Efficacy of rapamycin, RS-61443 and cyclophosphamide in the prolongation of survival of discordant pig to rabbit cardiac xenografts.
To evaluate the efficacy of two new immunosuppressive drugs, RS-61443 and rapamycin, alone and in combination with cyclophosphamide in the prolongation of heterotopic cardiac xenograft survival in a discordant neonatal pig to rabbit model. Animals were randomly assigned to receive rapamycin intravenously (1.0 mg/kg/day) or RS-61443 subcutaneously (160 mg/kg/day) commencing five days before surgery until rejection occurred. Cyclophosphamide, 20 mg/kg/day, was administered from one day prior to surgery. Combination of the above drugs (rapamycin 1.0 mg/kg/day and RS-61443 80 mg/kg/day) with and without treatment with cyclophosphamide was also evaluated. Trough blood concentrations of rapamycin and mycophenolic acid as well as rabbit antiporcine endothelial cell antibodies (immunoglobulin [Ig]M) were measured every second day from the commencement of drug therapy. The mean +/- SD survival time in control animals was 7.98 +/- 13.85 h (n = 11), with the majority of animals (n = 6) rejecting their grafts in less than 1 h. Rapamycin (11.5 +/- 9.5 h), RS-61443 (9.8 +/- 6.1 h), cyclophosphamide (17.9 +/- 16 h) alone, or the three drugs in combination (16.6 +/- 9.1 h) resulted in a trend to increase graft survival, which did not reach significance. In contrast, rapamycin and RS-61443 in combination (24.3 +/- 11.9 h) significantly (P < 0.05) prolonged graft survival. No significant (P > 0.05) decrease in rabbit antiporcine endothelial cell IgM concentrations was observed in all drug-treated groups; however, considerable variation was noted within each group. No relationship was found between trough concentrations of rapamycin and mycophenolic acid and xenograft survival or with a decrease in antibody concentrations. The data suggest that treatment modalities, in addition to the above drugs, is required for prolonged survival in cardiac xenografts in the discordant animal model used here.


Cross-species pharmacokinetic comparison from mouse to man of a second-generation antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100.
The pharmacokinetics of a 2'-O-(2-methoxyethyl)-modified oligonucleotide, ISIS 301012 [targeting human apolipoprotein B-100 (apoB-100)], was characterized in mouse, rat, monkey, and human. Plasma pharmacokinetics following parental administration was similar across species, exhibiting a rapid distribution phase with t(1/2alpha) of several hours and a prolonged elimination phase with t(1/2beta) of days. The prolonged elimination phase represents equilibrium between tissues and circulating drug due to slow elimination from tissues. Absorption was nearly complete following s.c. injection, with bioavailability ranging from 80 to 100% in monkeys. Plasma clearance scaled well across species as a function of body weight alone, and this correlation was improved when corrected for plasma protein binding. In all of the animal models studied, the highest tissue concentrations of ISIS 301012 were observed in kidney and liver. Urinary excretion was less than 3% in monkeys and human in the first 24 h. ISIS 301012 is highly bound to plasma proteins, probably preventing rapid removal by renal filtration. However, following 25 mg/kg s.c. administration in mouse and 5-mg/kg i.v. bolus administration in rat, plasma concentrations of ISIS 301012 exceeded their respective protein binding capacity. Thus, urinary excretion increased to 16% or greater within the first 24 h. Albeit slow, urinary excretion of ISIS 301012 and its shortened metabolites is the ultimate elimination pathway of this compound, as demonstrated by 32% of dose recovered in total excreta by 14 days in a rat mass balance study. The pharmacokinetics of ISIS 301012 in human is predictable from the pharmacokinetics measured in animals. The pharmacokinetic properties of ISIS 301012 provide guidance for clinical development and support infrequent dose administration.


Latent factor modeling of four schizotypy dimensions with theory of mind and empathy.
Preliminary evidence suggests that theory of mind and empathy relate differentially to factors of schizotypy. The current study assessed 686 undergraduate students and used structural equation modeling to examine links between a four-factor model of schizotypy with performance on measures of theory of mind (Reading the Mind in the Eyes Test [MIE]) and empathy (Interpersonal Reactivity Index [IRI]). Schizotypy was assessed using three self-report measures which were simultaneously entered into the model. Results revealed that the Negative factor of schizotypy showed a negative relationship with the Empathy factor, which was primarily driven by the Empathic Concern subscale of the IRI and the No Close Friends and Constricted Affect subscales of the Schizotypal Personality Questionnaire. These findings are consistent with a growing body of literature suggesting a relatively specific relationship between negative schizotypy and empathy, and are consistent with several previous studies that found no relationship between MIE performance and schizotypy.


A combination of alpha lipoic acid and calcium hydroxycitrate is efficient against mouse cancer models: preliminary results.
The impact of metabolic dysregulation on tumor development has long been established. We have targeted two enzymes that are altered during carcinogenesis: pyruvate dehydrogenase (PDH), which is down-regulated, and ATP citrate lyase, which is overexpressed in cancer cells. Alpha lipoic acid is a cofactor of PDH, while hydroxycitrate is a known inhibitor of ATP citrate lyase. Our hypothesis is that a combination of these drugs may have antitumoral potential. The efficacy of these molecules was screened in vitro by treatment of different human cancer and murine cell lines. Lipoic acid reduced the cell number by 10-50% depending on concentrations (0.1-10 microM) and cell types. Calcium hydroxycitrate reduced the cell number by 5-60% at different concentrations (10-500 microM). When hydroxycitrate and lipoic acid were used together, there was a major cytotoxic effect: complete cell death was seen following 8 microM lipoic acid and 300 microM hydroxycitrate treatment for 72 h. The combination of alpha lipoic acid and hydroxycitrate was administered to healthy mice, at doses currently utilized for other indications than cancer; no demonstrable toxicity was observed. The combination was used to treat mouse syngenic cancer models: MBT-2 bladder transitional cell carcinoma, B16-F10 melanoma and LL/2 Lewis lung carcinoma. The efficacy of this combination appears similar to conventional chemotherapy (cisplatin or 5-fluorouracil) as it resulted in significant tumor growth retardation and enhanced survival. This preliminary study suggests that this combination of drugs is efficient against cancer cell proliferation both in vitro and in vivo. A clinical trial is warranted.


Cellular automata modelling of biomolecular networks dynamics.
The modelling of biological systems dynamics is traditionally performed by ordinary differential equations (ODEs). When dealing with intracellular networks of genes, proteins and metabolites, however, this approach is hindered by network complexity and the lack of experimental kinetic parameters. This opened the field for other modelling techniques, such as cellular automata (CA) and agent-based modelling (ABM). This article reviews this emerging field of studies on network dynamics in molecular biology. The basics of the CA technique are discussed along with an extensive list of related software and websites. The application of CA to networks of biochemical reactions is exemplified in detail by the case studies of the mitogen-activated protein kinase (MAPK) signalling pathway, the FAS-ligand (FASL)-induced and Bcl-2-related apoptosis. The potential of the CA method to model basic pathways patterns, to identify ways to control pathway dynamics and to help in generating strategies to fight with cancer is demonstrated. The different line of CA applications presented includes the search for the best-performing network motifs, an analysis of importance for effective intracellular signalling and pathway cross-talk.


Diazoxide-induced long-term hyperglycemia. I. Preservation of B-cell insulin-releasing capacity.
Although several models of experimental diabetes mellitus are currently available, none of them appears to be optimally suited to study the possible deleterious effect of sustained hyperglycemia upon biochemical and functional variables in pancreatic islet cells in the absence of chronic stimulation of secretory activity. In the present study, oral diazoxide administration (0.33 g/Kg body wt. thrice per day for three days) to rats was used to cause both hypoinsulinemia and hyperglycemia (greater than or equal to 10.0 mM), the latter persisting, albeit at a somewhat lower level, for at least 1-2 days after cessation of diazoxide treatment. Ten hours after the last administration of diazoxide, the secretory response of isolated islets to D-glucose over 90 min incubation was not impaired. It is proposed that such a model may help to dissociate the influence of hyperglycemia itself upon islet cell behaviour from the consequences of sustained hypersecretion of insulin.


Vascular Access Guidelines: Summary, Rationale, and Controversies.
Dialysis vascular access management in the United States changed significantly after National Kidney Foundation-Kidney Disease Outcome Quality Initiative (NKF-KDOQI) clinical practice guidelines were first published in 1997. The Centers for Medicare and Medicaid Service adopted these guidelines and in collaboration with the End-Stage Renal Disease Networks established the Fistula First Breakthrough Initiative (FFBI) in 2003 to improve the rate of arteriovenous fistula use over arteriovenous graft and central venous catheter in the dialysis population. The implementation of guidelines and FFBI has led to a significant increase in the arteriovenous fistula use in the prevalent dialysis population. The guidelines are criticized for being opinion based and often impractical. Over the past 2 decades, the patient population undergoing dialysis has become older with complex comorbidities and challenges for creating an ideal vascular access. Advancing knowledge about access pathophysiology, improved treatment options, and improved process of care with team approach model point toward diminishing relevance of few of the existing guidelines. Moreover, several guidelines remain controversial and may be leading to clinical decisions that may be unfavorable to the patients. The review discusses the historical aspect of vascular access care in the United States and evolution of current practice standards and controversies surrounding few of these guidelines in the current time.


A retrospective measure of childhood behavior problems and its use in predicting adolescent problem behaviors.
Confirmatory factor analysis was used to support the dimensional structure of a four-factor retrospective measure of childhood behavior problems with a large, nonclinical adolescent sample. Acceptable levels of internal consistency and low-to-moderate levels of parent-adolescent interrater agreement were indicated for the four factors of attentional deficit/hyperactivity, oppositional behavior, conduct disorder symptoms and avoidance behaviors. The externalizing childhood problems (i.e., attentional deficit/hyperactivity, oppositional behavior, conduct disorder) were associated significantly with both internalizing (depression) and externalizing (e.g., alcohol consumption, delinquent activity) adolescent problem behaviors, as well as with an earlier age of onset for substance use. Avoidant behaviors in childhood were associated specifically with depressive symptomatology in adolescence. Results are discussed with regard to the role of childhood problems as precursors to adolescent/adult disorders.


In vitro activities of antifungal drugs against yeasts isolated from blood cultures and moulds isolated from various clinically significant sites in Singapore.
Fungaemia carries with it high mortality rates and appropriate as well as timely antifungal therapy has been shown to be life saving. We studied the invitro activities of antifungal agents using the Etest method, against 100 Candida isolates from blood cultures, 10 Cryptococcus isolates from blood or cerebrospinal fluid and 50 mould isolates from various clinically significant sites of patients in Singapore General Hospital, from June 2004 to December 2006. Overall, the yeasts appeared to have low minimum inhibitory concentrations (MICs) for all the 5 antifungal drugs tested except for fluconazole. The overall high MIC90 values of the moulds against the azoles were largely attributed to the non-Aspergillus moulds. Posaconazole, itraconazole, voriconazole and caspofungin appear effective against local strains of Aspergillus species, although there are no interpretive breakpoints. The results show that the local fungal strains studied appear to be susceptible to the usual antifungal drugs recommended in the literature.


Mutagenesis Study of the Cytochrome c Subunit Responsible for the Direct Electron Transfer-Type Catalytic Activity of FAD-Dependent Glucose Dehydrogenase.
The FAD-dependent glucose dehydrogenase from Burkholderia cepacia (FADGDH) is a hetero-oligomeric enzyme that is capable of direct electron transfer (DET) with an electrode. The cytochrome c (cyt c) subunit, which possesses three hemes (heme 1, heme 2, and heme 3, from the N-terminal sequence), is known to enable DET; however, details of the electron transfer pathway remain unknown. A mutagenesis investigation of the heme axial ligands was carried out to elucidate the electron transfer pathway to the electron mediators and/or the electrode. The sixth axial ligand for each of the three heme irons, Met109, Met263, and Met386 were substituted with His. The catalytic activities of the wild-type (WT) and mutant enzymes were compared by investigating their dye-mediated dehydrogenase activities and their DET abilities toward the electrode. The results suggested that (1) heme 1 with Met109 as an axial ligand is mainly responsible for the electron transfer with electron acceptors in the solution, but not for the DET with the electrode; (2) heme 2 with Met263 is responsible for the DET-type reaction with the electrode; and (3) heme 3 with Met386 seemed to be the electron acceptor from the catalytic subunit. From these results, two electron transfer pathways were proposed depending on the electron acceptors. Electrons are transferred from the catalytic subunit to heme 3, then to heme 2, to heme 1 and, finally, to electron acceptors in solution. However, if the enzyme complex is immobilized on the electrode and is used as electron acceptors, electrons are passed to the electrode from heme 2.


Determinants of duration of untreated psychosis among first-episode psychosis patients in Denmark: A nationwide register-based study.
Information on determinants of duration of untreated psychosis (DUP) is still needed to inform campaigns targeting people with first episode psychosis (FEP). This nation-wide study analysed the association between demographic factors (age, sex, ethnicity, marital status, and geographic area), premorbid and illness-related factors (global functional level, substance misuse, and contact to police), healthcare factors (referral source and first FEP contact) and DUP. The study population of 1266 patients aged 15-25years diagnosed with FEP (ICD10 F20.0-F20.99) was drawn from the Danish National Indicator Project during 2009-2011. The study population was combined with data from national administrative registers. A multinomial regression model was estimated to analyse the impact of demographic, premorbid and illness-related, and healthcare factors on DUP. One third of the population had a DUP below 6months. DUP longer than 12months was associated with older age at onset, being female, having cannabis misuse, and living in peripheral municipalities. Being charged by the criminal authorities during one year before FEP was associated with a DUP over 6months. DUP is related to a number of demographic, premorbid and healthcare factors. These findings suggest that future information campaigns should focus on increasing the awareness of early signs of psychosis not only among mental health professionals but also other professionals in contact with adolescents such as the police. It may also be useful to consider how to target information campaigns towards persons living in peripheral areas.


Effect of recombinant monokines, lymphokines, and other agents on clonal proliferation of human lung cancer cell lines.
The modulation of clonal growth of cells of 15 human lung cancer lines was examined by coculture with different recombinant lymphokines, monokines, and several agents which induce differentiation in other malignant cell systems. Recombinant human tumor necrosis factor alpha (TNF) was inhibitory to all non-small cell lung cancer cell lines with a 50% effective dose of clonal inhibition (ED50) in the range of 30-2000 units/ml. Two representative squamous lines (SK-MES and P3) had 150 to 250 high affinity (Kd approximately equal to pM) cell surface TNF receptors. In contrast, clonal growth of small cell lung cancer lines was not inhibited by TNF, and two representative lines (H69c and R592) expressed negligible cell surface TNF receptors. Recombinant alpha, beta, and gamma interferons (4000 units/ml) each inhibited greater than or equal to 30% clonal growth of more than 50% of the non-small cell lung cancer lines. TNF (100-1000 units/ml) in combination with gamma-interferon was synergistic in the inhibition of clonal growth of these cells. Further studies showed that synergism of clonal inhibition occurred even when the cells were initially exposed to gamma-interferon, washed, and plated in soft agar with TNF. All-trans-retinoic acid (ED50, 5 X 10(-7)-10(-6) M), dimethyl sulfoxide (ED50, 1.2-1.6%), and 12-O-tetradecanoylphorbol-13-acetate (ED50, 5 X 10(-8)-10(-10) M) inhibited clonal proliferation of 7 of 9, 7 of 9, and 8 of 9 non-small cell lung cancer lines, respectively. In contrast, clonal proliferation of cells of small cell lung cancer lines was decreased only slightly at almost all concentrations of each of the agents. Interleukin-1 and -2 and granulocyte-monocyte colony-stimulating factor had no effect on the clonal growth of any of the lung cancer lines. Our results suggest that TNF in combination with gamma-interferon may be therapeutically active for some patients with non-small cell lung cancer, but small cell lung cancer probably will be unresponsive to all the agents that we examined.


RNA Interference by Single- and Double-stranded siRNA With a DNA Extension Containing a 3' Nuclease-resistant Mini-hairpin Structure.
Selective gene silencing by RNA interference (RNAi) involves double-stranded small interfering RNA (ds siRNA) composed of single-stranded (ss) guide and passenger RNAs. siRNA is recognized and processed by Ago2 and C3PO, endonucleases of the RNA-induced silencing complex (RISC). RISC cleaves passenger RNA, exposing the guide RNA for base-pairing with its homologous mRNA target. Remarkably, the 3' end of passenger RNA can accommodate a DNA extension of 19-nucleotides without loss of RNAi function. This construct is termed passenger-3'-DNA/ds siRNA and includes a 3'-nuclease-resistant mini-hairpin structure. To test this novel modification further, we have now compared the following constructs: (I) guide-3'-DNA/ds siRNA, (II) passenger-3'-DNA/ds siRNA, (III) guide-3'-DNA/ss siRNA, and (IV) passenger-3'-DNA/ss siRNA. The RNAi target was SIRT1, a cancer-specific survival factor. Constructs I-III each induced selective knock-down of SIRT1 mRNA and protein in both noncancer and cancer cells, accompanied by apoptotic cell death in the cancer cells. Construct IV, which lacks the SIRT1 guide strand, had no effect. Importantly, the 3'-DNA mini-hairpin conferred nuclease resistance to constructs I and II. Resistance required the double-stranded RNA structure since single-stranded guide-3'-DNA/ss siRNA (construct III) was susceptible to serum nucleases with associated loss of RNAi activity. The potential applications of 3'-DNA/siRNA constructs are discussed.Molecular Therapy-Nucleic Acids (2014) 2, e141; doi:10.1038/mtna.2013.68; published online 7 January 2014.


Theoretical analysis of the magnetocardiographic pattern for reentry wave propagation in a three-dimensional human heart model.
We present a computational study of reentry wave propagation using electrophysiological models of human cardiac cells and the associated magnetic field map of a human heart. We examined the details of magnetic field variation and related physiological parameters for reentry waves in two-dimensional (2-D) human atrial tissue and a three-dimensional (3-D) human ventricle model. A 3-D mesh system representing the human ventricle was reconstructed from the surface geometry of a human heart. We used existing human cardiac cell models to simulate action potential (AP) propagation in atrial tissue and 3-D ventricular geometry, and a finite element method and the Galerkin approximation to discretize the 3-D domain spatially. The reentry wave was generated using an S1-S2 protocol. The calculations of the magnetic field pattern assumed a horizontally layered conductor for reentry wave propagation in the 3-D ventricle. We also compared the AP and magnetocardiograph (MCG) magnitudes during reentry wave propagation to those during normal wave propagation. The temporal changes in the reentry wave motion and magnetic field map patterns were also analyzed using two well-known MCG parameters: the current dipole direction and strength. The current vector in a reentry wave forms a rotating spiral. We delineated the magnetic field using the changes in the vector angle during a reentry wave, demonstrating that the MCG pattern can be helpful for theoretical analysis of reentry waves.


When is it permissible to dismiss a family who refuses vaccines? Legal, ethical and public health perspectives.
Although immunization is one of the most important health interventions of the 20th century, cases of infectious disease continue to occur. There are parents who refuse immunization for their children, creating a dilemma for the primary care physician who must consider the best interest of the individual child as well as that of the community. Some physicians, when faced with parents who refuse immunization on behalf of their children, choose to dismiss these families from their practice. Given the existing shortage of primary care physicians across Canada, this decision to dismiss families based on vaccine refusal has far-reaching implications. The present article explores this issue in the Canadian context from a legal, ethical and public health perspective.


Timing of puberty in boys and girls: A population-based study.
A secular trend towards earlier puberty has been observed in girls, while a similar trend has been more uncertain in boys. We estimated current ages at pubertal development in both boys and girls. In this population-based cohort study, 14 759 of 22 439 invited boys and girls born from 2000 to 2003 in the Danish National Birth Cohort gave half-yearly self-reported information on puberty from the age of 11.5 years and throughout puberty. This late start of follow-up limits the estimation of age at onset of puberty but not later pubertal milestones. We estimated mean age at attaining the following pubertal milestones in years with 95% confidence intervals (CI): age at menarche, voice break, first ejaculation of semen and Tanner stages for pubic hair development and breast development or genital development. Further, the difference in mean age at menarche between mothers and daughters was estimated. In boys, voice break occurred at 13.1 (95% CI 13.0, 13.1) years, first ejaculation of semen occurred at 13.4 (95% CI 13.3, 13.4) years, and Tanner Genital Stage 5 occurred at 15.6 (95% CI 15.5, 15.6) years. In girls, age at menarche occurred at 13.0 (95% CI 13.0, 13.1) years and Tanner Breast Stage 5 occurred at 15.8 (95% CI 15.7, 15.9) years. Daughters had menarche 3.6 (95% CI 3.1, 4.2) months earlier than their mothers had. These data indicate that age at menarche has declined and to some extent support a decline in age at attaining other markers of pubertal development among boys.


Stereoselective epoxidation of 4-deoxypentenosides: a polarized-pi model.
The high facioselectivity in the epoxidation of 4-deoxypentenosides (4-DPs) by dimethyldioxirane (DMDO) correlates with a stereoelectronic bias in the 4-DPs' ground-state conformations, as elucidated by polarized-pi frontier molecular orbital (PPFMO) analysis.


Matrix effect management in liquid chromatography mass spectrometry: the internal standard normalized matrix effect.
LC-MS is becoming a standard for many applications, thanks to high sensitivity and selectivity; nevertheless, some issues are still present, particularly due to matrix effect (ME). Considering this, the use of optimal internal standards (ISs, usually stable-isotope labeled) is important, but not always possible because of cost or availability. Therefore, a deep investigation of the inter-lot variability of the ME and of the correcting power of the chosen IS (isotope-labeled or not) is mandatory. While the adoption of isotopically labeled ISs considered as a 'gold standard' to mitigate ME impact on analytical results, there is not consensus about the standard technique to evaluate it during method validation. In this paper, currently available techniques to evaluate, reduce or counterbalance ME are presented and discussed. Finally, these techniques were summarized in a flowchart for a robust management of ME, particularly considering the concept of 'internal standard normalized ME'.


Postembryonic dimensional allometry of the human femur.
Developmental constraints can affect evolution. McMahon 's (1973, 1975a ) hypothesis of elastic similarity is tested as an epigenetic rule. This is an ontogenetic hypothesis that previously has not been tested with ontogenetic data. Cross-sectional data from the human femur are analyzed. Length-diameter relationships for phases of growth and aging are calculated with bivariate allometry. McMahon 's hypothesis cannot be rejected, although most of the calculations are not consistent with it. Ontogenetic skeletal allometry is complex because both material and geometric properties change during development.


[Cervical lymph node dissection and thyroid carcinoma].
After an anatomic recall of the cervical lymph node compartments we describe the surgical technique of the lymph node dissection in patients with differentiated thyroid carcinoma. These lymphadenectomies should be associated with total thyroidectomy. Cervical lymph node dissection always concerns central compartment and is sometimes extended to the cervico lateral compartments. Lymphadenectomy of a compartment should be complete, reoperations leading to an important morbidity. The two main complications of cervical lymph node dissection are inferior laryngeal nerve palsy and hypoparathyroidism.


Current and Future Trends in Hospital Utilization of Patients With Schizophrenia in Korea: A Time Series Analysis Using National Health Insurance Data.
This study aimed to investigate trends in hospital utilization of patients with schizophrenia during the last 10 years in Korea and to predict future trends using time series analysis. We determined the numbers of patients receiving outpatient or inpatient treatment for schizophrenia per month between 2010 and 2019, using National Health Insurance claims data. Facebook's Prophet was used to fit time series models based on observations for the previous 120 months, and to predict trends over the next 36 months. The number of hospitalized patients per month has declined rapidly since 2015, but the monthly number of outpatient visits has steadily increased. Monthly hospital utilization has increased in patients aged ≤29 and ≥50 years, but has declined rapidly since 2014-2015 in patients in their 30s and 40s. The upward trend in overall hospital utilization has slowed considerably in recent years. These trends are expected to continue over the next few years. This study revealed some notable changes in the hospital utilization patterns of patients with schizophrenia in recent years. There is a need to closely monitor and anticipate potential problems caused by these changing trends.


Synergistic protective role of mirazid (Commiphora molmol) and ascorbic acid against tilmicosin-induced cardiotoxicity in mice.
Tilmicosin (TIL) is a long-acting macrolide antibiotic approved for the treatment of cattle with Bovine Respiratory Disease. However, overdose of TIL has been reported to induce cardiotoxicity. The purpose of our experiment was to evaluate the protective effects of Commiphora molmol (mirazid (MRZ); myrrh) and (or) ascorbic acid (AA) against TIL-induced cardiotoxicity in mice. MRZ and AA were orally administered using stomach gavage, either alone or in combination for 5 consecutive days, followed with a single TIL overdose. TIL overdose induced a significant increase in serum levels of cardiac damage biomarkers (AST, LDH, CK, CK-MB, and cTnT), as well as cardiac lipid peroxidation, but cardiac levels of antioxidant biomarkers (GSH, SOD, CAT, and TAC) were decreased. Both MRZ and AA tended to normalize the elevated serum levels of cardiac injury biomarkers. Furthermore, MRZ and AA reduced TIL-induced lipid peroxidation and oxidative stress parameters. MRZ and AA combined produced a synergistic cardioprotective effect. We conclude that myrrh and (or) vitamin C administration minimizes the toxic effects of TIL through their free-radical-scavenging and potent antioxidant activities.


Immunoreactivity of N-terminal fragment of gastrin-releasing peptide as histochemical marker for pancreatobiliary duct-type cells.
Immunoreactivity of the N-terminal fragment of porcine gastrin-releasing peptide (GRP) was found, using the indirect immunoperoxidase technique, to be a good histochemical marker for the following normal human pancreatobiliary duct-type cells: epithelial cells of the intra- and extra-hepatic bile ducts, gallbladder, papilla vateri and intra- and extralobular pancreatic ducts, centroacinar cells of the pancreas, and accessory gland cells of the large pancreatobiliary duct system. These cells were stained with antiserum R-6902 which recognizes both the N- and C-terminal portions of porcine GRP; antiserum R-6903 with a specificity to the C-terminal fragment of porcine GRP failed to stain the cells. Duct-type cells in other human adult organs were almost negative with both antisera. The N-terminal fragment of the GRP of monkey and pig pancreatobiliary duct cells also showed immunoreactivity, whereas those of dog, pika, rat, chicken, frog, and trout did not. Immunoabsorption experiments confirmed that the immunoreactivity of human pancreatobiliary duct-type cells belonged to the N-terminal portion of porcine GRP. Under electron microscopy, the antigen was shown to be localized diffusely in the cytosol and partially in the nucleoplasm of the duct-type cells that contained no endocrine granules. Immunostaining with R-6902 serum was found to be useful in identifying duct-type cells in inflamed and/or fibrosing pancreatobiliary tissues. Most cells of a benign pancreatic duct tumor (microcystic adenoma) were positive with R-6902 serum. Mucosal cells of the fetal gastric antrum and intestine and some cancer cells of the stomach and colon also stained with R-6902 serum; adenocarcinoma cells and hyperplastic duct cells of the pancreatobiliary tree frequently showed less stainability. The significance of the specific detection of neuropeptide immunoreactivity on non-neuroendocrine duct-type cells is discussed.


Determining the statistical significance of survivorship prediction models.
The assessment of statistical significance of survivorship differences of model-predicted groups is an important step in survivorship studies. Some models determined to be significant using current methodologies are assumed to have predictive capabilities. These methods compare parameters from predicted classes, not random samples from homogenous populations, and they may be insensitive to prediction errors. Type I-like errors can result wherein models with high prediction error rates are accepted. We have developed and evaluated an alternate statistic for determining the significance of survivorship between or among model-derived survivorship classes. We propose and evaluate a new statistical test, the F* test, which incorporates parameters that reflect prediction errors that are unobserved by the current methods of evaluation. We found that the Log Rank test identified fewer failed models than the F* test. When both the tests were significant, we found a more accurate model. Using two prediction models applied to eight datasets, we found that the F* test gave a correct inference five out of eight times, whereas the Log Rank test only identified one model out of the eight correctly. Our empirical evaluation reveals that the hypothesis testing inferences derived using the F* test exhibit better parity with the accuracy of prediction models than the other options. The generalizable prediction accuracy of prediction models should be of paramount importance for model-based survivorship prediction studies.


Conformational change and human cytochrome c function: mutation of residue 41 modulates caspase activation and destabilizes Met-80 coordination.
Cytochrome c is a highly conserved protein, with 20 residues identical in all eukaryotic cytochromes c. Gly-41 is one of these invariant residues, and is the position of the only reported naturally occurring mutation in cytochrome c (human G41S). The basis, if any, for the conservation of Gly-41 is unknown. The mutation of Gly-41 to Ser enhances the apoptotic activity of cytochrome c without altering its role in mitochondrial electron transport. Here we have studied additional residue 41 variants and determined their effects on cytochrome c functions and conformation. A G41T mutation decreased the ability of cytochrome c to induce caspase activation and decreased the redox potential, whereas a G41A mutation had no impact on caspase induction but the redox potential increased. All residue 41 variants decreased the pK (a) of a structural transition of oxidized cytochrome c to the alkaline conformation, and this correlated with a destabilization of the interaction of Met-80 with the heme iron(III) at physiological pH. In reduced cytochrome c the G41T and G41S mutations had distinct effects on a network of hydrogen bonds involving Met-80, and in G41T the conformational mobility of two Ω-loops was altered. These results suggest the impact of residue 41 on the conformation of cytochrome c influences its ability to act in both of its physiological roles, electron transport and caspase activation.


[Indications and contraindications of peridural anesthesia in obstetrics. Review of the literature].
With the help of an extensive review of the french and foreign literature, and personal statistics concerning 500 peridural anesthesias (PDA), the authors analyze the indications and contraindications of this type of anesthesia, in 1987. It is possible to differentiate well accepted indications: caesarean section, inducement, labor test, dynamic dystocia, delivery of fragile fetus, desire of the patient; definite contraindications: patient's refusal, coagulation disorders, emergency situations, some cardiopathies; debatable indications: breech delivery, scarred uterus, twin delivery, maternal medical problem, where each particular case must be evaluated. In his study, the authors demonstrate that indications tend to become broader and contraindications to become more infrequent. They stress a necessary co-operation between obstetrician and anesthetist to make this decision.


Devices for visually impaired people: High technological devices with low user acceptance and no adaptability for children.
Considering that cortical plasticity is maximal in the child, why are the majority of technological devices available for visually impaired users meant for adults and not for children? Moreover, despite high technological advancements in recent years, why is there still no full user acceptance of existing sensory substitution devices? The goal of this review is to create a link between neuroscientists and engineers by opening a discussion about the direction that the development of technological devices for visually impaired people is taking. Firstly, we review works on spatial and social skills in children with visual impairments, showing that lack of vision is associated with other sensory and motor delays. Secondly, we present some of the technological solutions developed to date for visually impaired people. Doing this, we highlight the core features of these systems and discuss their limits. We also discuss the possible reasons behind the low adaptability in children.


Stauffer's syndrome with jaundice, a paraneoplastic manifestation of renal cell carcinoma: a case report.
To report an infrequent case of Stauffer's Syndrome with jaundice as a paraneoplastic syndrome of a metastatic renal cancer. We describe the set up of cholestatic jaundice without neoplastic liver infiltration in a patient with a metastatic renal cell carcinoma, which turned back with surgery and systemic treatment. Proper treatment of baseline disease enables turn back paraneoplastic signs and symptoms of Stauffer's Syndrome. Reversible cholestatic jaundice without evidence of hepatic disease is an infrequent form of the Stauffer's syndrome. This paraneoplastic syndrome is associated particularly with renal carcinoma but was described in lymphoproliferative diseases, prostate cancer and broncogenic tumors. This paraneoplastic entity is characterized by elevated alkaline phosphatase, erythrocyte sedimentation rate and gamma-glutamyl transferase without liver neoplastic infiltration.


Influence of chronic toxoplasmosis on some human personality factors.
An effect of parasites on host behaviour was tested on the toxoplasma-human model. Three hundred and thirty-eight (338) people were assessed with Cattell's personality questionnaire and then tested for Toxoplasma gondii infection with a delayed type hypersensitivity test for Toxoplasma. A highly significant correlation between chronic toxoplasmosis and two personality factors (G-Low Superego Strength and L-Protension) was found (p = 0.0032 and 0.0020, respectively). A correlation of the intensity of the personality factor-shifts with the duration of the infection (estimated from antibody titer) suggests that toxoplasmosis induces the shift in human personality, rather than the personality factors G and L influence an acquisition rate of Toxoplasma gondii infection.


Time benders: a model of subjective aging in aging adults.
This article develops a new model for understanding the aging experience. Drawing upon aging literature from the chronological, biological, mental, and social aging perspectives, the model offered is an integrated perspective that provides better understanding of the relationship between chronological age and an individual's perceived age. The article provides evidence of ways that consumers are trying to "time bend" and change today's perceived reality of aging. The article concludes with a discussion of implications for the health care industry and provides examples of how some businesses seem to already be looking at aging and health related issues through this lens.


Suboxone (buprenorphine/naloxone) toxicity in pediatric patients: a case report.
Suboxone, a combination of buprenorphine and naloxone in sublingual tablet form, was recently approved in the United States for management of opioid dependence. Little information exists regarding the potential for opioid toxicity after Suboxone exposure in the pediatric population. We report a case of opioid toxicity after exposure to Suboxone in a pediatric patient and a review of other cases of pediatric Suboxone ingestion in the literature. A previously healthy 2-year-old boy was found with 1 tablet of Suboxone (8 mg buprenorphine/2 mg naloxone) in his mouth. Remnants of the partly dissolved tablet were immediately removed from the child's oropharynx. The child experienced 1 episode of spontaneous emesis and became drowsy en route to the emergency department 30 minutes after the exposure. The patient was observed in the emergency department; no interventions were necessary, and the child was discharged asymptomatic and stable 6 hours post ingestion. Suboxone, a combination of buprenorphine and naloxone, may produce opioid toxicity via sublingual absorption or ingestion by children. We present the case of a child with mild central nervous system depression after exposure to Suboxone. Pediatric case reports that demonstrate more significant central nervous system and respiratory depressant effects from Suboxone ingestion are emerging.


Imaging molecular signatures for clinical detection of scleroderma in the hand by multispectral photoacoustic elastic tomography.
Scleroderma (SD) is a rare autoimmune disease, which is divided into 2 categories: the localized SD and systemic SD. The localized SD mainly causes skin thickening of the fingers, whereas the systemic SD can further affect the blood vessels and internal organs. In this pilot study, the multispectral photoacoustic elastic tomography (PAET) imaging technique was used to recover the quantitative physiological and elastic properties of biological tissues for the diagnosis of SD. Three healthy subjects and 3 SD patients were recruited and clinically examined by a rheumatologist, and then their hand/fingers were scanned by both magnetic resonance imaging and our home-made photoacoustic imaging system. Physiological parameters including oxygen saturation (ST O2 ), deoxy-hemoglobin (Hb) and oxy-hemoglobin (HbO2 ) concentrations and mechanical properties such as bulk elastic modulus images were reconstructed using the developed PAET reconstruction method. Our imaging results demonstrated that the physiological and elastic parameters exhibit striking differences between the SD and normal fingers, indicating that these biomarkers can serve as molecular signatures for early detection of SD. These quantitative physiological properties and bulk modulus may also pave a new path for improved understanding the pathological mechanism of SD.


Similar efficacy and safety of daptomycin versus linezolid for treatment of vancomycin-resistant enterococcal bloodstream infections: a meta-analysis.
Daptomycin and linezolid are the most commonly used antibiotics for bloodstream infection caused by vancomycin-resistant enterococci (VRE-BSI). However, the best therapeutic agent to treat VRE-BSI remains to be established. In order to provide evidence for an optimal treatment decision, a systematic review and meta-analysis was performed comparing the efficacy and safety of daptomycin and linezolid for the treatment of VRE-BSI. After thorough searching of relevant studies from MEDLINE, EMBASE, Clinicaltrials.gov and international meetings up to November 2015, 11 retrospective cohort studies were finally included with a sample size of 1339 patients. Among these 11 included studies, all patients in the daptomycin group received standard or high-dose daptomycin treatment (≥6 mg/kg/day). Data were extracted and pooled risk ratios (RRs) and 95% confidence intervals (95% CIs) were calculated using a random-effects model. The meta-analysis indicated similar crude overall mortality between patients receiving daptomycin and those treated with linezolid (RR = 1.07, 95% CI 0.83-1.37). Moreover, no difference regarding clinical cure (RR = 1.11, 95% CI 0.88-1.42), microbiological cure (RR = 0.99, 95% CI 0.90-1.09) or relapse rate of VRE-BSI (RR = 1.08, 95% CI 0.76-1.52) was found between daptomycin and linezolid. Adverse event rates were not significantly different between the two groups. Currently available evidence indicates similar efficacy and safety of daptomycin and linezolid for the treatment of VRE-BSI. However, the findings in the meta-analysis are limited by heterogeneity between relatively small-scale retrospective studies and should be interpreted cautiously.


Markers of cardiac collagen turnover are similar in patients with mild and more severe symptoms of heart failure.
Cardiac fibrosis plays an important role in the pathophysiology of heart failure. The authors sought to determine whether biomarkers of cardiac fibrosis for milder clinical degrees of heart failure are comparable to those of more advanced disease. Procollagen types I and III amino-terminal peptides (PINP and PIIINP) and type I collagen telopeptide (ICTP) were compared between aldosterone-antagonistnaive patients with heart failure and New York Heart Association class I or II (n=22/23) and class III or IV (n=42/3) symptoms. Median (interquartile) range concentrations of PINP (63.3 [44.2-88.8] vs 48.6 [37.8-74.9] microg/L), ICTP (7.0 [5.4-16.8] vs 6.5 [4.7-12.7] microg/L), and PIIINP (4.7 [3.2-7.0] vs 4.7 [2.9-7.3] microg/L) were comparable between patients with mild and moderate to severe disease, respectively. These data suggest that patients with mild heart failure may have similar degrees of cardiac fibrosis to patients with more severe disease and support the examination of antifibrotic therapy, including aldosterone antagonists, in milder degrees of heart failure.


Virtual Reference at Health Sciences Libraries in the Time of COVID-19.
Virtual reference services have become a staple in many libraries, but these services reached a new level of importance when in-person reference shut down in response to COVID-19. This descriptive study aims to discover how health sciences librarians utilized virtual reference services in response to the pandemic. A survey was developed and distributed to health sciences librarians. The survey addressed the status of virtual reference services before and during the COVID-19 pandemic as well as any changes that are seen as libraries reopen. Virtual reference shifted heavily to video conferencing during the pandemic both for librarians at home and those remaining onsite.


Identification and separation of secreted platelet proteins by isoelectric focusing. Evidence that low-affinity platelet factor 4 is converted to beta-thromboglobulin by limited proteolysis.
Low-affinity platelet factor 4 and beta-thromboglobulin are low molecular weight platelet secretory proteins that have common antigenic determinants. Four amino acids (Asn-Leu-Ala-Lys) at the amino terminus of beta-thromboglobulin are deleted, but the remaining sequences of the two peptides appear to be identical. Low-affinity platelet factor 4 and beta-thromboglobulin have respective isoelectric points at pH 8.0 and at pH 7.0. Identification, quantitation, and separation of both proteins was achieved by a method combining preparative isoelectric focusing and specific radioimmunoassay with anti-low-affinity platelet factor 4 antibody. It has been determined that the supernate processes immediately after platelet aggregation induced by ionophore A23187 or thrombin contains approximately 80% low-affinity platelet factor 4, 8% beta-thromboglobulin, and 12% highly cationic immunoreactive material (platelet basic protein). Experimental evidence suggests that low-affinity platelet factor 4 is originally secreted by platelets and then converted to beta-thromboglobulin by a platelet-derived, heat-labile protease that is inhibited by phenylmethylsulfonyl fluoride.


Infant antibody and B-cell responses following confirmed pediatric GII.17 norovirus infections functionally distinguish GII.17 genetic clusters.
Genogroup II (GII) noroviruses are a major cause of diarrheal disease burden in children in both high- and low-income countries. GII.17 noroviruses are composed of distinct genetic clusters (I, II, IIIa, and IIIb) and have shown potential for replacing historically more prevalent GII.4 strains, but the serological basis for GII.17 antigenic diversity has not been studied in children. Utilizing samples from a birth cohort, we investigated antibody and B-cell responses to GII.17 cluster variants in confirmed GII.17 infections in young children as well as demonstrated that the distinct genetic clusters co-circulate. Polyclonal serum antibodies bound multiple clusters but showed cluster-specific blockade activity in a surrogate virus neutralization assay. Antibodies secreted by immortalized memory B cells (MBCs) from an infant GII.17 case were highly specific to GII.17 and exhibited blockade activity against this genotype. We isolated an MBC-derived GII.17-specific Immunoglobulin A (IgA) monoclonal antibody called NVA.1 that potently and selectively blocked GII.17 cluster IIIb and recognized an epitope targeted in serum from cluster IIIb-infected children. These data indicate that multiple antigenically distinct GII.17 variants co-circulate in young children, suggesting retention of cluster diversity alongside potential for immune escape given the existence of antibody-defined cluster-specific epitopes elicited during infection.


Double-layer poly(vinyl alcohol)-coated capillary for highly sensitive and stable capillary electrophoresis and capillary electrophoresis with mass spectrometry glycan analysis.
Glycosylation plays an important role in protein conformations and functions as well as many biological activities. Capillary electrophoresis combined with various detection methods provided remarkable developments for high-sensitivity glycan profiling. The coating of the capillary is needed for highly polar molecules from complex biosamples. A poly(vinyl alcohol)-coated capillary is commonly utilized in the capillary electrophoresis separation of saccharides sample due to the high-hydrophilicity properties. A modified facile coating workflow was carried out to acquire a novel multiple-layer poly(vinyl alcohol)-coated capillary for highly sensitive and stable analysis of glycans. The migration time fluctuation was used as index in the optimization of layers and a double layer was finally chosen, considering both the effects and simplicity in fabrication. With migration time relative standard deviation less than 1% and theoretical plates kept stable during 100 consecutive separations, the method was presented to be suitable for the analysis of glycosylation with wide linear dynamic range and good reproducibility. The glycan profiling of enzymatically released N-glycans from human serum was obtained by the presented capillary electrophoresis method combined with mass spectrometry detection with acceptable results.


The clothes make the trans: region and geography in experiences of the body.
Written as an autoethnographic essay, the article explores the relationship between LGBT experience and geographic differences. The author discusses her experiences of forming a butch self while living in a suburban, subtropical environment and comparing herself to images of urban lesbian pop culture. If gender is performative, how do clothes permit us to or impede us from envisioning the body or being seen by others as butch/trans/masculine/multiple-gendered/diverse? Does the fashion uniform of the urban tranny boi and the publicizing of urban youth movements as the measure of LGBT experience impede LGBTs in other regions from envisioning themselves as "trans" or "butch: enough? Using interactionist sociological theory and gender performance theories, she considers the relationship between the visually sexed body and gendered embodiment. The goal in this piece is to open the conversation about regional LGBT experiences and their influence on physical embodiment.


Local and scientific knowledge in the school context: characterization and content of published works.
Bridging the gap between local and scientific knowledge can have useful implications in the teaching-learning process because it can create environments conducive to the valorization of sociocultural diversity in schools. The present review aims to analyze the profile and contributions of scientific publications dealing with articulations between local and scientific knowledge in basic formal education. Combined searches of 14 terms related to ethnoscience and 20 terms of education were conducted in English, Portuguese, and Spanish using the databases of Web of Science, Scopus, Science Direct, and Scielo. The recovered works were filtered, organized in a spreadsheet, and analyzed for publication characteristics (year, author, periodicals, countries of origin of the authors, and countries surveyed) and contents of the studies (epistemological bases, techniques of application, and record of the articulation of local and scientific knowledge). The research field that establishes these articulations is growing, with 81% of the works being written in the English language. A total of 494 researchers were recorded. The USA, South Africa, Brazil, Canada, and Australia were the countries of origin of the first author for the majority (64%) of the works considered. Multiculturalism, Vygotskian theory of learning, postcolonial theory, constructivism, critical pedagogy, and the argumentation theory were the main theoretical bases of half of the recovered works in which some explicit theoretical orientation could be found. Teacher training and interviews stood out as important tools in the application and record of links between local and scientific knowledge, respectively. Interdisciplinary approaches were common in the conception and application of pedagogical activities reported in the recovered works. Articulations between local and scientific knowledge are effective for culturally-sensitive scientific education, especially (but not exclusively) in schools directly related to traditional communities. There was a tendency to emphasize the teacher as a fundamental agent in the search for education that establishes these articulations. The authors of the analyzed works frequently indicated a need for greater proximity of the community to school spaces.


Identification of miRNAs and the target genes related to male infertility and smoking using bioinformatics approaches.
The impact of smoking on male fertility has been extensively acknowledged. Many studies have shown that smoking reduces sperm production, motility and fertilizing capacity by increasing seminal oxidative stress and DNA damage. In this study, expression profiles of miRNAs and their predicted target genes, showing dysregulation in smokers and associated with male infertility, were obtained, using Gene Expression Omnibus (GEO) datasets. Differentially expressed miRNAs, related to male infertility in sperm samples of smoking and non-smoking men, were picked out using the GEO2R online tool. Then, the target genes of each selected miRNA were predicted by using MiR-DIP. The target genes lists were compared to differentially expressed genes from the smoking and infertile men datasets. Common genes were chosen for further enrichment analysis such as GO, KEGG and PPI network analysis via STRING and MCODE. Then, four miRNAs (miR-26a, miR-32, miR-188-3p and miR-512-3p) which had shown differential expression in male infertility in other studies, and also had differential expression in smoking men compared to non-smokers, were screened out. Moreover, a module consisting of eight genes was identified as hub genes, including APC, NIPBL, ARID4B, TNRC6A, GIGYF2, ELAVL1, RHOF and SRSF1. These were highly correlated with male infertility and impairment of spermatogenesis. This study provides a comprehensive bioinformatics analysis of miRNAs and their target genes affecting male infertility in smokers. The results showed a collection of the most relevant genes and effective molecular pathways, which may serve as potential markers for the early detection of spermatogenesis disorders leading to infertility in smokers, after experimental validation.


Perceptions of Nature and Access to Green Space in Four Urban Neighborhoods.
Health benefits have been linked to spending time outdoors in nature and green space. However, there is some evidence of inequities to accessing safe outdoor space, particularly in low-resource communities. The primary aim of this study is to assess attitudes towards nature and use of green space in urban areas. A secondary aim is to describe perceptions of physician-initiated nature prescriptions that target local pediatric populations. We conducted six focus group interviews with 42 residents who were guardians or caretakers of children living in low-resource neighborhoods in Philadelphia, PA. We analyzed interview data using a conventional content analysis approach. Three major themes emerged: (1) perceived benefits of being in nature (physical and mental health benefits), (2) barriers to time spent in nature (unsafe and undesirable conditions of local parks), and (3) desired features of outdoor green spaces (amenities that would increase park use). Additionally, we describe participants' reactions to the idea of a pediatrician-delivered prescription for outdoor green space exposure for a child in their care. Adherence to nature prescriptions programs may hinge on local green space resources, as well as experiential and perceptual barriers and facilitators to nature and park accessibility among caregivers tasked with fulfilling a nature prescription for a child in their care.


Current Controversies on the Pathogenesis of Medication-Related Osteonecrosis of the Jaw.
Medication-related osteonecrosis of the jaw (MRONJ) was first reported more than a decade ago. Since then, numerous cases have been diagnosed. Currently, there are three groups of drugs related to MRONJ: bisphosphonates, denosumab and anti-angiogenic drugs. As MRONJ can lead to debilitating clinical sequels and limited effective treatment options are available, much research has been done in understanding its pathophysiology. Until now, the exact pathogenesis of MRONJ has not been fully elucidated. While history of invasive dental procedures or local trauma may be present, some cases occur spontaneously without any preceding factors. This review aims to examine and discuss the three main hypotheses for the pathogenesis of MRONJ, namely suppressed bone turnover, cellular toxicity and infection.


Haplotype analysis enables the diagnosis of Marfan syndrome.
Marfan syndrome is an inherited disorder of connective tissue associated with aneurysmal rupture of the ascending aorta. Timely and accurate diagnosis has reduced the mortality and morbidity associated with this disorder through expectant observation and implementation of appropriate prophylactic therapy. To this end, haplotype analysis using polymorphic genetic markers in close proximity to the Fibrillin-1 gene (FBN1) were employed to aid in the diagnosis of two individuals who did not meet the clinical diagnostic criteria.


Physical properties of canola oil based polyurethane networks.
A new generation polyol (generation-II) with significantly higher triol content and higher hydroxyl value was synthesized from canola oil by introducing a mild solvent (ethyl acetate) and a more efficient reductive reagent (zinc) to the previous synthetic procedure (Narine, S. S.; Yue, J.; Kong, X. J. Am. Oil Chem. Soc. 2007, 84, 173-179). Polyurethane (PUR) elastomers were prepared by reacting this type of polyol with aliphatic diisocyanates. The physical and thermal properties of the PUR elastomers were studied using dynamic mechanical analysis (DMA) and differential scanning calorimetry (DSC) and compared to the elastomers made from the old generation polyol (generation-I). The concentration of elastically active network chains (nue) of the polymer networks was calculated based on rubber elasticity theory. Larger nue and narrower distribution of nue was observed in the case of the PURs prepared from the generation-II polyol. The relatively faster relaxation at higher temperature for this type of PUR elastomer, suggests a tighter cross-linked network structure by reducing the dangling chains effect. With the same OH/NCO molar ratio, the PURs prepared from the generation-II polyol showed higher glass transition temperatures (Tg), higher Young's modulus and tensile strength, and longer elongation at break.


Miniopen oblique lateral L5-s1 interbody fusion: a report of 2 cases.
Extreme lateral interbody fusion (XLIF) has been widely used for minimally invasive anterior lumbar interbody fusion (ALIF), but an approach to L5-S1 is difficult because of the iliac crest. In the current study, we present 2 cases using minimally invasive oblique lateral interbody fusion (OLIF) of L5-S1. The patients showed foraminal stenosis between L5 and S1 and severe low back and leg pain. The patients were placed in a lateral decubitus position and underwent OLIF surgery (using a cage and bone graft from the iliac crest) without posterior decompression. Posterior screws were used in the patients. Pain scores significantly improved after surgery. There was no spinal nerve, major vessel, peritoneal, or urinary injury. OLIF surgery was minimally invasive and produced good surgical results without complications.


Outcomes of a specialist weight management programme in the UK National Health Service: prospective study of 1838 patients.
There is limited evidence on the effectiveness of weight management programmes provided within routine healthcare and inconsistent use of outcome measures. Our aim was to evaluate a large National Health Service (NHS) weight management service and report absolute and proportional weight losses over 12 months. Prospective observational study. Glasgow and Clyde Weight Management Service (GCWMS), which provides care for residents of NHS Greater Glasgow and Clyde area (population 1.2 million). All patients who began GCWMS between 1 October 2008 and 30 September 2009. Structured educational lifestyle programme employing cognitive behavioural therapy, 600 kcal deficit diet, physical activity advice, lower calorie diet and pharmacotherapy. Baseline observation carried forward (BOCF), last observation carried forward (LOCF) and changes in programme completers reported using outcomes of absolute 5 kg and 5% weight losses and mean weight changes at a variety of time points. 6505 referrals were made to GCWMS, 5637 were eligible, 3460 opted in and 1916 (34%) attended a first session. 78 patients were excluded from our analysis on 1838 patients. 72.9% of patients were women, mean age of all patients at baseline was 49.1 years, 43.3% lived in highly socioeconomically deprived areas and mean weights and body mass indices at baseline were 118.1 kg and 43.3 kg/m(2), respectively. 26% lost ≥5 kg by the end of phase 1, 30% by the end of phase 2 and 28% by the end of phase 3 (all LOCF). Weight loss was more successful among men, particularly those ≤29 years old. Routine NHS weight management services may achieve moderate weight losses through a comprehensive evidence-based dietary, activity and behavioural approach including psychological care. Weight losses should be reported using a range of outcome measures so that the effectiveness of different services can be compared.


Shorter discharge time after regional or intravenous anaesthesia in combination with laryngeal mask airway compared with balanced anaesthesia with endotracheal intubation.
The efficiency of operating room times can be significantly improved using rapid changes between operative procedures. We performed a retrospective analysis using electronic anaesthesia charts that compared anaesthesia-related times between the three most frequently performed types of anaesthesia (for orthopaedic surgery) to evaluate the potential for a quicker turn-around between cases. A total of 5614 anaesthetic procedures in trauma-related orthopaedic surgery were performed from 1997 to 1999. All were documented with an automatic record-keeping system. Data were compared for intravenous anaesthesia with the laryngeal mask airway, balanced anaesthesia with tracheal intubation and regional anaesthesia. The primary outcome measure was the time needed for emergence from anaesthesia after the end of surgery. Statistical evaluation was performed with matched triples for all three types of anaesthesia (155 triples for ambulatory surgery, 249 triples for in-patient care). For ambulatory surgery, the induction time was significantly shorter for general anaesthesia (23.7 min for intravenous anaesthesia, 22.7 min for balanced anaesthesia techniques) compared with regional anaesthesia (27.2 min). The time from the end of the surgical procedure to transfer of the patient out of the operating room was shortest for regional anaesthesia (6.3 min) compared with intravenous anaesthesia (9.0 min) and balanced anaesthesia (12.5 min) techniques. Results were comparable for in-patients: regional anaesthesia required significantly longer for its induction, but less time for patient discharge from the operating room. The use of a regional anaesthesia technique or one involving intravenous anaesthesia in combination with the laryngeal mask airway may lead to a reduction in discharge time compared with a balanced anaesthesia technique with endotracheal intubation. Thus, improved use of resources may be achieved.


Vaccines against a Major Cause of Abortion in Cattle, Neospora caninum Infection.
Neosporosis, caused by the apicomplexan parasite Neospora caninum, represents one of the economically most important causes of abortion in cattle. During pregnancy, the parasite infects the placental tissue and the fetus, which can lead to stillbirth, abortion, or birth of weak calves. Alternatively, calves are born without clinical symptoms, but they can carry over the parasite to the next generation. In addition, N. caninum causes neuromuscular disease in dogs. The economic importance of neosporosis has prompted researchers to invest in the development of measures to prevent infection of cattle by vaccination. A good vaccine must stimulate protective cellular immune responses as well as antibody responses at mucosal sites and, systemically, must activate T-helper cells to produce relevant cytokines, and must elicit specific antibodies that aid in limiting parasite proliferation, e.g., by interference with host cell invasion, activation of complement, and/or opsonization of parasites to have them killed by macrophages. Different types of vaccines have been investigated, either in bovines or in the mouse model. These include live vaccines such as naturally less virulent isolates of N. caninum, attenuated strains generated by irradiation or chemical means, or genetically modified transgenic strains. Live vaccines were shown to be very effective; however, there are serious disadvantages in terms of safety, costs of production, and stability of the final product. Subunit vaccines have been intensively studied, as they would have clear advantages such as reduced costs in production, processing and storage, increased stability and shelf life. The parasite antigens involved in adhesion and invasion of host cells, such as surface constituents, microneme-, rhoptry- and dense granule-components represent interesting targets. Subunit vaccines have been applied as bacterially expressed recombinant antigens or as DNA vaccines. Besides monovalent vaccines also polyvalent combinations of different antigens have been used, providing increased protection. Vaccines have been combined with immunostimulating carriers and, more recently, chimeric vaccines, incorporating immuno-relevant domains of several antigens into a single protein, have been developed.


Effect of Serum Phosphate on the Prognosis of Septic Patients: A Retrospective Study Based on MIMIC-IV Database.
To assess the effect of serum inorganic phosphate (Pi) on the prognosis of patients with sepsis. A retrospective analysis of patients with sepsis selected from the Medical Information Mart for Intensive Care (MIMIC)-IV database was performed. Sepsis was diagnosed according to the Third International Consensus Definition for sepsis and septic shock (Sepsis-3). The time-weighted values of the serum Pi measurements within the first 24 h of sepsis were analyzed. The association between serum Pi and in-hospital mortality was evaluated with a generalized linear model (log-binomial model). The analysis of 11,658 patients from six intensive care units (ICUs) showed a nearly linear correlation between serum Pi and in-hospital mortality in all patients with sepsis, especially in those with acute kidney injury (AKI). The increase of serum Pi was related to a higher risk of AKI, higher norepinephrine doses, ICU mortality, and in-hospital mortality. The generalized linear model showed that serum Pi was an independent predictor for in-hospital mortality in all patients with sepsis even within the normal range. The adjusted risk ratios (RRs) were also significant in subgroup analyses according to kidney function, gender, respiratory infection, vasopressor use, and Sequential Organ Failure Assessment (SOFA) score. Higher levels of serum Pi, even within the normal range, were significantly associated with a higher risk of in-hospital mortality in patients with sepsis regardless of kidney function, gender, respiratory infection, vasopressor use, and SOFA score.


Targeting the Vulnerability of RB Tumor Suppressor Loss in Triple-Negative Breast Cancer.
Approximately 30% of triple-negative breast cancers (TNBCs) exhibit functional loss of the RB tumor suppressor, suggesting a target for precision intervention. Here, we use drug screens to identify agents specifically antagonized by the retinoblastoma tumor suppressor (RB) using CDK4/6 inhibitors. A number of candidate RB-synthetic lethal small molecules were identified, including anti-helmenthics, chemotherapeutic agents, and small-molecule inhibitors targeting DNA-damage checkpoints (e.g., CHK) and chromosome segregation (e.g., PLK1). Counter-screens using isogenic TNBC tumor cell lines and cell panels with varying endogenous RB statuses confirmed that therapeutic effects were robust and selective for RB loss of function. By analyzing TNBC clinical specimens, RB-deficient tumors were found to express high levels of CHK1 and PLK1. Loss of RB specifically resulted in loss of checkpoint functions governing DNA replication, yielding increased drug sensitivity. Xenograft models demonstrated RB-selective efficacy of CHK inhibitors. This study supports the possibility of selectively targeting RB loss in the treatment of TNBC.


Surface characterization, electrochemical properties and in vitro biological properties of Zn-deposited TiO2 nanotube surfaces.
In this work, to improve antibacterial, biocompatible and bioactive properties of commercial pure titanium (cp-Ti) for implant applications, the Zn-deposited nanotube surfaces were fabricated on cp-Ti by using combined anodic oxidation (AO) and physical vapor deposition (PVD-TE) methods. Homogenous elemental distributions were observed through all surfaces. Moreover, Zn-deposited surfaces exhibited hydrophobic character while bare Ti surfaces were hydrophilic. Due to the biodegradable behavior of Zn on the nanotube surface, Zn-deposited nanotube surfaces showed higher corrosion current density than bare cp-Ti surface in SBF conditions as expected. In vitro biological properties such as cell viability, ALP activity, protein adsorption, hemolytic activity and antibacterial activity for Gram-positive and Gram-negative bacteria of all surfaces were investigated in detail. Cell viability, ALP activity and antibacterial properties of Zn-deposited nanotube surfaces were significantly improved with respect to bare cp-Ti. Moreover, hemolytic activity and protein adsorption of Zn-deposited nanotube surfaces were decreased. According to these results; a bioactive, biocompatible and antibacterial Zn-deposited nanotube surfaces produced on cp-Ti by using combined AO and PVD techniques can have potential for orthopedic and dental implant applications.


The Metrics of Acute Care Reentry and Emergency Department Visits by Recently Discharged Inpatients.
Research on acute care reentry by recently discharged inpatients has generally focused on hospital readmissions, with less attention given to presentations to the emergency department (ED). This omission results in underestimation of the extent of reentry and its impact on ED patient volumes and flow. This project involved an analysis of administrative data to examine the rate of ED presentations by recently discharged inpatients using 3 time metrics-within 0-3 days, 0-7 days, and 0-30 days of discharge. Descriptive-correlational analyses were conducted to examine the rates of reentry and ability to predict ED presentations using patient demographic (age and sex) and clinical profile (length of hospital stay and day of presentation). Approximately 12% of hospital discharges to home involved patients who presented to the ED within 30 days, and almost half occurred within the first week. Results of multivariable analyses suggest that the influences of ED presentations differ depending on the time metric examined. Emergency department presentations within 3 and 7 days of discharge compared with 30 days were not predicted by patient age or sex but were more likely to involve those with shorter hospital stays. A weekend presentation was also more likely among case patients presenting within 3 days of discharge. Only about one third of ED presentations resulted in readmission. Emergency department presentations are an important component of acute care reentry. Establishment of a common reentry metric for ED presentations would facilitate efforts to determine the impact of these events. Emergency nurses working in advanced practice roles are ideally positioned to assume a leadership role in addressing the needs of recently discharged inpatients who present to the ED. By reviewing these cases and collaborating with the inpatient unit staff, it may be possible to identify strategies for augmenting discharge planning and the provision of transitional care.


Use of a periodic vaccination strategy to control the spread of epidemics with seasonally varying contact rate.
In this paper, a general periodic vaccination has been applied to control the spread and transmission of an infectious disease with latency. A SEIRS(1) epidemic model with general periodic vaccination strategy is analyzed. We suppose that the contact rate has period T, and the vaccination function has period LT, where L is an integer. Also we apply this strategy in a model with seasonal variation in the contact rate. Both the vaccination strategy and the contact rate are general time-dependent periodic functions. The same SEIRS models have been examined for a mixed vaccination strategy composed of both the time-dependent periodic vaccination strategy and the conventional one. A key parameter of the paper is a conjectured value R(c)(0) for the basic reproduction number. We prove that the disease-free solution (DFS) is globally asymptotically stable (GAS) when R(sup)(0) < 1. If R(inf)(0) > 1, then the DFS is unstable, and we prove that there exists a nontrivial periodic solution whose period is the same as that of the vaccination strategy. Some persistence results are also discussed. Necessary and sufficient conditions for the eradication or control of the disease are derived. Threshold conditions for these vaccination strategies to ensure that R(sup)(0)& 1 and R(inf)(0) > 1 are also investigated.


Analysis of risk factors and survival in pediatric high-grade spinal cord astrocytoma: a population-based study.
Primary pediatric high-grade spinal cord astrocytomas are rare neoplasms with poor prognoses. Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed prognostic factors and survival. Pediatric patients with histologically confirmed diagnoses of primary high-grade spinal cord astrocytoma (WHO grade III-IV) from 1973 to 2008 in the SEER database were studied. Univariate and multivariate Cox proportional hazards models were used to analyze the relationship between demographic, tumor grade, and treatment factors on survival. Median survival in the 48 patient cohort was 10 months. Increasing age and higher tumor grade were found to be significantly associated with higher mortality. For children aged <7, 7-12, and 13-18 years, median survival was 22, 11, and 8 months, respectively. For children with anaplastic astrocytoma (WHO grade III), median survival was 12 months, compared with 7 months for those with glioblastoma multiforme (WHO grade IV). This study did not find a statistically significant relationship between sex, race, presence of radiation therapy or extent of surgical resection and mortality. Survival in primary pediatric high-grade spinal cord astrocytomas was positively associated with younger age and lower tumor grade. Survival was not associated with other demographic or treatment modality factors.


Therapy for severe interstitial lung disease in systemic sclerosis. A retrospective study.
This retrospective observational study attempted to determine whether any of the therapies used in the management of systemic sclerosis (SSc) patients held potential benefit for patients with interstitial lung disease. All patients with SSc who had a pulmonary function test (PFT) showing a forced vital capacity (FVC) of < 70% predicted and an additional PFT at least 4 months later were grouped according to the treatment they received. Changes in pulmonary function were analyzed by the mean percent predicted FVC from the initial and the final test, and by the rate of percent change in FVC (ml/year) in the first 2 years after therapy. Bronchoalveolar lavage was performed in a subset of these patients. Of 363 SSc patients who had an FVC < 70% predicted, 122 had a second PFT and fulfilled the criteria for one of the following drug groups: high-dose prednisone (n = 21), immunosuppressive other than cyclophosphamide (CYC) (n = 16), CYC (n = 14), D-penicillamine (n = 37), or no drug (n = 34). In both analyses, the CYC-treated group showed significantly more improvement in FVC than did the other groups. Patients with early disease had the greatest likelihood of responding to any drug. This retrospective study shows that patients treated with CYC had a significant improvement in FVC over time. Prospective controlled studies of CYC treatment in early disease are necessary to determine if it can significantly alter the natural history of interstitial lung disease.


Investigation of the light field of a semiconductor diode laser.
Scanning near-field optical microscopy was applied to study, with sub-wavelength spatial resolution, the near- and the far-field distributions of propagating modes from a high-power laser diode. Simple modeling was also performed and compared with experimental results. The simulated distributions were consistent with the experiment and permitted clarification of the configuration of the transverse modes of the laser.


Ceramides and other sphingolipids as predictors of incident dysglycemia (CASPID): Design, methods, and baseline characteristics.
The Ceramides and other Sphingolipids as Predictors of Incident Dysglycemia (CASPID) study tests the overall hypothesis that sphingolipids are pathophysiologic mediators of transition from normal glucose regulation (NGR) to prediabetes, type 2 diabetes (T2DM), and associated complications. The CASPID study utilizes two longitudinal cohorts - the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC)/Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) and the Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS). Normoglycemic POP-ABC/PROP-ABC were followed for 10 years for progression to prediabetes and offered lifestyle intervention to reverse prediabetes. The DPP/DPPOS participants had prediabetes at enrollment, were randomized to placebo, lifestyle intervention, or metformin treatment, and followed for 11 years for progression to T2DM. Using a case-control design, we analyze 76 targeted plasma sphingolipids as predictors of progression from NGR to prediabetes (Aim 1), prediabetes to T2DM (Aim 2), response to interventions (Aim 3), and development of diabetes complications (Aim 4). A sample size of 600 subjects provides >80% power to detect a 20% difference in sphingolipid profiles between comparison groups (alpha = 0.01). At enrollment, POP-ABC participants had a mean age of 47.7 ± 9.00 years, body mass index (BMI) 30.4 ± 6.10 kg/m2, fasting glucose 92.9 ± 6.90 mg/dL, and 2-h glucose 130 ± 28.8 mg/dL; DPP participants had a mean age of 51.9 ± 9.44 years, BMI 33.7 ± 6.33 kg/m2, fasting glucose 106 ± 7.88 mg/dL, and 2-h glucose 164 ± 16.9 mg/dL. Among normoglycemic participants, those with parental history of T2DM had significantly higher baseline levels of total sphingomyelins, and lower levels of total ceramides and sphingosine, compared with control subjects without familial diabetes history. As the first such study in longitudinal human cohorts, CASPID will elucidate the role of sphingolipids in the pathogenesis of dysglycemia and facilitate the discovery of novel predictive and prognostic biomarkers.


Clinical form of asthma and vaccine immunity in preschoolers.
Asthma is the most common chronic disease in children. Its exacerbation results from allergic and infectious diseases. To assess the influence of a clinical form of asthma on preschoolers' vaccine immunity following 3 years after the completion of the mandatory vaccination programme. The study encompassed 172 preschool children with asthma being newly diagnosed, including 140 patients with mild asthma and 32 with moderate asthma, whose vaccine immunity (level of IgG-specific antibodies) was assessed after the mandatory early vaccines had been administered in the early childhood. Monovalent vaccines (HBV + IPV + Hib) along with a three-component combined vaccine (DTwP) and MMR were given to 86 children while a six-component combined vaccine (DTaP + IPV + Hib + HBV) along with a three-component MMR vaccine were administered to the remaining 86 children. The immunity class for particular vaccinations was assessed according to the manufacturers' instructions. Children suffering from mild asthma had considerably more frequently vaccinations administered on time (p < 0.001) and the type of vaccines (monovalent or highly-combined) administered did not have a significant influence on the clinical form of asthma in the children examined (p = 0.6951). Apart from the vaccines against hepatitis B and rubella where considerably more frequently a high level of antibodies occurred in children with mild asthma, the antibody levels to other vaccines, namely diphtheria, tetanus, pertussis, Hib and mumps, were not associated with the severity of asthma. Moderate asthma may have a negative impact on remote vaccine immunity to HBV and rubella.


Placental changes in gestational diabetes. An ultrastructural study.
A light microscopic, an electron microscopic, and a ultrahistochemical study have been made of seven placentas from women with mild and excellently controlled chemical gestational diabetes. Only one placenta showed no significant abnormality; the remainder showed, to a varying degree, changes in the syncytiotrophoblast, cytotrophoblast, trophoblastic basement membrane, and fetal vessels. These abnormalities were identical to and in some cases as severe as those found in placentas from women with longstanding, moderately controlled, overt diabetes mellitus. These findings indicate that control of hyperglycemia only partially prevents the development of placental abnormalities which must be due to some other constituent factor of the diabetic state.


[Value of transrectal FNA in the diagnosis of prostate cancer in elderly patients].
To identify if there is a group elderly patients with clinical suspicion of prostate cancer in which pathological confirmation may be unnecessary, and if prostatic transrectal fine needle aspiration (FNA) may be a useful diagnostic tool for old patients. A total of 72 patients aged 75-93 years were evaluated by means of prostatic transrectal FNA. Antibiotic prophylaxis, analgesia or cessation of anticoagulant therapy were not necessary. In 35 patients (48.6%) cytological diagnosis was positive for prostatic adenocarcinoma, whereas in 37 cytology was negative for cancer. In 100% of patients with PSA > 30 ng/ml or with PSA > 20 ng/ml and suspicious digital rectal examination FNA results were positive for cancer. 4.1% minor and 1.3% major (acute prostatitis) complications after FNA were observed. In male patients older than 75 years with PSA > 30 ng/ml or with PSA > 20 ng/ml and suspicious digital rectal examination, histological confirmation of carcinoma by prostatic biopsy may be not necessary, because of the high probability of a positive result. When histological confirmation of prostatic carcinoma is required in elderly patients, transrectal prostatic FNA is a valid alternative to transrectal biopsy, due to its excellent tolerance and low complication rate.


Effect of Selenium Supplementation on Redox Status of the Aortic Wall in Young Spontaneously Hypertensive Rats.
Selenium (Se) is an exogenous antioxidant that performs its function via the expression of selenoproteins. The aim of this study was to explore the effect of varying Se intake on the redox status of the aortic wall in young spontaneously hypertensive rats (SHR). Sixteen male Wistar Kyoto (WKY) rats and nineteen male SHR, 16-week-old, were tested after being given diets with different Se content for eight weeks. They were divided into 4 groups: control groups of WKY NSe and SHR NSe on an adequate Se diet and groups of WKY HSe and SHR HSe that received Se supplementation. The Se nutritional status was assessed by measuring whole blood glutathione peroxidase-1 (GPx-1) activity. Serum concentration of lipid hydroperoxides and serum level of antibodies against advanced glycation end products (anti-AGEs abs) were determined. Expression of GPx-1 and endothelial nitric oxide synthase (eNOS) were examined in aortic wall. Se supplementation significantly increased GPx-1 activity of whole blood and in the aortas of WKY and SHR. Decreased lipid peroxidation level, eNOS-3 expression in the aortic wall, and serum level of anti-AGEs abs were found in SHR HSe compared with SHR NSe. In conclusion, Se supplementation improved the redox status of the aortic wall in young SHR.


A Systematic Review of Mobile Stroke Unit Among Acute Stroke Patients: Time Metrics, Adverse Events, Functional Result and Cost-Effectiveness.
Mobile stroke unit (MSU) is deployed to shorten the duration of ischemic stroke recognition to thrombolysis treatment, thus reducing disability, mortality after an acute stroke attack, and related economic burden. Therefore, we conducted a comprehensive systematic review of the clinical trial and economic literature focusing on various outcomes of MSU compared with conventional emergency medical services (EMS). An electronic search was conducted in four databases (PubMed, OVID Medline, Embase, and the Cochrane Controlled Register of Trials) from 1990 to 2021. In these trials, patients with acute stroke were assigned to receive either MSU or EMS, with clinical and economic outcomes. First, we extracted interested data in the pooled population and conducted a subgroup analysis to examine related heterogeneity. We then implemented a descriptive analysis of economic outcomes. All analyses were performed with R 4.0.1 software. A total of 22,766 patients from 16 publications were included. In total 7,682 (n = 33.8%) were treated in the MSU and 15,084 (n = 66.2%) in the conventional EMS. Economic analysis were available in four studies, of which two were based on trial data and the others on model simulations. The pooled analysis of time metrics indicated a mean reduction of 32.64 min (95% confidence interval: 23.38-41.89, p < 0.01) and 28.26 minutes (95% CI: 16.11-40.41, p < 0.01) in the time-to-therapy and time-to-CT completion, respectively in the MSU. However, there was no significant difference on stroke-related neurological events (OR = 0.94, 95% CI: 0.70-1.27, p = 0.69) and in-hospital mortality (OR = 1.11, 95% CI: 0.83-1.50, p = 0.48) between the MSU and EMS. The proportion of patients with modified Ranking scale (mRS) of 0-2 at 90 days from onset was higher in the MSU than EMS (p < 0.05). MSU displayed favorable benefit-cost ratios (2.16-6.85) and incremental cost-effectiveness ratio ($31,911 /QALY and $38,731 per DALY) comparing to EMS in multiple economic publications. Total cost data based on 2014 USD showed that the MSU has the highest cost in Australia ($1,410,708) and the lowest cost in the USA ($783,463). A comprehensive analysis of current research suggests that MUS, compared with conventional EMS, has a better performance in terms of time metrics, safety, long-term medical benefits, and cost-effectiveness.


Highly efficient and selective pressure-assisted photon-induced polymerization of styrene.
The polymerization process of condensed styrene to produce polystyrene as an industrially important polymeric material was investigated using a novel approach by combining external compression with ultraviolet radiation. The reaction evolution was monitored as a function of time and the reaction products were characterized by in situ Fourier transform infrared spectroscopy. By optimizing the loading pressures, we observed highly efficient and selective production of polystyrene of different tacticities. Specifically, at relatively low loading pressures, infrared spectra suggest that styrene monomers transform to amorphous atactic polystyrene (APS) with minor crystalline isotactic polystyrene. In contrast, APS was found to be the sole product when polymerization occurs at relatively higher loading pressures. The time-dependent reaction profiles allow the examination of the polymerization kinetics by analyzing the rate constant and activation volume as a function of pressure. As a result, an optimized pressure condition, which allows a barrierless reaction to proceed, was identified and attributed to the very desirable reaction yield and kinetics. Finally, the photoinitiated reaction mechanism and the growth geometry of the polymer chains were investigated from the energy diagram of styrene and by the topology analysis of the crystal styrene. This study shows strong promise to produce functional polymeric materials in a highly efficient and controlled manner.


Synthesis of L-2-oxothiazolidine-4-carboxylic acid.
An improved synthesis of L-2- oxothiazolidine -4-carboxylic acid is described. The new procedure, which leads to excellent yields of product, does not require the use of phosgene. The new method is thus less hazardous than the original one, and is readily adaptable to the preparation of 35S-labeled product.


Replicon Particle Expressing the E2 Glycoprotein of Bovine Viral Diarrhea Virus Immunization and Evaluation of Antibody Response.
The objective of this study was to develop a new antigen delivery system using an alphavirus replicon particle (RP) to induce humoral antibody responses against bovine viral diarrhea virus (BVDV) recombinant antigen produced from envelope glycoprotein E2. An alphavirus RP expressing the E2 glycoprotein of BVDV was used for immunization of pigs. A fluorescent microsphere immunoassay (FMIA) has been applied to detect BVDV E2 antigen-specific antibody isotype in pig immunized with alphavirus RP. Full-length BVDV E2 (aa 1-375) was cleaved into several pieces, eight E2 DNA fragments, including full-length DNA, were cloned into expression vector pHUE, and the recombinant proteins expressed in BL-21 (DE3) Escherichia coli. After successful conjugation of purified proteins with microsphere beads, a multiplex FMIA platform was constructed, and BVDV E2 alphavirus-based RP-immunized animal serum samples were tested in the presence of bead-bound antigen targets. The results were represented as mean fluorescence intensity (MFI); the MFI values were converted to sample value/positive value (S/P) ratios. BVDV E2 (aa 1-183) showed the highest MFI values of eight recombinant E2 fragments when the specific activity of each fragment was tested. In immunized animals, data for BVDV E2-specific IgA, IgG, and IgM in serum and only IgG and IgA in oral fluids were recorded. The MFI values for the positive serum sample showed a 100-fold increase compared with the negative serum sample. Antibody isotype to BVDV E2 antigens showed that IgG > IgM > IgA in serum, whereas IgG > IgA > IgM in oral fluids. The data presented in this study suggested that boosting with the same doses of alphavirus RP in 3-week intervals may potentially enhance antibody response. The experimental results demonstrate that alphavirus RP-expressing BVDV E2 antigen induces antibody response in pig.


Structural basis of DNA bending and oriented heterodimer binding by the basic leucine zipper domains of Fos and Jun.
Interactions among transcription factors that bind to separate sequence elements require bending of the intervening DNA and juxtaposition of interacting molecular surfaces in an appropriate orientation. Here, we examine the effects of single amino acid substitutions adjacent to the basic regions of Fos and Jun as well as changes in sequences flanking the AP-1 site on DNA bending. Substitution of charged amino acid residues at positions adjacent to the basic DNA-binding domains of Fos and Jun altered DNA bending. The change in DNA bending was directly proportional to the change in net charge for all heterodimeric combinations between these proteins. Fos and Jun induced distinct DNA bends at different binding sites. Exchange of a single base pair outside of the region contacted in the x-ray crystal structure altered DNA bending. Substitution of base pairs flanking the AP-1 site had converse effects on the opposite directions of DNA bending induced by homodimers and heterodimers. These results suggest that Fos and Jun induce DNA bending in part through electrostatic interactions between amino acid residues adjacent to the basic region and base pairs flanking the AP-1 site. DNA bending by Fos and Jun at inverted binding sites indicated that heterodimers bind to the AP-1 site in a preferred orientation. Mutation of a conserved arginine within the basic regions of Fos and transversion of the central C:G base pair in the AP-1 site to G:C had complementary effects on the orientation of heterodimer binding and DNA bending. The conformational variability of the Fos-Jun-AP-1 complex may contribute to its functional versatility at different promoters.


[Integrated approach to yellow fever surveillance: pilot study in Senegal in 2003-2004].
The aim was to undertake a pilot study of integrated surveillance of yellow fever (YF) in Senegal, based on i) a human surveillance involving healthcare centers in the 11 administrative regions of the country ii) an entomological surveillance including domestic and sylvatic environment and iii) screening mosquitoes for YF virus using RT-PCR method. The integrated approach of human and entomological surveillance was conducted for 2 years (2003-2004). Surveillance in human population was based on screening samples of YF suspected cases (i.e. patients with acute (< or = 15 days) febrile illness with jaundice) for YF specific IgM antibodies. The entomological surveillance was carried out by collecting mosquitoes using human landing catch method and attempt to detect YF virus on them by RT-PCR. Forty five percent of the healthcare centres notified at least one suspected YF case during 2003-2004 periods. Among the 342 sera collected over 2 years, 2 revealed anti-YF IgM antibodies leading to investigations which allowed identification of the source and place of infection and implementation of a reactive focused YF immunization campaign. In addition, YFV was detected by RT-PCR from 49 out of 1762 mosquitoes tested and distributed as follows: in the sylvatic environment, 29 from Aedes furcifer and 1 from Aedes aegypti while in the domestic area, 15 Aedes aegypti and 4 Aedes furcifer. RT-PCR was found more sensitive and rapid than viral isolation for YF virus detection in mosquitoes. The pilot study in Senegal for YF surveillance integrating human and entomological parameters in domestic and sylvatic areas showed that this approach is very efficient in detecting yellow fever virus circulation due to the complementarity of the two systems. Therefore, in the light of the encouraging results presented herein, similar studies in different context and areas are needed to further validate and allow the extension of its application to other endemic regions of Africa.


Relationship Between Warm Childhood Memories and Mobile Phone Addiction: A Moderated Mediation Model.
Childhood experiences have an important effect on mobile phone addiction, but the relationship between positive childhood experiences and mobile phone addiction and its underlying mechanisms should be explored further. This study aims to explore a model linking early memories of warmth and safeness to mobile phone addiction via the mediating role of alexithymia and moderating role of negative coping styles. A total of 379 Chinese college students (Mage = 19.80 years, SD = 1.38; 240 females) completed a questionnaire consisting of the Early Memories of Warmth and Safeness Scale, Toronto Alexithymia Scale, Mobile Phone Addiction Scale, and Negative Coping Styles Scale. Results indicate that early memories of warmth and safeness are negatively correlated with mobile phone addiction, and alexithymia plays a mediating role in the link between early memories of warmth and safeness and mobile phone addiction. In addition, negative coping styles significantly moderate the relationship between early memories of warmth and safeness and alexithymia, specifically, the negative association between early memories of warmth and safeness and alexithymia is highly significant at high (vs. low) negative coping styles levels. The findings suggest that early memories of warmth and safeness are an important protective factor against mobile phone addiction, which enrich the literature on mobile phone addiction and provide empirical support for the prevention of mobile phone addiction.