Sound velocity in perovskite manganites La0.67Ca0.33MnO3 with different grain sizes

The longitudinal and shear sound velocities in colossal magnetoresistive material La0.67Ca0.33MnO3 sintered at 1100, 1250 and 1350 1C with average grain size 1, 3 and 5 mm, respectively, have been measured from 80 to 300K using the pulse-echo-overlap method.A pronounced increase in the longitudinal sound velocity was observed in all samples around the insulator–metal transition temperature (TIM272 K). XRD patterns showed the orthorhombic structure for all samples. The longitudinal and shear velocities showed the largest hysteresis for the sample with 3 mm grain size. A step-like shear sound velocity anomaly near 120K during cooling or warming was observed to be dependent on the grain size

A novel treatment strategy for preterm birth: Intra-vaginal progesterone-loaded fibrous patches

Progesterone-loaded poly(lactic) acid fibrous polymeric patches were produced using electrospinning and pressurized gyration for intra-vaginal application to prevent preterm birth. The patches were intravaginally inserted into rats in the final week of their pregnancy, equivalent to the third trimester of human pregnancy. Maintenance tocolysis with progesterone-loaded patches was elucidated by recording the contractile response of uterine smooth muscle to noradrenaline in pregnant rats. Both progesterone-loaded patches indicated similar results from release and thermal studies, however, patches obtained by electrospinning had smaller average diameters and more uniform dispersion compared to pressurized gyration. Patches obtained by pressurized gyration had better results in production yield and tensile strength than electrospinning; thereby pressurized gyration is better suited for scaled-up production. The patches did not affect cell attachment, viability, and proliferation on Vero cells negatively. Consequently, progesterone-loaded patches are a novel and successful treatment strategy for preventing preterm birth

Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study

The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug

Visceral leishmaniasis in 26 HIV-negative adults

<p>Abstract</p> <p>Background</p> <p>Visceral leishmaniasis is a notifiable parasitic disease that had increased in incidence in our region on the past few years. It is common in children. In adults, it occurs more on a background of immunodeficiency, and frequently with incomplete clinical manifestations, making the diagnosis complicated.</p> <p>Findings</p> <p>The aim of our study is to reveal different features of visceral leishmaniasis in adults, through the analysis of its epidemiological, clinical and biological parameters, in a group of 26 patients. No one was infected with HIV or under immunosuppressive therapy Clinical presentation was generally conservative, but there was few differences in adults compared to children, concerning both the clinical symptoms and the laboratory parameters. Diagnosis was provided by direct examination of bone marrow smears in 24 cases (sensitivity 92%), and anti-leishmanial serology in the others.</p> <p>Conclusion</p> <p>We should think to the diagnosis of VL even if the patient is not known immunocompromised, and even if the clinical is incomplete, to avoid a delay of care which can lead to serious complications.</p

Expression and prognostic significance of cox-2 and p-53 in hodgkin lymphomas: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Cyclooxygenase (cox) is the rate-limiting enzyme, which catalyzes the conversion of arachidonic acid into prostaglandins and contributes to the inflammatory process. Cyclooxygenase-2 (cox-2), which is one of the two isoforms, plays a role in tumor progression and carcinogenesis. p53 contributes to apoptosis, DNA renewal and cell cycle. Studies concerning the relationship of cox-2 and p53 expressions and carcinogenesis are available, but the association between cox-2 and p53 in Hodgkin lymphoma (HL) is not exactly known.</p> <p>In our study, we examined the association of cox-2 and p53 expression, with age, stage, histopathological subtype, and survival in HL. We also examined correlation between cox-2 and p53 expression.</p> <p>Methods</p> <p>Cox-2 and p53 expressions in Hodgkin-Reed Sternberg cells (HRS) were examined in 54 patients with HL depending on cox-2 expression, stained cases were classified as positive, and unstained cases as negative. Nuclear staining of HRS cells with p53 was evaluated as positive. The classifications of positivity were as follows: negative if<10%; (1+) if 10-25%; (2+) if 25-50%; (3+) if 50-75%, (4+) if >75%.</p> <p>Results</p> <p>Cox-2 and p53 expressions were found in 49 (80%) and 29 (46%) patients, respectively. There were differences between histological subtypes according to cox-2 expression (p = 0.012). Mixed cellular (MC) and nodular sclerosing (NS) subtypes were seen most of the patients and cox-2 expression was evaluated mostly in the mixed cellular subtype.</p> <p>There were no statistically significant relationships between p53 and the histopathological subtypes; or between p53, cox-2 and the factors including stage, age and survival; or between p53 and cox-2 expression (p > 0.05).</p> <p>Conclusion</p> <p>Considering the significant relationship between the cox-2 expression and the subtypes of HL, cox-2 expression is higher in MC and NS subtypes. However the difference between these two subtypes was not significant. This submission must be advocated by studies with large series</p

Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

<p>Abstract</p> <p>Background</p> <p>The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation.</p> <p>Methods</p> <p>UVB-irradiated p53^+/-mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling.</p> <p>Results</p> <p>UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19⁺, CD5⁺, B220⁺, IgM⁺and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19) translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression.</p> <p>Conclusion</p> <p>UV-irradiated p53^+/-mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal tumors after chronic exposure to UV light. The induction of B cell lymphoma in UV-irradiated p53 heterozygous mice may provide a useful model for lymphoma development in humans.</p

Treatment and outcome analysis of 639 relapsed non-hodgkin lymphomas in children and adolescents and resulting treatment recommendations

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age < 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Resistance to checkpoint blockade therapy through inactivation of antigen presentation

Treatment with immune checkpoint blockade (CPB) therapies often leads to prolonged responses in patients with metastatic melanoma, but the common mechanisms of primary and acquired resistance to these agents remain incompletely characterized and have yet to be validated in large cohorts. By analyzing longitudinal tumor biopsies from 17 metastatic melanoma patients treated with CPB therapies, we observed point mutations, deletions or loss of heterozygosity (LOH) in beta-2-microglobulin (B2M), an essential component of MHC class I antigen presentation, in 29.4% of patients with progressing disease. In two independent cohorts of melanoma patients treated with anti-CTLA4 and anti-PD1, respectively, we find that B2M LOH is enriched threefold in non-responders (~30%) compared to responders (~10%) and associated with poorer overall survival. Loss of both copies of B2M is found only in non-responders. B2M loss is likely a common mechanism of resistance to therapies targeting CTLA4 or PD1