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A single stage transonic axial compressor was equipped with a casing treatment consisting of 3.5 axial slots per rotor pitch in order to investigate its influence on stall margin characteristics, as well as on the rotor near tip flow field, both numerically and experimentally. Contrary to most other studies, a generic casing treatment (CT) was designed to provide optimal optical access in the immediate vicinity of the CT, rather than for maximum benefit in terms of stall margin extension. The second part of this two-part paper deals with the numerical developments and their validation, carried out in order to efficiently perform time-accurate casing treatment simulations. The numerical developments focus on the extension of an existing coupling algorithm in order to carry out unsteady calculations with any exterior geometry coupled to the main flow passage (in this case a single slot), having an arbitrary pitch. This extension is done by incorporating frequency domain, phase-lagged boundary conditions into this coupling procedure. Whereas the phase lag approach itself is well established and validated for standard rotor-stator calculations, its application to casing treatment simulations is new. Its capabilities and validation will be demonstrated on the given compressor configuration, making extensive use of the detailed particle image velocimetry flow field measurements near the rotor tip. Instantaneous data at all measurement planes will be compared for different rotor positions with respect to the stationary slots in order to evaluate the time-dependent interaction between the rotor and the casing treatment. [ABSTRACT FROM AUTHOR]

A single-stage transonic axial compressor was equipped with a casing treatment (CT), consisting of 3.5 axial slots per rotor pitch in order to investigate the predicted extension of the stall margin characteristics both numerically and experimentally. Contrary to most other studies, the CT was designed especially accounting for an optimized optical access in the immediate vicinity of the CT, rather than giving maximum benefit in terms of stall margin extension. Part I of this two-part contribution describes the experimental investigation of the blade tip interaction with casing treatment using particle image velocimetry (PIV). The nearly rectangular geometry of the CT cavities allowed a portion of it to be made of quartz glass with curvatures matching the casing. Thus, the flow phenomena could be observed with essentially no disturbance caused by the optical access. Two periscope light sheet probes were specifically designed for this application to allow for precise alignment of the laser light sheet at three different radial positions in the rotor passage (87.5%, 95%, and 99%). For the outermost radial position, the light sheet probe was placed behind the rotor and aligned to pass the light sheet through the blade tip clearance. It was demonstrated that the PIV technique is capable of providing velocity information of high quality even in the tip clearance region of the rotor blades. The chosen type of smoke-based seeding with very small particles (about 0.5 μm in diameter) supported data evaluation with high spatial resolution, resulting in a final grid size of 0.5×0.5 mm². The PIV database established in this project forms the basis for further detailed evaluations of the flow phenomena present in the transonic compressor stage with CT and allows validation of accompanying computational fluid dynamics (CFD) calculations using the TRACE code. Based on the combined results of PIV measurements and CFD calculations of the same compressor and CT geometry, a better understanding of the complex flow characteristics can be achieved, as detailed in Part II of this paper. [ABSTRACT FROM AUTHOR]

Drug-based antiretroviral therapies (ART) efficiently suppress HIV replication in humans, but the virus persists as integrated proviral reservoirs in small numbers of cells. Importantly, ART cannot eliminate HIV from an infected individual, since it does not target the integrated provirus. Therefore, genome editing-based strategies that can inactivate or excise HIV genomes would provide the technology for novel curative therapies. In fact, the HIV-1 LTR-specific designer-recombinase Brec1 has been shown to remove integrated proviruses from infected cells and is highly efficacious on clinical HIV-1 isolates in vitro and in vivo, suggesting that Brec1 has the potential for clinical development of advanced HIV-1 eradication strategies in people living with HIV. In line with the preparation of a first-in-human advanced therapy medicinal product gene therapy trial, we here present an extensive preclinical evaluation of Brec1 and lentiviral vectors expressing the Brec1 transgene. This included detailed functional analysis of potential genomic off-target sites, assessing vector safety by investigating vector copy number (VCN) and the risk for potential vector-related insertional mutagenesis, as well as analyzing the potential of Brec1 to trigger an undesired strong T cell immune response. In conclusion, the antiviral designer-recombinase Brec1 is shown to lack any detectable cytopathic, genotoxic or T cell-related immunogenic effects, thereby meeting an important precondition for clinical application of the therapeutic lentiviral vector LV-Brec1 in novel HIV-1 curative strategies., Competing Interests: The author’s have read the journal’s policy and have the following competing interests: Jan Chemnitz, Joachim Hauber, Frank Buchholz, Ilona Hauber, Niklas Beschorner and Maike Voges are founding partners of PROVIREX Genome Editing Therapies GmbH, which is commercially developing Brec1 technology. Niklas Beschorner and Maike Voges are full-time employees of PROVIREX Genome Editing Therapies GmbH since 2022, and Jan Chemnitz, Frank Buchholz, Joachim Hauber and Ilona Hauber are part-time employees. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare., (Copyright: © 2024 Beschorner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The incidence of coronavirus disease 2019 (Covid-19) among adolescents between 12 and 17 years of age was approximately 900 per 100,000 population from April 1 through June 11, 2021. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in adolescents are unknown., Methods: In this ongoing phase 2-3, placebo-controlled trial, we randomly assigned healthy adolescents (12 to 17 years of age) in a 2:1 ratio to receive two injections of the mRNA-1273 vaccine (100 μg in each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of mRNA-1273 in adolescents and the noninferiority of the immune response in adolescents as compared with that in young adults (18 to 25 years of age) in a phase 3 trial. Secondary objectives included the efficacy of mRNA-1273 in preventing Covid-19 or asymptomatic severe acute respiratory syndrome coronavirus 2 infection., Results: A total of 3732 participants were randomly assigned to receive mRNA-1273 (2489 participants) or placebo (1243 participants). In the mRNA-1273 group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 93.1% and 92.4%, respectively), headache (in 44.6% and 70.2%, respectively), and fatigue (in 47.9% and 67.8%, respectively); in the placebo group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 34.8% or 30.3%, respectively), headache (in 38.5% and 30.2%, respectively), and fatigue (in 36.6% and 28.9%, respectively). No serious adverse events related to mRNA-1273 or placebo were noted. The geometric mean titer ratio of pseudovirus neutralizing antibody titers in adolescents relative to young adults was 1.08 (95% confidence interval [CI], 0.94 to 1.24), and the absolute difference in serologic response was 0.2 percentage points (95% CI, -1.8 to 2.4), which met the noninferiority criterion. No cases of Covid-19 with an onset of 14 days after the second injection were reported in the mRNA-1273 group, and four cases occurred in the placebo group., Conclusions: The mRNA-1273 vaccine had an acceptable safety profile in adolescents. The immune response was similar to that in young adults, and the vaccine was efficacious in preventing Covid-19. (Funded by Moderna and the Biomedical Advanced Research and Development Authority; Teen COVE ClinicalTrials.gov number, NCT04649151.)., (Copyright © 2021 Massachusetts Medical Society.)

Active haptic sensation is critical for object identification, but its neural circuit basis is poorly understood. We combined optogenetics, two-photon imaging, and high-speed behavioral tracking in mice solving a whisker-based object orientation discrimination task. We found that orientation discrimination required animals to summate input from multiple whiskers specifically along the whisker arc. Animals discriminated the orientation of the stimulus per se as their performance was invariant to the location of the presented stimulus. Populations of barrel cortex neurons summated across whiskers to encode each orientation. Finally, acute optogenetic inactivation of the barrel cortex and cell-type-specific optogenetic suppression of layer 4 excitatory neurons degraded performance, implying that infragranular layers alone are not sufficient to solve the task. These data suggest that spatial summation over an active haptic array generates representations of an object's orientation, which may facilitate encoding of complex three-dimensional objects during active exploration., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Short-term studies have demonstrated that nondirected donors (NDDs) have psychosocial outcomes that are similar to donors who donate directly, but long-term studies have not been done. NDDs at our center were surveyed regarding motivation; support during donation; stress related to donation; regret; financial resources used for donation; preferences about communication with the recipient; and cost reimbursement. Of 100 NDDs who donated at our center in the last 20 years, 95 remain in contact with us, and 77 responded to our survey (mean ± standard deviation [SD] 6.7 ± 4 years postdonation). The most common motivation for donation was the desire to help another (99%). Many NDDs received support from family, friends, and employers. NDDs voiced stress about the possibility of recipient kidney rejection, physical consequences to themselves, and financial burden. Only one donor expressed regret. Almost half wanted some recipient information at donation; 61% preferred routine recipient status updates; 56% believed meeting the recipient should occur at any mutually agreeable time; and 55% endorsed reimbursement for expenses. Stressors for NDDs are analogous to those of directed donors; NDDs prefer having some information about the recipient and prefer to be given a choice regarding the timing for communication with the recipient. NDDs supported donation being financially neutral., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Herpes Simplex Virus type 2 (HSV-2) is a neurotropic human pathogen. Upon de novo infection, the viral infected cell protein 0 (ICP0) is immediately expressed and interacts with various cellular components during the viral replication cycle. ICP0 is a multifunctional regulatory protein that has been shown to be important for both efficient viral replication and virus reactivation from latency. In particular, as previously demonstrated in transfected tissue culture models, ICP0 interacts with the cellular E3 ubiquitin ligase SIAH-1, which targets ICP0 for proteasomal degradation. However, the consequence of this virus-host interaction during the establishment of HSV-2 infection in vivo has not yet been elucidated. Here we confirmed that ICP0 of HSV-2 interacts with SIAH-1 via two conserved PxAxVxP amino acid binding motifs. We also demonstrate in vitro that a SIAH-1 binding-deficient HSV-2 strain, constructed by homologous recombination technology, exhibits an attenuated growth curve and impaired DNA and protein synthesis. This attenuated phenotype was also confirmed in an in vivo ocular infection mouse model. Specifically, viral load of the SIAH-1 binding-deficient HSV-2 mutant was significantly reduced in the trigeminal ganglia and brain stem at day 5 and 7 post infection. Our findings indicate that the interplay between ICP0 and SIAH-1 is important for efficient HSV-2 replication in vivo, thereby affecting viral dissemination kinetics in newly infected organisms, and possibly revealing novel targets for antiviral therapy., Competing Interests: The commercial affiliation of an author of this study [MME] (Biomedizinische Forschungsgesellschaft mbH, Vienna, Austria) does not alter our adherence to all PLOS ONE policies on sharing data and materials.

The distribution coefficients and selectivities required for extraction purposes were predicted with a thermodynamic equation of state for the ternary system formic acid/water/extraction solvent. These predictions were validated with experimental data from the literature and experimental data from the oxidation of biomass to formic acid process measured in this work. Extraction solvents discussed in this work are 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol, 1-octanol, 1-decanol, ethyl n -butyl ether, diisopropyl ether, di- n -butyl ether, benzyl formate, and heptyl formate. The considered temperature ranged from 273 to 363 K under atmospheric pressure. Perturbed-chain statistical associating fluid theory (PC-SAFT) was used for prediction purposes applying an approach as simple as possible and as complex as necessary to achieve trustworthy data for selecting the best extraction solvent. Using PC-SAFT allowed identifying 1-hexanol as the most promising solvent out of the 11 extraction agents. The predicted data were in good agreement with the experimental distribution coefficients and the selectivities, which are very sensitive to experimental uncertainties., Competing Interests: The authors declare no competing financial interest.

Background: HIV is primarily transmitted by sexual intercourse and predominantly infects people in Third World countries. Here an important medical need is self-protection for women, particularly in societies where condoms are not widely accepted. Therefore, availability of antiviral microbicides may significantly reduce sexual HIV transmission in such environments., Methods: Here, we investigated structural characteristics and the antiviral activity of the polypurine tract (PPT)-specific ODN A, a 54-mer oligodeoxynucleotide (ODN) that has been previously shown to trigger the destruction of viral RNA genomes by prematurely activating the retroviral RNase H. The stability of ODN A and mutants thereof was tested at various storage conditions. Furthermore, antiviral effects of ODN A were analyzed in various tissue culture HIV-1 infection models. Finally, circular dichroism spectroscopy was employed to gain insight into the structure of ODN A., Results: We show here that ODN A is a powerful tool to abolish HIV-1 particle infectivity, as required for a candidate compound in vaginal microbicide applications. We demonstrate that ODN A is not only capable to prematurely activate the retroviral RNase H, but also prevents HIV-1 from entering host cells. ODN A also exhibited extraordinary stability lasting several weeks. Notably, ODN A is biologically active under various storage conditions, as well as in the presence of carboxymethylcellulose CMC (K-Y Jelly), a potential carrier for application as a vaginal microbicide. ODN A's remarkable thermostability is apparently due to its specific, guanosine-rich sequence. Interestingly, these residues can form G-quadruplexes and may lead to G-based DNA hyperstructures. Importantly, the pronounced antiviral activity of ODN A is maintained in the presence of human semen or semen-derived enhancer of virus infection (SEVI; i.e. amyloid fibrils), both known to enhance HIV infectivity and reduce the efficacy of some antiviral microbicides., Conclusions: Since ODN A efficiently inactivates HIV-1 and also displays high stability and resistance against semen, it combines unique and promising features for its further development as a vaginal microbicide against HIV.

CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs), act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR), for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

The Gibbs energy of reaction (Δ(R)g) is the key quantity in the thermodynamic characterization of biological reactions. Its calculation requires precise standard Gibbs energy of reaction (Δ(R)g(+)) values. The value of Δ(R)g(+) is usually determined by measuring the apparent (concentration-dependent) equilibrium constants K, e.g., the molality-based Km. However, the thermodynamically consistent determination of Δ(R)g(+) requires the thermodynamic (activity-based) equilibrium constant Ka. These values (Km and Ka) are equal only if the ratio of the activity coefficients of the reactants to the activity coefficients of the products (Kγ) is equal to unity. In this work, the impact of Kγ on the estimation of Ka for biological reactions was investigated using methyl ferulate (MF) hydrolysis as a model reaction. The value of Kγ was experimentally determined from Km values that were measured at different reactant concentrations. Moreover, Kγ was independently predicted using the thermodynamic model ePC-SAFT. Both the experimentally determined and the predicted Kγ values indicate that this value cannot be assumed to be unity in the considered reaction. In fact, in the reaction conditions considered in this work, Kγ was shown to be in the range of 3

Background: Several pathogenic bacteria utilize receptors of the CEACAM family to attach to human cells. Binding to different members of this receptor family can result in uptake of the bacteria. Uptake of Neisseria gonorrhoeae, a gram-negative human pathogen, via CEACAMs found on epithelial cells, such as CEACAM1, CEA or CEACAM6, differs mechanistically from phagocytosis mediated by CEACAM3, a CEACAM family member expressed selectively by human granulocytes., Principal Findings: We find that CEACAM1- as well as CEACAM3-mediated bacterial internalization are accompanied by a rapid increase in phosphatidylinositol-3,4,5 phosphate (PI(3,4,5)P) at the site of bacterial entry. However, pharmacological inhibition of phosphatidylinositol-3' kinase (PI3K) selectively affects CEACAM1-mediated uptake of Neisseria gonorrhoeae. Accordingly, overexpression of the PI(3,4,5)P phosphatase SHIP diminishes and expression of a constitutive active PI3K increases CEACAM1-mediated internalization of gonococci, without influencing uptake by CEACAM3. Furthermore, bacterial uptake by GPI-linked members of the CEACAM family (CEA and CEACAM6) and CEACAM1-mediated internalization of N. meningitidis by endothelial cells require PI3K activity. Sensitivity of CEACAM1-mediated uptake toward PI3K inhibition is independent of receptor localization in cholesterol-rich membrane microdomains and does not require the cytoplasmic or the transmembrane domain of CEACAM1. However, PI3K inhibitor sensitivity requires the Ig(C2)-like domains of CEACAM1, which are also present in CEA and CEACAM6, but which are absent from CEACAM3. Accordingly, overexpression of CEACAM1 Ig(C2) domains blocks CEACAM1-mediated internalization., Conclusions: Our results provide novel mechanistic insight into CEACAM1-mediated endocytosis and suggest that epithelial CEACAMs associate in cis with other membrane receptor(s) via their extracellular domains to trigger bacterial uptake in a PI3K-dependent manner.

Persistent infections with human papillomavirus type 16 (HPV16), HPV18, or HPV31 are necessary for the development of cervical cancer, implying that HPVs have evolved immunoevasive mechanisms. Recent global transcriptome analyses indicated that these HPV types downregulate the constitutive expression of interferon (IFN)-stimulated genes (ISGs), but the underlying mechanism is not well understood. Comparative analyses of ISG transcription in keratinocytes with complete HPV16, -18, and -31 genomes revealed that antiviral genes (IFIT1 and MX1), genes involved in IFN signaling (STAT1), proapoptotic genes (TRAIL and XAF1), and pathogen recognition receptors (TLR3, RIG-I, and MDA5) are inhibited to similar extents by HPV16, -18, and -31. The lower expression of pathogen receptors in HPV-positive cells correlated with a greatly impaired induction of IFN-β and also of IFN-λ1, -2, and -3 upon receptor stimulation. IFN-κ is constitutively expressed in normal keratinocytes and is strongly repressed by HPV16, -18, and -31. ISGs downregulated in HPV-positive cells can be reactivated by IFN-κ expression. The viral E6 and E7 oncogenes are sufficient for IFN-κ repression, with E6 being mainly responsible. E6 inhibits IFN-κ transcription independently from binding to PDZ proteins. IFN-κ expression can be activated in only one cell line by E6AP knockdown but can be activated in all tested HPV-positive cells by addition of a DNA methyltransferase inhibitor, suggesting that HPVs modulate DNA methylation. Taken together, these results suggest that carcinogenic HPVs target IFN-κ by different pathways in keratinocytes to inhibit both antiviral ISGs and pathogen recognition receptors, which in turn reduces the expression of inducible IFNs.

Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) is an immunoglobulin-related receptor expressed on human granulocytes. CEACAM3 functions as a single chain phagocytotic receptor recognizing gram-negative bacteria such as Neisseria gonorrhoeae, which possess CEACAM-binding adhesins on their surface. The cytoplasmic domain of CEACAM3 contains an immunoreceptor tyrosine-based activation motif (ITAM)-like sequence that is phosphorylated upon receptor engagement. Here we show that the SH2 domains of the regulatory subunit of phosphatidylinositol 3'-kinase (PI3K) bind to tyrosine residue 230 of CEACAM3 in a phosphorylation-dependent manner. PI3K is rapidly recruited and directly associates with CEACAM3 upon bacterial binding as shown by FRET analysis. Although PI3K activity is not required for efficient uptake of the bacteria by CEACAM3-transfected cells or primary human granulocytes, it is critical for the stimulated production of reactive oxygen species by infected phagocytes and the intracellular degradation of CEACAM-binding bacteria. Together, our results highlight the ability of CEACAM3 to coordinate signaling events that not only mediate bacterial uptake, but also trigger the killing of internalized pathogens.

Background: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), an immunoglobulin (Ig)-related glycoprotein, serves as cellular receptor for a variety of Gram-negative bacterial pathogens associated with the human mucosa. In particular, Neisseria gonorrhoeae, N. meningitidis, Moraxella catarrhalis, and Haemophilus influenzae possess well-characterized CEACAM1-binding adhesins. CEACAM1 is typically involved in cell-cell attachment, epithelial differentiation, neovascularisation and regulation of T-cell proliferation, and is one of the few CEACAM family members with homologues in different mammalian lineages. However, it is unknown whether bacterial adhesins of human pathogens can recognize CEACAM1 orthologues from other mammals., Results: Sequence comparisons of the amino-terminal Ig-variable-like domain of CEACAM1 reveal that the highest sequence divergence between human, murine, canine and bovine orthologues is found in the beta-strands comprising the bacteria-binding CC'FG-face of the Ig-fold. Using GFP-tagged, soluble amino-terminal domains of CEACAM1, we demonstrate that bacterial pathogens selectively associate with human, but not other mammalian CEACAM1 orthologues. Whereas full-length human CEACAM1 can mediate internalization of Neisseria gonorrhoeae in transfected cells, murine CEACAM1 fails to support bacterial internalization, demonstrating that the sequence divergence of CEACAM1 orthologues has functional consequences with regard to bacterial recognition and cellular invasion., Conclusions: Our results establish the selective interaction of several human-restricted bacterial pathogens with human CEACAM1 and suggest that co-evolution of microbial adhesins with their corresponding receptors on mammalian cells contributes to the limited host range of these highly adapted infectious agents.

Objective: The purpose of our study was to evaluate the diagnostic accuracy and scan coverage of flat-detector C-arm CT compared with that of biphasic MDCT for depicting malignant hepatic lesions in patients with hypervascular liver tumors before they undergo transarterial chemoembolization (TACE)., Materials and Methods: Fifteen patients with either hepatocellular carcinoma (HCC, n = 8) or hypervascular liver metastases from uveal melanoma (n = 7) underwent arterial and portal venous C-arm CT of the liver using intraarterial contrast media administration directly before TACE. The number and location of their hepatic malignancies were compared with those on MDCT. The scan coverage was documented and the liver diameter measured on MDCT., Results: Compared with MDCT, the sensitivity and specificity for segmental tumor involvement were 97% (76/78) and 85% (28/33), respectively, for reader 1, and 99% (77/78) and 79% (24/29), respectively, for reader 2. Complete scan coverage of the liver was obtained in five of the 15 patients with C-arm CT. In patients with incomplete scan coverage on C-arm CT, the craniocaudal liver diameter was significantly larger than in those patients with complete scan coverage (mean [95% CI], 22.7 [19.5-25.9] cm vs 20.2 [15.4-25.0] cm, p = 0.0193)., Conclusion: Biphasic arterial and portal venous C-arm CT showed a high sensitivity for the detection of malignant liver lesions. However, the liver could not be visualized completely in two thirds of the patients. Therefore, the current scan range limitations need to be overcome to make C-arm CT a valuable adjunct to MDCT for preprocedure evaluation and postprocedure follow-up imaging.

Background: The purpose of this study was to evaluate potency changes in insulin in different solutions and bag materials used for peritoneal dialysis (PD). One of the PD solutions (Physioneal) tested is available in two different solution containers, PVC and Clear-Flex. Four insulin concentrations (4 IU/L, 10 IU/L, 20 IU/L, and 40 IU/L) were evaluated. This range of concentrations was defined in accordance with standard medical practice. All PD solutions made by Baxter, Castlebar, Ireland., Methods: Insulin determination was performed by immunoassay (ELISA)., Results: In Dianeal, more than 90% of the initial dose of insulin remained available up to 24 hours for all concentrations tested. In Physioneal, for the higher concentrations tested (10 IU/L, 20 IU/L, and 40 IU/L), more than 90% of the initial dose of insulin remained available up to 6 hours, and more than 80% up to 24 hours. For the Lowest concentration of insulin tested in Physioneal (4 IU/L), more than 90% of the initial dose of insulin remained available up to 3 hours, and more than 70% up to 24 hours. Also for the lowest concentration of insulin, recovery correlated with the pH of the tested solutions. This effect became apparent over the storage time., Conclusions: The data show that insulin adsorption is less than 10% during the first 3 hours for every PD solution tested. Insulin recovery tends to be stable or to decrease slightly over time for the lower insulin concentrations tested. The results for insulin recovery show a correlation with insulin concentration and with pH for the lowest insulin dose tested. From a solution-container interaction perspective, Clear-Flex is an equivalent alternative to standard PVC material.

The purpose of the study was to examine the relationship between social anxiety and social functioning in first episode psychosis, and to determine whether those with psychosis have any maladaptive or irrational beliefs regarding social situations. A sample of 60 first episode patients (41 males, 19 females) participated in the study. The presence of social phobia was determined using the Structured Clinical Interview for DSM-IV (SCID-I). Measures included The Social Phobia and Anxiety Inventory (SPAI), the Social Functioning Scale (SFS), the Quality of Life Scale (QLS) and the Social Interaction Self-Statement Test. Thirty-two percent of the sample met SCID-I criteria for social phobia and approximately 60% of participants were experiencing elevated levels of social anxiety according to the SPAI (M=69.57, S.D.=27.42). Results were that negative symptoms and negative self-statements, but not social anxiety, were significant predictors of social functioning. This has implications for addressing these negative cognitions in early psychosis.

Objective: To evaluate the stability of gentamicin, tobramycin, netilmycin, vancomycin, cefazolin, unfractionated heparin, and low molecular weight heparin when added to four different peritoneal dialysis (PD) solutions [Extraneal (Baxter Healthcare, Castlebar, Ireland); Physioneal, Nutrineal, and Dianeal (Baxter Healthcare, Grosotto, Italy)] in new, non-PVC Clear-Flex containers., Measurements: Gentamicin, tobramycin, netilmycin, vancomycin, cefazolin, unfractionated heparin, and low molecular weight heparin were injected into separate bags of PD solution. Samples were withdrawn at predefined sampling times and the concentration of each drug was analyzed using high-performance liquid chromatography (for gentamicin, tobramycin, vancomycin, and cefazolin), or bioassay (for netilmycin, gentamicin, and tobramycin in Nutrineal), or coagulation methods (heparins)., Results: Netilmycin, vancomycin, cefazolin, and heparin in Physioneal, Nutrineal, Extraneal, and Dianeal were stable for at least 24 hours at 25 degrees C and for an additional 4 hours at 37 degrees C. Gentamicin in Nutrineal, Extraneal, and Dianeal was stable for at least 24 hours at 25 degrees C and for an additional 4 hours at 37 degrees C; gentamicin in Physioneal was stable for less than 24 hours at 25 degrees C. Tobramycin in Nutrineal and Extraneal was stable for at least 24 hours at 25 degrees C and for an additional 4 hours at 37 degrees C; tobramycin in Physioneal and Dianeal was stable for less than 24 hours at 25 degrees C.