Infectious bronchitis virus infection in chicken: viral load and immune responses in Harderian gland, choanal cleft and turbinate tissues compared to trachea.

1. The role of the Harderian gland (HG), choanal cleft (CC) and turbinate in terms of IBV M41 viral load compared to the trachea, and immune (innate, cellular and mucosal) responses were studied in 21-day-old commercial broiler chickens.2. After virulent IBV M41 challenge, the antigen concentration detected either by quantitative RT-PCR or immunohistochemistry peaked at 2-3 days post challenge (dpc) in all tissues. Significant increases of lachrymal IBV-specific IgA and IgY levels were found at 4-5 dpc.3. Gene transcription showed a significant up-regulation of TLR3, MDA5, IL-6, IFN-α and IFN-ß, where patterns and magnitude fold-change of mRNA transcription were dependent on the gene and tissue type.4. The results demonstrated active IBV M41 replication in the HG, CC and turbinate, comparable to levels of replication found in the trachea. Data on immune-related genes in head-associated tissues provide further understanding on the immunobiology of IBV and offer opportunities to identify their use as quantitative biomarkers in pathogenicity and vaccination-challenge studies.

Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies.

Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to kidney allograft failure. Here we sought an objective, quantitative pathological assessment of these lesions to improve predictive utility and constructed a deep-learning-based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte infiltrates. Periodic acid- Schiff stained slides of transplant biopsies (60 training and 33 testing) were used to quantify pathological lesions specific for interstitium, tubules and mononuclear leukocyte infiltration. The pipeline was applied to the whole slide images from 789 transplant biopsies (478 baseline [pre-implantation] and 311 post-transplant 12-month protocol biopsies) in two independent cohorts (GoCAR: 404 patients, AUSCAD: 212 patients) of transplant recipients to correlate composite lesion features with graft loss. Our model accurately recognized kidney tissue compartments and mononuclear leukocytes. The digital features significantly correlated with revised Banff 2007 scores but were more sensitive to subtle pathological changes below the thresholds in the Banff scores. The Interstitial and Tubular Abnormality Score (ITAS) in baseline samples was highly predictive of one-year graft loss, while a Composite Damage Score in 12-month post-transplant protocol biopsies predicted later graft loss. ITASs and Composite Damage Scores outperformed Banff scores or clinical predictors with superior graft loss prediction accuracy. High/intermediate risk groups stratified by ITASs or Composite Damage Scores also demonstrated significantly higher incidence of estimated glomerular filtration rate decline and subsequent graft damage. Thus, our deep-learning approach accurately detected and quantified pathological lesions from baseline or post-transplant biopsies and demonstrated superior ability for prediction of post-transplant graft loss with potential application as a prevention, risk stratification or monitoring tool.

Successful use of rituximab in refractory idiopathic thrombocytopenic purpura in a patient with common variable immunodeficiency.

Idiopathic thrombocytopenic purpura (ITP) is a common autoimmune disease in patients with common variable immunodeficiency (CVID). We describe a 36-year-old woman with CVID. The clinical course of her disease was complicated by bronchiectasis, antiphospholipid antibody syndrome, and portal vein thrombosis. She developed recurrent attacks of ITP refractory to high doses of corticosteroid, intravenous immunoglobulin (IVIG), and splenectomy. She received a total of 5 doses of rituximab (375 mg/m2) and achieved an immediate and persistent response. Therapy was well tolerated. Her platelet count remained above 370,000/microL for 8 months of follow-up, despite repeated infections. During this period the patient remained off corticosteroids and on continuous IVIG replacement therapy.

RAD52 polymorphisms contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population.

Genetic polymorphisms of DNA repair genes seem to determine the DNA repair capacity. We hypothesized that polymorphisms of genes responsible for DNA repair may be associated with risk of thyroid cancer. To evaluate the role of genetic polymorphisms of DNA repair genes in thyroid cancer, we conducted a hospital-based case-control study in Saudi population. Two hundred and twenty-three incident papillary thyroid cancer cases and 229 controls recruited from Saudi Arabian population were analyzed for 21 loci in 8 selected DNA repair genes by PCR-restriction fragment length polymorphism including non-homologous end joining pathway genes LIGIV (LIGlV ASP62HIS, PRO231SER, TRP46TER), XRCC4 Splice 33243301G>A and XRCC7 ILE3434THR; homologous recombination pathway genes XRCC3 ARG94HIS and THR241MET, RAD51 UTR 15452658T>C, 15455419A>G, RAD52 2259 and GLN221GLU, conserved DNA damage response gene Tp53 PRO47SER, PRO72ARG, Tp53 UTR 7178189A>C and base excision repair gene XRCC1 ARG194TRP, ARG280HIS, ARG399GLN, ARG559GLN. RAD52 GLN221GLU genotypes CG and variants carrying G allele showed statistical significance and very high risk of developing thyroid cancer compared to wild type [CG vs CC; p<0.001, odds ratio (OR)=15.57, 95% confidence interval (CI)=6.56-36.98, CG+GG vs CC; p<0.001, OR=17.58, 95% CI=7.44-41.58]. Similarly, RAD52 2259 genotypes CT and variant allele T showed a significant difference in terms of risk estimation (CT vs CC; p<0.05, OR=1.53, 95% CI=1.03-2.28, CT+TT vs CC; p<0.001, OR=1.922, 95% CI=1.31-2.82). Remaining loci demonstrated no significance with risk. Of the 21 loci screened, RAD52 2259 and RAD52 GLN221GLU may be of importance to disease process and may be associated with papillary thyroid cancer risk in Saudi Arabian population.

Curcumin induces apoptosis via inhibition of PI3'-kinase/AKT pathway in acute T cell leukemias.

Curcumin has been shown to possess variety of biological functions including anti-tumor activity. The mechanism by which curcumin inhibit cell proliferation remains poorly understood. In the present report, we investigated the effect of curcumin on the activation of apoptotic pathway in T-cell acute lymphoblastic leukemia (T-ALL) malignant cells. Our data demonstrate that curcumin causes dose dependent suppression of proliferation in several T cell lines. Curcumin treatment causes the de-phosphorylation/inactivation of constitutively active AKT, FOXO transcription factor and GSK3. Curcumin also induces release of cytochrome c accompanied by activation of caspase-3 and PARP cleavage. In addition, zVAD-fmk, a universal inhibitor of caspases, prevents caspase-3 activation and abrogates cell death induced by curcumin treatment. Finally, treatment of T-ALL cells with curcumin down-regulated the expression of inhibitor of apoptosis protein (IAPs). Taken together, our finding suggest that curcumin suppresses constitutively activated targets of PI3'-kinase (AKT, FOXO and GSK3) in T cells leading to the inhibition of proliferation and induction of caspase-dependent apoptosis.

Variable drug metabolism genes in Arab population.

Cataloging interethnic differences in the distribution of genotypes of drug metabolic genes provides valuable information for profiling the pharmacogenetics of a population. We used PCR analysis to catalog the frequencies of alleles and genotypes for CYP1A1, NAT2, GSTs, MTHFR, MTR (MS) and NQO*1 in Arabs. The frequencies of alleles and/or genotypes for CYP1A1*2A, GSTT1 null, GSTT1 and GSTM1 double null, and GSTP1 A1578G in Arabs were significantly higher than those reported in Caucasians. However, the distribution of NAT2 acetylator phenotypes in both populations was similar. In contrast, the frequencies of MTHFR 677T allele and the combined (677+1298) genotypes for low activity were lower than those reported in Caucasians. Other alleles in Arabs, including CYP1A1 T3801C and GSTP1 A1578G were present in frequencies similar to Africans. The overall profile of variations in metabolism genes in Arabs is thus unique.

Mediastinitis due to Mycobacterium fortuitum infection following Fontan operation in a child.

Here we report a case of mediastinitis due to Mycobacterium fortuitum infection in a child after a Fontan operation. To our knowledge this is the first report of atypical mycobacterial mediastinal infection after congenital heart surgery. Atypical mycobacteria can be the cause of "culture negative" sternal and thoracotomy wound infections. A brief review of the literature is included in the discussion.