Differences in Mental Health and Sexual Outcomes Based on Type of Nonconsensual Sexual Penetration.
Little is known based on the stratification and localization of penetration type of rape: oral, vaginal, and/or anal. The current study examined associations between type of rape and mental and sexual health symptoms in 865 community women. All penetration types were positively associated with negative mental and sexual health symptoms. Oral and/or anal rape accounted for additional variance in anxiety, depression, some trauma-related symptoms, and dysfunctional sexual behavior than the association with vaginal rape alone. Findings suggest that penetration type can be an important facet of a rape experience and may be useful to assess in research and clinical settings.


Clinical efficacy of gangliosides on premature infants suffering from white matter damage and its effect on the levels of IL-6, NSE and S100β.
This study investigated the clinical efficacy of gangliosides on premature infants suffering from white matter damage and its effect on the levels of IL-6, neuron-specific enolase (NSE) and S100β. Seventy-six cases of premature infants suffering from white matter damage admitted to the Tianjin Central Hospital of Obstetrics and Gynecology from February 2016 to March 2017 were enrolled in this study. They were randomly divided into the control group and the observation group with 38 cases in each group. Control group was given conventional treatment, while the observation group was given ganglioside treatment on the basis of the treatment given to the control group. Craniocerebrum ultrasonic detection was used to observe the condition of white matter around the ventricle of child patients in the two groups, before and after treatment. ELISA was used to detect the levels of IL-6, NSE and S100β. Gesell developmental scale was used to compare the developmental quotient (DQ) of various function regions of the children. The total effective rate of the observation group was higher than that of the control group (P<0.05). The gray value of craniocerebrum ultrasonic detection in the observation group was significantly lower than that in the control group (P<0.05). IL-6, S100β and NSE levels of the child patients in the two groups were significantly declined at 7 and 14 days after birth (P<0.05). After 1 year, the observation group scored significantly higher DQ than the control group in the aspects of social adaptation, gross motor, fine motor, language and personal social contact. The sequel incidence of patients in the observation group was significantly lower than that of the control group (P<0.05). In conclusion, the intervention treatment with ganglioside for premature infants suffering from white matter damage was beneficial and provided a protective effect. It also reduced sequel and produced some promising results.


Rotavirus Vaccine Schedules and Vaccine Response Among Infants in Low- and Middle-Income Countries: A Systematic Review.
Rotavirus vaccine schedules may impact vaccine response among children in low- and middle-income countries (LMICs). Our objective was to review the literature evaluating the effects of monovalent (RV1) or pentavalent rotavirus vaccines schedules on vaccine response. We searched PubMed, Web of Science, Embase, and ClinicalTrials.gov for eligible trials conducted in LMICs comparing ≥2 vaccine schedules and reporting immunologic response or efficacy. We calculated seroconversion proportion differences and geometric mean concentration (GMC) ratios with 95% confidence intervals. We abstracted data from 8 eligible trials of RV1. The point estimates for seroconversion proportions difference ranged from -0.25 to -0.09 for the 6/10-week schedule compared with 10/14. The range for the 6/10/14- compared with 10/14-week schedule was -0.02 to 0.10. Patterns were similar for GMC ratios and efficacy estimates. The commonly used 6/10-week RV1 schedule in LMICs may not be optimal. Further research on the effect of rotavirus schedules using clinical endpoints is essential.


Cavity ring-down spectroscopy sensor for ion beam etch monitoring and end-point detection of multilayer structures.
This contribution reports on the development of in situ sputter monitoring and end-point detection for ion beam etch systems using continuous-wave cavity ring-down spectroscopy (cw-CRDS). The demonstrated system is based on the detection of sputtered manganese atoms using a tunable external cavity diode laser in the vicinity of 403.07 nm. The cw-CRDS system is described and measurements from a manganese-iron target are presented. End-point detection is demonstrated by monitoring the time dependence of manganese concentration for a multilayer target comprised of alternating layers of manganese/iron and titanium. Detection limits are shown to be adequate for today's commercial ion beam sputter systems.


Hepatitis B virus polymerase disrupts K63-linked ubiquitination of STING to block innate cytosolic DNA-sensing pathways.
The cellular innate immune system recognizing pathogen infection is essential for host defense against viruses. In parallel, viruses have developed a variety of strategies to evade the innate immunity. The hepatitis B virus (HBV), a DNA virus that causes chronic hepatitis, has been shown to inhibit RNA helicase RIG-I-mediated interferon (IFN) induction. However, it is still unknown whether HBV could affect the host DNA-sensing pathways. Here we report that in transiently HBV-transfected Huh7 cells, the stably HBV-producing cell line HepAD38, and HBV-infected HepaRG cells and primary human hepatocytes, HBV markedly interfered with IFN-β induction and antiviral immunity mediated by the stimulator of interferon genes (STING), which has been identified as a central factor in foreign DNA recognition and antiviral innate immunity. Screening analysis demonstrated that the viral polymerase (Pol), but not other HBV-encoded proteins, was able to inhibit STING-stimulated interferon regulatory factor 3 (IRF3) activation and IFN-β induction. Moreover, the reverse transcriptase (RT) and the RNase H (RH) domains of Pol were identified to be responsible for the inhibitory effects. Furthermore, Pol was shown to physically associate with STING and dramatically decrease the K63-linked polyubiquitination of STING via its RT domain without altering the expression level of STING. Taken together, these observations suggest that besides its inherent catalytic function, Pol has a role in suppression of IFN-β production by direct interaction with STING and subsequent disruption of its K63-linked ubiquitination, providing a new mechanism for HBV to counteract the innate DNA-sensing pathways. Although whether and how HBV infection induces the innate immune responses are still controversial, it has become increasingly clear that HBV has developed strategies to counteract the pattern recognition receptor-mediated signaling pathways. Previous studies have shown that type I IFN induction activated by the host RNA sensors could be inhibited by HBV. However, it remains unknown whether HBV as a DNA virus utilizes evasion mechanisms against foreign DNA-elicited antiviral signaling. In recent years, the cytosolic DNA sensor and key adaptor STING has been demonstrated to be essential in multiple foreign DNA-elicited innate immune signalings. Here, for the first time, we report STING as a new target of HBV to antagonize IFN induction and identify the viral polymerase responsible for the inhibitory effect, thus providing an additional molecular mechanism by which HBV evades the innate immunity; this implies that in addition to its inherent catalytic function, HBV polymerase is a multifunctional immunomodulatory protein.


Effect on mortality of community-based maternity-care programme in rural Bangladesh.
Various community-based interventions have been proposed to improve maternity care, but hardly any studies have reported the effect of these measures on maternal mortality. In this study, the efficacy of a maternity-care programme to reduce maternal mortality has been evaluated in the context of a primary health-care project in rural Bangladesh. Trained midwives were posted in villages, and asked to attend as many home-deliveries as possible, detect and manage obstetric complications at onset, and accompany patients requiring referral for higher-level care to the project central maternity clinic. The effect of the programme was evaluated by comparison of direct obstetric maternal mortality ratios between the programme area and a neighbouring control area without midwives. Random assignment of the intervention was not possible but potentially confounding characteristics, including coverage and use of other health and family planning services, were similar in both areas. Maternal mortality ratios due to obstetric complications were similar in both areas during the 3 years preceding the start of the programme. By contrast, during the following 3 years, the ratio was significantly lower in the programme than in the control area (1.4 vs 3.8 per 1000 live births, p = 0.02). The findings suggest that maternal survival can be improved by the posting of midwives at village level, if they are given proper training, means, supervision, and back-up. The inputs for such a programme to succeed and the constraints of its replication on a large scale should not be underestimated.


Natural Killers Are Made Not Born: How to Exploit NK Cells in Lung Malignancies.
In recent years, progress has been made in the characterization of natural killer (NK) cells in lung malignancies, and we have now gained a better understanding of the frequency, localization, phenotype, and functional status of NK cells infiltrating these tumors. NK cell subset recruited in lung cancer is mainly capable of producing relevant cytokines rather than exerting direct cancer cell killing. Thus, the relevance of NK cells in tumor microenvironment might also go beyond the killing of tumor cells, being NK cells endowed with regulatory functions toward an ample array of immune effectors. Nevertheless, boosting their cytotoxic functions and redirecting the migration of cytotoxic NK cell subset to the tumor site might open new therapeutic avenues for lung cancer. Also, we believe that a deeper investigation into the impact of both conventional (e.g., chemotherapy) or new therapies (e.g., anti-immune checkpoints mAbs) on NK cell homeostasis in lung cancer patients is now required.


Recovery of polysome function of T4-infected Escherichia coli after brief treatment with chloramphenicol and rifampin.
T4-infected Escherichia coli cells briefly exposed to rifampin, or to rifampin plus chloramphenicol, were capable of protein synthesis for some time after removal of the antibiotics, although ribonucleic acid synthesis was irreversibly inhibited. Partially completed peptides trapped on polysomes by high levels of chloramphenicol were eventually completed after removal of the drug, as demonstrated by subjecting labeled peptides from appropriate polysome regions to polyacrylamide disc gel electrophoresis. Thus, the effect of the drug appears to be reversible on the molecular as well as the cellular level.


2-Acetylpyridine thiosemicarbazones. 9. Derivatives of 2-acetylpyridine 1-oxide as potential antimalarial agents.
In view of the antimalarial activity in mice of 2-acetylpyridine thiosemicarbazones, a series of analogous 1-oxides was prepared for evaluation. Their synthesis was achieved by the reaction of 2-acetylpyridine 1-oxide with methyl hydrazinecarbodithioate to give methyl 3-[1-(2-pyridinyl 1-oxide)ethylidene]hydrazinecarbodithioate (II). Reaction of the latter intermediate with secondary amines afforded the desired 2-acetylpyridine 1-oxide thiosemicarbazones (III). Reduction of the azomethine linkage of II with NaBH4 gave methyl 3-[1-(2-pyridinyl 1-oxide)ethyl]-hydrazinecarbodithioate (IV) whose S-methyl group was then displaced by amines to give a 1-[1-(2-pyridinyl 1-oxide)ethyl]thiosemicarbazide, V. Antimalarial activity of III was evaluated against both Plasmodium berghei in the mouse and Plasmodium falciparum in an automated in vitro test system. In both cases, 2-acetylpyridine 1-oxide thiosemicarbazones were found to be less active than the corresponding de-1-oxide analogues. When compounds V were evaluated against Plasmodium berghei in the mouse, a diminution of activity was similarly seen in comparison to the analogues not bearing the 1-oxide moiety.


[Spanish version of the Memory Impairment Screen (MIS): normative data and discriminant validity].
Present data on discriminative and normative validity for the Memory Impairment Screen (MIS) in a cross-sectional validation study within a dementia-clinic setting using a Spanish adaptation of the MIS. Assess its usefulness as a screening instrument for memory problems related to primary dementing disorders, foremost Alzheimer's Disease (AD). 403 subjects, including 188 demented subjects according to DSM-IV criteria (119 of which presented AD according to NINCDS-ADRDA criteria) and 215 controls, over 50 years. The MIS, a four word memory test using a specific encoding technique and scoring on a 0-8 range, formed part of the neuropsychological workup, but it was not used for diagnosis. Sensitivity, specificity and predictive values positive (PPV) and negative (NPV) were calculated for the MIS against the gold-standard of clinical diagnosis by two blinded clinicians. ROC curves for the discrimination between demented subjects and controls, and AD subjects and controls were plotted. Control subjects were significantly younger and better educated than the demented samples (p<0.001). No sex differences could be established. ROC curves demonstrated excellent discriminative validity of the MIS 402 for dementia on a whole (0.944) and even better for AD (0.978). The MIS presents satisfying results regarding sensitivity and specificity as well as PPV for different base rates, but the most effective cut-off score lies at < or = 4 points. For all demented subjects this cut-off represents a sensitivity of 0.74 and specificity of 0.96; for AD results are 0.86 and 0.96. More importantly, PPV values are above 0.65 for assumed base rates of 10% and more. Negative predictive values are almost 1 for all assumed base rates. The Spanish version of the MIS reliably differentiates between normal and demented subjects. Nevertheless one has to consider the setting of the study when interpreting the results. The use of the S-MIS seems to be justified as first level dementia screening tool.


Nicotine suppresses bone sialoprotein gene expression.
Tobacco smoking is a risk factor for periodontitis and osteoporosis. Nicotine is a major component of tobacco, and has been reported to inhibit proliferation and differentiation of osteoblasts. Bone sialoprotein (BSP) is a mineralized tissue-specific protein expressed by differentiated osteoblasts that appears to function in the initial mineralization of bone. The purpose of this study was to determine the effects of nicotine on bone metabolism. We used rat osteobast-like UMR106 and ROS 17/2.8 cells and rat stromal bone marrow RBMC-D8 cells. To determine the molecular basis of the transcriptional regulation of the BSP gene by nicotine, we conducted Northern hybridization, transient transfection analyses with chimeric constructs of the BSP gene promoter linked to a luciferase reporter gene and gel mobility shift assays. Nicotine (250 microg/mL) decreased the BSP mRNA levels at 12 and 24 h in UMR106 and ROS 17/2.8 cells. From transient transfection assays using various sized BSP promoter-luciferase constructs, nicotine decreased the luciferase activities of the construct, including the promoter sequence nucleotides -116 to +60, in UMR106 and RBMC-D8 cells. Nicotine decreased the nuclear protein binding to the cAMP response element (CRE), fibroblast growth factor 2 response element (FRE) and homeodomain protein-binding site (HOX) at 12 and 24 h. This study indicates that nicotine suppresses BSP transcription mediated through CRE, FRE and HOX elements in the proximal promoter of the rat BSP gene.


Diphtheria outbreak with high mortality in northeastern Nigeria.
SUMMARY A diphtheria outbreak occurred from February to November 2011 in the village of Kimba and its surrounding settlements, in Borno State, northeastern Nigeria. We conducted a retrospective outbreak investigation in Kimba village and the surrounding settlements to better describe the extent and clinical characteristics of this outbreak. Ninety-eight cases met the criteria of the case definition of diphtheria, 63 (64.3%) of whom were children aged <10 years; 98% of cases had never been immunized against diphtheria. None of the 98 cases received diphtheria antitoxin, penicillin, or erythromycin during their illness. The overall case-fatality ratio was 21.4%, and was highest in children aged 0-4 years (42.9%). Low rates of immunization, delayed clinical recognition of diphtheria and absence of treatment with antitoxin and appropriate antibiotics contributed to this epidemic and its severity.


Controlled trial of hydroxychloroquine and D-penicillamine singly and in combination in the treatment of rheumatoid arthritis.
A 2-year, controlled, double-blind trial of D-penicillamine and hydroxychloroquine either alone or in combination was conducted on patients with progressive rheumatoid arthritis. The group given D-penicillamine alone improved most, but a linear fall-off in efficacy occurred. Surprisingly, the group receiving combination drug therapy did not fare as well as the group receiving D-penicillamine therapy. A subset of patients receiving hydroxychloroquine therapy had prolonged benefit. Toxicity, though not uncommon, was generally not severe.


Domino Reaction for the Synthesis of Polysubstituted Pyrroles and Lamellarin R.
A three-component annulation reaction was developed for the synthesis of pyrroles, a class of compounds with various properties valuable to biomedical and polymer industries. Treatment of α-silylaryl triflates, Schiff bases, and alkynes generated polysubstituted pyrroles in good yields (61-86%) with regioselectivity. This domino reaction involved completion of five sequential steps in a single flask, which comprised aryne formation through 1,2-elimination, their alkylation by Schiff bases through 1,2-addition, 1,4-intramolecular proton transfer, Hüisgen 1,3-dipolar cycloaddition, and dehydrogenative aromatization. It was then successfully applied as the key step in the synthesis of the natural product lamellarin R. This new reaction represents an efficient, sustainable process for the production of chemical materials.


Gradual collapse of nuclear wave functions regulated by frequency tuned X-ray scattering.
As is well established, the symmetry breaking by isotope substitution in the water molecule results in localisation of the vibrations along one of the two bonds in the ground state. In this study we find that this localisation may be broken in excited electronic states. Contrary to the ground state, the stretching vibrations of HDO are delocalised in the bound core-excited state in spite of the mass difference between hydrogen and deuterium. The reason for this effect can be traced to the narrow "canyon-like" shape of the potential of the state along the symmetric stretching mode, which dominates over the localisation mass-difference effect. In contrast, the localisation of nuclear motion to one of the HDO bonds is preserved in the dissociative core-excited state . The dynamics of the delocalisation of nuclear motion in these core-excited states is studied using resonant inelastic X-ray scattering of the vibrationally excited HDO molecule. The results shed light on the process of a wave function collapse. After core-excitation into the state of HDO the initial wave packet collapses gradually, rather than instantaneously, to a single vibrational eigenstate.


Antibiotic resistance differentiates Echinacea purpurea endophytic bacterial communities with respect to plant organs.
Recent findings have shown that antibiotic resistance is widespread in multiple environments and multicellular organisms, as plants, harboring rich and complex bacterial communities, could be hot spot for emergence of antibiotic resistances as a response to bioactive molecules production by members of the same community. Here, we investigated a panel of 137 bacterial isolates present in different organs of the medicinal plant Echinacea purpurea, aiming to evaluate if different plant organs harbor strains with different antibiotic resistance profiles, implying then the presence of different biological interactions in the communities inhabiting different plant organs. Data obtained showed a large antibiotic resistance variability among strains, which was strongly related to the different plant organs (26% of total variance, P < 0.0001). Interestingly this uneven antibiotic resistance pattern was present also when a single genus (Pseudomonas), ubiquitous in all organs, was analyzed and no correlation of antibiotic resistance pattern with genomic relatedness among strains was found. In conclusion, we speculate that antibiotic resistance patterns are tightly linked to the type of plant organ under investigation, suggesting the presence of differential forms of biological interaction in stem/leaves, roots and rhizosphere.


Tissular growth factors profile after teduglutide administration on an animal model of intestinal anastomosis.
Teduglutide is an enterotrophic analogue of glucagon-like peptide-2, with an indirect and poorly understood mechanism of action, approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the response of tissue growth factors to surgical injury and teduglutide administration on an animal model of intestinal anastomosis. Wistar rats (n = 59) were distributed into four groups: "ileal resection" or "laparotomy", each one subdivided into "postoperative teduglutide administration" or "no treatment"; and sacrificed at the third or the seventh day, with ileal sample harvesting. Gene expression of insulin-like growth factor 1 (Igf1), vascular endothelial growth factor a (Vegfa), transforming growth factor β1 (Tgfβ1), connective tissue growth factor (Ctgf), fibroblast growth factor 2 (Fgf2), fibroblast growth factor 7 (Fgf7), epidermal growth factor (Egf), heparin-binding epidermal-like growth factor (Hbegf), platelet-derived growth factor b (Pdgfb) and glucagon-like peptide 2 receptor (Glp2r)was studied by real-time polymerase chain reaction. Upregulation of Fgf7, Fgf2, Egf, Vegfaand Glp2rat the third day and of Pdgfat the seventh day was verified in the perianastomotic segment. Teduglutide administration was associated with higher fold-change of relative gene expression of Vegfa(3.6 ± 1.3 vs.1.9 ± 2.0, p = 0.0001), Hbegf(2.2 ± 2.3 vs. 1.1 ± 0.9, p = 0.001), Igf1(1.6 ± 7.6 vs. 0.9 ± 0.7, p = 0.002) and Ctgf(1.1 ± 2.1 vs. 0.6 ± 2.0, p = 0.013); and lower fold-change of Tgfβ1, Fgf7and Glp2r. Those results underscore the recognized role of Igf1and Hbegfas molecular mediators of the effects of teduglutide and suggest that other humoral factors, like Vegfand Ctgf, may also be relevant in the perioperative context. Induction of Vegfa, Igf1and Ctgfgene expressions might indicate a favorable influence of teduglutide on the intestinal anastomotic healing.


Deletion of F4L (ribonucleotide reductase) in vaccinia virus produces a selective oncolytic virus and promotes anti-tumor immunity with superior safety in bladder cancer models.
Bladder cancer has a recurrence rate of up to 80% and many patients require multiple treatments that often fail, eventually leading to disease progression. In particular, standard of care for high-grade disease, Bacillus Calmette-Guérin (BCG), fails in 30% of patients. We have generated a novel oncolytic vaccinia virus (VACV) by mutating the F4L gene that encodes the virus homolog of the cell-cycle-regulated small subunit of ribonucleotide reductase (RRM2). The F4L-deleted VACVs are highly attenuated in normal tissues, and since cancer cells commonly express elevated RRM2 levels, have tumor-selective replication and cell killing. These F4L-deleted VACVs replicated selectively in immune-competent rat AY-27 and xenografted human RT112-luc orthotopic bladder cancer models, causing significant tumor regression or complete ablation with no toxicity. It was also observed that rats cured of AY-27 tumors by VACV treatment developed anti-tumor immunity as evidenced by tumor rejection upon challenge and by ex vivo cytotoxic T-lymphocyte assays. Finally, F4L-deleted VACVs replicated in primary human bladder cancer explants. Our findings demonstrate the enhanced safety and selectivity of F4L-deleted VACVs, with application as a promising therapy for patients with BCG-refractory cancers and immune dysregulation.


Interaction of Z form poly(dG-dC).poly(dG-dC) with divalent metal ions: localization of the binding sites by I.R. spectroscopy.
The secondary structures of poly(dG-dC).poly(dG-dC) in the presence of alcaline , alcaline earth and first row transition metal ions (Na+, Mg2+, Co2+, Ni2+) are investigated by infrared spectroscopy. The conformational transitions are studied as a function of the hydration of the polynucleotide and counter-ion nature and content. The use of selectively deuterated poly(dG-dC).poly(dG-dC) on the 8-carbon of guanines allows to show that a direct interaction occurs between the N7 site of guanines and the transition metal ions Co2+ and Ni2+. In the case of Mg2+, for high ion/nucleotide ratios, the interaction occurs essentially at the level of the phosphate groups. This interaction leads to a modification of the left-handed conformation. Based on the IR spectroscopy results, an explanation is proposed for the different efficiencies of these various ions to induce the B----Z transition.


Design of an Anti-HMGB1 Synthetic Antibody for In Vivo Ischemic/Reperfusion Injury Therapy.
High-mobility group box 1 (HMGB1) is a multifunctional protein. Upon injury or infection, HMGB1 is passively released from necrotic and activated dendritic cells and macrophages, where it functions as a cytokine, acting as a ligand for RAGE, a major receptor of innate immunity stimulating inflammation responses including the pathogenesis of cerebral ischemia/reperfusion (I/R) injury. Blocking the HMGB1/RAGE axis offers a therapeutic approach to treating these inflammatory conditions. Here, we describe a synthetic antibody (SA), a copolymer nanoparticle (NP) that binds HMGB1. A lightly cross-linked N-isopropylacrylamide (NIPAm) hydrogel copolymer with nanomolar affinity for HMGB1 was selected from a small library containing trisulfated 3,4,6S-GlcNAc and hydrophobic N-tert-butylacrylamide (TBAm) monomers. Competition binding experiments with heparin established that the dominant interaction between SA and HMGB1 occurs at the heparin-binding domain. In vitro studies established that anti-HMGB1-SA inhibits HMGB1-dependent ICAM-1 expression and ERK phosphorylation of HUVECs, confirming that SA binding to HMGB1 inhibits the proteins' interaction with the RAGE receptor. Using temporary middle cerebral artery occlusion (t-MCAO) model rats, anti-HMGB1-SA was found to accumulate in the ischemic brain by crossing the blood-brain barrier. Significantly, administration of anti-HMGB1-SA to t-MCAO rats dramatically reduced brain damage caused by cerebral ischemia/reperfusion. These results establish that a statistical copolymer, selected from a small library of candidates synthesized using an "informed" selection of functional monomers, can yield a functional synthetic antibody. The knowledge gained from these experiments can facilitate the discovery, design, and development of a new category of drug.


Structure and function of contractile proteins in muscle fibres.
The structural unit of muscle has long been defined as the myofibril, a supramolecular assembly of a dozen or more proteins of which two, actin and myosin, comprise more than 75%. In the past 40 years since Albert Szent-Gyorgyi first described the contractile response from the complex of actin and myosin, knowledge of the structure and function of these contractile proteins has been substantially refined. This paper describes these new discoveries and identifies the problems which remain to be elucidated.


Preliminary results on the uptake and biochemical response to water-exposure of Tamiflu® (oseltamivir phosphate) in two marine bivalves.
Tamiflu® (oseltamivir phosphate, OST) is an antiviral drug used for the pandemic treatment of avian influenza but few data are available regarding its toxicity. It should be noted that acute adverse responses are not likely to occur due to low environmental presence of this drug. Nonetheless, water concentration levels of this compound may reach the µg/L range under influenza episodes. Bivalves are reliable sentinels of chemical exposure due to their low metabolism; however, biotransformation of drugs does occur in these aquatic invertebrates. Two species of bivalves, namely mussels Mytilus galloprovincialis and clams Ruditapes philippinarum, were exposed for 48 h to 100 µg/L OST. Hemolymph from control and treated bivalves was withdrawn and the presence of OST and its metabolite oseltamivir carboxylate (OST-C) determined by LC-MS/MS. Gills and digestive gland were excised from control and exposed bivalves and carboxylesterase (CE) activities measured using different substrates. In addition, antioxidant defences and lipid peroxidation levels were determined. Higher metabolism of OST seemed to occur in mussels, since both OST and OST-C were found in hemolymph, whereas in clams only the parent compound was detected. In contrast, biomarker responses were more evident in exposed clams which indicate that this species may be considered as more sensitive to OST exposure. CE-related activities successfully reflected OST exposure, with substrates 1-naphthyl acetate (1NA) and 1-naphthyl butyrate (1NB) displaying the highest sensitivity in the two bivalve species. Data thus indicate the usefulness of CE-related activities as biomarkers for OST exposure in bivalves.


Ratiometric electrochemical detection of hydrogen peroxide and glucose.
Hydrogen peroxide (H2O2) detection is of high importance as it is a versatile (bio)marker whose detection can indicate the presence of explosives, enzyme activity and cell signalling pathways. Herein, we demonstrate the rapid and accurate ratiometric electrochemical detection of H2O2 using disposable screen-printed electrodes through a reaction-based indicator assay. Ferrocene derivatives equipped with self-immolative linkers and boronic acid ester moieties were synthesised and tested, and, through a thorough assay optimisation, the optimum probe showed good stability, sensitivity and selectivity towards H2O2. The optimised conditions were then applied to the indirect detection of glucose via an enzymatic assay, capable of distinguishing 10 μM from the background within minutes.


The lipid transfer properties of CETP define the concentration and composition of plasma lipoproteins.
Cholesteryl ester transfer protein (CETP) facilitates the net transfer of cholesteryl esters (CEs) and TGs between lipoproteins, impacting the metabolic fate of these lipoproteins. Previous studies have shown that a CETP antibody can alter CETP's preference for CE versus TG as transfer substrate, suggesting that CETP substrate preference can be manipulated in vivo. Hamster and human CETPs have very different preferences for CE and TG. To assess the effect of altering CETP's substrate preference on lipoproteins in vivo, here, we expressed human CETP in hamsters. Chow-fed hamsters received adenoviruses expressing no CETP, hamster CETP, or human CETP. Plasma CETP mass increased 2-fold in both the hamster and human CETP groups. Although the animals expressing human CETP still had low levels of hamster CETP, the CE versus TG preference of their plasma CETP was similar to that of the human ortholog. Hamster CETP overexpression had little impact on lipoproteins. However, expression of human CETP reduced HDL up to 50% and increased VLDL cholesterol 2.5-fold. LDL contained 20% more CE, whereas HDL CE was reduced 40%, and TG increased 6-fold. The HDL3:HDL2 ratio increased from 0.32 to 0.60. Hepatic expression of three cholesterol-related genes (LDLR, SCARB1, and CYP7A1) was reduced up to 40%. However, HDL-associated CE excretion into feces was unchanged. We conclude that expression of human CETP in hamsters humanizes their lipoprotein profile with respect to the relative concentrations of VLDL, LDL, HDL, and the HDL3:HDL2 ratio. Altering the lipid substrate preference of CETP provides a novel approach for modifying plasma lipoproteins.


Combination of high-dose chemotherapy and monoclonal antibody in breast-cancer patients: a pilot trial to monitor treatment effects on disseminated tumor cells.
Tumor relapse occurring in high-risk breast cancer patients after high-dose chemotherapy (HDC) and autologous stem-cell transplantation may arise from cells resistant to chemotherapy, as well as from tumor cells reinfused with autologous stem cell grafts. This pilot study was designed to investigate whether ex vivo immunomagnetic purging of PBSC and subsequent immunotherapy with MAb 17-1A is feasible and can reduce the number of disseminated tumor cells in BM. Twelve high-risk breast-cancer patients, seven in Stage II/III and five in Stage IV (UICC breast cancer classification) underwent surgery of the primary tumor and received two cycles of induction chemotherapy, followed by HDC. After each cycle of induction chemotherapy PBSC were collected and incubated with Ab-coated immunomagnetic beads, to remove contaminating tumor cells. Prepared stem-cell grafts were transplanted 24 h after completion of HDC. After recovering from HDC all 12 patients received a total dose of 900 mg MAb 17-1A within 4 months. The effect of in vivo purging with MAb 17-1A after HDC was controlled by examining bone aspirates of the patients with an immunocytochemical assay, allowing the detection of one cytokeratin-positive tumor cell in 10(6) total nucleated cells (TNC). Tumor cells were found in 5/12 BM aspirates prior to chemotherapy and even after HDC. Further monitoring of BM aspirates for cancer cells during Ab therapy showed a consistent reduction of tumor cells in four out of these five patients. After a median clinical follow-up of 41 (32-48) months all four patients are alive. These results are different from those of a historical control group of six patients with breast cancer treated with the same chemotherapy schedule, but without 17/1A consolidation. In comparison with the patients from the study group, all patients of this control group revealed a significantly increased number of tumor cells in BM (p < 0.01) after HDC during follow-up of 5 (3-7) months. These preliminary results indicate that induction chemotherapy, followed by HDC, may reduce disseminated tumor cells in BM. Immunotherapy with MAb 17-1A after HDC may further eliminate residual disease without severe toxicity.


Timing, prevalence, determinants and outcomes of homelessness among patients admitted to acute psychiatric wards.
To document the prevalence, timing, associations and short-term housing outcomes of homelessness among acute psychiatric inpatients. Cross-sectional study of 4,386 acute psychiatric admissions discharged from a single NHS Trust in 2008-2009. Homelessness occurred in 16%. Most homelessness (70%) was either recorded as present at admission or started within 1 week. It was associated with younger age; male gender; ethnicity other than White British or Black African/Caribbean; being single, divorced, separated or widowed; diagnosis of drug and alcohol disorder; detention under a forensic section of the Mental Health Act; having no previous admission or alternatively having a longer previous admission; having a low score on the depressed mood or hallucinations and delusions items of the Health of the Nation Outcome Scales (HoNOS); and having a high score on the HoNOS relationship difficulties and occupation and activities items. Of those who were followed-up for 28 days after discharge, 53% had a new address recorded; of those who were not, only 22% did. Homelessness affects a substantial minority of psychiatric admissions in the UK. Housing outcomes are uncertain, and it is possible that more than half continue to be homeless or living in very transient situations. Demographic and diagnostic associations with homelessness were consistent with US studies; associations with HoNOS item scores and having had no admission in the preceding 2 years suggest that, in many cases, social adversity predominates over active psychopathology at the time of admission.


Impact Analysis of Flow Shaping in Ethernet-AVB/TSN and AFDX from Network Calculus and Simulation Perspective.
Ethernet-AVB/TSN (Audio Video Bridging/Time-Sensitive Networking) and AFDX (Avionics Full DupleX switched Ethernet) are switched Ethernet technologies, which are both candidates for real-time communication in the context of transportation systems. AFDX implements a fixed priority scheduling strategy with two priority levels. Ethernet-AVB/TSN supports a similar fixed priority scheduling with an additional Credit-Based Shaper (CBS) mechanism. Besides, TSN can support time-triggered scheduling strategy. One direct effect of CBS mechanism is to increase the delay of its flows while decreasing the delay of other priority ones. The former effect can be seen as the shaping restriction and the latter effect can be seen as the shaping benefit from CBS. The goal of this paper is to investigate the impact of CBS on different priority flows, especially on the intermediate priority ones, as well as the effect of CBS bandwidth allocation. It is based on a performance comparison of AVB/TSN and AFDX by simulation in an automotive case study. Furthermore, the shaping benefit is modeled based on integral operation from network calculus perspective. Combing with the analysis of shaping restriction and shaping benefit, some configuration suggestions on the setting of CBS bandwidth are given. Results show that the effect of CBS depends on flow loads and CBS configurations. A larger load of high priority flows in AVB tends to a better performance for the intermediate priority flows when compared with AFDX. Shaping benefit can be explained and calculated according to the changing from the permitted maximum burst.


Gold-catalyzed domino aminocyclization/1,3-sulfonyl migration of N-substituted N-sulfonyl-aminobut-3-yn-2-ols to 1-substituted 3-sulfonyl-1H-pyrroles.
A method to prepare 1-substituted 3-sulfonyl-1H-pyrroles efficiently that relies on the gold(I)-catalyzed cycloisomerization of N-substituted N-sulfonyl-aminobut-3-yn-2-ols is described. The method was shown to be applicable to a broad range of 1,7-enyne alcohols containing electron-withdrawing, electron-donating, and sterically demanding substrate combinations. The mechanism is suggested to involve activation of the propargylic alcohol by the Au(I) catalyst, which causes the intramolecular nucleophilic addition of the sulfonamide unit to the alkyne moiety. The resulting nitrogen-containing heterocyclic intermediate undergoes dehydration and deaurative 1,3-sulfonyl migration, a process that remains rare in gold catalysis, to give the aromatic nitrogen-containing product.


3,5-Difluoro-4-nitropyridine N-oxide and 3,5-diamino-4-nitropyridine N-oxide monohydrate.
The molecule of 3,5-difluoro-4-nitropyridine N-oxide, C(5)H(2)F(2)N(2)O(3), is twisted around the C-NO(2) bond by 38.5 (1) degrees, while the 3,5-diamino analogue, 3,5-diamino-4-nitropyridine N-oxide monohydrate, C(5)H(6)N(4)O(3).H(2)O, adopts a planar conformation stabilized by intramolecular hydrogen bonds, with a significant redistribution of pi electrons.


Oat cell carcinoma of the bronchus and acute pancreatitis.
A case of small cell carcinoma of the lung presenting with acute pancreatitis is described. We believe this to be the first such case reported, despite the frequency of metastasis to the pancreas from such tumours. We discuss the investigation and management of such cases.


Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNA.
Uracil-DNA glycosylase (UDG) is one of the most important base excision repair (BER) enzymes involved in the repair of uracil-induced DNA lesion by removing uracil from the damaged DNA. Uracil in DNA may occur due to cytosine deamination or deoxy uridine monophosphate (dUMP) residue misincorporation during DNA synthesis. Medical evidences show that an abnormal expression of UDG is related to different types of cancer, including colorectal cancer, lung cancer, and liver cancer. Therefore, the research of UDG is crucial in cancer treatment and prevention as well as other clinical activities. Here we applied multiple computational methods to study UDG in several perspectives: Understanding the stability of the UDG enzyme in different pH conditions; studying the differences in charge distribution between the pocket side and non-pocket side of UDG; analyzing the field line distribution at the interfacial area between UDG and DNA; and performing electrostatic binding force analyses of the special region of UDG (pocket area) and the target DNA base (uracil) as well as investigating the charged residues on the UDG binding pocket and binding interface. Our results show that the whole UDG binding interface, and not the UDG binding pocket area alone, provides the binding attractive force to the damaged DNA at the uracil base.


Increased plasma calcitonin levels in systemic mast cell disease.
Aspirin therapy for patients with systemic mast cell disease (SMCD) decreases the production of prostaglandin D2, which is thought to be a major mediator of flushing. Paradoxically, in 5 to 10% of patients with SMCD, administration of aspirin causes massive mediator release and an anaphylactoid reaction. We attempted aspirin desensitization in a 34-year-old man with SMCD (confirmed by bone marrow biopsy) who was incapacitated by severe flushing episodes and hypotension. His baseline mediator levels of plasma calcitonin, urinary histamine, and urinary N-methyl-imidazoleacetic acid were abnormal. Pentagastrin stimulation increased the plasma level of calcitonin from 47 pg/mL to 130 pg/mL (normal, less than or equal to 110) at 5 minutes. Oral aspirin desensitization was begun; however, after a cumulative dose of 620 mg, an anaphylactoid reaction ensued in conjunction with hypotension, abdominal cramping, and flushing. Coincidentally, 1 hour after the episode, the plasma calcitonin level increased from 37 pg/mL to 540 pg/mL, and the serum tryptase level increased from 1 ng/mL to 3.9 ng/mL. Six hours after the episode, the urine level of histamine increased from 90 micrograms/g creatinine to 337 micrograms/g creatinine, and the urinary N-methylimidazoleacetic acid increased from 32 mg/24 h to 81 mg/24 h. Hence, the patient had increased basal levels of plasma calcitonin that increased substantially during aspirin desensitization and increased to above the upper limit of normal during pentagastrin stimulation. Human mast cells may be capable of producing calcitonin or causing secretion of calcitonin in response to skeletal changes.


Electrocatalytic intramolecular oxidative annulation of N-aryl enamines into substituted indoles mediated by iodides.
An electrocatalytic reaction protocol is developed for achieving intramolecular dehydrogenative annulation of N-aryl enamines. It offers a simple and efficient way for the synthesis of indoles in an undivided cell. Good to excellent yields are obtained under oxidant-free and transition-metal-free conditions. Moreover, imidazo[1,2-a]pyridines could also be produced when N-pyridyl enamines were used as the substrates.


Stretching district nursing services to meet rural needs.
This article evaluates the adequacy of District Nursing Service (DNS) provision in the Goulburn Murray region in Victoria. It draws on a survey of the region's DNS and communication with several community health agencies in response to problems identified by service providers. The results suggest that these rural health services face problems not experienced in urban areas. District nurses in rural areas have to travel far and wide to accommodate their clients and they put in extra unpaid hours if necessary. Their travel time, management and communication skills are not sufficiently recognised in the current funding formula. Although this includes some weighting for rurality, it is insufficient for District Nursing Services catering for smaller, more dispersed populations. Current and future demand pressures on home and community-based nursing services highlight the importance of redressing this deficiency. Several issues raised in this article may reflect problems that are common in rural regions, including funding inadequacies, unpaid additional work, access and equity difficulties and boundary issues. As a result, recommendations to improve service delivery may have broader applicability.


Synthetic peptide AT20 coupled to KLH elicits antibodies against a conserved conformational epitope from a major functional area of the HIV-1 matrix protein p17.
The major challenge for the development of a highly effective peptide-based vaccine is represented by the diversity of HIV-1 strains among human population. HIV-1 matrix protein p17 is a candidate antigen for therapeutic vaccines against AIDS. Here we show that antibodies elicited in animals by immunizing them with a synthetic peptide representative of the p17 functional epitope (AT20) derived from HIV-1 BH10 (clade B), neutralize the biological activity of p17 derived from divergent strains displaying critical mutations within AT20, by recognizing a highly conserved conformational epitope. This finding shows that AT20, as an immunogenic molecule, elicits broadly neutralizing anti-p17 antibodies.


Patient satisfaction with continuous epidural analgesia after major surgical procedures at a Swedish University hospital.
The use of epidural analgesia after major surgery is a well-established analgesia method. Epidural analgesia for postoperative pain relief needs to be monitored regularly in order to evaluate patient satisfaction and avoid side effects. However, due to the new available regional techniques, the role of epidural analgesia is being questioned and data about patient satisfaction is lacking. The current study was designed to evaluate patient satisfaction with epidural analgesia, its efficacy and reasons for premature termination of epidural analgesia. We conducted a retrospective survey of all patients who undergone surgery at Uppsala University hospital between October 2012 and January 2014 requiring continuous epidural analgesia for postoperative pain relief. Patients' satisfaction with epidural analgesia and its effectiveness were evaluated by using paper questionnaire. During the study period 579 epidurals were inserted in patients scheduled for vascular, hepatobiliary, esophageal and other major abdominal surgery. The average treatment time was 3.8±1.8 days. Epidural analgesia consisted either of bupivacaine 0.1%+sufentanil 1 μg/ml solution or ropivacaine 0.2% solution. If patient needed opiates during treatment with epidural analgesia, only ropivacaine 0,2% solution was used. 494 (87.9%) patients were satisfied with their analgesia with no difference in satisfaction between sexes being observed. In 62 cases (11.2%) patient controlled analgesia was used on top of epidural analgesia with ropivacaine 0.2% solution, and 50.8% of patients were satisfied in this group. 514 (91.4%) patients were reported as having a good effect, 24 (4.3%) patients reported or were tested to show some effect, and 24 (4.3%) had no effect. No major neurological complications (epidural hematoma or abscess) were observed. Our retrospective survey indicates that patients are satisfied with continuous epidural analgesia used in major surgery.


Is speech learning 'gated' by the social brain?
I advance the hypothesis that the earliest phases of language acquisition -- the developmental transition from an initial universal state of language processing to one that is language-specific -- requires social interaction. Relating human language learning to a broader set of neurobiological cases of communicative development, I argue that the social brain 'gates' the computational mechanisms involved in human language learning.


Characteristics and Influencing Factors of Healthcare Utilization in Post-conflict Primary Care Attendees in Northern Sri Lanka.
Sri Lanka's healthcare systems attempts to provides access to universal healthcare services for all citizens and is designed to be free of out-of-pocket payments. Despite a 30-year civil conflict, natural disasters, and COVID-19, the healthcare system within the country remains robust and strong. However, due to a lack of formalized pathways and centralized record keeping, the pattern of service utilization is still relatively unknown, which raises concerns regarding effective allocation of scarce resources and efficiency of referral pathways. To address this gap in knowledge, part of the parent study (COMGAP-S), consisted of a survey on healthcare service use conducted among adults attending primary care facilities. The results from this quantitative data analysis indicate the majority of people seeking care originate from rural areas, are older (50+), attend divisional hospitals, and report paying fees at point of contact. Our findings indicate a need for more efficient use of healthcare services, creation of referral routes to ensure limited healthcare resources are used effectively. Additionally, further investment in services is needed to ensure Sri Lanka's healthcare system meets the standard of universal healthcare as proposed by the World Health Organization. These findings address a gap in knowledge for national decision-makers within Sri Lanka along with other similar post-conflict healthcare settings across the globe.


Caring for the Mental Health of Youth and Families: What is the Role of the Psychiatric Mental Health Advanced Practice Nurse?
Children in our nation are experiencing the social, emotional, and physical impacts of an unprecedented time in history. Advanced practice nurses prepared as psychiatric clinical nurse specialists and nurse practitioners bring therapeutic interventions, psychopharmacologic management, and systems thinking to clinical environments of care. Insight into the mental health of youth and families and how clinical nurse specialists may provide solutions for forthcoming challenges is discussed. Barriers to mental healthcare such as the invisibility of nurses at state and federal levels must be eradicated to mitigate the mental health challenges that youth, families, and communities endure. Contemporary issues such as effects of social media, stigma, and suicide present burdens that can be moderated through nursing interventions. The psychiatric clinical nurse specialist provides evidence and community-based nursing interventions that, through early identification and advocacy, contribute to positive mental health outcomes for youth and families. The need for well-educated advanced practice nurses has never been greater for our vulnerable populations of children, adolescents, and families with mental health challenges. Nurse-delivered programs demonstrate that interventions are necessary for communication, psychoeducation, and prevention of consequences from unacknowledged social media, stigma, and suicide problems.


Robust Bayesian clustering.
A new variational Bayesian learning algorithm for Student-t mixture models is introduced. This algorithm leads to (i) robust density estimation, (ii) robust clustering and (iii) robust automatic model selection. Gaussian mixture models are learning machines which are based on a divide-and-conquer approach. They are commonly used for density estimation and clustering tasks, but are sensitive to outliers. The Student-t distribution has heavier tails than the Gaussian distribution and is therefore less sensitive to any departure of the empirical distribution from Gaussianity. As a consequence, the Student-t distribution is suitable for constructing robust mixture models. In this work, we formalize the Bayesian Student-t mixture model as a latent variable model in a different way from Svensén and Bishop [Svensén, M., & Bishop, C. M. (2005). Robust Bayesian mixture modelling. Neurocomputing, 64, 235-252]. The main difference resides in the fact that it is not necessary to assume a factorized approximation of the posterior distribution on the latent indicator variables and the latent scale variables in order to obtain a tractable solution. Not neglecting the correlations between these unobserved random variables leads to a Bayesian model having an increased robustness. Furthermore, it is expected that the lower bound on the log-evidence is tighter. Based on this bound, the model complexity, i.e. the number of components in the mixture, can be inferred with a higher confidence.


Influencing factors on cardiac structure and function beyond glycemic control in patients with type 2 diabetes mellitus.
We hypothesized that clinical factors other than glycemic control may influence abnormal cardiac function in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the independent factors for abnormal cardiac function among clinical factors in T2DM. We studied 148 asymptomatic patients with T2DM without overt heart disease. Echocardiographic findings were compared between diabetic patients and 68 age-matched healthy subjects. Early (E) and late (A) diastolic mitral flow velocity and early diastolic mitral annular velocity (e') were measured for assessing left ventricular (LV) diastolic function. We evaluated insulin resistance, non-esterified fatty acid, high-sensitive CRP, estimated glomerular filtration rate, waist/hip ratio, abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and other clinical characteristics in addition to glycemic control. VAT and SAT were quantified by computed tomography. In T2DM, E/A and e' were significantly lower, and E/e', left atrial volume and LV mass were significantly greater than in control subjects. In multivariate liner regression analysis, VAT was an independent determinant of left atrial volume (β =0.203, p=0.011), E/A (β =-0.208, p=0.002), e' (β =-0.354, p<0.001) and E/e' (β=0.220, p=0.003). Age was also an independent determinant, whereas fasting plasma glucose and hemoglobin A1c levels were not. In addition to systolic blood pressure, waist-hip ratio (β=0.173, p=0.024) and VAT/SAT ratio (β=0.162, p=0.049) were independent determinants of LV mass. Excessive visceral fat accompanied by adipocyte dysfunction may play a greater role than glycemic control in the development of diastolic dysfunction and LV hypertrophy in T2DM.


Responsive alginate-cisplatin nanogels for selective imaging and combined chemo/radio therapy of proliferating macrophages.
Atherosclerosis is a major global health concern. Targeting macrophages is hypothesized as an alternative treatment for atherosclerosis. We synthesized alginate-based cisplatin-loaded nanogels (TANgel) as a pH-responsive drug-releasing theranostic nanoplatform for macrophage cells. Carboxylic acid groups of alginic acid were modified with iminodiacetic acid (IDA) to enhance chelation of platinum ions. The near infrared (NIR) fluorophore ATTO655 was conjugated to the modified alginic acid. Cisplatin was used as an antiproliferation drug and as a crosslinking agent between alginate molecules to form TANgel. Release behavior of cisplatin from TANgel was analyzed under different pH conditions. Cellular uptake and therapeutic efficacy of TANgel were tested in the macrophage cell line J774A.1 and normal human cell lines such as HDMVECn. The nanogel had a narrow size distribution of approximately 100 nm. The nanogel showed highly pH-responsive drug release behavior. All incorporated cisplatin was released at pH 5 within 48 h, while less than 15% was released at pH 7.4. The nanogel was preferentially taken up by J774A.1 cells compared to normal human cells, enabling selective NIR fluorescence imaging and chemotherapy of macrophage cells. In addition, the nanogel formulation lowered the therapeutic concentration of the drug with and without low dose radiation therapy (RT) compared to the free drug form. This nanogel system may have potential utility for selective NIR fluorescence imaging and combined chemo/radio therapy of proliferating macrophage cells in atherosclerotic regions, allowing for reduction of systemic toxicity.


Optimization of enzymatic lysis of yeast.
In enzymatic lysis of yeast for the recovery of intracellular proteins, the rupture of whole cells is caused by the action of a lytic system consisting primarily of protease and glucanase. A first-principles mechanism for the lytic reaction based on a two-layer model of the wall structure and a burst model for the disruption of cells is pre sented. The fed-batch model results in a dynamic optimization problem, with the enzymes, activities being the control variables. Orthogonal collocation is applied to discretize the state equations, and the resulting non linear program is solved using successive quadratic pro gramming to determine the enzyme and protease inhibitor add-in rates and pH control profiles that maximize the recovery of intracellular protein. Applying the proposed approach, optimal profiles were determined such that a significant increase of the production of proteins in a fed-batch reactor is realized. Also, the optimal control policies in a series of continuous-flow stirred tank reactors (CFSTRs) are determined.


Evaluation of a market in wetland credits: entrepreneurial wetland banking in Chicago.
With the rise of market-led approaches to environmental policy, compensation for permitted discharge of dredge or fill material into wetlands under Section 404 of the U.S. Clean Water Act has been purchased increasingly from entrepreneurial third-party providers. The growth of this practice (i.e., entrepreneurial wetland banking) has resolved many challenges associated with wetland compensation. But it has also produced (1) quantifiable temporal loss of wetland ecological functions, (2) spatial redistribution of wetland area, and (3) a degree of regulatory instability that may pose a threat to entrepreneurial compensation as a sustainable component of wetland-compensation policy. We used achieved compensation ratios, lapse between bank credit sale and the attainment of performance standards, distance between impact and bank site, and changes in bank market area to examine these 3 factors. We analyzed data from a census of all such transactions in the Chicago District of the U.S. Army Corps of Engineers, compiled from site visits, Corps databases, and contacts with consultants and Section 404 permittees. Entrepreneurial banking provided compensation at a lower overall ratio than nonbank forms of compensation. Approximately 60% of bank credits were sold after site-protection standards were met but before ecological performance standards were met at the bank site. The average distance between bank and impact site was approximately 26 km. The area of markets within which established banks can sell wetland credits has fluctuated considerably over the study period. Comparing these data with similar data for other compensation mechanisms will assist in evaluating banking as an element of conservation policy. Data characterizing the performance of entrepreneurial wetland banks in actual regulatory environments are scarce, even though it is the most established of similar markets that have become instrumental to federal policy in administering several major environmental protection laws.


Modeling the interaction of paclitaxel with beta-tubulin.
The natural product cytotoxic agent, paclitaxel, partly induces cell death through its ability to disrupt mitosis by binding to the microtubule protein beta-tubulin. Structural characterization of the paclitaxel-beta-tubulin complex, a first stage in the design of new antimitotics, has been complicated by contradictory observations obtained from different experimental techniques [electron crystallography, fluorescence resonance energy transfer (FRET), and photo-affinity labeling (PAL)] used to examine the complex. In this study we have used a range of molecular modeling techniques including restrained conformational searching and computer-assisted docking to propose that these contradictions may be resolved by the hypothesis that the nature of the interaction of paclitaxel with beta-tubulin depends on the physical form of the tubulin examined. In particular, our analysis identified a binding mode that is consistent with available data for the interaction of paclitaxel with beta-tubulin in polymerized tubulin or microtubules. This orientation is characterized by an alternate conformation (inverted orientation of side chains) and inverted orientation of the taxane core of paclitaxel within its tubulin binding site compared with the electron crystallographic structure. The proposed structure, however, is only marginally consistent with electron crystallographic data for the interaction of paclitaxel with beta-tubulin in Zn-induced tubulin sheets. Similarly, the electron crystallographic structure shows poor correlation with FRET, solid-state NMR, and some observed SAR relationships for paclitaxel interacting with polymerized tubulin or microtubules. These observations suggest to us that the interaction of paclitaxel with Zn-induced tubulin sheets may not reflect paclitaxel's interaction with tubulin in microtubules and hence may not be an appropriate guide for rational drug design programs.


Energy minimization method using automata network for sequence and side-chain conformation prediction from given backbone geometry.
Globular proteins have high packing densities as a result of residue side chains in the core achieving a tight, complementary packing. The internal packing is considered the main determinant of native protein structure. From that point of view, we present here a method of energy minimization using an automata network to predict a set of amino acid sequences and their side-chain conformations from a desired backbone geometry for de novo design of proteins. Using discrete side-chain conformations, that is, rotamers, the sequence generation problem from a given backbone geometry becomes one of combinatorial problems. We focused on the residues composing the interior core region and predicted a set of amino acid sequences and their side-chain conformations only from a given backbone geometry. The kinds of residues were restricted to six hydrophobic amino acids (Ala, Ile, Met, Leu, Phe, and Val) because the core regions are almost always composed of hydrophobic residues. The obtained sequences were well packed as was the native sequence. The method can be used for automated sequence generation in the de novo design of proteins.


The effect of theophylline on parkinsonian symptoms.
Adenosine is known to inhibit the release of dopamine from central synaptic terminals. The present open trial was therefore conducted to determine whether the adenosine receptor-antagonist theophylline would be of value in Parkinson's disease. Fifteen parkinsonian patients were treated for up to 12 weeks with a slow release oral theophylline preparation (150 mg day-1), yielding serum theophylline levels of 4.44 mg L-1 after one week. The patients exhibited significant improvements in mean objective disability scores and 11 reported moderate or marked subjective improvement. It is suggested that theophylline might be a useful adjunct to the routine therapy of parkinsonian patients.


Epigenetic deregulation of microRNAs in rhabdomyosarcoma and neuroblastoma and translational perspectives.
Gene expression control mediated by microRNAs and epigenetic remodeling of chromatin are interconnected processes often involved in feedback regulatory loops, which strictly guide proper tissue differentiation during embryonal development. Altered expression of microRNAs is one of the mechanisms leading to pathologic conditions, such as cancer. Several lines of evidence pointed to epigenetic alterations as responsible for aberrant microRNA expression in human cancers. Rhabdomyosarcoma and neuroblastoma are pediatric cancers derived from cells presenting features of skeletal muscle and neuronal precursors, respectively, blocked at different stages of differentiation. Consistently, tumor cells express tissue markers of origin but are unable to terminally differentiate. Several microRNAs playing a key role during tissue differentiation are often epigenetically downregulated in rhabdomyosarcoma and neuroblastoma and behave as tumor suppressors when re-expressed. Recently, inhibition of epigenetic modulators in adult tumors has provided encouraging results causing re-expression of anti-tumor master gene pathways. Thus, a similar approach could be used to correct the aberrant epigenetic regulation of microRNAs in rhabdomyosarcoma and neuroblastoma. The present review highlights the current insights on epigenetically deregulated microRNAs in rhabdomyosarcoma and neuroblastoma and their role in tumorigenesis and developmental pathways. The translational clinical implications and challenges regarding modulation of epigenetic chromatin remodeling/microRNAs interconnections are also discussed.


Determinants of an autism spectrum disorder diagnosis in childhood and adolescence: Evidence from the UK Millennium Cohort Study.
This study aimed to identify determinants of a late autism spectrum disorder diagnosis, including diagnoses made 'very late' (i.e., in adolescence), using the Millennium Cohort Study, a nationally representative population-based cohort in the United Kingdom. Children diagnosed with autism spectrum disorder by age 14 (N = 581) were included and grouped by the parent-reported timing of diagnosis: before school (up to age 5), during primary school (age 5-11) and during secondary school (age 11-14). Predictors of diagnostic timing, at the child, family and school levels, were investigated using multinomial logistic regression. Most (79%) children with autism spectrum disorder were diagnosed after school entry, and 28% were not diagnosed until secondary school. Among those not diagnosed until secondary school, 75% had been identified at age 5 years by a parent and/or teacher as having socio-behavioural difficulties. Being diagnosed after starting school was predicted by living in poverty (adjusted relative risk ratio: primary = 1.90, 95% confidence interval: 1.03-3.53; secondary = 2.15, 1.05-4.42) and/or having no initial parental concerns (primary = 0.32, 0.15-0.70; secondary = 0.19, 0.09-0.43). Having typical-range intelligence also predicted diagnosis during secondary school. The result indicates that those without cognitive delays and poorer children were at risk of 'very late' (i.e. adolescent) diagnosis. Strategies to promote earlier identification, targeting age at primary school entry, could help those more likely to be diagnosed late.Lay abstractDespite policy emphasis on early identification, many children with autism spectrum disorder are diagnosed late, with some being diagnosed as late as in adolescence. However, evidence on what determines the timing of autism spectrum disorder diagnosis including children diagnosed in adolescence is lacking. Understanding these determinants, particularly in those diagnosed later than is ideal, can inform the development of effective strategies to improve earlier identification of autism spectrum disorder. This study used a nationally representative population-based cohort in the United Kingdom to explore child, family and school level predictors of timing of autism spectrum disorder diagnosis. In the United Kingdom, 79% of the children with autism spectrum disorder were diagnosed after entering primary school and 28% during secondary school. Among those not diagnosed until secondary school, 75% had shown social difficulties noticed by parents and/or teachers at age 5 years. The results suggest that healthcare providers should be aware that, even for universal systems of care, those living in poverty and having higher intelligence are most likely to miss out on a timely diagnosis. Strategies to promote earlier identification among school-aged children, including targeting primary school entry age (i.e. around age 5) and that encouraging referrals for a formal assessment at the first report of concerns over the child's social development may benefit those children who would otherwise be diagnosed later.


Tuning the Binding Dynamics of a Guest-Octaacid Capsule through Noncovalent Anchoring.
Hydrophobic or hydrophilic substituents have different effects on the binding dynamics of pyrene derivatives with a 2:1 capsule formed from two octaacid cavitands, showing a subtle interplay of different kinetic factors. Anchoring of the methyl group of 1-methylpyrene within one cavitand slowed the association and dissociation dynamics of the 1:1 complex by at least 1000 times when compared to the 1:1 complex for pyrene. This slow down for the transient formation of the 1:1 complex is responsible for the overall increase in stability of the 2:1 complex without affecting the overall capsule dissociation. For 1-pyrenemethanol, its residence time in the 2:1 capsule is shorter compared to that of pyrene despite both guests having similar equilibrium constants for the binding of the second cavitand, suggesting that the hydroxymethyl substituent close to the equatorial region of the capsule can interact with water during the partial opening of the capsule.


Modified and improved anti-acetylcholine receptor (AchR) antibody assay: comparison of analytical and clinical performance with conventional anti-AChR antibody assay.
We developed a modified anti-acetylcholine receptor (AChR) antibody (Ab) assay based on a radioreceptor assay and a calibration curve. We compared the analytical and clinical performances of this modified assay with those of the conventional anti-AChR Ab radioreceptor assay. Serum specimens were from patients with myasthenia gravis (MG) (n = 156) and from control subjects (n = 106). The modified assay demonstrated lower within-assay (4.0-6.6%) and between-assay (5.3-7.8%) CVs, greater linearity, lower cost, and shorter assay time than the conventional method. ROC curve analysis indicated almost identical specificity and sensitivity (> 0.92) for these two anti-AChR Ab assays. The modified and conventional assays were also equivalent for blocking anti-AChR Ab assay. Moreover, the modified anti-AChR Ab assay, differently from the conventional assay, allowed us to reveal anti-AChR Ab concentration differences among different clinical grades of MG.


Inflammation of bronchial smooth muscle in allergic asthma.
Recent observations in asthma suggest that bronchial smooth muscle is infiltrated by inflammatory cells including mast cells. Such an infiltration may contribute to airway remodelling that is partly due to an increase in smooth muscle mass. Whether muscle increase is the result of smooth muscle cell hypertrophy remains controversial and has not been studied by ultrastructural analysis. A morphometric analysis of airway smooth muscle (ASM) was undertaken in asthmatic patients using electron microscopy to examine the interactions between ASM cells and inflammatory cells. ASM specimens were obtained from 14 asthmatic subjects and nine non-asthmatic controls undergoing fibreoptic endoscopy. Inflammatory cell counts were assessed by immunohistochemistry, and ultrastructural parameters were measured using electron microscopy in a blinded fashion on smooth muscle cells and inflammatory cells. ASM from asthmatic patients was infiltrated by an increased number of mast cells and lymphocytes. Smooth muscle cells and their basal lamina were thicker in asthmatic patients (9.5 (0.8) and 1.4 (0.2) microm) than in controls (6.7 (0.4) and 0.7 (0.1) microm). In asthmatics the extracellular matrix was frequently organised in large amounts between ASM cells. Myofibroblasts within smooth muscle bundles were only observed in asthmatics, some of them displaying a close contact with ASM cells. In asthma, airway myositis is characterised by a direct interaction between ASM cells and mast cells and lymphocytes. Smooth muscle remodelling was present, including cell hypertrophy and abnormal extracellular matrix deposition moulding ASM cells.


Felodipine is more effective than hydrochlorothiazide when added to a beta-blocker in treating elderly hypertensive patients.
This randomized, double-blind, parallel-group study compared felodipine and hydrochlorothiazide (HCT) given in addition to a beta-blocker in 134 elderly hypertensive patients aged 56-79 years (mean of 66 +/- 5 years). In the felodipine-treated group (n = 57), supine blood pressure (BP) was reduced from 171 +/- 16/101 +/- 6 mm Hg at randomization to 147 +/- 12/86 +/- 6 mm Hg after 8 weeks, whereas in the HCT-treated group (n = 66), BP was reduced from 170 +/- 4/101 +/- 5 to 151 +/- 16/89 +/- 9 mm Hg. The reduction in diastolic blood pressure (DBP) was significantly greater in the felodipine than in the HCT group (p less than 0.003). In the felodipine-treated group, 87% of the patients were controlled (DBP less than or equal to 90 mm Hg) compared with 58% in the HCT group (p less than 0.001). Reported adverse events were generally mild. Six patients withdrew from the study due to adverse events, five in the felodipine group and one in the HCT group.


Endogenous sex hormones, sex hormone-binding globulin, and the risk of incident vertebral fractures in elderly men and women: the Rotterdam Study.
In an age-matched, case-control study, we investigated the association between endogenous sex steroid hormones and incident vertebral fractures in both elderly men and women (aged 67.7 +/- 6.8 yr). Drawn from the Rotterdam Study, participants required radiographs of the lumbar spine at both baseline and follow-up (average time of follow-up, 6.5 yr) and frozen blood samples, taken at baseline. One hundred and seventy-eight men (45 cases) and 454 women (115 cases) were thus selected. Serum estradiol, SHBG, testosterone, and insulin were measured, along with bone mineral density at both spine and hip. Women in the lowest tertile of serum estradiol (< or =15.5 pmol/liter) had a 2.1 times increased risk (95% confidence interval, 1.3-3.5) of incident vertebral fractures, independently of bone mineral density measured at either site. SHBG levels in the lowest two tertiles were associated with a 50% reduction in incident vertebral fracture risk. Women with a combination of both low estradiol and high SHBG had a 7.8 times higher risk of an incident vertebral fracture (95% confidence interval, 2.7-22.5; P < 0.001), adjusted for age and weight. This increased risk did not change when non-SHBG-bound estradiol was used instead of total estradiol. For men, no clear association was found, possibly due to insufficient power. No clear association between testosterone and incident vertebral fractures was observed in either men or women.


Concanavalin agglutinin levels are decreased in peripheral blood of Alzheimer's disease patients.
Alzheimer's disease (AD) seriously threatens patients' lives and causes severe burden to the families. Early prevention and treatment can alleviate the development of the disease; therefore it is important to find new effective and non-traumatic biomarkers for early diagnosis. In this study, peripheral blood samples were collected from 24 AD patients and the same number of age- and gender-matched control subjects. Lectin reactive glycosylation levels including beta-D-galactosyl ricinus communis agglutinin 120 (RCA), peanut agglutinin (PNA), concanavalin agglutinin (Con A), alpha-L-fucosyl ulex europeus agglutinin (UEA), dolichos biflorus agglutinin (DBA), and galanthus nivalis (GNL), in the red blood cells of peripheral blood were examined by western blotting. We found that lectin levels were altered with aging and gender; some lectin levels were different between AD patients and the control subjects. Only Con A levels were significantly decreased in AD patients compared to age-matched control subjects. These results suggest that Con A levels in peripheral blood may be a potent diagnostic marker for AD.


Note: optical receiver system for 152-channel magnetoencephalography.
An optical receiver system composing 13 serial data restore/synchronizer modules and a single module combiner converted optical 32-bit serial data into 32-bit synchronous parallel data for a computer to acquire 152-channel magnetoencephalography (MEG) signals. A serial data restore/synchronizer module identified 32-bit channel-voltage bits from 48-bit streaming serial data, and then consecutively reproduced 13 times of 32-bit serial data, acting in a synchronous clock. After selecting a single among 13 reproduced data in each module, a module combiner converted it into 32-bit parallel data, which were carried to 32-port digital input board in a computer. When the receiver system together with optical transmitters were applied to 152-channel superconducting quantum interference device sensors, this MEG system maintained a field noise level of 3 fT/√Hz @ 100 Hz at a sample rate of 1 kSample/s per channel.


How do Thai children and adolescents describe asthma symptoms?
Prevalence of childhood asthma appears to be increasing worldwide. In Thailand, the prevalence of childhood asthma increased from 4.2% to 13% within the past decade. The last epidemiologic survey in Thailand utilized the International Study of Asthma and Allergies in Childhood (ISAAC) phase I questionnaire translated into Thai language. Language in the questionnaire can affect the reliability and validity of results of the survey. The purpose of this study is to determine common Thai wordings actually used by Thai children and adolescents to describe wheeze, chest tightness, shortness of breath and dyspnea. Sixty asthmatic Thai children, aged 9.2-18 years with asthmatic attacks less than 1 yr prior to the study, and 178 age-matched controls were recruited into the study. Asthmatic children spontaneously expressed their terms describing their asthma symptoms (in Thai) and then answered a preoutlined questionnaire regarding asthma terminology during an interview session after viewing the severe attack scene of the International ISAAC video questionnaire. Controls responded only to the preoutlined questionnaire after viewing the video scene. Of the 60 asthmatic children (38 males and 22 females, mean age 11.9 yr), 75% had their last asthmatic attacks within 2 months prior to the study. Wheeze was referred to as " and '/wi:d/' in 50% and 33% of patients, respectively, and " in 93.8% among controls. Using only the word '/wi:d/' in our previous ISAAC-I survey, as it sounded like the English word 'wheeze', it appears that up to 67% of the cases could have been missed. Dyspnea was referred to as rapid breathing and feeling tired in 78.2% of cases and as rapid and difficult breathing in 76.3% of controls. Chest tightness was referred to as chest discomfort in 65.7%. Shortness of breath was referred to as not being able to catch a breath, too short a breath, not enough breath and feeling suffocated in 88.8%. Local terms for asthma symptoms should be established and validated into each language to obtain reliable epidemiologic data.


Decision Scheduling for Cloud Computing Tasks Relying on Solving Large Linear Systems of Equations.
With the continuous reform and innovation of Internet technology and the continuous development and progress of social economy, Big Data cloud computing technology is more and more widely used in people's work and life. Many parallel algorithms play a very important role in solving large linear equations in various applications. To this end, this article aims to propose and summarize a cloud computing task scheduling model that relies on the solution of large linear equations. The method of this paper is to study the technology of solving large-scale linear equations and propose an M-QoS-OCCSM scheduling model. The function of the experimental method is to solve the problem of efficiently executing N mutually dependent parallel tasks within limited resources, while fully satisfying users' expectations of task completion time, bandwidth rate, reliability, and cost. In this paper, the application experiment of large-scale linear equations in task scheduling is used to study task scheduling algorithms. The results show that when the task load is 10 and 20, the convergence speed of the MPQGA algorithm is 32 seconds and 95 seconds faster than that of the BGA algorithm, respectively.


Asp1 from Schizosaccharomyces pombe binds a [2Fe-2S](2+) cluster which inhibits inositol pyrophosphate 1-phosphatase activity.
Iron-sulfur (Fe-S) clusters are widely distributed protein cofactors that are vital to cellular biochemistry and the maintenance of bioenergetic homeostasis, but to our knowledge, they have never been identified in any phosphatase. Here, we describe an iron-sulfur cluster in Asp1, a dual-function kinase/phosphatase that regulates cell morphogenesis in Schizosaccharomyces pombe. Full-length Asp1, and its phosphatase domain (Asp1(371-920)), were each heterologously expressed in Escherichia coli. The phosphatase activity is exquisitely specific: it hydrolyzes the 1-diphosphate from just two members of the inositol pyrophosphate (PP-InsP) signaling family, namely, 1-InsP7 and 1,5-InsP8. We demonstrate that Asp1 does not hydrolyze either InsP6, 2-InsP7, 3-InsP7, 4-InsP7, 5-InsP7, 6-InsP7, or 3,5-InsP8. We also recorded 1-phosphatase activity in a human homologue of Asp1, hPPIP5K1, which was heterologously expressed in Drosophila S3 cells with a biotinylated N-terminal tag, and then isolated from cell lysates with avidin beads. Purified, recombinant Asp1(371-920) contained iron and acid-labile sulfide, but the stoichiometry (0.8 atoms of each per protein molecule) indicates incomplete iron-sulfur cluster assembly. We reconstituted the Fe-S cluster in vitro under anaerobic conditions, which increased the stoichiometry to approximately 2 atoms of iron and acid-labile sulfide per Asp1 molecule. The presence of a [2Fe-2S](2+) cluster in Asp1(371-920) was demonstrated by UV-visible absorption, resonance Raman spectroscopy, and electron paramagnetic resonance spectroscopy. We determined that this [2Fe-2S](2+) cluster is unlikely to participate in redox chemistry, since it rapidly degraded upon reduction by dithionite. Biochemical and mutagenic studies demonstrated that the [2Fe-2S](2+) cluster substantially inhibits the phosphatase activity of Asp1, thereby increasing its net kinase activity.


Blueberry anthocyanins at doses of 0.5 and 1 % lowered plasma cholesterol by increasing fecal excretion of acidic and neutral sterols in hamsters fed a cholesterol-enriched diet.
The present study investigated the underlying mechanism associated with the hypocholesterolemic activity of blueberry anthocyanins by examining its effect on fecal sterol excretion and gene expression of major receptors, enzymes, and transporters involved in cholesterol metabolism. Hamsters were divided into three groups and fed a 0.1 % cholesterol diet containing 0 % (CTL), 0.5 % (BL), and 1.0 % (BH) blueberry anthocyanins, respectively, for six weeks. Plasma total cholesterol (TC), triacylglycerols (TAG), and non-high-density lipoproteins cholesterol (non-HDL-C) were measured using the enzymatic kits, and the gene expression of transporters, enzymes, and receptors involved in cholesterol absorption and metabolism was quantified using the quantitative PCR. GC analysis was used to quantify hepatic cholesterol and fecal acidic and neutral sterols. Dietary supplementation of 0.5 and 1.0 % blueberry anthocyanins for 6 weeks decreased plasma TC concentration by 6-12 % in a dose-dependent manner. This was accompanied by increasing the excretion of fecal neutral and acidic sterols by 22-29 % and 41-74 %, respectively. Real-time PCR analyses demonstrated that incorporation of blueberry anthocyanins into diet down-regulated the genes of NPC1L1, ACAT-2, MTP, and ABCG 8. In addition, blueberry anthocyanins were also able to down-regulate the gene expression of hepatic HMG-CoA reductase. The cholesterol-lowering activity of blueberry anthocyanins was most likely mediated by enhancing the excretion of sterols accompanied with down-regulation on gene expression of intestinal NPC1L1, ACAT-2, MTP, and ABCG 8.


Using quantitative sensory testing to predict attrition in an interdisciplinary pain management program: a pilot study.
Aim: To determine the extent to which quantitative sensory testing (QST) predicted attrition in an interdisciplinary pain program (IPP). Patients & methods: Participants (n = 53) enrolled in an IPP completed pretreatment assessments of QST and the PROMIS-29 quality of life survey. Results & conclusion: Compared with completers, non-completers (24.5%) reported significantly higher pain intensity (7.1, 95% CI [5.8, 8.4] versus 5.4, 95% CI [4.8, 6.1]) and cold hyperalgesia (14.6°C, 95% CI [8.8, 20.4] versus 7.5°C, 95% CI [4.8, 6.1]), with both variables also predicting attrition. This finding highlights a potentially novel and clinically significant use of QST. Higher overall pain intensity and the presence of remote cold hyperalgesia may identify patients at risk for dropping out of an IPP.


Selective hydrogenation of lactic acid to 1,2-propanediol over highly active ruthenium-molybdenum oxide catalysts.
Modification of Ru/C with a small amount of MoOx (RuMoOx /C) enhanced the catalytic activity in the hydrogenation of L-lactic acid to form 1,2-propanediol and maintained high selectivity. The turnover frequency based on the amount of Ru over the optimized RuMoOx /C catalyst (Mo/Ru molar ratio=1:16) was 114 h(-1) at 393 K, which was about 4 times higher than that over Ru/C. The same effect of MoOx was obtained over RuMoOx /SiO2 , although RuMoOx /SiO2 showed slightly lower activity than that of RuMoOx /C. RuMoOx /C achieved a high yield of 95 % in 18 h at 393 K and was applicable to various carboxylic acids to provide the corresponding alcohols in high yields. Modification with MoOx also brought about suppression of racemization and (S)-1,2-propanediol was obtained in high enantiomeric excess at 353 K. Based on kinetic analysis and characterization data, such as XRD, TEM, CO adsorption by a volumetric method, FTIR spectroscopy, and X-ray absorption spectroscopy, for RuMoOx /C and RuMoOx /SiO2 , the catalyst structure and reaction mechanism are proposed.


Effect of mercury on rabbit myelin CNP-ase in vitro.
2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) catalyzes hydrolysis of 2',3'-cyclic nucleotides to form the corresponding 2'-monophosphates. Rabbit myelin fraction with CNPase specific activity between 30-40 mumoles/min/mg protein was incubated in the presence of various inorganic and organic heavy metal compounds: HgCl2; (CH3Hg)OH; Pb(NO3)2; Pb(C2H302)2.3H20; (C2H5)2Pb; (C2H5)3SnCl. The enzyme has been shown to be almost exclusively sensitive to mercurials in microM concentration range. This would arise from the high solubility of mercurials in organic solvents, which allows them to penetrate into hydrophobic regions of the enzyme to react with active sulfhydryl groups. CNP-ase inhibition by methylmercury was biphasic: A reversible, non-competitive inhibition with an apparent Ki = 1 microM occurred after a 5 min preincubation time of the enzyme with the inhibitor. In the case of longer preincubation time, as well as in the presence of HgCl2, the graph of enzyme activity versus protein concentration intercepted the abscissa to the right of the origin, indicating that mercurials are irreversible inhibitors of the enzyme. After 45 min of preincubation of the inhibitors with the enzyme 1 nmol of HgCl2 completely blocks CNP-ase activity equivalent to 15.6 micrograms of myelin protein, whereas 1 nmole of Met-Hg blocks activity in 9.9 micrograms proteins. This apparently irreversible inhibition of CNP-ase activity by HgCl2 could be fully restored by the use of an excess of hydrophobic low molecular weight thiols, lipoic acid being the most efficient. Dithiothreitol, a hydrophilic complexing agent, was potent to reverse the inhibition caused by Met-Hg only during the short time experiments. Both low molecular weight thiols, and also EDTA in the case of inorganic mercury could prevent the inhibition of CNP-ase by mercurials, if preincubated for 15 min with the inhibitors, prior to the addition of the enzyme. The irreversible type of inhibition of CNP-ase by Met-Hg was only partially reversed in the presence of low molecular weight thiols. This suggests that the formation of a metal-mercaptide complex is not the only mechanism of inhibition by methylmercury. The possibility of lipid peroxidation triggered by methylmercury with subsequent inhibition of the enzyme activity was not supported by the experimental results. In fact, myelin associated CNP-ase activity appears to be very resistant to the structural membrane alterations caused by lipid peroxidation.


Crohn's duodeno-colonic fistula preoperatively closed using a detachable endoloop and hemoclips: a case report.
Duodeno-colonic fistula is an enterocolonic fistula that occurs as a complication of Crohn's disease. Symptoms of duodeno-colonic fistula are similar to those of Crohn's disease, such as weight loss and diarrhea. The treatment of choice is surgery, although medical treatment may also be considered. However, surgery is recommended when all available medical therapies have been ineffective. In this case, we report a secondary duodeno-colonic fistula due to Crohn's disease that was temporarily managed by an endoscopic procedure with a detached endoloop and hemoclips as a bridging therapy to final surgical repair.


The PerFect lipid optimizer kit for maximizing lipid-mediated transfection of eukaryotic cells.
The transfection efficiencies of a panel of eight uniquely different lipid reagents has been evaluated with two other commercially available lipids for use in transfecting a diversity of eukaryotic cell lines. The PerFect lipids are available individually or together in an optimization panel format that can be tested in any given cell line, enabling one to evaluate the optimal lipid for transfecting each individual cell line. Our results demonstrate that no single lipid is optimal for plasmid transfection over a broad range of cell types, thus emphasizing the need for multiple unique lipid reagents and a simple format for testing their transfection efficiency on a given cell type.


A multistrain approach to studying the mechanisms underlying compatibility in the interaction between Biomphalaria glabrata and Schistosoma mansoni.
In recent decades, numerous studies have sought to better understand the mechanisms underlying the compatibility between Biomphalaria glabrata and Schistosoma mansoni. The developments of comparative transcriptomics, comparative genomics, interactomics and more targeted approaches have enabled researchers to identify a series of candidate genes. However, no molecular comparative work has yet been performed on multiple populations displaying different levels of compatibility. Here, we seek to fill this gap in the literature. We focused on B. glabrata FREPs and S. mansoni SmPoMucs, which were previously demonstrated to be involved in snail/schistosome compatibility. We studied the expression and polymorphisms of these factors in combinations of snail and schistosome isolates that display different levels of compatibility. We found that the polymorphism and expression levels of FREPs and SmPoMucs could be linked to the compatibility level of S. mansoni. These data and our complementary results obtained by RNA-seq of samples from various snail strains indicate that the mechanism of compatibility is much more complex than previously thought, and that it is likely to be highly variable within and between populations. This complexity must be taken into account if we hope to identify the molecular pathways that are most likely to be good targets for strategies aimed at blocking transmission of the parasite through the snail intermediate host.


Stable-form screening: overcoming trace impurities that inhibit solution-mediated phase transformation to the stable polymorph of sulfamerazine.
Solution-mediated phase transformation (SMPT) has been used as a focused technique to rapidly identify the stable polymorph of a given substance. Despite ample precedence for acetonitrile being a good solvent for SMPT of sulfamerazine (SMZ), samples from specific lots of SMZ failed to convert from Form I to Form II after suspension for 2 weeks in acetonitrile. In these lots, an acetyl derivative of SMZ was identified and shown to impede transformation to the stable polymorph. The inhibitory effect of this impurity on polymorphic conversion was overcome with practical adjustments to experimental procedure, which hastened the kinetics of SMPT. The critical factors considered were (1) modifying the solvent to increase solubility, (2) minimizing the level of impurity in the slurries, (3) pre-treatment of the solid to quickly reach maximum supersaturation, and (4) temperatures that optimized kinetics as well as the free energy difference between enantiotropically related polymorphs.


Interleukin (IL)-4-independent maintenance of histone modification of the IL-4 gene loci in memory Th2 cells.
Interleukin (IL)-4-induced STAT6 activation and the subsequent up-regulation of GATA3 are crucial for the induction of chromatin remodeling of the Th2 cytokine gene loci as Th2 cells undergo development. This study probes the role of these molecules in the maintenance of memory Th2 cells. IL-4 was not required to maintain the capability for Th2 cytokine production in in vivo generated antigen-specific memory Th2 cells. Histone H3-K9/14 hyperacetylation and intergenic transcripts associated with the IL-4 gene locus were preserved in the absence of IL-4, but those associated with the IL-13 gene were partially IL-4-dependent. Histone H3-K4 methylation of the IL-13 and IL-4 gene loci was fully preserved in memory Th2 cells and accompanied by memory cell-specific accumulation of Pol II complex to highly restricted sites. Thus, memory Th2 cells maintain a unique Th2-specific remodeled chromatin in the IL-4 and IL-13 gene loci by active molecular events that are IL-4-independent.


Analysis of Human Body Shadowing Effect on Wireless Sensor Networks Operating in the 2.4 GHz Band.
Miniaturized wireless sensors are designed to run on limited power resources, requiring minimization of transmit power and lowering of the fade margin in the link budget. One factor that has an important impact on wireless sensor network design is path loss between the transmitter and the receiver. This paper presents an analysis of the influence of human bodies on path loss in the 2.4 GHz band, which is commonly used for wireless sensor networks. The effect of body shadowing was first analyzed in full wave computer simulations using the finite-difference time-domain method. Due to the high numerical burden, the simulations were limited to only a small region around the human body. To analyze the performance of networks in larger indoor environments, a human body model is proposed that can be used for simulations with a ray-based computer program. The proposed model of human body is the main contribution of this paper. It was used to analyze the body shadowing effect in a typical indoor environment. The results were found to be in good agreement with measurements.


Can Network Linkage Effects Determine Return? Evidence from Chinese Stock Market.
This study used the dynamic conditional correlations (DCC) method to identify the linkage effects of Chinese stock market, and further detected the influence of network linkage effects on magnitude of security returns across different industries. Applying two physics-derived techniques, the minimum spanning tree and the hierarchical tree, we analyzed the stock interdependence within the network of the China Securities Index (CSI) industry index basket. We observed that that obvious linkage effects existed among stock networks. CII and CCE, CAG and ITH as well as COU, CHA and REI were confirmed as the core nodes in the three different networks respectively. We also investigated the stability of linkage effects by estimating the mean correlations and mean distances, as well as the normalized tree length of these indices. In addition, using the GMM model approach, we found inter-node influence within the stock network had a pronounced effect on stock returns. Our results generally suggested that there appeared to be greater clustering effect among the indexes belonging to related industrial sectors than those of diverse sectors, and network comovement was significantly affected by impactive financial events in the reality. Besides, stocks that were more central within the network of stock market usually had higher returns for compensation because they endured greater exposure to correlation risk.


Time trends and case fatality rate of in-hospital treated pulmonary embolism during 11 years of observation in Northwestern Italy.
Pulmonary embolism (PE) is a common disorder with high mortality and morbidity rates. However, population-based information on its incidence and prognosis remains limited. We conducted a large epidemiology study collecting data on hospitalisation for PE (from 2002 to 2012) in a population of about 13 million people in Northwestern Italy. Patients were identified using the ICD-9-CM codes: 415.11, 415.19; gender and age specific incidence rate of PE during the study period were estimated using the resident population for each year of the study. Furthermore, time trends in the in-hospital PE-related mortality and case fatality rate were calculated. Results were adjusted for possible confounders. A total of 60,853 patients (mean age 72.8 years, ± 14.1, 59.6% females) with PE were included; the overall crude incidence rate for the entire study period was 55.4 and 40.6 events per year per 100,000 inhabitants for women and men, respectively (p <0.001). However, this difference was completely lost after standardisation for age. The incidence of PE significantly increased in both genders during the study period. In-hospital case fatality rate significantly decreased throughout the study period (p < 0.001) in women (from 15.6% to 10.2%) and in men (from 17.6% to 10.1%). The observed decrease of the in-hospital case-fatality throughout the study period remained significant also after adjustment for possible confounders. In conclusion, time trends over an 11-year period show an increasing incidence of PE, but a significant reduction in mortality during hospitalisation. Reduction in the case fatality rate remained significant after adjustment for these possible confounders.