classic CD (Cel) and 38 healthy controls (HC). Analysis of cell surface and/or intracellular antigens was performed in anti-CD3-treated PB mononuclear cells (PBMC) before and after treatment with recombinant IL-15 (rIL-15), and in IE and LP cellular suspensions prepared from duodenal biopsies pre-treated with/without rIL-15. RESULTS: A subpopulation of CD3+OX40+ T blasts was induced in Cel and HC by a 3days treatment of PBMC with anti-CD3 and decreased its size thereafter, regardless of the presence of rIL-15. However, the addition of rIL-15 to T blasts distinctively induced the survival of T cells with a regulatory phenotype that expresses OX40 antigen in Cel (p<0.05). Celiac patients showed higher frequencies of IFN-γ-producing CD3+CD30+ blasts before and after treatment with rIL-15 (p<0.05, vs. HC). IL-15 increased the frequencies of CD3+CD30+ LPL (HC: p<0.05, Cel: p<0.05) but not of CD3+OX40+ LPL, and CD30 or OX40 positive IEL. CONCLUSIONS: The distinctive control of OX40+ cells with a T regulatory phenotype mediated by the influence of IL-15 comes out as new function of this cytokine in the context of CD. The higher production of IFN-γ by a subpopulation of peripheral CD3+CD30+ cells contributes to the type I biased immune response.

Altered expression of the lymphocyte activation antigen CD30 in active celiac disease.

Interleukin (IL)-15 and CD30 may be associated with the ongoing intestinal immunologic activation in celiac disease (CD). We studied duodenal biopsies and blood samples of patients with active CD (Cel) and controls in order to determine the regulatory role proposed for CD30(+) T cells in this Th1-driven disease and the potential influences of IL-15 on CD30 expression. We detected that a CD30(+) T-cell subpopulation persists longer in Cel after a 5 day incubation with anti-CD3 antibody than in controls (p = 0.0063). CD30 upregulation by IL-15 in T blasts was greater in Cel than in controls (p = 0.0062). At the mucosal compartment, the CD30 antigen was examined by immunohistochemistry and quantified on isolated lamina propria (LP) and epithelial T cells by flow cytometry. For Cel and controls, similar mean percentages of CD3(+)CD30(+) intraepithelial T cells (5.88 vs. 5.51, p = ns) and LP T cells (7.38 vs. 7.49, p = ns) were observed at baseline and after in vitro gliadin challenge of duodenal biopsy samples. Our study demonstrates the occurrence of potentially important alterations of the immune response at the peripheral compartment. Our findings also allow us to speculate that a negative effect of soluble mediators at the mucosal compartment might counteract the latent influence of IL-15 on CD30 expression precluding a more severe course of active CD.

Quality of life in celiac disease patients: prospective analysis on the importance of clinical severity at diagnosis and the impact of treatment.

BACKGROUND/AIMS: Celiac disease (CD) patients are affected in their quality of life (QoL). Our objectives were to assess differences in quality of life of patients according to the clinical presentation at diagnosis, and to determine the time-course impact of a gluten-free diet. PATIENTS/METHODS: We prospectively evaluated 132 newly diagnosed adult CD patients and 70 healthy controls using self-administered questionnaires: the Short Form-36 health survey, the Gastrointestinal Symptoms Rating Scale; the Beck Depression Inventory both, at diagnosis and at 3-, 6- and 12-months on treatment. RESULTS: At diagnosis, patients with classical symptoms (n=97) exhibited a significantly more pronounced alteration of all items of the three questionnaires than atypical/silent cases (n=35) (p<0.01 to <0.00001). Silent CD patients had even better baseline scores (p<0.05 to <0.00001). Treatment produced a substantial and rapid (3-month) improvement of most outcome measures in classical and atypical patients but not in asymptomatic cases. Both subgroups attained comparable final scores with no differences comparing strictly adherents with partially compliant. CONCLUSIONS: Atypical/silent celiac disease patients have a significantly better baseline quality of life than those with classical symptoms. Treatment induces a rapid and significant improvement in symptomatic cases but not in silent patients with all subgroups having similar 1-year scores comparable to healthy controls.

Systematic review and meta-analysis of observational studies on the prevalence of fractures in coeliac disease.

BACKGROUND/AIMS: Evidence of an increased bone fracture risk in coeliac disease is on debate. Our aim was to review systematically the current published information on fractures in coeliac disease and to perform a meta-analysis. METHODS: Case-control and cohort designs were identified by searching MEDLINE (1966-April 2007) and LILACS (1982-April 2007). Participants were adult coeliac disease patients of any sex and the outcome measure was the presence of any fracture. Studies were screened for inclusion by two authors who independently extracted the data. Methodological quality was assessed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology Statement) recommendations. Data were analysed using the RevMan Analyses statistical package in Review Manager (version 4.2.8) and reported as pooled odds ratio using a random effect model. Heterogeneity was investigated (standard chi(2) test) and sensitivity analysis was performed based on the reported quality and design type. RESULTS: While 60 of 405 studies met the initial screening criteria, only 8 met inclusion criteria after detailed review. These studies evaluated a total of 20,955 coeliac disease patients having 1819 (8.7%) fractures and 96,777 controls with 5955 (6.1%) fractures (pooled odds ratio=1.43; 95% confidence interval 1.15-1.78) with considerable heterogeneity among studies (p<0.00001). CONCLUSIONS: Our meta-analysis confirms a significant association between bone fractures and coeliac disease. However, qualitative and quantitative differences among studies were evident. Further research is necessary to investigate the relevance of this heterogeneity.

Clinical utility of counting intraepithelial lymphocytes in celiac disease intestinal mucosa / Utilidad clínica del recuento de linfocitos intraepiteliales en la mucosa intestinal para el diagnóstico de enfermedad celíaca

BACKGROUND/AIMS: Our aims were to establish the clinical utility of assessing the intraepithelial lymphocyte (IEL) density in intestinal biopsies from a large series of individuals and to determine the best threshold discriminating celiac disease (CD) patients and controls in two populations with different pre-test prevalence. METHODS: We prospectively performed intestinal biopsy and CD-related serology in 349 subjects undergoing upper GI endoscopy. While 116 had symptoms suggestive of a small bowel disorder (high prevalence), 233 individuals were randomly selected from patients referred to endoscopy because upper GIsymptoms (low prevalence). Diagnosis of CD was based on the concordance of classical histological features and a positive CD serology. RESULTS: While 58 patients had a newly diagnosed CD (52 in the high and 6 in the low prevalence groups), 291 subjects did not meet diagnostic criteria of the disorder. Patients had a highly significant greater IEL density than controls (p < 0.00001). Based on the ROC curve, a count of 22.8 IEL/100 epithelial cells had the highest performance for diagnosing CD in the overall population and for subjects in the high pre-test probability subgroup and 22.5% was ,he best cut-off for those diagnosed in the low risk population (area under the curves: 0.979, 0.979 and 0.993, respectively). An abnormal CD serology confirmed the diagnosis of CD in all the four patients with counts below 22.8%. CONCLUSIONS: Our study confirms that an IEL density of 22.8% is an adequate threshold to discriminate CD patients and controls in individuals irrespective of the prevalence of the disorder.(AU)

Introducción: El recuento elevado de linfocitos intraepiteliales (LIEs) es un rasgo destacado aunque inespecífico de la enteropatía de la enfermedad celíaca (EC). Un recuento mayor a 40 LIEs/100 células epiteliales ha sido considerado por mucho tiempo esencial para el diagnóstico. Sin embargo, estudios recientes con escaso número de muestras han cuestionado este valor de corte. Objetivos: Determinar el rango normal de LIEs en biopsias intestinales y establecer su capacidad diagnóstica de EC en dos poblaciones con diferente prevalencia. Métodos: Realizamos prospectivamente biopsias de duodeno distal y serología para EC en 349 pacientesconsecutivos a quienes se les realizó una videoendoscopia digestiva alta. El grupo A consistió en 116 pacientes derivados a biopsia intestinal por síntomas sugestivos de malabsorción (considerados de alta prevalencia de EC) y el grupo B consistió en 233 pacientes randomizados entre quienes fueron derivados a endoscopía alta por síntomas gastrointestinales no sugestivos de EC (baja prevalencia de EC). El diagnóstico de EC se basó en criterios histológicos clásicos y serología positiva. Resultados: Cincuenta y ocho pacientes tuvieron EC (52 en el grupo de alto riesgo y 6 en el de baja prevalencia) y 291 individuos no tuvieron criterios de la enfermedad. Los pacientes tuvieron una densidad de LIEs significativamente mayor que los controles (p<0.00001). Basado en las curvas ROC, el conteo de 22.8 LIEs/100 células epiteliales tuvo la mejor sensibilidad y especificidad para el diagnóstico de EC en la población general y entre los sujetos con alta probabilidad y 22.5% fue el mejor valor de corte para la población de bajo riesgo (áreas bajo las curvas: 0.979, 0.979 y 0.993, respectivamente). Todos aquellos pacientes celíacos con recuento de LIEs por debajo de 22% (n=4), tuvieron serología positiva para EC. El clásico valor de 40% tuvo una sensibilidad del 55%. Conclusiones: Nuestro estudio confirma que una...(AU)