Truncation of the Catalytic Domain of the Cylindromatosis Tumor Suppressor Impairs Lung Maturation

Cyld encodes a 956-amino acid deubiquitinating enzyme (CYLD), which is a negative regulator of nuclear factor κB and mitogen-activated protein kinase pathways. Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer. To establish an animal model of human CYLD inactivation and characterize the biological role of CYLD in vivo, we generated mice carrying a homozygous deletion of Cyld exon 9 (Cyld^Δ9/Δ9 mice) using a conditional approach. Deletion of exon 9 would cause a carboxyl-terminal truncation of CYLD and inactivation of its deubiquitinating activity. In accordance with previous studies, fibroblasts from Cyld^Δ9/Δ9 embryos had hyperactive nuclear factor κB and c-Jun kinase pathways compared with control fibroblasts. Cyld^Δ9/Δ9 newborn mice were smaller than wild-type littermates with a short and kinky tail and nomajor developmental defects. However, Cyld^Δ9/Δ9 mice died shortly after birth from apparent respiratory dysfunction. Histological examination of E18.5 Cyld^Δ9/Δ9 lungs demonstrated an immature phenotype characterized by hyperplasic mesenchyme but apparently normal epithelial, smooth muscle. and endothelial structures. Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer.     

The central-pedicled intracorial skin-flap technique for reconstruction of the nipple-areola complex (NAC)

Nipple-areola complex (NAC) reconstruction tends to be the final phase of post-mastectomy reconstruction for many cancer patients, as it transforms the amorphous breast mound into a more aesthetically realistic breast. A variety of local-flap based techniques have been reported. In this paper we will describe a cantral-pedicled intracorial skin flap technique. Review of 12 patients showed aesthetic pleasing NAC and durable long-term results of nipple projection.     

Passive optical separation within a 'nondiffracting' light beam

A passive, optical cell sorter is created using the light pattern of a 'nondiffracting' beam-the Bessel beam. As a precursor to cell sorting studies, microspheres are used to test the resolution of the sorter on the basis of particle size and refractive index. Variations in size and, more noticeably, refractive index, lead to a marked difference in the migration time of spheres in the Bessel beam. Intrinsic differences (size, refractive index) between native (unlabeled) cell populations are utilized for cell sorting. The large difference in size between erythrocytes and lymphocytes results in their successful separation in this beam pattern. The intrinsic differences in size and refractive index of other cells in the study (HL60 human promyelocytic leukaemic cells, murine bone marrow, and murine stem/progenitor cells) are not large enough to induce passive optical separation. Silica microsphere tags are attached to cells of interest to modify their size and refractive index, resulting in the separation of labeled cells. Cells collected after separation are viable, as evidenced by trypan blue dye exclusion, their ability to clone in vitro, continued growth in culture, and lack of expression of Caspase 3, a marker of apoptosis.     

The Lymph Node in HIV Pathogenesis

Lymph nodes play a central role in the development of adaptive immunity against pathogens and particularly the generation of antigen-specific B cell responses in specialized areas called germinal centers (GCs). Lymph node (LN) pathology was recognized as an important consequence of human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. Investigation into the structural and functional alterations induced by HIV and Simian immunodeficiency virus (SIV) has further cemented the central role that lymphoid tissue plays in HIV/SIV pathogenesis. The coexistence of constant local inflammation, altered tissue architecture, and relative exclusion of virus-specific CD8 T cells from the GCs creates a unique environment for the virus evolution and establishment of viral reservoir in specific GC cells, namely T follicular helper CD4 T cells (Tfh). A better understanding of the biology of immune cells in HIV-infected lymph nodes is a prerequisite to attaining the ultimate goal of complete viral eradication.     

Laryngopharyngeal reflux disease in the Greek general population,prevalence and risk factors

Gait function may be impaired in patients with vestibular disorders, making gait assessment in the clinical setting relevant for this patient population. The purpose of this study was to evaluate the discriminant validity of a gait assessment protocol between patients with vestibular disorders and healthy participants. Furthermore, test re-test reproducibility and the measurement error of gait performance measures in patients with vestibular lesions was performed under different walking conditions. Gait parameters of thirty-five patients with vestibular disorders and twenty-seven healthy controls were assessed twice with the GAITRite® system. Discriminant validity, reproducibility (intra class correlation [ICC]) and the measurement error (standard error of measurement [SEM], smallest detectable change [SDC]) were determined for gait speed, cadence and step length. Bland-Altman plots were made to assess systematic bias between tests. A significant effect of grouping on gait performance indicates discriminant validity of gait assessment. All tests revealed differences between patients and healthy controls (p < 0.01). The ICCs for test re-test reproducibility were excellent (0.70-0.96) and measurement error showed acceptable SDC values for gait parameters derived from three walking conditions (9-19 %). Bland-Altman plots indicated no systematic bias. Good validity and reproducibility of GAITRite® system measurements suggest that this system could facilitate the study of gait in patients with vestibular disorders in clinical settings. The SDC values for gait are generally small enough to detect changes after a rehabilitation program for patients with vestibular disorders.     

Biological interactions of a calcium silicate based cement (Biodentine™) with Stem Cells from Human Exfoliated Deciduous teeth

Objective

To investigate the biological interactions of a calcium silicate based cement (Biodentine?) with Stem Cells from Human Exfoliated Deciduous teeth (SHED), focusing on viability/proliferation, odontogenic differentiation, biomineralization and elemental release/exchange.

Expression of genes that regulate follicle development and maturation during ovarian stimulation in poor responders

Research questionSex hormone-binding globulin (SHBG), androgen receptor (AR), LH beta polypeptide (LHB), progesterone receptor membrane component 1 (PGRMC1) and progesterone receptor membrane component 2 (PGRMC2) regulate follicle development and maturation. Their mRNA expression was assessed in peripheral blood mononuclear cells (PBMC) of normal and poor responders, during ovarian stimulation.DesignFifty-two normal responders and 15 poor responders according to the Bologna criteria were enrolled for IVF and intracytoplasmic sperm injection and stimulated with 200 IU of follitrophin alpha and gonadotrophin-releasing hormone antagonist. HCG was administered for final oocyte maturation. On days 1, 6 and 10 of stimulation, blood samples were obtained, serum hormone levels were measured, RNA was extracted from PBMC and real-time polymerase chain reaction was carried out to identify the mRNA levels. Relative mRNA expression of each gene was calculated by the comparative 2^?DDCt method.ResultsDifferences between mRNA levels of each gene on the same time point between the two groups were not significant. PGRMC1 and PGRMC2 mRNA levels were downregulated, adjusted for ovarian response and age. Positive correlations between PGRMC1 and AR (standardized beta = 0.890, P < 0.001) from day 1 to 6 and PGRMC1 and LHB (standardized beta = 0.806, P < 0.001) from day 1 to 10 were found in poor responders. PGRMC1 and PGRMC2 were positively correlated on days 6 and 10 in normal responders.ConclusionsPGRMC1 and PGRMC2 mRNA are significantly decreased during ovarian stimulation, with some potential differences between normal and poor responders.