The STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) were published in five journals in 2001 and 2002. These guidelines, in the form of a checklist and explanations for use by authors and journal editors, were designed to improve reporting of acupuncture trials, particularly the interventions, thereby facilitating their interpretation and replication. Subsequent reviews of the application and impact of STRICTA have highlighted the value of STRICTA as well as scope for improvements and revision.To manage the revision process a collaboration between the STRICTA Group, the CONSORT Group and the Chinese Cochrane Centre was developed in 2008. An expert panel with 47 participants was convened that provided electronic feedback on a revised draft of the checklist. At a subsequent face-to-face meeting in Freiburg, a group of 21 participants further revised the STRICTA checklist and planned dissemination.The new STRICTA checklist, which is an official extension of CONSORT, includes 6 items and 17 subitems. These set out reporting guidelines for the acupuncture rationale, the details of needling, the treatment regimen, other components of treatment, the practitioner background and the control or comparator interventions. In addition, and as part of this revision process, the explanations for each item have been elaborated, and examples of good reporting for each item are provided. In addition, the word ‘controlled’ in STRICTA is replaced by ‘clinical’, to indicate that STRICTA is applicable to a broad range of clinical evaluation designs, including uncontrolled outcome studies and case reports. It is intended that the revised STRICTA checklist, in conjunction with both the main CONSORT statement and extension for non-pharmacological treatment, will raise the quality of reporting of clinical trials of acupuncture.

Hugh MacPherson and colleagues present an updated reporting guideline called STRICTA, which stands for Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture.

No abstract

Recent work in human glioblastoma (GBM) has documented recurrent mutations in the histone chaperone protein ATRX. We developed an animal model of ATRX-deficient GBM and show that loss of ATRX reduces median survival and increases genetic instability. Further, analysis of genome-wide data for human gliomas showed that ATRX mutation is associated with increased mutation rate at the single nucleotide variant (SNV) level. In mouse tumors, ATRX deficiency impairs non-homologous end joining (NHEJ) and increases sensitivity to DNA-damaging agents that induce double-stranded DNA breaks. We propose that ATRX loss results in a genetically unstable tumor, which is more aggressive when left untreated, but is more responsive to double-stranded DNA-damaging agents, resulting in improved overall survival.

SummaryWithin 1 wk ofliqnid culture in granulocyte/macrophage colony-stimulating factor (GM-CSF), normal B10 BR (H-2 k I-E +) mouse liver nonparenchymal cells (NPC) formed loosely adherent mydoid cell clusters that have been shown to contain dendritic cell (DC) progenitors in similar studies of mouse blood or bone marrow. Mononuclear cell progeny released from these clusters at and beyond 4 d exhibited distinct dendritic morphology and were actively phagocytic. After 6-10 d of culture, these cells strongly expressed CD45, CDllb, heat stable antigen, and CD44. However, the intensity of expression of the DC-restricted markers NLDC 145, 33D1, and N418, and the macrophage marker F4/80, intercellular adhesion molecule 1, and Fc~RII was low to moderate, whereas the cells were negative for CD3, CD45RA, and NKI.1. Splenocytes prepared in the same way also had a similar range and intensity of expression of these immunophenotypic markers. Unlike the splenic DC, however, most of the GM-CSF-propagated putative liver DC harvested at 6-10 d expressed only a low level of major histocompatibility complex (MHC) class II (I-Ek), and they failed to induce primary allogeneic responses in naive T cells, even when propagated additionally in GM-CSF and tumor necrosis factor ot and/or interferon V-supplemented medium. However, when 7-d cultured GM-CSF-stimulated liver cells were maintained additionally for three or more days on type-1 collagen-coated plates in the continued presence of GM-CSF, they exhibited characteristics of mature DC: MHC class II expression was markedly upregulated, mixed leukocyte reaction stimulatory activity was increased, and phagocytic function was decreased. Similar observations were made when Ia + cells were depleted from the GM-CSF-propagated cells before exposure to collagen. Further evidence that the GM-CSF-stimnlated class II ~ or dass II-depleted hepatic NPC were immature DC was obtained by injecting them into allogeneic B10 (H-2 s I-E-) recipients. They "homed" to T cell-dependent areas of lymph nodes and spleen where they strongly expressed donor MHC dass II antigen 1-5 d later. These observations provide insight into the regulation of DC maturation, and are congruent with the possibility that the migration of immature DC from normal liver and perhaps other organ allografrs may help explain their inherent tolerogenicity.

We have shown previously that granulocyte-macrophage colony-stimulating factor-stimulated mouse bone marrow-derived MIIC class II+ dendritic cell (DC) progenitors that are deficient in cell surface expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) can induce alloantigen-specific T-cell anergy in vitro. To test the in vivo relevance of these findings, 2x 10 6 BI0 (H2 b ) mouse bone marrow-derived DC progenitors (NLDC 145+, MIIC class II+, B7-1 ditn , B7_2-/dim ) that induced T-cell hyporesponsiveness in vitro were injected systemically into normal C3H (H2k) recipients. Seven days later, the mice received heterotopic heart transplants from BI0 donors. No immunosuppressive treatment was given. Median graft survival time was prolonged significantly from 9.5 to 22 days. Median graft survival time was also increased, although to a lesser extent (16.5 days), in mice that received third-party (BALB/c; H2 d ) DC progenitors. Ex vivo analysis of host T-cell responses to donor and third-party alloantigens 7 days after the injection of DC progenitors (the time of heart transplant) revealed minimal anti-donor mixed leukocyte reaction and cytotoxic T lymphocyte reactivity. These responses were reduced substantially compared with those of spleen cells from animals pretreated with "mature" granulocyte-macrophage colony-stimulating factor + interleukin-4-stimulated DC (MHC class nbr'ght, B7-1 +, B7_2brlght), many of which rejected their heart grafts in an accelerated fashion. Among the injected donor MHC class 11+ DC progenitors that migrated to recipient secondary lymphoid tissue were cells that appeared to have up-regulated cell surface B7-1 and B7-2 molecule expression. This observation may explain, at least in part, the temporary or unstable nature of the hyporesponsiveness induced by the DC progenitors in nonimmunosuppressed recipients.

The STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) were published in five journals in 2001 and 2002. These guidelines, in the form of a checklist and explanations for use by authors and journal editors, were designed to improve reporting of acupuncture trials, particularly the interventions, thereby facilitating their interpretation and replication. Subsequent reviews of the application and impact of STRICTA have highlighted the value of STRICTA as well as scope for improvements and revision. To manage the revision process a collaboration between the STRICTA Group, the CONSORT Group, and the Chinese Cochrane Centre was developed in 2008. An expert panel with 47 participants was convened that provided electronic feedback on a revised draft of the checklist. At a subsequent face-to-face meeting in Freiburg, a group of 21 participants further revised the STRICTA checklist and planned dissemination. The new STRICTA checklist, which is an official extension of CONSORT, includes six items and 17 sub-items. These set out reporting guidelines for the acupuncture rationale, the details of needling, the treatment regimen, other components of treatment, the practitioner background, and the control or comparator interventions. In addition, and as part of this revision process, the explanations for each item have been elaborated, and examples of good reporting for each item are provided. In addition, the word "controlled" in STRICTA is replaced by "clinical," to indicate that STRICTA is applicable to a broad range of clinical evaluation designs, including uncontrolled outcome studies and case reports. It is intended that the revised STRICTA, in conjunction with both the main CONSORT Statement and extension for nonpharmacologic treatment, will raise the quality of reporting of clinical trials of acupuncture.

Survival of glioma (GBM) patients treated with the current standard of care remains dismal. Immunotherapeutic approaches that harness the cytotoxic and memory potential of the host immune system have shown great benefit in other cancers. GBMs have developed multiple strategies, including the accumulation of myeloid-derived suppressor cells (MDSCs) to induce immunosuppression. It is therefore imperative to develop multipronged approaches when aiming to generate a robust anti-tumor immune response. Herein, we tested whether combining MDSC depletion or checkpoint blockade would augment the efficacy of immune-stimulatory herpes simplex type-I thymidine kinase (TK) plus Fms-like tyrosine kinase ligand (Flt3L)-mediated immune stimulatory gene therapy. Our results show that MDSCs constitute >40% of the tumorinfiltrating immune cells. These cells express IL-4Ra, inducible nitric oxide synthase (iNOS), arginase, programmed death ligand 1 (PDL1), and CD80, molecules that are critically involved in antigen-specific T cell suppression. Depletion of MDSCs strongly enhanced the TK/Flt3L gene therapy-induced tumor-specific CD8 T cell response, which lead to increased median survival and percentage of long-term survivors. Also, combining PDL1 or CTLA-4 immune checkpoint blockade greatly improved the efficacy of TK/Flt3L gene therapy. Our results, therefore, indicate that blocking MDSC-mediated immunosuppression holds great promise for increasing the efficacy of gene therapy-mediated immunotherapies for GBM.