The role of histone variant H2A.J in radiation dermatitis

Histone variant H2A.J is connected with premature senescence following ionizing radiation (IR) and modifies senescence-associated secretory phenotype (SASP). Using a preclinical in-vivo model the role of H2A.J was investigated in the acute phase of radiation dermatitis. H2A.J wild-type (WT) and knock-out (KO) mice were exposed to moderate (1x or 5x 2Gy, whole-body IR) or high doses (10Gy or 20Gy, dorsal skinfold IR). Radiation-induced skin reactions were analysed at 24h/ 72h/ 1w/ 2w post-IR at the macroscopic (skin lesions) and microscopic level (hair follicle density, epidermal thickness). H2A.J and other senescence markers (SA-β-Gal, laminB1) were analysed in epidermal keratinocytes by immunohistochemistry and immunofluorescence microscopy. ELISA measurements showed higher cytokine expression in conditioned medium acquired from skin cultures of KO and WT mice. In WT skin epidermal keratinocytes showed a time- and dose-dependent H2A.J accumulation following IR exposure. Unexpectedly, significantly stronger radiation reactions were observed in irradiated KO versus WT skin with stronger inflammatory reactions and hair follicles loss. Clearly more radiation-induced senescence was observed in epidermal keratinocytes of KO versus WT skin after moderate and high IR doses. Among various keratinocyte populations significant differences in senescence induction were observed, with hair follicle stem cells (HFSCs) in bulge regions of KO skin being particularly badly damaged at high doses, leading to increased hair follicle atrophy. Neutrophil-derived myeloperoxidase led to increased tissue damage in irradiated KO skin, and subsequently to excessive proliferation and abnormal differentiation of keratinocytes, probably through regulatory mechanisms of transcription-factor JunB, eventually leading to more pronounced epidermal hyperplasia. In conclusion, through epigenetic regulation of pro-inflammatory genes in response to IR exposure, H2A.J expression in epidermal keratinocytes plays an obligatory role in balancing the innate immune response during radiation dermatitis.Die Histonvariante H2A.J ist mit vorzeitiger Seneszenz nach ionisierender Strahlung (IR) assoziiert und moduliert den Seneszenz-assoziierten sekretorischen Phänotyp (SASP). Anhand eines präklinischen in-vivo-Modells wurde die Rolle von H2A.J in der akuten Phase der Strahlendermatitis untersucht. H2A.J-wild-typ (WT) und knock-out (KO) Mäuse wurden moderaten (1x oder 5x 2Gy, Ganzkörper-IR) oder hohen Dosen (10Gy oder 20Gy, dorsale Hautfalten-IR) ausgesetzt. Strahleninduzierte Hautreaktionen wurden 24h/ 72h/ 1w/ 2w post- IR auf makroskopischer (Hautläsionen) und mikroskopischer Ebene (Haarfollikeldichte, epidermale Dicke) analysiert. H2A.J und andere Seneszenzmarker (SA-β-Gal, LaminB1) wurden in epidermalen Keratinozyten durch Immunhistochemie und Immunfluoreszenzmikroskopie analysiert. In WT-Haut zeigten epidermale Keratinozyten eine zeit- und dosisabhängige H2A.J-Akkumulation nach IR Exposition. Unerwarteterweise wurden signifikant stärkere Strahlenreaktionen bei bestrahlter KO versus WT Haut mit stärkeren Entzündungsreaktionen und Haarfollikelverlust beobachtet. Deutlich mehr strahleninduzierte Seneszenz wurde in epidermalen Keratinozyten von KO im Vergleich zu WT Haut nach moderaten und hohen IR-Dosen beobachtet. Unter verschiedenen Keratinozyten-Populationen wurden signifikante Unterschiede in der Seneszenz-Induktion beobachtet, wobei Haarfollikel-Stammzellen (HFSCs) in Bulge-Regionen der KO Haut bei hohen Dosen besonders stark geschädigt wurden, was zu einer erhöhten Haarfollikel-Atrophie führte. Aus Neutrophilen stammende Myeloperoxidase führte zu einer erhöhten Gewebeschädigung in bestrahlter KO Haut und anschließend zu einer übermäßigen Proliferation und abnormalen Differenzierung von Keratinozyten, wahrscheinlich durch regulatorische Mechanismen des Transkriptionsfaktors JunB, was schließlich zu einer ausgeprägteren epidermalen Hyperplasie führte. Zusammenfassend lässt sich sagen, dass die strahleninduzierte H2A.J Expression in epidermalen Keratinozyten die Entzündungsreaktionen im Rahmen der Strahlendermatitis durch epigenetische Regulationsmechanismen wesentlich beeinflusst

Comparative study with or without application of enhanced recovery after surgery protocols in patients undergoing elective cesarean section

Background: Concept of enhanced recovery after surgery (ERAS) has been applied in various surgical branches. Evidence regarding the necessary components of ERAS for obstetric population is limited. Therefore, objective of this study was to test the application of ERAS in patients undergoing elective caesarean section on the post-operative recovery process.Methods: The study was conducted in the Department of Obstetrics and Gynecology, NMCH, Patna from January 2014 to December 2014. A total of 100 patients (n=100) undergoing elective caesarean section were included in the study. Cases were allocated into two groups a) Study group included 60 patients (n=60) and ERAS protocol was followed b) Control group included 40 patients (n=40) and standard post-operative care protocol was followed. Two groups were compared with respect to recovery parameters, post-operative complications and satisfaction rates.Results: More patients in the ERAS group were discharged on post-operative day 4 than the standard postoperative care group (90% vs 12.5%, p<0.0001). More patient in the ERAS group were significantly satisfied with the protocol compared to standard post-operative care (77% vs 70%, p<0.04). Approximately 77 percent of the patients in the ERAS group rated the satisfication score between 8-10 compared to 70 percent of the patients in control group (p<0.04). There was no difference between two groups with respect to recatheterization rate, readmission rate and post-discharge complaints.Conclusions: In this study with application of ERAS protocol, we reported reduced hospital stay which may reduce financial burden of patients and healthcare facilities

Piloting Service Oriented Architecture—A Case Study in the Oil Industry

The Service Oriented Architecture (SOA) paradigm introduced a few years back has already become the driving force behind enterprise systems. It is also a force behind most cutting edge technologies today. Although much is written about SOA, empirical studies on its implementation are next to none. This exploratory case study examines a pilot implementation at an oil-drilling equipment manufacturing company to understand the process and issues involved in SOA adoption. The study depicts the implementation methodology and the roadmap adopted by this organization to help connect its disparate systems using enterprise SOA. This paper can help researcher better understand SOA implementation and help them further explore the managerial issues involved in implementing this new technology

Vaccination with Leishmania soluble antigen and immunostimulatory oligodeoxynucleotides induces specific immunity and protection against Leishmania donovani infection

In this report, we investigated the effect of ODN containing immunostimulatory CG motifs as adjuvant with soluble antigen (SA) from Leishmania donovani. BALB/c mice were vaccinated with the soluble antigen with or without CpG-ODN as adjuvant and then challenged with L. donovani metacyclic promastigotes. CpG-ODN alone resulted in partial protection against challenge with L. donovani. Immunization of mice with SA and CpG-ODN showed enhanced reduction in parasite load (~60%) when compared to SA (~40%) immunized mice. Immunization with SA by itself resulted in a mixed Th1/Th2 response whereas co-administration of SA with CpG-ODN resulted in a strong Th1 promoting isotype as they together promoted production of immunoglobulin G2a. Leishmania-specific Th1 cytokine response was induced by co-administering CpG-ODN and SA as they together promoted production of IFN-γ and IL-12. In the present study, we demonstrate that immunostimulatory phosphorothioate-modified ODN are promising immune enhancers for vaccination against visceral leishmaniaisis