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The Immersed Boundary (IB) method has been widely used to solve fluid-structure interaction problems, including those where the structure interacts with polymeric fluids. In this paper, we examine the convergence of one such scheme for a well known two-dimensional benchmark flow for the Oldroyd-B constitutive model, and we show that the traditional IB-based scheme fails to adequately capture the polymeric stress near to embedded boundaries. We analyze the reason for such failure, and we argue that this feature is not specific to the case study chosen, but a general feature of such methods due to lack of convergence in velocity gradients near interfaces. In order to remedy this problem, we build a different scheme for the Oldroyd-B system using the Immersed Boundary Smooth Extension (IBSE) scheme, which provides convergent viscous stresses near boundaries. We show that this modified scheme produces convergent polymeric stresses through the whole domain, including on embedded boundaries, and produces solutions in good agreement with known benchmarks. [ABSTRACT FROM AUTHOR]

Abstract: This meta-analysis summarizes 41 studies that examined associations between characteristics of adolescent participants in juvenile drug treatment court and outcomes (i.e., premature termination, recidivism). A summary of within- and post-program recidivism rates was calculated, as was a global estimate of the premature drop-out rate. One clear trend in the available studies was the dramatic difference in recidivism rates for adolescents who succeed in graduating from drug court, relative to those who do not. In addition, the review revealed that behavior patterns evidenced during drug court participation were most strongly associated with both the probability of graduating successfully from drug court and recidivism (e.g., few in-program arrests, citations, detentions, and referrals; greater length of time in program or amount of treatment; lower use of drug and alcohol use, few positive urine screens, greater school attendance). Unfortunately, non-white participants tend to have a lower probability of graduation from drug court and experience higher recidivism during and following the program. Available juvenile drug treatment court studies confirm a number of reputed adolescent risk factors associated with substance abuse, criminality, treatment failure, and recidivism among adolescents (e.g., higher levels of emotional and behavioral problems, higher levels and severity of pre-program substance abuse, male gender). Suggestions for improving the effects of juvenile drug treatment court based on key results of the meta-analysis are offered. [Copyright &y& Elsevier]

Abstract: This exploratory study examined the effect of a coaching and feedback intervention in teaching presence and social presence on higher-order thinking in an online community of inquiry. Coaching occurred before each chat, and feedback was provided immediately afterwards. The findings suggest that over time, the frequency of higher-order thinking will increase more in a group that receives coaching and feedback than in a group that does not receive coaching and feedback. In addition, the findings suggest that the Community of Inquiry framework has benefits beyond its use in course design, facilitation, and assessment to include serving as a guide to coaching. [Copyright &y& Elsevier]

Abstract: A significant consequence of equine arteritis virus (EAV) infection of horses is persistence of the virus in a variable percentage of infected stallions. We recently established an in vitro model of EAV persistence in cell culture for the purpose of furthering our understanding of EAV biology in general and viral persistence in the stallion in particular. In this study we investigated whether persistently infected HeLa cells could be cured of EAV infection by treatment with an antisense peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) designed to target the 5′-terminal region of the EAV genome. We found that persistently infected HeLa cells passaged three times in the presence of 5–10μM EAV-specific PPMO produced no detectable virus. The PPMO-cured HeLa cells were free of infectious virus, viral antigen and EAV RNA as measured by plaque assay, indirect immunofluorescence assay and RT-PCR, respectively. Furthermore, when re-challenged with EAV at several passages after discontinuation of PPMO treatments, PPMO-cured HeLa cells were found to be refractory to re-infection and to the re-establishment of viral persistence. While these findings demonstrate that PPMO can be used to eliminate persistent EAV infection in cell culture, the efficacy of PPMO against EAV in vivo remains to be addressed. [Copyright &y& Elsevier]

Abstract: Alternative therapies are needed for HSV-1 infections in patients refractory to treatment with Acyclovir (ACV) and its derivatives. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single-stranded DNA analogues that enter cells readily and reduce target gene expression through steric blockage of complementary RNA. When applied before or soon after infection PPMO targeting the translation-start-site regions of HSV-1 ICP0 or ICP27 mRNA reduced HSV-1 plaque formation by 70–98% in vitro. The ICP0 PPMO also reduced ACV-resistant HSV-1 (strain 615.9) plaque formation by 70–90%, while an equivalent dose of ACV produced only 40–50% inhibition when the treatment was applied between 1 and 3hpi. Seven daily topical treatments of 100μg ICP0 PPMO caused no gross or microscopic damage to the corneas of uninfected mice. Topical application of 10μg ICP0 PPMO to the eyes of HSV-1 infected mice reduced the incidence of eye disease by 37.5–50% compared to controls. This study demonstrates that topically applied PPMO holds promise as an antiviral drug candidate against HSV-1 ocular infection. [Copyright &y& Elsevier]

Abstract: Measles virus (MeV) is a highly contagious human pathogen. Despite the success of measles vaccination programs, measles is still responsible for an estimated 245,000 deaths each year. There are currently no antiviral compounds available for the treatment of measles. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are antisense compounds that enter cells readily and can interfere with mRNA function by steric blocking. A panel of PPMO was designed to target various sequences of MeV RNA that are known to be important for viral replication. Five PPMO, targeting MeV genomic RNA or mRNA, inhibited the replication of MeV, in a dose-responsive and sequence-specific manner in cultured cells. One of the highly active PPMO (PPMO 454), targeting a conserved sequence in the translation start site of the mRNA coding for the nucleocapsid protein, inhibited multiple genotypes of MeV. This report provides evidence that PPMO treatment represents a promising approach for developing antiviral agents against measles and other paramyxoviruses. [Copyright &y& Elsevier]

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infants, young children, and high-risk adults. Currently, there is no vaccine to prevent RSV infection, and the available therapeutic agents are of limited utility. Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) are a class of antisense agents that can enter cells readily and interfere with viral protein expression through steric blocking of complementary RNA. Two antisense PPMOs, designed to target sequence that includes the 5′-terminal region and translation start-site region of RSV L mRNA, were tested for anti-RSV activity in cultures of two human-airway cell lines. Both PPMOs showed minimal cytotoxicity and one of them, (AUG-2), reduced viral titers by >2.0 log10. Intranasal (i.n.) treatment of BALB/c mice with AUG-2 PPMO before the RSV inoculation produced a reduction in viral titer of 1.2 log10 in lung tissue at day 5 postinfection (p.i.), and attenuated pulmonary inflammation at day 7 postinfection. These data show that the AUG-2 PPMO possesses potent anti-RSV activity and is worthy of further investigation as a candidate for potential therapeutic application.Molecular Therapy (2008) 16 6, 1120–1128 doi:10.1038/mt.2008.81 [ABSTRACT FROM AUTHOR]

Abstract: This study investigated the process by which shared understanding develops in a chat learning space. It used a practical inquiry model to assess the development of cognitive presence. The study also explored how the pattern of conversation in synchronous discussion supports cognitive presence and how cognitive presence changes over time. Results show that there is a pattern among group members that involves reacquainting themselves through social presence and orienting themselves to the cognitive task through teaching presence. Individual meaning contributed by each member of the group through triggering events and exploratory statements is transformed as members see the text on the screen and respond to it through questioning and collective exploration. This group exploration enables the transition to shared understanding. [Copyright &y& Elsevier]

Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of a contagious disease characterized by reproductive failure in sows and respiratory disease in piglets. This infectious disease results in significant losses in the swine industry and specific anti-PRRSV drugs are needed. In this study, we evaluated a novel class of antisense compounds, peptide-conjugated phosphorodiamidate morpholino oligomers (P-PMOs), for their ability to suppress PRRSV replication in cell culture. P-PMOs are analogs of single-stranded DNA and contain a modified backbone that confers highly specific binding to RNA and resistance to nucleases. Of six P-PMOs tested, one (‘5UP1’), with sequence complementary to the 5′-terminal 21 nucleotides of the PRRSV genome, was found to be highly effective at reducing PRRSV replication in a specific and dose-dependent manner in CRL11171 cells in culture. 5UP1 treatment generated up to a 4.5log reduction in infectious PRRSV yield, while a control P-PMO had no effect on viral titer. Immunofluorescence assay with an anti-PRRSV monoclonal antibody confirmed the titer observations. The sequence-specificity of 5UP1 effect was confirmed in part by a cell-free luciferase reporter assay system, which showed that 5UP1-mediated inhibition of translation decreased if the target-RNA contained mispairings in relation to the 5UP1 P-PMO. Real-time RT-PCR showed that the production of PRRSV negative-sense RNA was reduced if 5UP1 was added to cells at up to 6h post-virus inoculation. Cell viability assays detected no cytotoxicity of 5UP1 within the concentration-range of this study. These results indicate that P-PMO 5UP1 has potential as an anti-PRRSV agent. [Copyright &y& Elsevier]

This study examined whether elevations on four variables (drive for thinness, depressed mood, maladaptive cognitions, and ineffectiveness) were related to increased severity of eating disorder symptoms over a 4-year prospective interval in a sample of female undergraduates (N=80). Results indicated that initial scores on the four variables were related to severity of anorexic and bulimic symptoms 4 years later. Examination of each variable individually indicated that anorexia and bulimia may have different risk pathways, and that initial maladaptive cognitions and drive for thinness scores were more related to later eating disorder symptoms than were depressed mood or ineffectiveness. [Copyright &y& Elsevier]

Provides the empirical bases for the division of the disorder anorexia nervosa into two subgroups in the revision of the book `Diagnostic and Statistical Manual of Mental Disorders' (DSM-IV). Binge eating (bulimic) subtype; Severe food restriction subtype; Comparison of psychological descriptions of bulimic and restricting anorexics; Research and treatment implications.

BACKGROUND: Pay-for-performance measures incorporate surgical site infection rates into reimbursement algorithms without accounting for patient-specific risk factors predictive for surgical site infections and other adverse postoperative outcomes. METHODS: Using American College of Surgeons National Surgical Quality Improvement Program data of 67,445 colorectal patients, multivariable logistic regression was performed to determine independent risk factors associated with various measures of adverse postoperative outcomes. RESULTS: Notable patient-specific factors included (number of models containing predictor variable; range of odds ratios [ORs] from all models): American Society of Anesthesiologists class 3, 4, or 5 (7 of 7 models; OR 1.25 to 1.74), open procedures (7 of 7 models; OR .51 to 4.37), increased body mass index (6 of 7 models; OR 1.15 to 2.19), history of COPD (6 of 7 models; OR 1.19 to 1.64), smoking (6 of 7 models; OR 1.15 to 1.61), wound class 3 or 4 (6 of 7 models; OR 1.22 to 1.56), sepsis (6 of 7 models; OR 1.14 to 1.89), corticosteroid administration (5 of 7 models; OR 1.11 to 2.24), and operation duration more than 3 hours (5 of 7 models; OR 1.41 to 1.76). CONCLUSIONS: These findings may be used to pre-emptively identify colorectal surgery patients at increased risk of experiencing adverse outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study was to identify unique risk factors for mortality in patients with end-stage renal disease undergoing nonemergent colorectal surgery. METHODS: A multivariate logistic regression model predicting 30-day mortality was constructed for patients with end-stage renal disease undergoing nonemergent colorectal procedures. Data were obtained from the National Surgical Quality Improvement Program (2005-2010). RESULTS: Among the 394 patients analyzed, those with serum creatinine levels >7.5 mg/dL had .07 times the adjusted mortality risk of those with levels >3.5 mg/dL. For colorectal surgery patients, the average serum creatinine level was 5.52 ± 2.6 mg/dL, and mortality was 13% (n = 50). CONCLUSIONS: High serum creatinine was associated with a lower risk for mortality in patients with end-stage renal disease, even though creatinine is often considered a risk factor for surgery. These results show how variables from a patient-centered subpopulation can differ in meaning from the general population. [ABSTRACT FROM AUTHOR]

Abstract: Porcine reproductive and respiratory syndrome (PRRS) has been devastating the global swine industry for more than a decade, and current strategies to control PRRS are inadequate. In this study we characterized the inhibition of PRRS virus (PRRSV) replication by antisense phosphorodiamidate morpholino oligomers (PMO). Of 12 peptide-conjugated PMO (PPMO), four were found to be highly effective at inhibiting PRRSV replication in cell culture in a dose-dependant and sequence-specific manner. PPMO 5UP2 and 5HP are complementary to sequence in the 5′ end of the PRRSV genome, and 6P1 and 7P1 to sequence in the translation initiation regions of ORF6 and ORF7, respectively. Treatment of cells with 5UP2 or 5HP caused a 4.5log10 reduction in PRRSV yield, compared to a control PPMO. Combination of 6P1 and 7P1 led to higher level reduction than 6P1 or 7P1 alone. 5UP2, 5HP, and a combination of 6P1 and 7P1 inhibited PRRSV replication in porcine alveolar macrophages and protected the cells from PRRSV-induced cytopathic effect. Northern blot and real-time RT-PCR results demonstrated that the effective PPMO led to a reduction of PRRSV RNA level. 5UP2 and 5HP inhibited virus replication of 10 other strains of PRRSV. Results from this study suggest potential applications of PPMO for PRRS control. [Copyright &y& Elsevier]

Abstract: Exploitation of groundfish off the U.S. Pacific coast reached maximum levels during the 1990s, resulting in severe declines in at least nine species of groundfish. From 1988 to 1990, we used the 2-man submersible Delta to make 42 dives and run replicate visual belt transects at six stations ranging from 67–360 m in depth at Heceta Bank on the outer continental shelf of Oregon. We identified four major habitats and associated benthic macroinvertebrate and groundfish assemblages: (1) shallow rock ridges and large boulders (<100 m deep) dominated by basket stars, juvenile rockfishes, yelloweye rockfish, and lingcod; (2) mid-depth small boulder-cobbles (100–150 m) dominated by crinoids, brittle stars, rosethorn, pygmy/Puget sound, and canary rockfishes; (3) deep cobble (150–200 m) dominated by crinoids, brittle stars and various small rockfish species, and (4) deep mud slope (>200 m) dominated by fragile urchins, sea cucumbers, shortspine thornyhead, and flatfishes. Although substantial interannual variation in groundfish abundance among seafloor types was evident in the 12 most abundant and/or commercially important fish taxa sampled, high variance resulted in statistically significant differences among years only in juvenile rockfishes. These data provide a baseline for future comparisons exploring long-term change this continental-shelf ecosystem. [Copyright &y& Elsevier]

Abstract: Kaposi''s sarcoma-associated herpesvirus (KSHV) is associated with Kaposi''s sarcoma and primary effusion lymphoma (PEL). The KSHV replication and transcription activator (RTA) and latency-associated nuclear antigen (LANA) play key roles in activating KSHV lytic replication and maintaining KSHV latency, respectively. Phosphorodiamidate morpholino oligomers (PMO) are similar to short single-stranded DNA oligomers, but possess a modified backbone that confers highly specific binding and resistance to nucleases. In this study, RTA and LANA mRNA in PEL cells were targeted by antisense peptide-conjugated PMO (P-PMO) in an effort to suppress KSHV replication. Highly efficient P-PMO uptake by PEL cells was observed. Treatment of PEL cells with a RTA P-PMO (RP1) reduced RTA expression in a dose-dependent and sequence-specific manner, and also caused a significant decrease in several KSHV early and late gene products, including vIL-6, vIRF-1, and ORF-K8.1A. KSHV viral DNA levels were reduced both in cells and culture supernatants of RP1 P-PMO-treated cells, indicating that KSHV lytic replication was suppressed. Treatment of BCBL-1 cells with P-PMO against LANA resulted in a reduction of LANA expression. Cell viability assays detected no cytotoxicity from P-PMO alone, within the concentration range used for the experiments in this study. These results suggest that RP1 P-PMO can specifically block KSHV replication, and further study is warranted. [Copyright &y& Elsevier]

Abstract Curcumin, the main molecular ingredient of the turmeric spice, has been reported to exhibit therapeutic properties for varied diseases and pathological conditions. While curcumin appears to trigger multiple signaling pathways, the precise mechanisms accounting for its therapeutic activity have not been deciphered. Here we show that curcumin exhibits significant interactions with cardiolipin (CL), a lipid exclusively residing in the mitochondrial membrane. Specifically, we found that curcumin affected the structures and dynamics of CL-containing biomimetic and biological mitochondrial membranes. Application of several biophysical techniques reveals the CL-promoted association and internalization of curcumin into lipid bilayers. In parallel, curcumin association with CL containing bilayers increased their fluidity and reduced lipid ordering. These findings suggest that membrane modifications mediated by CL interactions may play a role in the therapeutic functions of curcumin, and that the inner mitochondrial membrane in general might constitute a potential drug target. [ABSTRACT FROM AUTHOR]

Background: Small bowel lesions (SBL) are rare, representing diagnostic and management challenges. The purpose of this cross-sectional study was to evaluate diagnostic modalities used and management practices of patients with SBL at an advanced endoscopic referral center.Methods: We analyzed patients undergoing surgical management for SBL from 2005 to 2015 at a single tertiary care center. Patients were stratified into gastrointestinal bleed/anemia (GIBA) or obstruction/pain (OP).Results: One hundred and twelve patients underwent surgery after presenting with either GIBA (n = 67) or OP (n = 45). The mean age of our study population was 61.8 years and 45% were women. Patients with GIBA were more likely to have chronic or acute-on-chronic symptoms (100% vs 67%) and more often referred from outside hospitals (82 vs. 44%) (p < 0.01). The most common preoperative imaging modalities were video capsule endoscopy (VCE) (96%) for GIBA and computer tomography CT (78%) for OP. Findings on VCE and CT were most frequently concordant with operative findings in GIBA (67%) and OP (54%) patients, respectively. Intraoperatively, visual inspection or palpation of the bowel successfully identified lesions in 71% of patients. When performed in GIBA (n = 26), intraoperative enteroscopy (IE) confirmed or identified lesions in 69% of patients. Almost all (90%) GIBA patients underwent small bowel resections; most were laparoscopic-assisted (93%). Among patients with OP, 58% had a small bowel resection and the majority (81%) were laparoscopic-assisted. Surgical exploration failed to identify lesions in 10% of GIBA patients and 24% of OP patients. Among patients who underwent resections, 20% of GIBA patients had recurrent symptoms compared with 13% of OP patients.Conclusion: Management and identification of SBL is governed by presenting symptomatology. Optimal management includes VCE and IE for GIBA and CT scans for OP patients. Comprehensive evaluation may require referral to specialized centers. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) infection is a cause of hepatitis in humans worldwide and has been associated with a case-fatality rate of up to 30% in pregnant women. Recently, persistent and chronic HEV infections have been recognized as a serious clinical problem, especially in immunocompromised individuals. To date, there are no FDA-approved HEV-specific antiviral drugs. In this study, we evaluated antisense peptide-conjugated morpholino oligomers (PPMO) designed against HEV genomic sequences as potential HEV-specific antiviral compounds. Two genetically-distinct strains of human HEV, genotype 1 Sar55 and genotype 3 Kernow-C1, isolated from patients with acute and chronic hepatitis, respectively, were used to evaluate inhibition of viral replication by PPMO in liver cells. The anti-HEV PPMO produced a significant reduction in the levels of HEV RNA and capsid protein, indicating effective inhibition of HEV replication. PPMO HP1, which targets a highly conserved sequence in the start site region of ORF1, was also effective against the genotype 3 Kernow-C1 strain in stably-infected HepG2/C3A liver cells. The antiviral activity observed was specific, dose-responsive and potent, suggesting that further exploration of PPMO HP1 as a potential HEV-specific antiviral agent is warranted. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether different doses and dosing regimens of intravitreal vascular endothelial growth factor (VEGF) Trap-Eye are superior to focal/grid photocoagulation in eyes with diabetic macular edema (DME). Design: Multicenter, randomized, double-masked, phase 2 clinical trial. Participants: A total of 221 diabetic patients with clinically significant macular edema involving the central macula. Methods: Patients were assigned to 1 of 5 treatment regimens: 0.5 mg VEGF Trap-Eye every 4 weeks; 2 mg VEGF Trap-Eye every 4 weeks; 2 mg VEGF Trap-Eye for 3 initial monthly doses and then every 8 weeks; 2 mg VEGF Trap-Eye for 3 initial monthly doses and then on an as-needed (PRN) basis; or macular laser photocoagulation. Assessments were completed at baseline and every 4 weeks thereafter. Main Outcome Measures: Mean change in visual acuity and central retinal thickness (CRT) at 24 weeks. Results: Patients in the 4 VEGF Trap-Eye groups experienced mean visual acuity benefits ranging from +8.5 to +11.4 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters versus only +2.5 letters in the laser group (P ≤ 0.0085 for each VEGF Trap-Eye group vs. laser). Gains from baseline of 0+, 10+, and 15+ letters were seen in up to 93%, 64%, and 34% of VEGF Trap-Eye groups versus up to 68%, 32%, and 21% in the laser group, respectively. Mean reductions in CRT in the 4 VEGF Trap-Eye groups ranged from −127.3 to −194.5 μm compared with only −67.9 μm in the laser group (P = 0.0066 for each VEGF Trap-Eye group vs. laser). VEGF Trap-Eye was generally well tolerated. Ocular adverse events in patients treated with VEGF Trap-Eye were generally consistent with those seen with other intravitreal anti-VEGF agents. Conclusions: Intravitreal VEGF Trap-Eye produced a statistically significant and clinically relevant improvement in visual acuity when compared with macular laser photocoagulation in patients with DME. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]

Abstract: Porcine reproductive and respiratory syndrome (PRRS) causes substantial economic losses to the swine industry in many countries, and current control strategies are inadequate. Previously, we explored the strategy of using peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) to inhibit PRRS virus (PRRSV) replication. PPMOs are nuclease-resistant and single-stranded DNA analogs containing a modified backbone conjugated to a cell-penetrating peptide and can act as antisense agents through steric blockade of complementary messenger RNA. A PPMO (designated 5UP2) targeting highly conserved sequence in the 5′-terminal region of the PRRSV genome was found to produce multi-log10 inhibition of PRRSV replication in cultured cells. To evaluate 5UP2 in vivo, we here administrated the PPMO to 3-week-old piglets via intranasal instillation at 24h before, and 2 and 24h after infection with PRRSV (strain VR2385). Blood samples were collected at 6, 10 and 14days post-infection (dpi) for detection of PRRSV RNA and antibodies. Necropsy was performed at 14dpi. Monitoring weight gain in all piglet groups throughout the experiment indicated that PPMO was well tolerated at the doses used. PPMO 5UP2 treatment significantly reduced PRRSV viremia at 6dpi. On day 14, piglets receiving 5UP2 had significantly less interstitial pneumonia and lower level of anti-PRRSV antibodies than untreated piglets. In alveolar macrophages isolated at the time of necropsy, the expression of antiviral genes in PPMO-treated piglets was elevated in comparison with untreated. This study provides further data indicating that the 5UP2 PPMO can be considered a candidate component for a novel PRRS control strategy. [Copyright &y& Elsevier]

Abstract: Background context: Elective lumbar discectomy among injured workers is a prevalent spine surgery that often requires a lengthy rehabilitation. It is important to determine presurgical biopsychosocial predictors of compensation and medical costs in such patients. Purpose: To determine if presurgical biopsychosocial variables are predictive of compensation and medical costs in a cohort of Utah patients who have undergone open or microlumbar discectomy that are receiving workers'' compensation. Study design/setting: A retrospective cohort study consisting of a review of presurgical medical records and accrued medical and compensation costs. Patient sample: A consecutive sample of 266 compensated workers from Utah who had undergone either open discectomy or microlumbar discectomy from 1994 to 2000. All patients were at least 2 years postsurgery at the time of follow-up. Outcome measures: Total accrued medical, compensation, and aggregate costs. Methods: A retrospective review of presurgical biopsychosocial variables and total accrued medical, compensation, and aggregate costs. Results: Presurgical variables were statistically significantly correlated with medical and compensation costs. Multiple linear regression models accounted for 31% of variation in compensation costs, 32% in medical costs, and 43% in total aggregate costs. Conclusions: Presurgical biopsychosocial variables are important predictors of compensated lumbar discectomy costs. Medical cost control programs might benefit from identifying biopsychosocial variables related to increased costs. [Copyright &y& Elsevier]

Abstract: Charge neutral steric block oligonucleotide analogues, such as peptide nucleic acids (PNA) or phosphorodiamidate morpholino oligomers (PMO), have promising biological and pharmacological properties for antisense applications, such as for example in mRNA splicing redirection. However, cellular uptake of free oligomers is poor and the utility of conjugates of PNA or PMO to cell penetrating peptides (CPP), such as Tat or Penetratin, is limited by endosomal sequestration. Two new families of arginine-rich CPPs named (R-Ahx-R)4 AhxB and R6Pen allow efficient nuclear delivery of splice correcting PNA and PMO at micromolar concentrations in the absence of endosomolytic agents. The in vivo efficacy of (R-Ahx-R)4 AhxB PMO conjugates has been demonstrated in mouse models of Duchenne muscular dystrophy and in various viral infections. [Copyright &y& Elsevier]

Here we report the cloning and functional characterization of eight members of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase gene family from Drosophila melanogaster (polypeptide GalNAc transferase = pgant1-8). Full-length cDNAs were isolated from a Drosophila embryonic library based on homology to known ppGaNTases. Alignments with characterized mammalian isoforms revealed strong sequence similarities between certain fly and mammalian isoforms, highlighting putative orthologues between the species. In vitro activity assays demonstrated biochemical transferase activity for each gene, with three isoforms requiring glycosylated substrates. Comparison of the activities of Drosophila and mammalian orthologues revealed conservation of substrate preferences against a panel of peptide and glycopeptide substrates. Furthermore, Edman degradation analysis demonstrated that preferred sites of GalNac addition were also conserved between certain fly and mammalian orthologues. Semiquantitative PCR amplification of Drosophila cDNA revealed expression of most isoforms at each developmental stage, with some isoforms being less abundant at certain stages relative to others. In situ hybridization to Drosophila embryos revealed specific staining of pgant5 and pgant6 in the salivary glands and pgant5 in the developing hindgut. Additionally, pgant5 and pgant6 expression within the egg chamber was restricted to the follicle cells, cells known to be involved in egg formation and subsequent embryonic patterning. The characterization reported here provides additional insight into the use of this model system to dissect the biological role of this enzyme family in vivo during both fly and maremalian development. [ABSTRACT FROM AUTHOR]

Backgroud:Neointimal hyperplasia following percutaneous transluminal coronary angioplasty (PTCA) is one of the major components of the process of restenosis. We evaluated the long-term impact of local delivery of c-myc neutrally charged antisense oligonucleotides (Resten-NG) upon neointimal formation following PTCA in a rabbit model.Methods:PTCA was performed in the iliac arteries of 10 New Zealand white rabbits at 8 atm for 30 s, three times. An infusion of 500 μg Resten-NG (n=6) or saline (n=4) was delivered to the site at 2 atm via the outer balloon pores of the transport™ catheter over 2 min. The diet was supplemented with 0.25% cholesterol for 10 days before and 6 months following PTCA.Results:After 6 months, animals were sacrificed and vessels were fixed in formalin, processed and stained with hematoxylin, eosin, and movat. Histological analysis revealed complete vascular healing in both groups of animals. Planimetry showed that intimal areas were 1.71±0.25 and 0.65±0.36 mm2 in the control and antisense delivery groups, respectively (P<.05).Conclusion:We conclude that local delivery of Resten-NG significantly inhibited neointimal thickening following PTCA in a rabbit for up to 6 months. [Copyright &y& Elsevier]

Mitochondria have emerged as important determinants in cancer progression and malignancy. However, the role of mitochondrial membranes in cancer onset and progression has not been thoroughly investigated. This study compares the structural and functional properties of mitochondrial membranes in prostate and colon cancer cells in comparison to normal mitochondria, and possible therapeutic implications of these membrane changes. Specifically, isolation of cell mitochondria and preparation of inverted sub-mitochondrial particles (SMPs) illuminated significant cancer-induced modulations of membrane lipid compositions, fluidity, and activity of cytochrome c oxidase, one of the key mitochondrial enzymes. The experimental data further show that cancer-associated membrane transformations may account for mitochondria targeting by betulinic acid and resveratrol, known anti-cancer molecules. Overall, this study probes the relationship between cancer and mitochondrial membrane transformations, underlying a potential therapeutic significance for mitochondrial membrane targeting in cancer. Unlabelled Image • Transformation of lipid composition in colon and prostate cancers identified • Significantly increased concentration of cardiolipin detected • Elevated cardiolipin concentration was shown to affect enzyme functionalities in sub-mitochondria particles (SMPs) • The elevated cardiolipin level in cancer mitochondria is linked with mitochondrial targeting by betulinic acid and reservatrol. [ABSTRACT FROM AUTHOR]

Background: Many enteroviruses as well as hepatitis C have been increasingly found in association with cardiomyopathies, even though, the evidence has been inconclusive. Methods: From 1998 to 2001, at the liver clinic of our community-based hospital, in the cohort of hepatitis C patients, infection evidence by PCR confirmation and echocardiographic measures of left ventricular (LV) function were obtained. Results: One hundred-eight patients were identified. Fifty percent of them have echocardiographic abnormalities. Patient''s mean age was 55±10 years; 45% women, 55% men; 32% had LVH, 13.8% had high right ventricular systolic pressures, and 4% displayed contractility abnormalities. No cases of dilated or hypertrophic cardiomiopathies were found. Conclusions: Echocardiographic abnormalities are not uncommon findings associated with hepatitis C infection, however all these findings can easily be explained by existing co-morbidities. High right ventricular systolic pressure, suggestive of pulmonary hypertension, which may be secondary to portal hypertension, is an independent finding for hepatitis C. [Copyright &y& Elsevier]

Background As minimally invasive spine surgery evolves, spine surgeons increasingly rely on advanced intraoperative computed tomography (iCT). iCT provides rapid acquisition of high-resolution images, reduces radiation exposure, improves surgical accuracy, and decreases operative time. However, all iCT systems currently available pose a patient safety risk as their physical space requirements limit patient access in the event of an emergency, particularly when patients are in the prone position. After a near-cardiac arrest at our institution during posterior cervical spine surgery, it was apparent that the presence of the iCT complicated the ability to rapidly reposition the patient in order to provide appropriate resuscitation. Methods To ensure our ability to provide timely care during an emergency, we determined that a process which included all members of the operating room (OR) team was required. We held an initial planning meeting where a detailed plan-of-action was created, reviewed, and revised in response to feedback from all stakeholders. We then simulated a cardiac arrest to test our resuscitation plan with all members of the neurosurgery team. A mannequin was positioned prone on an OR table within the iCT, and a resuscitation plan was created. Results The team orchestrated the mock resuscitation, and the time of cardiac arrest in the prone position to supine repositioning required 110 seconds. The simulation was recorded for post-"code" performance review. Application of the protocol during an actual cardiac arrest was associated with successful restoration of spontaneous circulation and full recovery. Conclusions The development and rehearsal of an emergency plan of action greatly facilitated the timely responsiveness of the neurosurgical OR team during a simulated cardiac arrest and was an effective way to identify and address key logistical issues regarding the use of an iCT system. Highlights • To ensure timely, effective care during an IA emergency when iCT is used, we determined that a process. • All members of the operating room (OR) team were involved. • A detailed plan was created, reviewed, and revised in response to feedback from all neurosurgical OR team members. • We simulated a cardiac arrest to test our resuscitation plan with all members of the neurosurgery OR team participating. • The plan enabled us to reposition a "patient" in head pins on an iCT table from prone to supine position in 110 seconds. [ABSTRACT FROM AUTHOR]