Stlmmsr~Human immunodeficiency virus (HIV) infection of brain macrophages and astroglial proliferation are central features of HIV-induced central nervous system (CNS) disorders. These observations suggest that glial cellular interactions participate in disease. In an experimental system to examine this process, we found that cocultures of HIV-infected monocytes and astroglia release high levels of cytokines and arachidonate metabolites leading to neuronotoxicity. HIV-l^D^-infected monocytes cocultured with human glia (astrocytoma, neuroglia, and primary human astrocytes) synthesized tumor necrosis factor (TNF-o 0 and interleukin 1B (IblB) as assayed by coupled reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and biological activity. The cytokine induction was selective, cell specific, and associated with induction of arachidonic acid metabolites. TNF-B, Iblc~, IL-6, interferon c~ (IFN-c~), and IFN-'y were not produced. Leukotriene B4, leukotriene D4, lipoxin A4, and platelet-activating factor were detected in large amounts after high-performance liquid chromatography separation and correlated with cytokine activity. Specific inhibitors of the arachidonic cascade markedly diminished the cytokine response suggesting regulatory relationships between these factors. Cocultures of HIV-infected monocytes and neuroblastoma or endothelial cells, or HIV-infected monocyte fluids, sucrose gradient-concentrated viral particles, and paraformaldehyde-fixed or freeze-thawed HIV-infected monocytes placed onto astroglia failed to induce cytokines and neuronotoxins. This demonstrated that viable monocyte-astroglia interactions were required for the cell reactions. The addition of actinomycin D or cycloheximide to the HIV-infected monocytes before coculture reduced, >2.5-fold, the levels of TNF-o~. These results, taken together, suggest that the neuronotoxicity associated with HIV central nervous system disorders is mediated, in part, through cytokines and arachidonic acid metabolites, produced during cell-to-cell interactions between HIV-infected brain macrophages and astrocytes.

SUMMARY Forty-nine Israeli Jewish patients with rheumatoid arthritis (RA) were studied for their HLA A, B, C, DR antigen frequency. A significant increase in HLA Aw3l and HLA DR1 was observed (p<5 100' and p<5 10 ' respectively). 45% of Aw31 positive patients were seronegative for rheumatoid factor, while most HLA DR1 positive individuals were seropositive. DR5 was found to be significantly decreased (p<5 10-4). Contrary to previous reports, DRw4 was found to be within the range of antigen frequency of the controls (34*7 % vs. 32 %). It is suggested that in our population of patients Aw3l and DR1 and not DR4 are highly associated with adult onset of RA.Rheumatoid arthritis (RA) is a diseases with abundant evidence for immunological abnormalities, and it was therefore of interest to look for its associations with the major histocompatibility complex.' In the past, testing for the HLA A and B polymorphisms did not yield any significant associations with RA,' but, when HLA D and DR were described and tested for, it was readily established that adult onset of RA is significantly associated with HLA Dw4 and DR4.3-6 These observations were later confirmed by several investigators working collaboratively during the 7th and 8th International Histocompatibility Workshops.7 8 In familial RA it was later possible to map the susceptibility locus RLA-1 to chromosome 6, centromeric to locus HLA D.9We have observed in the past that our population does not always follow the same HLA and disease association,'01' and it seemed important to reevaluate the situation in our RA patients. Table. HLA Aw3l and DR1 were both increased. Aw3l frequency was 18 4 % in the total patient group compared with less than 1 % in the control population (p<5 10-'). Similar results were obtained when the 403 on 11 May 2018 by guest. Protected by copyright.

BACKGROUND Freeze-all IVF cycles are becoming increasingly prevalent for a variety of clinical indications. However, the actual treatment objectives and preferred treatment regimens for freeze-all cycles have not been clearly established. OBJECTIVE AND RATIONALE We aimed to conduct a systematic review of all aspects of ovarian stimulation for freeze-all cycles. SEARCH METHODS A comprehensive search in Medline, Embase and The Cochrane Library was performed. The search strategy included keywords related to freeze-all, cycle segmentation, cumulative live birth rate, preimplantation genetic diagnosis, preimplantation genetic testing for aneuploidy, fertility preservation, oocyte donation and frozen-thawed embryo transfer. We included relevant studies published in English from 2000 to 2018. OUTCOMES Our search generated 3292 records. Overall, 69 articles were included in the final review. Good-quality evidence indicates that in freeze-all cycles the cumulative live birth rate increases as the number of oocytes retrieved increases. Although the risk of severe ovarian hyperstimulation syndrome (OHSS) is virtually eliminated in freeze-all cycles, there are certain risks associated with retrieval of large oocyte cohorts. Therefore, ovarian stimulation should be planned to yield between 15 and 20 oocytes. The early follicular phase is currently the preferred starting point for ovarian stimulation, although luteal phase stimulation can be used if necessary. The improved safety associated with the GnRH antagonist regimen makes it the regimen of choice for ovarian stimulation in freeze-all cycles. Ovulation triggering with a GnRH agonist almost completely eliminates the risk of OHSS without affecting oocyte and embryo quality and is therefore the trigger of choice. The addition of low-dose hCG in a dual trigger has been suggested to improve oocyte and embryo quality, but further research in freeze-all cycles is required. Moderate-quality evidence indicates that in freeze-all cycles, a moderate delay of 2–3 days in ovulation triggering may result in the retrieval of an increased number of mature oocytes without impairing the pregnancy rate. There are no high-quality studies evaluating the effects of sustained supraphysiological estradiol (E2) levels on the safety and efficacy of freeze-all cycles. However, no significant adverse effects have been described. There is conflicting evidence regarding the effect of late follicular progesterone elevation in freeze-all cycles. WIDER IMPLICATIONS Ovarian stimulation for freeze-all cycles is different in many aspects from conventional stimulation for fresh IVF cycles. Optimisation of ovarian stimulation for freeze-all cycles should result in enhanced treatment safety along with improved cumulative live birth rates and should become the focus of future studies.

In our experience, laparoscopic surgery in advanced pregnancy was found to be feasible and safe as in early pregnancy, without any adverse effects on pregnancy outcome.