The diverse chemistry of protoplanetary disks as revealed by JWST.

Early results from the James Webb Space Telescope-Mid-InfraRed Instrument (JWST-MIRI) guaranteed time programs on protostars (JOYS) and disks (MINDS) are presented. Thanks to the increased sensitivity, spectral and spatial resolution of the MIRI spectrometer, the chemical inventory of the planet-forming zones in disks can be investigated with unprecedented detail across stellar mass range and age. Here, data are presented for five disks, four around low-mass stars and one around a very young high-mass star. The mid-infrared spectra show some similarities but also significant diversity: some sources are rich in CO2, others in H2O or C2H2. In one disk around a very low-mass star, booming C2H2 emission provides evidence for a "soot" line at which carbon grains are eroded and sublimated, leading to a rich hydrocarbon chemistry in which even di-acetylene (C4H2) and benzene (C6H6) are detected. Together the data point to an active inner disk gas-phase chemistry that is closely linked to the physical structure (temperature, snowlines, presence of cavities and dust traps) of the entire disk and which may result in varying CO2/H2O abundances and high C/O ratios >1 in some cases. Ultimately, this diversity in disk chemistry will also be reflected in the diversity of the chemical composition of exoplanets.

Flow Diversion of Posterior Circulation Aneurysms: Systematic Review of Disaggregated Individual Patient Data.

BACKGROUND: Experience with endoluminal flow diversion for the treatment of posterior circulation aneurysms is limited. PURPOSE: We sought to investigate factors associated with the safety and efficacy of this treatment by collecting disaggregated patient-level data from the literature. DATA SOURCES: PubMed, EMBASE, and Ovid were searched up through 2019 for articles reporting flow diversion of posterior circulation aneurysms. STUDY SELECTION: Eighty-four studies reported disaggregated data for 301 separate posterior circulation aneurysms. DATA ANALYSIS: Patient, aneurysm, and treatment factors were collected for each patient. Outcomes included the occurrence of major complications, angiographic occlusion, and functional outcomes based on the mRS. DATA SYNTHESIS: Significant differences in aneurysm and treatment characteristics were seen among different locations. Major complications occurred in 22%, angiographic occlusion was reported in 65% (11.3 months of mean follow-up), and good functional outcomes (mRS 0-2) were achieved in 67% (13.3 months of mean follow-up). Multivariate analysis identified age, number of flow diverters used, size, and prior treatment to be associated with outcome measures. Meta-analysis combining the current study with prior large nondisaggregated series of posterior circulation aneurysms treated with flow diversion found a pooled incidence of 20% (n = 712 patients) major complications and 75% (n = 581 patients) angiographic occlusions. LIMITATIONS: This study design is susceptible to publication bias. Use of antiplatelet therapy was not uniformly reported. CONCLUSIONS: Endoluminal flow diversion is an important tool in the treatment of posterior circulation aneurysms. Patient age, aneurysm size, prior treatment, and the number of flow diverters used are important factors associated with complications and outcomes.

Carotid Stenting without Embolic Protection Increases Major Adverse Events: Analysis of the National Surgical Quality Improvement Program.

BACKGROUND AND PURPOSE: Published data regarding embolic protection device efficacy is mixed, and its use during carotid artery stent placement remains variable. We, therefore, examined the frequency of embolic protection device use and its association with outcomes after carotid artery stent placement using a national quality improvement data base. MATERIALS AND METHODS: Patients undergoing carotid artery stent placement with or without embolic protection devices were identified in the American College of Surgeons National Surgical Quality Improvement Program data base. The primary outcome was the incidence of major adverse cardiovascular events (defined as death, stroke, or myocardial infarction/arrhythmia) within 30 days. Propensity scoring was used to create 2 matching cohorts of patients using demographic and baseline variables. RESULTS: Between 2011 and 2018, among 1200 adult patients undergoing carotid artery stent placement, 23.8% did not have embolic protection devices. There was no trend toward increased embolic protection device use with time. Patients without embolic protection device use received preoperative antiplatelets less frequently (90.6% versus 94.6%, P = .02), underwent more emergent carotid artery stent placement (7.2% versus 3.6%, P = .01), and had a higher incidence of major adverse cardiovascular events (OR = 1.81; 95% CI, 1.11-2.94) and stroke (OR = 3.31; 95% CI, 1.71-6.39). After compensating for baseline imbalances using propensity-matched cohorts (n = 261 for both), carotid artery stent placement without an embolic protection device remained associated with increased major adverse cardiovascular events (9.2% versus 4.2%; OR = 2.30; 95% CI, 1.10-4.80) and stroke (6.5% versus 1.5%; OR = 4.48; 95% CI, 1.49-13.49). CONCLUSIONS: Lack of embolic protection device use during carotid artery stent placement is associated with a 4-fold increase in the likelihood of perioperative stroke. Nevertheless, nearly one-quarter of patients in the American College of Surgeons National Surgical Quality Improvement Program underwent unprotected carotid artery stent placement. Efforts targeting improved embolic protection device use during carotid artery stent placement are warranted.

Combination of isocitrate dehydrogenase 1 (IDH1) mutation and podoplanin expression in brain tumors identifies patients at high or low risk of venous thromboembolism.

Essentials Risk stratification for venous thromboembolism (VTE) in patients with brain tumors is challenging. Patients with IDH1 wildtype and high podoplanin expression have a 6-month VTE risk of 18.2%. Patients with IDH1 mutation and no podoplanin expression have a 6-month VTE risk of 0%. IDH1 mutation and podoplanin overexpression in primary brain tumors appear to be exclusive. SUMMARY: Background Venous thromboembolism (VTE) is a frequent complication in primary brain tumor patients. Independent studies revealed that podoplanin expression in brain tumors is associated with increased VTE risk, whereas the isocitrate dehydrogenase 1 (IDH1) mutation is associated with very low VTE risk. Objectives To investigate the interrelation between intratumoral podoplanin expression and IDH1 mutation, and their mutual impact on VTE development. Patients/Methods In a prospective cohort study, intratumoral IDH1 R132H mutation and podoplanin were determined in brain tumor specimens (mainly glioma) by immunohistochemistry. The primary endpoint of the study was symptomatic VTE during a 2-year follow-up. Results All brain tumors that expressed podoplanin to a medium-high extent showed also an IDH1 wild-type status. A score based on IDH1 status and podoplanin expression levels allowed prediction of the risk of VTE. Patients with wild-type IDH1 brain tumors and high podoplanin expression had a significantly increased VTE risk compared with those with mutant IDH1 tumors and no podoplanin expression (6-month risk 18.2% vs. 0%). Conclusions IDH1 mutation and podoplanin overexpression seem to be exclusive. Although brain tumor patients with IDH1 mutation are at very low risk of VTE, the risk of VTE in patients with IDH1 wild-type tumors is strongly linked to podoplanin expression levels.

All-inorganic large-area low-cost and durable flexible perovskite solar cells using copper foil as a substrate.

Here, a low-cost perovskite solar cell using CuI and ZnO as the respective inorganic hole and electron transport layers is introduced. Copper foil is chosen as a cheap and low-weight conductive substrate which has a similar work function to ITO. Besides, copper foil is an interesting copper atom source for the growth of the upper cuprous iodide layer on copper foil. A spray coating of a transparent silver nanowire electrode is used as a top contact. The prepared device shows a maximum power conversion efficiency of 12.80% and long-term durability providing an environmentally and market friendly perovskite solar cell.

The antimicrobial effects and metabolomic footprinting of carboxyl-capped bismuth nanoparticles against Helicobacter pylori.

Organic salts of bismuth are currently used as antimicrobial agents against Helicobacter pylori. This study evaluated the antibacterial effect of elemental bismuth nanoparticles (Bi NPs) using a serial agar dilution method for the first time against different clinical isolates and a standard strain of H. pylori. The Bi NPs were biologically prepared and purified by a recently described method and subjected to further characterization by infrared spectroscopy and anti-H. pylori evaluation. Infrared spectroscopy results showed the presence of carboxyl functional groups on the surface of biogenic Bi NPs. These biogenic nanoparticles showed good antibacterial activity against all tested H. pylori strains. The resulting MICs varied between 60 and 100 µg/ml for clinical isolates of H. pylori and H. pylori (ATCC 26695). The antibacterial effect of bismuth ions was also tested against all test strains. The antimicrobial effect of Bi ions was lower than antimicrobial effect of bismuth in the form of elemental NPs. The effect of Bi NPs on metabolomic footprinting of H. pylori was further evaluated by (1)H NMR spectroscopy. Exposure of H. pylori to an inhibitory concentration of Bi NPs (100 µg/ml) led to release of some metabolites such as acetate, formic acid, glutamate, valine, glycine, and uracil from bacteria into their supernatant. These findings confirm that these nanoparticles interfere with Krebs cycle, nucleotide, and amino acid metabolism and shows anti-H. pylori activity.

Biosynthesis of bismuth nanoparticles using Serratia marcescens isolated from the Caspian Sea and their characterisation.

Today, synthesis of nanoparticles (NPs) using micro-organisms has been receiving increasing attention. In this investigation, a bismuth-reducing bacterium was isolated from the Caspian Sea in Northern Iran and was used for intracellular biosynthesis of elemental bismuth NPs. This isolate was identified as non-pigmented Serratia marcescens using conventional identification assays and the 16s rDNA fragment amplification method and used to prepare bismuth NPs. The biogenic bismuth NPs were released by liquid nitrogen and highly purified using an n-octanol water two-phase extraction system. Different characterisations of the purified NPs such as particle shapes, size and purity were carried out with different instruments. The energy-dispersive X-ray and X-ray diffraction (XRD) patterns demonstrated that the purified NPs consisted of only bismuth and are amorphous. In addition, the transmission electron micrograph showed that the small NPs formed larger aggregated NPs around <150 nm. Although the chemical syntheses of elemental bismuth NPs have been reported in the literature, the biological synthesis of elemental bismuth NPs has not been published yet. This is the first report to demonstrate a biological method for synthesising bismuth NPs and their purification with a simple solvent partitioning method.

Evidence that the adverse effect of controlled ovarian hyperstimulation on successful pregnancy outcome following embryo transfer may be related to premature trophoblast invasion.

PURPOSE: To determine if premature trophoblast invasion may be a contributing factor to lower fecundity associated with controlled ovarian hyperstimulation (COH) and in vitro fertilization (IVF). METHODS: Blood samples were obtained three-five days after ET to measure expression by lymphocytes of a 34 kDa protein known as the progesterone-induced blocking factor (PIBF) using an immunocytochemistry technique. Clinical and viable pregnancy rates were determined according to whether PIBF was detected or not. RESULTS: Progesterone-induced blocking factor was positive in 14 of 67 (21%). Clinical pregnancy rates following fresh ET were 7.1% for those positive for PIBF versus 43.4% for those negative for PIBF. CONCLUSIONS: Progesterone-induced blocking factor production requires allogeneic induction of progesterone receptors in gamma/delta T-cells. This suggests early detection of PIBF may be related to premature trophoblast invasion possibly into an endometrium not yet prepared for the trophoblast, thus possibly leading to early immune rejection of the fetus.

Prognosis following in vitro fertilization-embryo transfer (IVF-ET) in patients with elevated day 2 or 3 serum follicle stimulating hormone (FSH) is better in younger vs older patients.

PURPOSE: To determine if younger women with increased day 2 or 3 serum follicle stimulating hormone (FSH) levels have a better prognosis than older women with similar FSH elevations. METHODS: Retrospective comparison of in vitro fertilization (IVF) outcome from cycles from 1/1/97 to 9/30/99 according to serum FSH < or = 12 vs > 12 and age < or = 38 or > 38. Only cycles where follicular phase leuprolide acetate was used were included. RESULTS: Age group < or = 38 - clinical pregnancy rate (PR)/transfer was 32% with lower FSH vs 28.6% with higher FSH. The respective PRs for the older group were 30.3% and 5.5%. CONCLUSIONS: Oocyte quality as evidenced by PRs following IVF-ET seems to be better in younger vs older patients despite increased basal serum FSH levels.

Presence of LH in gonadotropins associated with higher IVF pregnancy rates when basal serum LH is increased.

PURPOSE: To determine if pregnancy rates following in vitro fertilization-embryo transfer (IVF-ET) correlate with the presence or not of luteinizing hormone (LH) in the gonadotropins used for stimulation. Furthermore to see if the early follicular phase serum LH level affects pregnancy outcome according to the type of gonadotropins used. METHODS: The type of gonadotropins were prescribed randomly according to finances and convenience. Serum LH was obtained on day 2 or 3 of the menstrual cycle. RESULTS: When LH was > the median, significantly higher pregnancy rates were obtained in those treated with the follicle stimulating hormone (FSH)/human menopausal gonadotropin combination. When LH was < or = the median, significantly more oocytes were retrieved with FSH exclusively. No confounding variables were found to explain the data. CONCLUSIONS: Considering concerns of published studies that LH may have a toxic effect on pregnancy outcome, and if LH is suppressed too low, gonadotropins with exclusive FSH may not stimulate sufficient oocytes, the results were opposite to expectations.

A model for potential tumor immunotherapy based on knowledge of immune mechanisms responsible for spontaneous abortion.

Attempts to treat various cancers by immunotherapy have been tried for about 50 years. Most studies have focused on improving cytotoxic T lymphocyte (CTL) responses against various tumors. Immunotherapy has been both active and passive, and results have been modest at best. Spontaneous abortion (SAB) of pregnancies could in some ways resemble remission of a tumor. Both tumors and conceptusses are faced with a similar problem -- how to grow in a host in a vascular rich area, and yet escape immune surveillance despite both entities being an allogenic stimulus. In general, the fetus is far more immunogenic than a spontaneous tumor, and yet abortuses seem to avoid CTL responses but are sometimes invaded by natural killer (NK) cells. There are data suggesting that SAB will occur if there is inhibition of production of an immunosuppressive protein called progesterone-induced blocking factor (PIBF). This protein inhibits NK cell cytolysis and influences TH2 cytokine dominance over TH1. If some tumors avoid NK cell destruction through a PIBF mechanism, perhaps an active rejection of these tumors could be achieved by inhibiting PIBF production by treating with a progesterone receptor antagonist. Passive immunization could also be considered by conjugative radionuclide or toxic chemical to a PIBF antibody which may be tumor specific since PIBF is not produced in normal tissue. The first step should be to see if PIBF can be detected in the peripheral circulation in patients with certain tumors.

A corpus luteum is not a prerequisite for the expression of progesterone induced blocking factor by T-lymphocytes a week after implantation.

PURPOSE: To determine if production of the immunomodulatory protein, progesterone induced blocking factor (PIBF), requires merely progesterone or whether other factors made by the corpus luteum are required. METHODS: The percentage of peripheral lymphocytes expressing PIBF was determined by obtaining a blood sample from women 9-12 days after embryo transfer. The embryos were either fresh ones following hyperstimulation and oocyte retrieval or were frozen-thawed embryos. Preparation for frozen embryo transfer required corpus luteum suppression with exogenous estrogen. The percentage of lymphocytes expressing PIBF was determined by an immunocytochemistry method. RESULTS: PIBF expression (>1%) was found in 20.5% of COH and 13.3% of frozen embryo transfer cycles. There either was a significant difference or a trend for higher pregnancy rates when PIBF expression was detected. CONCLUSIONS: These data corroborate previous conclusions that PIBF is detected in a minority of women in the late luteal phase. A corpus luteum is not required for its expression.

Evaluation of live attenuated measles vaccines prepared in human diploid cells for reimmunization.

Two live attenuated measles vaccines developed in baby calf kidney cells, a similar vaccine produced in chick embryo chorioallantoic cells and five vaccines prepared from human diploid cells (HDC) have been studied by subcutaneous injection in groups of susceptible and immune children in three field trials. The results indicated that the vaccine developed in chick embryo cells which caused mild clinical reactions, had induced a lower seroprotection rate in susceptible children and only a low rise in hemagglutination-inhibition (HI) antibody titre in previously immunized children. The serological responses induced by vaccines developed in HDC or in calf kidney cells were satisfactory in both susceptible and immune children. The superiority of HDC grown measles vaccine for revaccination is discussed.

Improvement in the yield of oral poliovirus vaccine (Sabin strains) produced in human diploid cells.

When stationary cultures of human diploid cells in conventional Roux bottles were replaced by the development of cells in roller bottles, the yield of poliovirus, Sabin strains type 1 and 2, showed an increase of 0.5 to 1 log10. No significant difference was noticed in the yield of these viruses cultured in WI-38 and MRC-5 human diploid cells.

Isolation and characterization of a defective measles virus from brain biopsies of three patients in Iran with subacute sclerosing panencephalitis.

Three cytopathic strains of subacute sclerosing panencephalitis (SSPE) virus were isolated from brain biopsies of three patients. These strains were isolated and maintained by cocultivation of infected brain cells with fresh Vero cells. The biological characteristics of two strains were studied. It was found that these strains remain cell-associated after repeated cocultivations with Vero cells and produce plaques under fluid medium or tragacanth overlay. The correlation with measles virus was demonstrated by the plaque reduction test as well as by the immunofluorescence test. Large numbers of nucleocapsids were observed in the cytoplasm of infected cells but none in nuclei. Intracerebral inoculation of monkeys, adult guinea pigs, newborn and adult hamsters or mice was followed by acute encephalitis and death.

Age of measles immunization in tropics.

Maternal immunity to measles was studied in a group of 500 newborn children and another group of 500 children aged one to 12 months, before vaccination. The geometric mean titer of detectable hemagglutination-inhibition antibody was 16 for newborn children. This titer was absent in most children aged 3 to 5 months. Our previous studies indicate that from 1970 to 1972, children from the lower socio-economic classes aged 5 to 9 months were the main target of measles complications and deaths. Based on the present data, we suggest that children in developing countries should be vaccinated as young as 6 months and should be revaccinated 3 to 4 months later to assure full protection.

Stabilizing effect of magnesium chloride and sucrose on Sabin live polio vaccine.

A trivalent vaccine was stabilized with (a) 70% sucrose, (b) MgCl2 1M, and (c) 35% sucrose plus MgCl2 1/2M. A portion of each batch was kept at +4 degrees C and 22-25 degrees C. No change in titre for all 3 preparations was recorded after 9 weeks storage at +4 degrees C. While the potency of vaccines containing MgCl2 alone or mixed with sucrose and kept at +25-28 degrees C for 5 weeks was not altered, the vaccine containing only sucrose was less stable, and a drop of titre was noticed after 2 weeks of storage at +22-25 degrees C. Monovalent polio vaccines were also stabilized as above and kept at +4 degrees C or at -20 degrees C. It was found that regardless of the type of stabilizer used, 82 to 97 per cent of potency was retained after 9 months of storage at +4 degrees C or at -20 degrees C.

Use of human diploid cell MRC-5, for production of measles and rubella virus vaccines.

A further attenuated strain of measles virus, called AIK strain, developed by Makino and his colleagues at the Kitasato Institute, Tokyo, was adapted to human diploid cells (HDC), MRC-5. In a field trial it was found that this strain initiates a low rate of clinical reactions and 100% seroconversion in vaccines. An attenuated strain of rubella virus, called Takahashi strain, isolated by Shishido at the National Institute of Health, Japan, was also adapted to HDC, MRC-5. Brief details of production of an experimental rubella vaccine are given. Up to 20 harvests of virus were made from each culture without any apparent alteration of diploid cells.