Renal Lymph Oxygen Tension During Graded Renal Ischemia

Renal lymph oxygen tension in dogs during graded renal ischemi

The use of nitinol rods in stabilization of the lumbar spine for patients under 21 years

The outcomes of surgical treatment of 25 young patients with degenerative diseases of the lumbar spine in two groups were compared in patients with nitinol rods (dynamic stabilization) without spondylodesis and with rigid lumbar fixation of titanium rods. Men - 12, women - 13, the average age is 17.6 years (from 16 to 21 years). These patients are divided into 2 groups depending on the stabilization method. Clinical and radiological results were monitored at least 1 year after the operation. In our study we used nitinol rods of 2 standard sizes - 60 and 80 mm. The size and curvature of the bending of the rods is calculated from the average anatomical parameters characteristic of the lumbar spine and lumbosacral junction. In all groups, there were no statistically significant differences in preoperative values and in the control periods of observation of the VAS (for both the back and the lower limb), Oswestry and SF-36 between patients with nitinol and titanium rods (p> 0.05). In both cases (rigid and dynamic stabilization), statistically significant changes were noted in the postoperative period (p <0.01). In both groups, in comparison with preoperative values, improvement was observed in all control periods, which were highly statistically significant (p <0.01). When studying the mobility in stabilized segment with dynamic nitinol rods, it is determined that the mobility, which persists in 1 segment, averages 4.8°. This index is within the limits of measurement error (up to 5°), however, when measuring mobility in two segments, the mobility is 9.6°. Transpedicular fixation of the lumbosacral spine with the use of nitinol rods is an effective technology that allows to keep movements in the lumbosacral spine in combination with a stable fixation. Further study of this technology should continue, including with reference to deformations of the spine

Transcriptomics of the vaccine immune response: Priming with adjuvant modulates recall innate responses after boosting

Transcriptomic profiling of the immune response induced by vaccine adjuvants is of critical importance for the rational design of vaccination strategies. In this study, transcriptomics was employed to profile the effect of the vaccine adjuvant used for priming on the immune response following re-exposure to the vaccine antigen alone. Mice were primed with the chimeric vaccine antigen H56 of Mycobacterium tuberculosis administered alone or with the CAF01 adjuvant and boosted with the antigen alone. mRNA sequencing was performed on blood samples collected 1, 2, and 7 days after priming and after boosting. Gene expression analysis at day 2 after priming showed that the CAF01 adjuvanted vaccine induced a stronger upregulation of the innate immunity modules compared with the unadjuvanted formulation. The immunostimulant effect of the CAF01 adjuvant, used in the primary immunization, was clearly seen after a booster immunization with a low dose of antigen alone. One day after boost, we observed a strong upregulation of multiple genes in blood of mice primed with H56 + CAF01 compared with mice primed with the H56 alone. In particular, blood transcription modules related to innate immune response, such as monocyte and neutrophil recruitment, activation of antigen-presenting cells, and interferon response were activated. Seven days after boost, differential expression of innate response genes faded while a moderate differential expression of T cell activation modules was appreciable. Indeed, immunological analysis showed a higher frequency of H56-specific CD4+ T cells and germinal center B cells in draining lymph nodes, a strong H56-specific humoral response and a higher frequency of antibody-secreting cells in spleen of mice primed with H56 + CAF01. Taken together, these data indicate that the adjuvant used for priming strongly reprograms the immune response that, upon boosting, results in a stronger recall innate response essential for shaping the downstream adaptive response

Extraribosomal functions associated with the C terminus of the 37/67 kDa laminin receptor are required for maintaining cell viability

The 37/67 kDa laminin receptor (LAMR) is a multifunctional protein, acting as an extracellular receptor, localizing to the nucleus, and playing roles in rRNA processing and ribosome assembly. LAMR is important for cell viability; however, it is unclear which of its functions are essential. We developed a silent mutant LAMR construct, resistant to siRNA, to rescue the phenotypic effects of knocking down endogenous LAMR, which include inhibition of protein synthesis, cell cycle arrest, and apoptosis. In addition, we generated a C-terminal-truncated silent mutant LAMR construct structurally homologous to the Archaeoglobus fulgidus S2 ribosomal protein and missing the C-terminal 75 residues of LAMR, which displays more sequence divergence. We found that HT1080 cells stably expressing either silent mutant LAMR construct still undergo arrest in the G1 phase of the cell cycle when treated with siRNA. However, the expression of full-length silent mutant LAMR rescues cell viability, whereas the expression of the C-terminal-truncated LAMR does not. Interestingly, we also found that both silent mutant constructs restore protein translation and localize to the nucleus. Our findings indicate that the ability of LAMR to regulate viability is associated with its C-terminal 75 residues. Furthermore, this function is distinct from its role in cell proliferation, independent of its ribosomal functions, and may be regulated by a nonnuclear localization

Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

Background Secukinumab is an anti–interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis. Methods In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16. Results In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients. Conclusions Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375.

The Sanandaj–Sirjan Zone in the Neo-Tethyan suture, western Iran: Zircon U–Pb evidence of late Palaeozoic rifting of northern Gondwana and mid-Jurassic orogenesis

The Zagros Orogen, marking the closure of the Neo-Tethyan Ocean, formed by continental collision beginning in the late Eocene to early Miocene. Collision was preceded by a complicated tectonic history involving Pan-African orogenesis, Late Palaeozoic rifting forming Neo-Tethys, followed by Mesozoic convergence on the ocean\u27s northern margin and ophiolite obduction on its southern margin. The Sanandaj-Sirjan Zone is a metamorphic belt in the Zagros Orogen of Gondwanan provenance. Zircon ages have established Pan-African basement igneous and metamorphic complexes in addition to uncommon late Palaeozoic plutons and abundant Jurassic plutonic rocks. We have determined zircon ages from units in the northwestern Sanandaj-Sirjan Zone (Golpaygan region). A sample of quartzite from the June Complex has detrital zircons with U-Pb ages mainly in 800-1050 Ma with a maximum depositional age of 547 ± 32 Ma (latest Neoproterozoic¿earliest Cambrian). A SHRIMP U-Pb zircon age of 336 ± 9 Ma from gabbro in the June Complex indicates a Carboniferous plutonic event that is also recorded in the far northwestern Sanandaj-Sirjan Zone. Together with the Permian Hasanrobat Granite near Golpaygan, they all are considered related to rifting marking formation of Neo-Tethys. Scarce detrital zircons from an extensive package of metasedimentary rocks (Hamadan Phyllite) have ages consistent with the Triassic to Early Jurassic age previously determined from fossils. These ages confirm that an orogenic episode affected the Sanandaj-Sirjan Zone in the Early to Middle Jurassic (Cimmerian Orogeny). Although the Cimmerian Orogeny in northern Iran reflects late Triassic to Jurassic collision of the Turan platform (southern Eurasia) and the Cimmerian microcontinent, we consider that in the Sanandaj-Sirjan Zone a tectonothermal event coeval with the Cimmerian Orogeny resulted from initiation of subduction and closure of rift basins along the northern margin of Neo-Tethys

Early intervention in Moscow preschool education system: shift from rapid growth to quality improvement in preschool early intervention programs in Moscow

Early intervention services and lekoteks in Moscow preschool education system are aimed to help children from several months to 7 years of age with developmental disorders and their parents. The number of such programs reached 200 in 2012 and was growing faster than the number of professionals skilled to work at them. This obvious mismatch situation emerged the need for quality assessment and structured educational programs for specialist initial education and recertification. In this article we discuss the most commonly used protocols in early intervention programs, and current trends in their improvement. We also propose a model for quality standard development in early intervention services and lekoteks, based on worldwide experience and ISO (ISO 9001:2000) quality management principles