Direct Ink Write Printing of Chitin-Based Gel Fibers with Customizable Fibril Alignment, Porosity, and Mechanical Properties for Biomedical Applications

A fine control over different dimensional scales is a challenging target for material science since it could grant control over many properties of the final material. In this study, we developed a multivariable additive manufacturing process, direct ink write printing, to control different architectural features from the nano- to the millimeter scale during extrusion. Chitin-based gel fibers with a water content of around 1500% were obtained extruding a polymeric solution of chitin into a counter solvent, water, inducing instant solidification of the material. A certain degree of fibrillar alignment was achieved basing on the shear stress induced by the nozzle. In this study we took into account a single variable, the nozzle's internal diameter (NID). In fact, a positive correlation between NID, fibril alignment, and mechanical resistance was observed. A negative correlation with NID was observed with porosity, exposed surface, and lightly with water content. No correlation was observed with maximum elongation (similar to 50%), and the scaffold's excellent biocompatibility, which appeared unaltered. Overall, a single variable allowed a customization of different material features, which could be further tuned, adding control over other aspects of the synthetic process. Moreover, this manufacturing could be potentially applied to any polymer

A20 (TNFAIP3) Alterations in Primary Intestinal Diffuse Large B-cell Lymphoma

The gastrointestinal (GI) tract is the most frequently involved site of extranodal non-Hodgkin lymphomas, and diffuse large B-cell lymphoma (DLBCL) is the most common subtype occurring in the GI tract. TNFAIP3 (A20) genetic alterations were reported to be involved in DLBCL’s pathogenesis and a portion of GI-DLBCL cases harbor this alteration. However, the frequency and clinicopathological relations focusing on small and large intestinal DLBCL are unclear. Here, we examined A20 deletion and protein expression and analyzed the clinicopathological features of 52 cases of primary intestinal DLBCL. The most frequently involved site was the ileocecal region (75%), followed by small bowel (13.5%) and large intestine. Immunohistochemically, the ileocecal cases expressed BCL6 (p=0.027) and MUM1 (p=0.0001) significantly more frequently than the small intestinal cases. Six of 47 cases (13%) had A20 heterozygous deletion, whereas all 6 heterozygously deleted cases had detectable A20 protein expression. In summary, A20 abnormality was less prevalent among intestinal DLBCLs with some discordancy between gene deletion and protein expression. Although the A20 alteration status did not affect any clinicopathological characteristics in this series, further studies exploring alterations of A20 and other NF-κB components in primary intestinal DLBCL are needed

Up-regulation of activation-induced cytidine deaminase and its strong expression in extra- germinal centres in IgG4-related disease

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a systemic disorder involving benign mass formation due to fibrosis and intense lymphoplasmacytosis; the chronic inflammation associated with the disease might also contribute to oncogenesis. Activation-induced cytidine deaminase (AID), normally expressed in germinal centre activated B-cells, is an enzyme that edits DNA/RNA and induces somatic hypermutation and Ig class switching. AID expression is strictly controlled under physiological conditions; however, chronic inflammation and some infectious agents induce its up-regulation. AID is overexpressed in various cancers and may be important in chronic inflammation-associated oncogenesis. We examined AID expression in IgG4-related sialadenitis (n = 14), sialolithiasis (nonspecific inflammation, n = 13), and normal submandibular glands (n = 13) using immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). Immunohistochemistry revealed significantly more AID-expressing cells in IgG4-related sialadenitis than in sialolithiasis or normal submandibular gland samples (P = 0.02 and P < 0.01, respectively); qPCR yielded similar results. Thus, AID was significantly more up-regulated and had higher expression in extra-germinal centres in IgG4-RD than in non-specific inflammation or normal conditions. This report suggests that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation. Furthermore, chronic inflammation-associated AID-mediated oncogenesis is possible in IgG4-RD

Urinary Myoinositol Index: A New and Better Marker for Postmeal Hyperglycemia

We investigated the usefulness of the urinary myoinositol index (UMI) for identifying postmeal hyperglycemia in type 2 diabetics undergoing a meal tolerance test. Fifty-eight patients (18 males, 40 females) were enrolled, fasted overnight and blood collected prior to and 1 and 2 hours following the test meal. Urine was collected 2 hours after the test meal. Plasma 1,5-anhydroglucitol (1,5-AG) was measured enzymatically, and UMI with an improved enzymatic cycling method. Simple and multiple regression analyses were employed to determine correlations between plasma glucose (PG) and three PG markers; HbA1C (Japan Diabetes Society), 1,5-AG and UMI. Study population characteristics were age 67.6±7.9 years, body mass index 24.9±3.8kg/m2 and waist circumference 90.2±10.4cm. Mean concentrations for PG were 130±23mg/dL (fasting), 179±46mg/dL (1h postmeal) and 150±49mg/dL (2h postmeal), HbA1C (6.3±0.6%), 1,5-AG (11.9±5.7μg/mL) and 2h UMI (52.0±35.9mg/gCr). Correlation coefficients were calculated between 1h postmeal PG and HbA1C (r=0.558), 1,5-AG (r=0.256), and 2h UMI (r=0.496), and 2h postmeal PG HbA1C (r=0.605), 1,5-AG (r=0.306), and 2h UMI (r=0.606). Two hour UMI and HbA1C (Japan Diabetes Society) were significant determinants of 2h postmeal PG. As HbA1C reflects PG excursion during the previous 1-3 months, UMI may be a useful marker for monitoring and management of postmeal hyperglycemia in type 2 diabetics

Detection of RBM15-MKL1 Fusion Was Useful for Diagnosis and Monitoring of Minimal Residual Disease in Infant Acute Megakaryoblastic Leukemia

Acute megakaryocytic leukemia (AMKL) with t(1;22)(p13;q13) is a distinct category of myeloid leukemia by WHO classification and mainly reported in infants and young children. Accurate diagnosis of this type of AMKL can be difficult, because a subset of patients have a bone marrow (BM) blast percentage of less than 20% due to BM fibrosis. Therefore, it is possible that past studies have underestimated this type of AMKL. We present here the case of a 4-month-old female AMKL patient who was diagnosed by presence of the RBM15-MKL1 (OTT-MAL) fusion transcript by RT-PCR. In addition, we monitored RBM15-MKL1 fusion at several time points as a marker of minimal residual disease (MRD), and found that it was continuously negative after the first induction chemotherapy even by nested RT-PCR. Detection of the RBM15-MKL1 fusion transcript thus seems to be useful for accurate diagnosis of AMKL with t(1;22)(p13;q13). We recommend that the RBM15-MKL1 fusion transcript be analyzed for all suspected AMKL in infants and young children. Furthermore, monitoring of MRD using this fusion transcript would be useful in treatment of AMKL with t(1;22)(p13;q13)

A subset of ocular adnexal marginal zone lymphomas may arise in association with IgG4-related disease

We previously suggested a relationship between ocular immunoglobulin (Ig)G4-related disease (IgG4-RD) and marginal zone lymphomas (MZLs). However, the cytokine background associated with these disorders and whether it differs between ocular adnexal MZLs with (IgG4-associated MZL) and without (IgG4-negative MZL) numerous IgG4+ plasma cells are unknown. In this study, we identified the mRNA expression pattern of Th2 and regulatory T-cell (Treg) cytokines in IgG4-RD and in IgG4-associated MZL and IgG4-negative MZL using real-time polymerase chain reaction analysis. Ocular IgG4-RD and IgG4-associated MZL exhibited significantly higher expression ratios of interleukin (IL)-4/β-actin, IL-10/β-actin, IL-13/β-actin, transforming growth factor (TGF) β1/β-actin, and FOXP3/β-actin than did IgG4-negative MZL (p < 0.05). This finding further supports our prior observations that a significant subset of ocular MZLs arises in the setting of IgG4-RD. Furthermore, the presence of a different inflammatory background in IgG4-negative MZLs suggests that IgG4-associated MZLs may have a different pathogenesis

Update on the Keio collection of Escherichia coli single-gene deletion mutants

The Keio collection (Baba et al, 2006) has been established as a set of single‐gene deletion mutants of Escherichia coli K‐12. These mutants have a precisely designed deletion from the second codon from the seventh to the last codon of each predicted ORF. Further information is available at http://sal.cs.purdue.edu:8097/GB7/index.jsp or http://ecoli.naist.jp/. The distribution is now being handled by the National Institute of Genetics of Japan (http://www.shigen.nig.ac.jp/ecoli/pec/index.jsp). To date more than 4 million samples have been distributed worldwide. As we described earlier (Baba et al, 2006), gene amplification during construction is likely to have led to a small number of mutants with genetic duplications

Low-grade B-cell lymphoma presenting primarily in the bone marrow

Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma