FasL and TRAIL signaling in the skin during cutaneous leishmaniasis - implications for tissue immunopathology and infectious control

Cutaneous leishmaniasis (CL) is associated with chronic inflammation and ulceration of the skin. Tissue macrophages serve as host cells and immune activation is necessary for parasite clearance. The balance between immune-mediated tissue destruction and successful clearance of infection is delicate and ulceration has been proposed to be a result of infiltration of activated immune cells into the skin. FasL and TRAIL play a dual role in skin homeostasis through induction of apoptosis as well as proinflammatory signaling. During leishmaniasis, dysregulation of both FasL and TRAIL has been described by us and others but the resulting pathogenic effects in the skin during human leishmaniasis are not fully elucidated. Targeting disease specific immune deviations has proven to be a promising new approach for the therapy of autoimmune diseases. Potentially, targeting FasL or TRAIL in combination with microcidals could offer a future treatment strategy to reduce the disfiguring immunopathology associated with CL. In this mini review we will discuss how FasL and TRAIL-induced signaling may influence on the extent of tissue inflammation and the efficacy of parasite clearance in leishmaniasis

USAHA MENINGKATKAN INFORMASI SEKSUAL DENGAN MENGGUNAKAN TEKNIK DISKUSI DALAM BIMBINGAN KELOMPOK PADA SISWA KELAS XI IPA 2 SMA NEGERI 1 GAMPING TAHUN AJARAN 2016/2017

Pemberian informasi seksual pada siswa sangat penting. Hal ini bisa menjadi bekal siswa dalam menjalani aktivitas sosialnya baik di masyarakat maupun di sekolah, selain itu juga dapat mencegah aktivitas-aktivitas seksual yang tidak sehat dan terhindar dari informasi seksual yang tidak benar. Siswa dalam memperoleh informasi seksual dirasa masih minim, hal tersebut disebabkan karena pengetahuan orang tua maupun masyarakat yang masih menganggap tabu untuk memberi informasi mengenai seksual. Siswa membutuhkan informasi yang relavan untuk menambah pengetahuan terkait infornasi seksual yang benar. Penelitian ini bertujuan mengetahui peningkatan informasi seksual dengan menggunakan teknik diskusi dalam bimbingan kelompok pada siswa kelas XI IPA 2 SMA Negeri 1 Gamping tahun ajaran 2016/2017. Penelitian ini termasuk dalam penelitian eksperimen dengan desain penelitian one group pre-test and post-test. Media yang digunakan dalam penelitian ini adalah artikel, video dan handout power point. Subyek penelitian sebanyak 10 siswa yang memiliki nilai rata-rata rendah. Pengumpulan data dengan menggunakan instrumen berupa obseravsi dan tes mengenai informasi seksual, untuk uji validitas dan reliabilitas menggunakan validitas butir soal. Media tersebut digunakan agar siswa lebih antusias serta membantu siswa agar lebih mudah memahami materi dan lebih aktif dalam proses diskusi. Berdasarkan hasil penelitian yang dilakukan, bahwa dengan pemberian layanan diskusi kelompok dapat meningkatkan informasi seksual pada siswa. Hal tersebut ditunjukkan dari adanya perbedaan yang signifikan dilihat dari mean sebelum dilakukan diskusi kelompok sebesar 17,5 sedangkan mean setelah dilakukan diskusi kelompok sebesar 28,9. Berdasarkan uji Kolmogorov-Smirnov, harga Asymp Sig (2- tailed) pre test yaitu 0,502 dan post tes 0,995 yaitu lebih besar dari alpha yang ditetapkan yaitu 5% (0,05) sehingga Ho diterima. Dengan demikian variabel penelitian membentuk distribusi normal terhadap populasinya. Jadi dapat disimpulkan “adanya peningkatan informasi seksual dengan menggunakan teknik diskusi dalam bimbingan kelompok pada siswa kelas XI IPA 2 SMA Negeri 1 Gamping tahun ajaran 2016/2017”

Corruption as Business Challenge in Pakistan

Corruption is a curse for any country, as it negatively affects the economic activities and drags the whole society to worst conditions by increasing the poverty and social inequities. Recently the most critical factor for doing business in Pakistan is corruption. In order to give a comprehensive picture of corruption in Pakistan this article (1) critically analyses the literature regarding corruption, its impact on society and the business environment specifically in Pakistan, (2) focuses on business-related factors of corruption, (3) presents various anti-corruption initiatives of Pakistani companies and foreign good examples. Based on our research this study emphasizes that the government should take corrective actions and strengthen institutions and should work in collaboration with the private and civil sector to control the uprising corruption problems. Awareness against corruption in business sphere and general public is very much needed and implementing possible anti-corruption tools, companies can positively contribute to the fight against corruption and Pakistan's economic and social development

Assessment of Antibacterial Activity of Four Endodontic Sealers against Enterococcus Faecalis by a Direct Contact Test: An In-Vitro Study

Antibiotic activity of endodontic sealers can improve the success rate of endodontic treatment provided the physical properties are not compromised. The dentin adhesive sealers are superior in case of manipulation, radio opacity, setting time, and excellent adaptation to canal walls, but the antibacterial activity of the Urethane dimethacrylate resin based and Polydimethyl siloxane based sealers is questionable. An in-vitro experimental study was formulated to evaluate the antibacterial activity of four endodontic sealers on Enterococcus faecalis by a Direct Contact Test. The study materials grouped and selected were Group I, Calcium- hydroxide based sealer (Sealapex), Group II, Polydimethyl siloxane based (RoekoSeal), Group III ,Urethane dimethacrylate resin based sealer (Endo Rez), Group IV Zinc Oxide Eugenol based sealer (Tubli-Seal EWT). The sealers were mixed in strict compliance with the manufacturer's recommendations. The direct contact test was performed based on turbidometric determination of bacterial growth in 96 well microtiter plates. The kinetics of the outgrowth in each well was monitored at 600 nm at 370C. Side walls of the microtiter plate wells were coated with freshly mixed tested material and a 10 μL bacterial suspension was placed. After 1 hr of incubation at 37°C which ensured direct contact between bacteria and tested material, Brain Heart Infusion broth (245 μL) was added to each of these wells and gently mixed for 2 min. These were designated as ‘A’ wells. 15 μL were then transferred from these A wells to an adjacent set of 4 wells containing fresh medium (215 μL) which were designated as ‘B’ wells. The bacterial outgrowth was monitored both in the presence (A wells) and in the absence of the tested material (B wells). The recordings were based on the reading of the transmittance values in the spectrophotometer. Higher the transmittance value, the higher was the antimicrobial activity (i.e. less microbial growth).The microbial growth was recorded every 1 hour using a spectrophotometer for 7 hours at time intervals of 20mts, 1 day and 7 days. The results obtained were subjected to statistical analysis by Kruskal Wallis One way Anova and Mann –Whitney ‘U’ test. CONCLUSION: Under the limitations of this study, the following conclusions were inferred: 1. Endodontic root canal sealers had different inhibitory effects on Enterococcus faecalis during the growth period. 2. Calcium hydroxide based sealer (Sealapex) had an initial antibacterial activity for 10 hours, which slowly reduced with time. 3. Polydimethyl siloxane based (RoekoSeal) endodontic sealer underwent a brisk decrease in antibacterial activity after 3 hours followed by a decrease in its antibacterial activity at 1day and 7 days. 4. Urethane dimethacrylate resin (EndoRez) based sealer had no antimicrobial property. 5. Zinc oxide Eugenol based sealer (Tubli-Seal EWT) was the most effective and Urethane dimethacrylate resin based sealer (EndoRez) was the least effective against Enterococcus faecalis

The Impact of Inflammation and Immune Activation on B Cell Differentiation during HIV-1 Infection

One important pathogenic feature of human immunodeficiency virus (HIV)-1 infection is chronic immune activation and impaired survival of T and B cells. A decline of resting memory B cells was reported to occur in both children and adults infected with HIV-1; these cells are responsible for maintaining an adequate serological response to antigens previously encountered in life through natural infection or vaccination. Further understanding of the mechanisms leading to impaired B cell differentiation and germinal center reaction might be essential to design new HIV vaccines and therapies that could improve humoral immune responses in HIV-1 infected individuals. In the present article we summarize the literature and present our view on critical mechanisms of B cell development impaired during HIV-1 infection. We also discuss the impact of microbial translocation, a driving force for persistent inflammation during HIV-1 infection, on survival of terminally differentiated B cells and how the altered expression of cytokines/chemokines pivotal for communication between T and B cells in lymphoid tissues may impair formation of memory B cells

Diagnosis of Spinocerebellar Ataxia in the West Indies

Background: Access to medical care in many regions is limited by socioeconomic status, at both the individual and the community level. This report describes the diagnostic process of a family residing on an underserved Caribbean island where routine neurological care is typically addressed by general practitioners, and genetic diagnosis is not available through regular medical channels. The diagnosis and management of neurodegenerative disorders is especially challenging in this setting. Case Report: We diagnosed a family with spinocerebellar ataxia type 3 (SCA3) in an underdeveloped nation with limited access to genetic medicine and no full-time neurologist. Discussion: Molecular diagnosis of the SCAs can be challenging, even in developed countries. In the Caribbean, genetic testing is generally only available at a small number of academic centers. Diagnosis in this family was ultimately made by utilizing an international, pro bono, research-based collaborative process. Although access to appropriate resources, such as speech, physical, and occupational therapies, is limited on this island because of economic and geographical factors, the provision of a diagnosis appeared to be ultimately beneficial for this family. Identification of affected families highlights the need for access to genetic diagnosis in all communities, and can help direct resources where needed

Case Report Idiopathic Gingival Fibromatosis Rehabilitation: A Case Report with Two-Year Followup

Gingival enlargements are quite common and may be either inflammatory, noninflammatory, or a combination of both. Gingival hyperplasia is a bizarre condition causing esthetic, functional, psychological, and masticatory disturbances of the oral cavity. Causes of gingival enlargement can be due to plaque accumulation, due to poor oral hygiene, inadequate nutrition, or systemic hormonal stimulatio

Supplementation with fish oil and genistein, individually or in combination, protects bone against the adverse effects of methotrexate chemotherapy in rats

Cancer chemotherapy has been shown to induce long-term skeletal side effects such as osteoporosis and fractures; however, there are no preventative treatments. This study investigated the damaging effects of anti-metabolite methotrexate (MTX) subcutaneous injections (0.75 mg/kg BW) for five days and the potential protective benefits of daily oral gavage of fish oil at 0.5 mL/100 g BW (containing 375 mg of n-3 PUFA/100 g BW), genistein (2 mg/100 g BW), or their combination in young adult rats. MTX treatment alone significantly reduced primary spongiosa height and secondary spongiosa trabecular bone volume. Bone marrow stromal cells from the treated rats showed a significant reduction in osteogenic differentiation but an increase in adipogenesis ex vivo. Consistently, stromal cells had significantly higher mRNA levels of adipogenesis-related proliferator activator activated receptor-γ (PPAR-γ) and fatty acid binding protein (FABP4). MTX significantly increased the numbers of bone-resorbing osteoclasts and marrow osteoclast precursor cell pool while significantly enhancing the mRNA expression of receptor activator for nuclear factor kappa B ligand (RANKL), the RANKL/osteoprotegerin (OPG) ratio, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the bone. Supplementary treatment with fish oil and/or genistein significantly preserved trabecular bone volume and osteogenesis but suppressed MTX-induced adipogenesis and increases in osteoclast numbers and pro-osteoclastogenic cytokine expression. Thus, Fish oil and/or genistein supplementation during MTX treatment enabled not only preservation of osteogenic differentiation, osteoblast number and bone volume, but also prevention of MTX treatment-induced increases in bone marrow adiposity, osteoclastogenic cytokine expression and osteoclast formation, and thus bone loss. © 2013 Raghu Nadhanan et al

IL-7 Promotes CD95-Induced Apoptosis in B Cells via the IFN-γ/STAT1 Pathway

Interleukin-7 (IL-7) concentrations are increased in the blood of CD4+ T cell depleted individuals, including HIV-1 infected patients. High IL-7 levels might stimulate T cell activation and, as we have shown earlier, IL-7 can prime resting T cell to CD95 induced apoptosis as well. HIV-1 infection leads to B cell abnormalities including increased apoptosis via the CD95 (Fas) death receptor pathway and loss of memory B cells. Peripheral B cells are not sensitive for IL-7, due to the lack of IL-7Ra expression on their surface; however, here we demonstrate that high IL-7 concentration can prime resting B cells to CD95-mediated apoptosis via an indirect mechanism. T cells cultured with IL-7 induced high CD95 expression on resting B cells together with an increased sensitivity to CD95 mediated apoptosis. As the mediator molecule responsible for B cell priming to CD95 mediated apoptosis we identified the cytokine IFN-γ that T cells secreted in high amounts in response to IL-7. These results suggest that the lymphopenia induced cytokine IL-7 can contribute to the increased B cell apoptosis observed in HIV-1 infected individuals

Novel perspectives of target-binding by the evolutionarily conserved PP4 phosphatase

Protein phosphatase 4 (PP4) is an evolutionarily conserved and essential Ser/Thr phosphatase that regulates cell division, development and DNA repair in eukaryotes. The major form of PP4, present from yeast to human, is the PP4c-R2-R3 heterotrimeric complex. The R3 subunit is responsible for substrate-recognition via its EVH1 domain. In typical EVH1 domains, conserved phenylalanine, tyrosine and tryptophan residues form the specific recognition site for their target's proline-rich sequences. Here, we identify novel binding partners of the EVH1 domain of the Drosophila R3 subunit, Falafel, and demonstrate that instead of binding to proline-rich sequences this EVH1 variant specifically recognizes atypical ligands, namely the FxxP and MxPP short linear consensus motifs. This interaction is dependent on an exclusively conserved leucine that replaces the phenylalanine invariant of all canonical EVH1 domains. We propose that the EVH1 domain of PP4 represents a new class of the EVH1 family that can accommodate low proline content sequences, such as the FxxP motif. Finally, our data implicate the conserved Smk-1 domain of Falafel in target-binding. These findings greatly enhance our understanding of the substrate-recognition mechanisms and function of PP4