Background: Mutations in NOD2, a putative intracellular receptor for bacterial peptidoglycans, are associated with a subset of Crohn's disease but the molecular mechanism linking this protein with the disease pathogenesis remains unclear. Human a defensins (HD-5 and HD-6) are antibiotic effector molecules predominantly expressed in Paneth cells of the ileum. Paneth cells also express NOD2. To address the hypothesis that the function of NOD2 may affect expression of Paneth cell defensins, we compared their expression levels with respect to NOD2 mutations in Crohn's disease. Methods: Forty five Crohn's disease patients (24 with NOD2 mutations, 21 with wild-type NOD2) and 12 controls were studied. Real time reverse transcription-polymerase chain reaction was performed with mucosal mRNA for HD-5, HD-6, lysozyme, secretory phospholipase A 2 (sPLA 2 ), tumour necrosis factor a, interleukin 8, and human hypoxanthine phosphoribosyltransferase (housekeeping gene). Immunohistochemistry with anti-HD-5 and histological Paneth cell staining were performed in 10 patients with NOD2 mutations or wild-type genotypes. Results: Ileal expression of HD-5 and HD-6, but not sPLA 2 or lysozyme, were diminished in affected ileum, and the decrease was significantly more pronounced in patients with NOD2 mutations. In the colon, HD-5, HD-6, and sPLA 2 were increased during inflammation in wild-type but not in NOD2 mutated patients. In both the colon and ileum, proinflammatory cytokines and lysozyme were unaffected by NOD2 status. Immunohistochemistry identified Paneth cells as the sole source of HD-5. Conclusion: As alpha defensins are important in the mucosal antibacterial barrier, their diminished expression may explain, in part, the bacterial induced mucosal inflammation and ileal involvement of Crohn's disease, especially in the case of NOD2 mutations.

The authors demonstrate expression of the vitamin D receptor (VDR) and its hydroxylases in the endometrium and ovaries of women with and without endometriosis and endometrial or ovarian cancer. Immunohistochemistry showed strong staining of the VDR in endometriosis and endometrial cancer, with the most intense staining in epithelial cells. The VDR mRNA was significantly increased in patients with endometrial and ovarian cancer compared to the control group. There was a significantly higher 1 alpha-hydroxylase expression in the endometrium of patients with endometriosis compared to healthy controls. The observed differences in VDR and 1 alpha -hydroxylase mRNA levels were maintained at the protein level. The authors found no differences in 25-OH vitamin D levels between the serum of patients with endometriosis (25.7 +/- 2.1 ng/mL, n = 46) and healthy controls (22.6 +/- 2.0 ng/mL, n = 33, P = .31). They hypothesize that vitamin D might influence the local activity of immune cells and cytokines thought to play important pathogenic roles in the development and maintenance of endometriosis.

The aim of this study was to determine the pathological complete remission (pCR) rate, and its relationship to clinical outcome, in patients with adenocarcinoma of the stomach or oesophagogastric junction receiving preoperative 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) every 2 weeks. Data from these patients who received at least one cycle of preoperative FLOT followed by surgery were prospectively collected in three German centres. Outcome analyses were conducted and tumour samples were evaluated for pathological remission by a central pathologist. A total of 46 patients were included in this analysis. All patients had clinical T3-and/or N1-stages and 11 (23.9%) had distant metastases (M1). After a median of 4 (range 2-8) preoperative cycles, 8 of 46 patients (17.4%) achieved a pCR. The pCR rate was highest in tumours of intestinal type histology (30.8%) and in those located in the oesophagogastric junction (30.4%) and lowest in patients with diffuse/mixed type tumours (0%) or tumours located in the stomach (4.3%; p < 0.05 for both comparisons). Patients with pCR had 100% probability of overall and disease-free survival (DFS) during the observation period, which was significantly higher (p 5 0.037 and p 5 0.009, respectively) than the survival probability in patients without pCR. In conclusion, treatment intensification using FLOT was associated with significant pCR rates in patients with oesophagogastric cancer. The distribution of pCR appeared to be significantly different according to histological type and location of the tumours.Despite a worldwide decline in incidence, gastric cancer remains a major health problem and is the fourth most prevalent cancer worldwide.

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We review the physical properties, linear and nonlinear optical characteristics, and phase-matching configurations of BiB3O6 (BIBO), the first low-symmetry (monoclinic) inorganic nonlinear crystal that has found broad applications for frequency conversion of laser sources from the UV, across the visible, to the near-IR based on three-wave interactions. We describe in detail the most relevant optical properties that make this material an attractive candidate for nonlinear frequency conversion of laser light in general, and ultrafast femtosecond laser sources in particular. With special focus on ultrafast frequency conversion, characteristics such as group-velocity mismatch and spectral acceptance, parametric gain bandwidth, group-velocity dispersion, as well as angular acceptance and spatial walk-off are evaluated and optimum configurations for the attainment of maximum conversion efficiency, minimum pulse duration, and highest spatial beam quality are identified and compared with the most widely established alternative borate crystal, β-BaB2O4. Experimental results are presented on both parametric up-and down-conversion of femtosecond pulses, from the high-energy, low-repetition-rate (1 kHz) to the low-energy, high-repetitionrate (56-76 MHz) regime, demonstrating the unique versatility of BIBO for efficient frequency conversion of femtosecond pulses with broad tunability from 250 nm in the UV, throughout the visible, up to ∼ 3000 nm in the IR.Photograph of a femtosecond synchronously pumped optical parametric oscillator (SPOPO) based on BiB3O6 emitting in the yellow region of the spectrum. Pumped near 400 nm in the blue by the second harmonic of a Kerr-lens mode-locked Ti:sapphire laser, the SPOPO can generate femtosecond pulses across the full visible range of 480-710 nm, from the blue-green, through to yellow, orange and red.

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We used non-phase-matched second-harmonic generation (SHG) in the highly nonlinear but low-birefringence crystal SrB4O7 for temporal characterization (autocorrelation) of femtosecond UV pulses to convert these pulses to wavelengths as low as 125 nm, close to the transparency limit of SrB4O7. The sensitivity of this method was approximately 1 microJ at the fundamental for a repetition rate of 1 kHz. We also used SHG at longer wavelengths to estimate the three nonlinear coefficients of SrB4O7.

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