Predicting diffuse large B-cell lymphoma outcomes with lesion-to-liver maximum standardized uptake value for interim-treatment and end-of-treatment positron emission tomography-computed tomography.
18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) has been used in response evaluation systems for malignant lymphomas and is an important tool for determining efficacy and prognosis. The Deauville 5-point scale (D-5PS) is an 18F-FDG PET-CT image-interpretation protocol for patients with lymphoma. Nevertheless, a number of limitations in visual image interpretation, such as interobserver disagreement and the increase of false-positive results, suggests that new parameters are needed. In this study, we aimed to evaluate the prognostic values of interim-treatment (I-) and end-of-treatment (EOT) PET-CT by comparing D-5PS to the semiquantitative lesion-to-liver maximum standardized uptake value ratio (RLL). A total of 90 patients with diffuse large B-cell lymphoma (DLBCL) (45 I-PET and 45 EOT-PET) were analyzed, and the RLL was calculated. Patients were additionally evaluated using the D-5PS system. We determined the optimal cutoff value of RLL using receiver operating characteristic (ROC) analysis. Kaplan-Meier survival analysis was used to compare the outcome predictions, while multivariate Cox regression analysis was used to identify the predictive factors. Among the patients examined, 41 (20 I-PET and 21 EOT-PET) experienced progression, and 49 (25 I-PET, 24 EOT-PET) did not. The optimal cutoff values of the RLL for predicting disease progression were 1.37 for I-PET (sensitivity 75%, specificity 88%) and 2.03 for EOT-PET (sensitivity 45.5%, specificity 100%), while the cutoffs of the D-5PS were scores 4 for I-PET (sensitivity 80%, specificity 72%) and 5 for EOT-PET (sensitivity 40.9%, specificity 100%). The prognostic efficacy was higher for the RLL at interim than for the D-5PS [area under the curve (AUC) =0.848 vs. 0.741]. The EOT prognostic efficacy of both evaluation methods was essentially equivalent (AUC =0.785 vs. 0.725). Univariate and multivariate analyses showed that RLL and D-5PS were independent factors affecting DLBCL outcomes for both interim and EOT assessment. RLL and D-5PS have independent predictive values for the interim and EOT evaluation of outcomes in patients with DLBCL. The RLL has better interim predictive ability than does D-5PS and can optimize D-5PS interpretation, thus improving interim outcome prediction.


Preliminary analysis of failures in the radiotherapy of head and neck cancer with a dynamic dose-fractionation in combination with breathing oxygen at ambient pressure.
Treatment failures were analysed in 43 head and neck cancer patients treated with a dynamic dose-fractionation in combination with breathing oxygen at ambient pressure. Infiltrative T3-4 lesions with necrosis showed poorer results than exophytic and necrosis-free infiltrative lesions. Possible differences in the oxygenation of the different types of lesion were considered to explain the results.


Median lethal dose determination for percutaneous exposure to soman and VX in guinea pigs and the effectiveness of decontamination with M291 SDK or SANDIA foam.
Soman (GD) and VX are chemical warfare agents that can be absorbed through the skin. We determined the median lethal dose (MLD) for the cutaneous application of GD and VX in anesthetized haired guinea pigs and then tested the ability of a currently fielded decontamination kit, the M291 Skin Decontamination Kit (SDK), and decontaminating foam made by SANDIA Labs to decontaminate areas that have been exposed to cutaneous applications of GD and VX. The fur of guinea pigs was clipped on the left flank 24h prior to exposure. Animals were anesthetized and 5 min later neat GD or neat VX was applied. The MLD for percutaneous exposure to GD was 11.6 mg/kg, and to VX it was 0.10mg/kg. To test the ability of the M291 SDK, either GD or VX was applied and removed 1 min later with the pads of the M291 SDK clasped in a pair of forceps and wiped across the flank of the animal. The MLDs for GD and VX removed with the M291 SDK pads were 76.9 mg/kg and 0.87 mg/kg, respectively. When neat GD or neat VX was applied and removed 1 min later in the same manner with gauze soaked in SANDIA foam (MDF-100), the MLDs were 412 mg/kg and 10.4 mg/kg respectively. These data demonstrate that GD and VX are significantly less potent when applied cutaneously than previously reported for subcutaneous injections and indicate that improvement is needed on the limited protective ratio provided by the M291 SDK.


Acute renal failure and cardiac surgery.
Acute renal failure (ARF) is s a major complication after cardiac surgery and its prevalence still remains high. Even minor changes in serum creatinine are related to an increase morbidity and mortality. Recently two consensus conferences have suggested new diagnostic criteria to define acute kidney injury and risk scores to better identify patients who will probably develop ARF after cardiac surgery. In fact a prompt recognition of high risk patients could allow a more aggressive therapy at a reversible stage of an incoming ARF. To date prophylactic strategies of renal function preservation during surgery include the avoidance of nephrotoxic insult and the prevention or correction of renal hypoperfusion. Although there are still no pharmacological agents able to prevent the perioperative ARF, several trials are investigating new pharmacological approaches. When prophylactic strategies fail and severe ARF occurs, renal replacement therapy becomes mandatory. The timing and the kind of renal replacement therapy remain an open issue. Further randomized case-control studies with adequate statistical power are needed to have more conclusive data. Aim of this paper is to start from the acute renal injury physiopathology to analyze the most common prophylactic and pharmacological strategies.


Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages.
Bacteria are able to secrete a variety of molecules via various secretory systems. Besides the secretion of molecules into the extracellular space or directly into another cell, Gram-negative bacteria can also form outer membrane vesicles (OMVs). These membrane vesicles can deliver their cargo over long distances, and the cargo is protected from degradation by proteases and nucleases. Legionella pneumophila (L. pneumophila) is an intracellular, Gram-negative pathogen that causes a severe form of pneumonia. In humans, it infects alveolar macrophages, where it blocks lysosomal degradation and forms a specialized replication vacuole. Moreover, L. pneumophila produces OMVs under various growth conditions. To understand the role of OMVs in the infection process of human macrophages, we set up a protocol to purify bacterial membrane vesicles from liquid culture. The method is based on differential ultracentrifugation. The enriched OMVs were subsequently analyzed with regard to their protein and lipopolysaccharide (LPS) amount and were then used for the treatment of a human monocytic cell line or murine bone marrow-derived macrophages. The pro-inflammatory responses of those cells were analyzed by enzyme-linked immunosorbent assay. Furthermore, alterations in a subsequent infection were analyzed. To this end, the bacterial replication of L. pneumophila in macrophages was studied by colony-forming unit assays. Here, we describe a detailed protocol for the purification of L. pneumophila OMVs from liquid culture by ultracentrifugation and for the downstream analysis of their pro-inflammatory potential on macrophages.


Synthesis and Pharmacological Evolution of Tetrahydroisoquinolines as Anti Breast Cancer Agents.
Breast cancer is leading cause of mortality among women, resulting in more than half a million deaths worldwide each year. Unfortunately, the recovery rate of advanced breast cancer by current available drug treatment is till unacceptably low. Chemotherapy is the main stay of cancer treatment and most of the drugs cause general toxicity to any non-proliferating cells, which can severely limit the therapeutic values of these drugs. Tetrahydroisoqinoline derivatives (THIQs) were identified as subtype selective estrogen receptor antagonists/agonists hence, potential therapeutic agents for breast cancer. Substituted THIQs were synthesized and well characterized. Antiproliferative activity against human ER (+) MCF-7 (Breast), ER(-) MDA-MB-231 (breast) and Ishikawa (endometrial) cancer cell lines were studied after 72 hours drug exposure employing CellTiter-Glo assay at concentrations ranging from 0.01-100,000 nM. The activities of these compounds were compared with Tamoxifen (TAM). In-vitro results indicated that most of the compounds showed better activity than TAM. The most active compounds obtained in this study were 6a, 6b, 6d and 6j (IC50=0.63, 0.23; 0.93, 0.21; 043, 0.01; 0.7, 0.02 μg/ml) against MCF-7 and Ishikawa cell lines, in comparison to Tamoxifen activity (IC50=5.14, 4.55 μg/ml). The newly synthesized molecules were docked in the active sites of the ER-α (PDB: 3ERT) and ER-β (PDB: 3ERT) crystal structures and probable binding modes of this class of molecules were determined.


Alkaloid biosynthesis in Papaver sp. cells in culture and during organogenesis.
In vitro cell cultures of two Papaver species, P. somniferum and P. bracteatum initiated from mature seeds were screened for their ability to produce alkaloids. Protocols for callus induction, somatic embryogenesis and organogenesis were established. The alkaloid contents were analysed by high-performance-liquid chromatography, thin-layer chromatography and spectrophotometric assays. Undifferentiated callus produced small amounts of sanguinarine, which increased with the degree of tissue differentiation. Embryogenic calli were maintained in culture for more than 2 years, retaining a high regeneration capability. Thin-layer chromatography analysis revealed variations in alkaloid spectrum between parallel cell lines. The morphinan alkaloid, thebaine, was found to be accumulated exclusively in morphogenous strains of P. bracteatum, and morphine was the major alkaloid in the spectrum of P. somniferum dedifferentiated callus. Regenerant plants synthesized thebaine and sanguinarine at the same level as juvenile plants grown from P. bracteatum seeds. We revealed differences in the ability to produce different types of alkaloids: seed-derived plants were able to accumulate thebaine while undifferentiated primary cell cultures produced only sanguinarine. The production of either sanguinarine and morphinan alkaloids are found in regenerants showing that both metabolic pathways were active in young plantlets.


MOF-Templated Fabrication of Hollow Co4N@N-Doped Carbon Porous Nanocages with Superior Catalytic Activity.
Metallic Co4N catalysts have been considered as one of the most promising non-noble materials for heterogeneous catalysis because of their high electrical conductivity, great magnetic property, and high intrinsic activity. However, the metastable properties seriously limit their applications for heterogeneous water phase catalysis. In this work, a novel Co-metal-organic framework (MOF)-derived hollow porous nanocages (PNCs) composed of metallic Co4N and N-doped carbon (NC) were synthesized for the first time. This hollow three-dimensional (3D) PNC catalyst was synthesized by taking advantage of Co-MOF as a precursor for fabricating 3D hollow Co3O4@C PNCs, along with the NH3 treatment of Co-oxide frames to promote the in situ conversion of Co-MOF to Co4N@NC PNCs, benefiting from the high intrinsic activity and electron conductivity of the metallic Co4N phase and the good permeability of the hollow porous nanostructure as well as the efficient doping of N into the carbon layer. Besides, the covalent bridge between the active Co4N surface and PNC shells also provides facile pathways for electron and mass transport. The obtained Co4N@NC PNCs exhibit excellent catalytic activity and stability for 4-nitrophenol reduction in terms of low activation energy (Ea = 23.53 kJ mol-1), high turnover frequency (52.01 × 1020 molecule g-1 min-1), and high apparent rate constant (kapp = 2.106 min-1). Furthermore, its magnetic property and stable configuration account for the excellent recyclability of the catalyst. It is hoped that our finding could pave the way for the construction of other hollow transition metal-based nitride@NC PNC catalysts for wide applications.


Mechanical phase diagram of shrinking cylindrical gels.
When polymer gels are subjected to an external stimulus such as temperature or solvent change, they undergo a phase transition often driving pattern formation. In this paper, we use an elastic model to investigate the linear stability of shrinking cylindrical NIPA gels. This model exhibits bubble and bamboo patterns. The wavelengths of these patterns and their phase diagram are in agreement with the experiment of Matsuo and Tanaka [Nature (London) 358, 482 (1992)].


Inequality in provision of sexual health information.
Sexual health is important to quality of life, and therefore to all areas of nursing, generalist and specialist. Disparity exists between what is available to men and to women, as regards range and availability of information and services. The lack of information available for men has potential consequences for health, and for the provision of quality nursing and health care.


15-deoxy-delta-12-14-PGJ2 regulates apoptosis induction and nuclear factor-kappaB activation via a peroxisome proliferator-activated receptor-gamma-independent mechanism in hepatocellular carcinoma.
The peroxisome proliferator-activated receptor-gamma (PPARgamma) high-affinity ligand, 15-deoxy-Delta-12,14-PGJ(2) (15d-PGJ(2)), is toxic to malignant cells through cell cycle arrest and apoptosis induction. In this study, we investigated the effects of 15d-PGJ(2) on apoptosis induction and expression of apoptosis-related proteins in hepatocellular carcinoma (HCC) cells. 15d-PGJ(2) induced apoptosis in SK-Hep1 and HepG2 cells at a 50 micro M concentration. Pretreatment with the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethyl ketone (2-VAD-fmk), only partially blocked apoptosis induced by 40 micro M 15d-PGJ(2). This indicated that 15d-PGJ(2) induction of apoptosis was associated with a caspase-3-independent pathway. 15d-PGJ(2) also induced down-regulation of the X chromosome-linked inhibitor of apoptosis (XIAP), Bclx, and apoptotic protease-activating factor-1 in SK-Hep1 cells but not in HepG2 cells. However, 15d-PGJ(2) sensitized both HCC cell lines to TNF-related apoptosis-induced ligand-induced apoptosis. In SK-Hep1 cells, cell toxicity, nuclear factor-kappaB (NF-kappaB) suppression, and XIAP down-regulation were induced by 15d-PGJ(2) treatment under conditions in which PPARgamma was down-regulated. These results suggest that the effect of 15d-PGJ(2) was through a PPARgamma-independent mechanism. Although cell toxicity was induced when PPARgamma was down-regulated in HepG2 cells, NF-kappaB suppression and XIAP down-regulation were not induced. In conclusion, 15d-PGJ(2) induces apoptosis of HCC cell lines via caspase-dependent and -independent pathways. In SK-Hep1 cells, the ability of 15d-PGJ(2) to induce cell toxicity, NF-kappaB suppression, or XIAP down-regulation seemed to occur via a PPARgamma-independent mechanism, but in HepG2 cells, NF-kappaB suppression by 15d-PGJ(2) was dependent on PPARgamma.


Efficacy of collagenase in patients who did and did not have previous hand surgery for Dupuytren's contracture.
Collagenase Clostridium histolyticum (CCH) is a non-surgical, efficacious therapy for Dupuytren's contracture (DC). This study evaluated the efficacy and safety of CCH in patients with previous DC surgery. Data from 12 CCH clinical trials were pooled. At screening, patients provided details about the type/date of previous DC surgery. Reviewers coded descriptions to the Operated Hand, finger, and joint. Of 1082 patients, 422 (39%) had previous DC surgery. For these patients with previous surgery, the CCH treatment was coded on the Operated (n = 206) or Non-operated Hand (n = 196). End-points included changes in fixed-flexion contracture (FFC) and range of motion (ROM). Adverse events (AEs) were monitored. After treatment with CCH, FFC at metacarpophalangeal joints was reduced by 75% in previously Operated Hands and by 80% for Non-operated Hands (p = 0.6). Improvements in ROM were 32° and 32°, respectively (p = 0.9). For proximal inter-phalangeal joints, the reductions in FFC for the Operated and Non-operated Hands were 52% and 50%, respectively (p = 0.6); improvements in ROM were 24° and 26°, respectively (p = 0.3). Some AE rates were significantly higher in the Operated vs Non-operated Hand groups, but were not clinically relevant. There were no between-group significant differences in AE duration (p > 0.08). Previous surgery for DC does not affect efficacy or safety of CCH, suggesting CCH is an option in patients with recurring DC. Some AE rates were significantly higher, but not clinically relevant.


Influence of different withering conditions on phenolic composition of Avanà, Chatus and Nebbiolo grapes for the production of 'Reinforced' wines.
The impact of postharvest withering rates on the phenolic composition of 'reinforced' wines produced with partially dehydrated grapes was evaluated. The study was performed on winegrape varieties with anthocyanin profiles differently constituted of di- and tri-substituted forms. Dehydration induced limited changes in the anthocyanin profile of berry skins. Nevertheless, the greatest abundance of total anthocyanins and their more stable forms (malvidin-3-glucoside and acylated glucosides) corresponded to the wines made from slow withered Chatus grapes, which were in turn the darkest. In contrast, the wines made from withered Avanà grapes did not meet good chromatic characteristics due to low contents of total anthocyanins and high ratios between di- and tri-substituted forms. Nebbiolo wines showed intermediate values of this ratio, and therefore of clarity and color intensity. The fast process is recommended because higher percentages of galloylated flavanols in the seeds of slow withered Nebbiolo grapes may have a negative influence on wine astringency.


A randomised controlled trial of adjuvant hormono-chemotherapy in Stage II breast cancer.
From 1979 to 1984 women with histologically proven Stage II breast cancer were entered into a randomised controlled trial of adjuvant hormono-chemotherapy following mastectomy. Adjuvant therapy was started within 2 weeks of surgery and was given for 6 months as continuous 'Tamoxifen' and 6-monthly cycles of vincristine, adriamycin and cyclophosphamide (VAC). Of the 157 women randomised 82 were assigned to the control group and 75 to the adjuvant group. Comparing the two groups by life table analysis the rate of recurrence was found to be significantly greater in the control group (n = 46) than in the adjuvant group (n = 25) (Peto log rank test chi 2 = 7.46 P less than 0.01). Although there were more deaths amongst the control patients (n = 31) than in those randomised to receive adjuvant therapy (n = 18), this difference did not achieve statistical significance (chi 2 = 2.80 P less than 0.1). This analysis has shown that although adjuvant hormono-chemotherapy may significantly delay recurrence the trial has failed to demonstrate any significant improvement in the survival of women with Stage II breast cancer following mastectomy.


Effect of fiber orientation and fiber contents on the tensile strength in fiber-reinforced composites.
The study for strength calculation of one direction fiber-reinforced composites and the study measuring precisely fiber orientation distribution were presented. Need the systematic study for the data base that can predict mechanical properties of composite material and fiber orientation distribution by the fiber content was not constructed. Therefore, this study was investigated what affect the fiber content and fiber orientation distribution have on the strength of composites. Fiber-reinforced thermoplastic composites by changing fiber orientation distribution and the fiber content were made. Tensile strength ratio of 0 degrees direction of fiber-reinforced composites increased being proportional the fiber content and fiber orientation function as change from isotropy (J = 0) to anisotropy (J = 1). But, tensile strength ratio of 90 degrees direction by separation of fiber filament decreased when tensile load is imposed for width direction of reinforcement fiber length direction.


Hereditary hemorrhagic telangiectasia, factor V Leiden and antiphospholipid syndrome: a case report.
We report on a 57-year-old woman with three episodes of ischemic strokes and hereditary hemorrhagic telangiectasia (HHT). Tests for inherited and acquired thrombophilia showed elevated anticardiolipin immunoglobulin (Ig)M antibodies (on three separate occasions), anti-prothrombin IgG antibodies, and the heterozygous form of factor V Leiden. This is the first case of HHT, a primary antiphospholipid syndrome, combined with factor V Leiden. No detectable arteriovenous malformation was found and ischemic episodes, documented by computer tomography, were related to the presence of antiphospholipid antibodies and possibly the carriership of factor V Leiden mutation. Since aspirin provoked severe nasal hemorrhages, treatment with ticlopidine was initiated after the third stroke. Over an 18-month follow-up, ischemic episodes were absent and we regarded oral anticoagulation as unjustifiable.


Co-localization of transforming growth factor beta 2 with alpha 1(I) procollagen mRNA in tissue sections of patients with systemic sclerosis.
The role of transforming growth factor beta 2 (TGF-beta 2) in the pathogenesis of systemic sclerosis (SSc) was investigated by in situ hybridization of skin biopsies from six patients with SSc. Two patients with acute systemic lupus erythematosis (SLE), one with acute dermatomyositis (DM), and three healthy individuals were used as controls. TGF-beta 2 mRNA was found to be co-localized with pro alpha 1(I) collagen expression around dermal blood vessels in all patients with the inflammatory stage of SSc, whereas there was no expression of either gene in the dermis of patients in the fibrotic stage, the SLE patients or the normal controls. These findings provide evidence that TGF-beta 2 released by inflammatory cells around blood vessels may play a role in mediating the collagen gene disregulation in fibrosis.


Time-resolved determination of the potential of zero charge at polycrystalline Au/ionic liquid interfaces.
The potential of zero charge (PZC) is a fundamental property that describes the electrode/electrolyte interface. The determination of the PZC at electrode/ionic liquid interfaces has been challenging due to the lack of models that fully describe these complex interfaces as well as the non-standardized approaches used to characterize them. In this work, we present a method that combines electrode immersion transient and impedance measurements for the determination of the PZC. This combined approach allows the distinction of the potential of zero free charge (pzfc), related to fast double layer charging on a millisecond timescale, from a potential of zero charge on a timescale of tens of seconds related to slower ion transport processes at the interface. Our method highlights the complementarity of these electrochemical techniques and the importance of selecting the correct timescale to execute experiments and interpret the results.


Assessment of adherence to malaria chemoprophylaxis in a French Navy frigate deployed in Southeast Asia.
During a 2-month mission in Southeast Asia, including numerous stopovers in coastal cities, the crew of a frigate of the French Navy received doxycycline for antimalarial prophylaxis. Adherence to this chemoprophylaxis was evaluated with an anonymous questionnaire distributed at the end of the malaria exposure period. The response rate was 74 % (72 crew members). Among them, 67 sailors felt they had received clear information about the risks of malaria. Overall, 19 (27 %) respondents reported adherence (one forgotten pill, by no more than 15 days), 18 (25 %) irregular adherence (one or more pills forgotten weekly or stopped during the mission), and 35 recognized that they had not taken the treatment. These results, in the light of recent international recommendations, suggest that strategies for the prevention of malaria without systematic use of chemoprophylaxis (personal vector protection measures, an "Army posture" strategy), would be more suitable for medicalized ships cruising in this area.


Complement activation in Staphylococcus aureus bacteraemia.
Serum levels of complement components C3, C4 and factor B were measured in twenty-five patients with Staphylococcus aureus bacteraemia. The levels of C3 were depressed in nine patients, five of whom also had low C4 levels, indicating activation of complement via the classical pathway. Two patients with low C3 levels also had low factor B levels, one of these being in association with a low C4 level, which indicates activation of both the classical and alternative pathways, the latter being via the C3b feedback cycle. The protein A content of the S. aureus cultures, as shown by the indirect haemagglutination titre, was high in nine patients with C3 hypocomplementaemia. There was some correlation between the presence of a high protein A content of the S. aureus culture and a low serum C3 level in the patient. Some clinical evidence of immune complex disease was found in three patients. Complement activation in S. aureus bacteraemia is most likely due to complex formation resulting from the interaction between the Fc portion of IgG and staphylococcal protein A. These complexes may also result in clinical symptoms of immune complex disease.


[New therapeutic strategies for human papillomavirus related anogenital lesions in HIV patients: highly active antiretroviral therapy and HPV vaccines].
This review focuses on the recent therapeutic advances that may affect the management of neoplastic anogenital human papillomavirus (HPV)-related lesions in human immunodeficiency virus patients: highly active antiretroviral therapy (HAART) and HPV vaccines. HAART shows limited benefit on the incidence of high grade intraepithelial lesions and cancer in cervix, vulva and anus. On the other hand, it seems to raise discretely the spontaneous regression rates of cervical low grade lesions -cervical intraepithelial neoplasia (CIN) grade I- and condylomas, as well as the regression after treatment of CIN II-III. The benefit of HAART in squamous intraepithelial lesion seems to be modest, mostly due to the improvement of the immune status. The usefulness of DNA-HPV in HIV is not well established. HPV vaccines represent a mid-term new possibility of prevention for these lesions according to the high effectiveness shown in clinical trials, although the lack of data about effectiveness and security in HIV patients restrict its application. Second generation vaccines, still to be developed, might better adapt the specific needs of these patients.


A Need-based model for determining staffing needs for the public sector outpatient mental health service system.
This article proposes a need-based model for determining staffing needs for regional or national public sector outpatient mental health services. It constitutes a spreadsheet method involving a sequence of calculations relating demographic variables, workers' productivity, anticipated demand, and standards pertaining to annual visits per client distributed among the core mental health professions. The authors demonstrate the application of the model to national planning of adult outpatient mental health services using standards based on both expert consensus and existing staffing patterns while they note the need for more rigorously derived and empirically based standards. It is suggested that by using clearly stated assumptions and quantifiable variables, the model can facilitate constructive negotiations among various agencies and community organizations involved in policymaking and in budget allocations.


Human salivary microRNAs in Cancer.
Circulating microRNAs (miRNAs) have emerged as excellent candidates for cancer biomarkers. Several recent studies have highlighted the potential use of saliva for the identification of miRNAs as novel biomarkers, which represents a great opportunity to improve diagnosis and monitor general health and disease. This review summarises the mechanisms of miRNAs deregulation in cancer, the value of targeting them with a therapeutic intention and the evidence of the potential clinical use of miRNAs expressed in saliva for the detection of different cancer types. We also provide a comprehensive review of the different methods for normalising the levels of specific miRNAs present in saliva, as this is a critical step in their analysis, and the challenge to validate salivary miRNAs as a reality to manage cancer patients.


Supercritical water gasification of phenol over Ni-Ru bimetallic catalysts.
Incorporating Ru in a Ni catalyst for gasification of phenol in supercritical water at 450 °C and 30 min promoted formation of cyclohexanol via hydrogenation, which is a key step toward gasification. Both Ni and Ni-Ru catalysts were effective to reduce the formation of cyclohexanone and oligomerization products, compared with the case with no catalyst. H2 and CH4 yields increased as the Ru/Ni ratio increased, as did the carbon and hydrogen yields in the gas phase products. The Ni80Ru20/Al2O3 catalyst provided good gasification performance and it exhibits Ru (101), Ru (100) and Ni (111) facets and evidence of overlaid bimetallic particles. DFT calculations show that the presence of Ru (either as pure Ru or as a Ni-Ru alloy) reduces the energy barrier for phenol hydrogenation by close to 0.2 eV relative to pure Ni, and that the energy barrier is not as largely affected by the amount of Ru present, provided it is non-zero.


Valproate-associated stomatitis.
The purpose of this article is to report a case of severe stomatitis in a patient with pediatric epilepsy taking divalproex sodium. The case was reviewed with detailed oral examinations. This 5-year-old child developed severe stomatitis 18 months after institution of divalproex sodium. Cessation of the medication was associated with resolution of the stomatitis. A review of the pertinent literature is also provided. Stomatitis is a rare but potentially serious adverse effect of divalproex sodium administration.


Strategy and planning for chemopreventive drug development: clinical development plans II.
This is the second publication of Clinical Development Plans from the National Cancer Institute, Division of Cancer Prevention and Control, Chemoprevention Branch and Agent Development Committee. The Clinical Development Plans summarize the status of promising chemopreventive agents regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. They also contain the strategy for further development of these drugs, addressing pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen new Clinical Development Plans are presented here: curcumin, dehydroepiandrosterone, folic acid, genistein, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, 13-cis-retinoic acid, l-selenomethionine and 1, 4-phenylenebis(methylene)selenocyanate, sulindac sulfone, tea, ursodiol, vitamin A, and (+)-vorozole. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing these and future generations of chemopreventive drugs.


Skeletal anomalies in the adriamycin-exposed prenatal rat: a model for VATER association.
Vertebral and radial anomalies are prominent features of VATER (vertebral defects, anorectal anomaly, tracheoesophageal fistula with esophageal atresia, and radial dysplasia) association. It has been shown that exposure of the rat fetus to adriamycin produces a spectrum of anomalies, including esophageal atresia and other features of VATER association. We aimed to document the skeletal defects found in rats exposed to teratogenic doses of adriamycin in utero. Vertebral, rib, and limb anomalies were found in 54, 54, and 35% of these examined fetuses, respectively. The range of bone lesions seen in this animal model was similar to the range of lesions seen in infants born with VATER association.


Tracing Mercury Pollution along the Norwegian Coast via Elemental, Speciation, and Isotopic Analysis of Liver and Muscle Tissue of Deep-Water Marine Fish ( Brosme brosme).
Liver and muscle tissue of tusks ( Brosme brosme) have been analyzed for their THg and MeHg concentrations and Hg isotopic signatures for tracing Hg pollution along the Norwegian coast. Clear differences between tissue types and locations were established. At five of the eight locations, the Hg concentration in muscle exceeded the maximum allowable level of 0.5 mg kg-1 wet weight. δ202Hg values in both tissue types indicated that Hg speciation affects the bulk Hg isotopic signature. Tusk liver seems to be more sensitive to immediate changes and to anthropogenic inorganic Hg, while the muscle rather reflects the Hg accumulated over a longer period of exposure. The δ202Hg values of liver and muscle also enabled different sources of Hg and exposure pathways to be distinguished. δ202Hgmuscle-δ202Hgliver showed a clear correlation with the % MeHg in tusk liver for the coastal waters, but not for the fjords. The absence of significant differences in Δ199Hg values between both tissues of tusk from the same location suggests that in vivo metabolic processes are the underlying reason for the differences in Hg speciation and in δ202Hg values. This work highlights the importance of selecting different tissues of marine fish in future Hg monitoring programs.


Improving faculty feedback to resident trainees during a simulated case: a randomized, controlled trial of an educational intervention.
Although feedback conversations are an essential component of learning, three challenges make them difficult: the fear that direct task feedback will harm the relationship with the learner, overcoming faculty cognitive biases that interfere with their eliciting the frames that drive trainees' performances, and time pressure. Decades of research on developmental conversations suggest solutions to these challenges: hold generous inferences about learners, subject one's own thinking to test by making it public, and inquire directly about learners' cognitive frames. The authors conducted a randomized, controlled trial to determine whether a 1-h educational intervention for anesthesia faculty improved feedback quality in a simulated case. The primary outcome was an analysis of the feedback conversation between faculty and a simulated resident (actor) by using averages of six elements of a Behaviorally Anchored Rating Scale and an objective structured assessment of feedback. Seventy-one Harvard faculty anesthesiologists from five academic hospitals participated. The intervention group scored higher when averaging all ratings. Scores for individual elements showed that the intervention group performed better in maintaining a psychologically safe environment (4.3 ± 1.21 vs. 3.8 ± 1.16; P = 0.001), identifying and exploring performance gaps (4.1 ± 1.38 vs. 3.7 ± 1.34; P = 0.048), and they more frequently emphasized the professionalism error of failing to call for help over the clinical topic of anaphylaxis (66 vs. 41%; P = 0.008). Quality of faculty feedback to a simulated resident was improved in the interventional group in a number of areas after a 1-h educational intervention, and this short intervention allowed a group of faculty to overcome enough discomfort in addressing a professionalism lapse to discuss it directly.


Complete Nucleotide Sequences of Two VIM-1-Encoding Plasmids from Klebsiella pneumoniae and Leclercia adecarboxylata Isolates of Czech Origin.
Two multidrug resistance (MDR) plasmids, carrying the VIM-1-encoding integron In110, were characterized. Plasmid pLec-476cz (311,758 bp), from a Leclercia adecarboxylata isolate, consisted of an IncHI1 backbone, a MDR region, and two accessory elements. Plasmid pKpn-431cz (142,876 bp), from a sequence type 323 (ST323) Klebsiella pneumoniae isolate, comprised IncFIIY-derived and pKPN3-like sequences and a mosaic region. A 40,400-bp sequence of pKpn-431cz was identical to the MDR region of pLec-476cz, indicating the en bloc acquisition of the VIM-1-encoding region from one plasmid by the other.


Treatment outcomes in type A and B alcohol dependence 6 months after serotonergic pharmacotherapy.
Evidence supporting the use of serotonergic medications for the treatment of alcohol dependence is available from studies where pharmacotherapy targeted specific alcoholic subtypes. We previously established with Babor's alcohol typology that type A "lower risk/severity" alcoholics (n = 55) had better treatment response to 14 weeks of sertraline (200 mg/day) than placebo, and this was not found for type B "higher risk/severity" alcoholics (n = 45). The purpose of this study was to assess in this original study group whether treatment gains in the type A alcoholics were maintained or whether treatment outcomes changed for the type B alcoholics after discontinuing pharmacotherapy. After the end of a 3-month course of 200 mg/day sertraline, the subjects were interviewed at several time points about their alcohol drinking, if any, using the timeline follow-back method. For 90% of the original study group, mixed effects and generalized estimating equation models were used to compare monthly drinking amounts over a 6-month posttreatment period with drinking amounts in the last month of treatment. We found that type A alcoholics who had been treated with sertraline, in contrast to placebo, maintained the good outcomes they had achieved during treatment for at least 6 months after pharmacotherapy. We found that type B alcoholics who had been treated with sertraline, in contrast to placebo, continued to show no advantage for pharmacotherapy in the 6 months after completing treatment. In addition, heavy drinking in type B alcoholics increased over the 6 months postpharmacotherapy in those initially treated with sertraline compared with placebo. These data support the importance of considering alcohol subtype when pharmacologically treating alcohol dependence.


A word-association technique as a psychotherapeutic tool.
A way of using a word-association technique psychotherapeutically, although not experimental, has been employed as a shortcut "royal road" to understanding a presenting problem.


New transmission-type X-ray filters consisting of amorphous multilayer films.
New transmission-type X-ray filters have been developed. The filters consist of X-ray-amorphous metal (less than 30 A)/metalloid ( approximately 10 A) multilayer films sputter-deposited on X-ray-transparent polymer substrates. Such metal/metalloid multilayer films show only very broad diffraction peaks, since the metal and metalloid layers forming the multilayer films are usually X-ray amorphous if the layers are sufficiently thin. The filters use the wavelength-dependent absorption phenomena near absorption edges of elements to reduce the intensity of transmitted X-rays, without generating any crystalline sharp peaks which cause serious problems in experiments such as fluorescence XAFS measurements. The multilayer-film filters were prepared by a multi-target magnetron sputtering deposition technique, paying special attention to the homogeneity of the layer thickness by spinning substrates of the films. The filters are useful in reducing the intensity of undesirable fluorescence emissions and improving the signal-to-background ratios of data acquired in various measurements using a solid-state detector.


Surgical treatment of plantar fasciitis.
Ten patients were operated on for plantar fasciitis (12 heels) by stripping the plantar fascia and superficial plantar muscles from the calcaneus. All patients were refractory to conservative treatment for an average of 12.4 months prior to operation and were followed up for a minimum of 24 months after operation. Complete symptomatic relief was obtained in all patients despite the presence of massive obesity in six. Hypoesthesia of the heel, which was present in five feet after operation, may have enhanced pain relief. Three patients who were receiving workmen's compensation returned to work within 16 weeks of surgery. One deep wound infection occurred and required surgical debridement before healing could occur. Surgical treatment is efficacious in selected cases of plantar fasciitis that are refractory to conservative measures.


Synthesis of phase-pure U2N3 microspheres and its decomposition into UN.
Uranium mononitride (UN) is important as a nuclear fuel. Fabrication of UN in its microspherical form also has its own merits since the advent of the concept of accident-tolerant fuel, where UN is being considered as a potential fuel in the form of TRISO particles. However, not many processes have been well established to synthesize kernels of UN. Therefore, a process for synthesis of microspherical UN with a minimum amount of carbon is discussed herein. First, a series of single-phased microspheres of uranium sesquinitride (U2N3) were synthesized by nitridation of UO2+C microspheres at a few different temperatures. Resulting microspheres were of low-density U2N3 and decomposed into low-density UN. The variation of density of the synthesized sesquinitrides as a function of its chemical composition indicated the presence of extra (interstitial) nitrogen atoms corresponding to its hyperstoichiometry, which is normally indicated as α-U2N3. Average grain sizes of both U2N3 and UN varied in a range of 1-2.5 μm. These also had a considerably large amount of pore spacing, indicating the potential sinterability of UN toward its use as a nuclear fuel.


Using HLA typing to support patients with cancer.
The human leukocyte antigen (HLA) system plays a crucial role in immune function, and HLA testing is often needed in the support of patients with cancer. We briefly review the published literature to clarify the nomenclature of the HLA system, currently available methods for HLA testing, and commonly used HLA assays. The uses of HLA testing in pharmacogenomics, disease association, platelet transfusion support, and in the management of both solid organ and hematopoietic stem cell transplantation are also reviewed. HLA testing is commonly performed for select patient populations, including patients with cancer and in those requiring solid organ and hematopoietic stem cell transplantation. Newer molecular typing methods have helped improve patient outcomes following hematopoietic stem cell transplantation.


Effect of the chemical structure of N-(2-hydroxypropyl)methacrylamide copolymers on their ability to induce antibody formation in inbred strains of mice.
The homopolymer of N-(2-hydroxypropyl)methacrylamide (HPMA) and copolymers of HPMA differing in oligopeptide side chains (-Gly-Gly-OH; -Acap-Phe-OH; -Acap-Leu-HMDA and -Gly-Phe-Tyr-OH) or in their content (1%, 3.5% and 8.4% mole of -Gly-Gly-OH side chains) were investigated with respect to their ability to induce antibody formation and mitogenic reaction in inbred strains of mice. The dependence on the antigen dose, on composition of the side chain and on the genetic background of the immunized organism was defined. It was demonstrated that the specificity of the antibody formed is predominantly directed against oligopeptide side chains, though some part of the antibody is also produced against hydroxypropyl chains. Neither the homopolymer nor the copolymers behave in the tissue culture as mitogens.


From CAR-T Cells to CAR-NK Cells: A Developing Immunotherapy Method for Hematological Malignancies.
The approval of CD19 chimeric antigen receptor (CAR)-engineered T (CAR-T) cell products in B-cell malignancies represents a breakthrough in CAR-T cell immunotherapy. However, the remaining limitations concerning the graft-versus-host disease (GVHD) and other adverse effects (e.g., cytokine release syndromes [CRS] and neurotoxicity) still restrict their wider applications. Natural killer (NK) cells have been identified as promising candidates for CAR-based cellular immunotherapy because of their unique characteristics. No HLA-matching restriction and abundant sources make CAR-engineered NK (CAR-NK) cells potentially available to be off-the-shelf products that could be readily available for immediate clinical use. Therefore, researchers have gradually shifted their focus from CAR-T cells to CAR-NK cells in hematological malignancies. This review discusses the current status and applications of CAR-NK cells in hematological malignancies, as well as the unique advantages of CAR-NK cells compared with CAR-T cells. It also discusses challenges and prospects regarding clinical applications of CAR-NK cells.


An intronic polymorphism in the porcine IRF7 gene is associated with better health and immunity of the host during Sarcocystis infection, and affects interferon signalling.
Interferon regulatory factor 7 (IRF7), as a key regulator of type I interferon response, plays an important role during innate response against viral infection. Although well conserved across species, the structure of IRF7 and its function during parasite infection are not well documented in farm animals, such as the pig. To bridge this gap, we have determined the porcine IRF7 gene structure and identified two intronic single nucleotide polymorphisms (SNPs), SNP g.748G>C and SNP g.761A>G, in commercial pig breeds. The distribution of SNP g.761A>G in multiple breeds suggested that it was in Hardy-Weinberg equilibrium and allowed us to map it at the top of SSC2. We found that during Sarcocystis miescheriana infection, the G allele was associated with high lymphocyte levels (P < 0.02), reduced drop in platelet levels (P < 0.002) and IgG1-Th2-dominated response (P < 0.05). This suggests that the G allele was associated with better health and immunity of the host during Sarcocystis infection. Furthermore, we have also provided suggestive evidence that the G allele of SNPc.761A>G enhances the transactivation activity of IRF7, possibly by improving IRF7 transcript splicing of intron-3. These findings would suggest that IRF7, as a transcriptional regulator, is involved in the defence mechanism against a larger spectrum of pathogens, and in more host species, than initially anticipated.


[Effects of different fungi on symbiotic seed germination of two Dendrobium species].
The epiphytic orchid, Dendrobium aphyllum and D. devonianum are used as traditional Chinese medicine, and became locally endangered in recent years because of over-collection. We test the effect of inoculations of endophytic fungi FDaI7 (Tulasnella sp.), FDd1 (Epulorhiza sp. ) and FCb4 (Epulorhiza sp.), which isolated from D. aphyllum, D. denonianum and Cymbidium mannii, respectively, on artificial substrate in these two Dendrobium species. In the symbiotic germination experiment, FDaI7 and FDd1 were effective for protocorm formation and seedling development of D. aphyllum and D. denonianum separately. After 60 days, 14.46% of the D. aphyllum seeds grown to protocorms and 12.07% developed to seedlings inoculated only with FDaI7, while contrasted with 0 when inoculated the other two isolates and non-inoculation treatment. However, in D. denonianum, seeds only grown to protocorms and developed to seedlings when inoculated with FDd1, the percentages were 44.36% and 42.91% distinguishingly. High specificity was shown in symbiotic germination on artificial substrate of Dendrobium. Protocorms could further develop to seedlings within or without light when inoculated the compatible fungi. However, light condition (12/12 h Light/Dark) produced the normal seedlings, while dark condition (0/24 h L/D) produced the abnormal seedlings. These may suggest that the development of young seedlings require light based on the effective symbiotic fungi. These findings will aid in seedling production of simulation-forestry ecology cultivation, conservation and reintroduction of Dendrobium.


Electrochemically Synthesized Nanoporous Molybdenum Carbide as a Durable Electrocatalyst for Hydrogen Evolution Reaction.
Demands for sustainable production of hydrogen are rapidly increasing because of environmental considerations for fossil fuel consumption and development of fuel cell technologies. Thus, the development of high-performance and economical catalysts has been extensively investigated. In this study, a nanoporous Mo carbide electrode is prepared using a top-down electrochemical process and it is applied as an electrocatalyst for the hydrogen evolution reaction (HER). Anodic oxidation of Mo foil followed by heat treatment in a carbon monoxide (CO) atmosphere forms a nanostructured Mo carbide with excellent interconnections, and these structural characteristics lead to high activity and durability when applied to the HER. Additionally, characteristic behavior of Mo is observed; metallic Mo nanosheets form during electrochemical anodization by exfoliation along the (110) planes. These nanosheets are viable for chemical modification, indicating their feasibility in various applications. Moreover, the role of carbon shells is investigated on the surface of the electrocatalysts, whereby it is suggested that carbon shells serve as a mechanical barrier against the oxidative degradation of catalysts that accompanies unavoidable volume expansion.


Adenocarcinoma of the cervix and adenocarcinoma of the endometrium: distinction with PCR-mediated detection of HPV DNA.
The differential diagnosis between primary endocervical adenocarcinoma and adenocarcinoma originating in the endometrium may in some cases be difficult. The two cancer types have a different genesis, with human papillomavirus (HPV) as an important causal factor in the development of primary cervical carcinoma. In this study, the paraffin-embedded cervical tissues from 23 patients with stage II endometrial carcinoma and from 50 patients with primary cervical adenocarcinoma were examined for HPV DNA of types 16, 18, and 33. HPV DNA was demonstrated in 70% of the primary endocervical adenocarcinomas and in none of the endometrial carcinomas. It is concluded that HPV detection may be useful in the differential diagnosis of some cases of cervical and endometrial adenocarcinoma.


Suicide attempts and clinical features of bipolar patients.
To identify clinical predictors of suicide attempts in patients with bipolar disorder. This study included bipolar patients who were treated in the Psychiatry Department, Haseki Training and Research Hospital, Istanbul, Turkey, between 2013 and 2014; an informed consent was obtained from the participants. Two hundred and eighteen bipolar patients were assessed by using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis-I (SCID-I) in order to detect all possible psychiatric comorbid diagnoses. Clinical predictors of suicide attempts were examined in attempters and non-attempters. The study design was retrospective. The lifetime suicide attempt rate for the entire sample was 19.2%. Suicide attempters with bipolar disorder had more lifetime comorbidity of eating disorder. Female gender and family history of mood disorder were significant predictors for suicide attempts. There was no difference between groups in terms of bipolar disorder subtype, onset age of bipolar disorder, total number of episodes, first and predominant episode type, suicide history in first degree relatives, severity of episodes, and hospitalization and being psychotic. Our study revealed that female gender, family history of mood disorder, and eating disorder are more frequent in bipolar patients with at least one suicide attempt.


Density dependence governs when population responses to multiple stressors are magnified or mitigated.
Population endangerment typically arises from multiple, potentially interacting anthropogenic stressors. Extensive research has investigated the consequences of multiple stressors on organisms, frequently focusing on individual life stages. Less is known about population-level consequences of exposure to multiple stressors, especially when exposure varies through life. We provide the first theoretical basis for identifying species at risk of magnified effects from multiple stressors across life history. By applying a population modeling framework, we reveal conditions under which population responses from stressors applied to distinct life stages are either magnified (synergistic) or mitigated. We find that magnification or mitigation critically depends on the shape of density dependence, but not the life stage in which it occurs. Stressors are always magnified when density dependence is linear or concave, and magnified or mitigated when it is convex. Using Bayesian numerical methods, we estimated the shape of density dependence for eight species across diverse taxa, finding support for all three shapes.


A quantitative solid-state Raman spectroscopic method for control of fungicides.
A new analytical procedure using solid-state Raman spectroscopy within the THz-region for the quantitative determination of mixtures of different conformations of trifloxystrobin (EE, EZ, ZE and ZZ), tebuconazole (1), and propiconazole (2) as an effective method for the fungicide product quality monitoring programmes and control has been developed and validated. The obtained quantities were controlled independently by the validated hybrid HPLC electrospray ionization (ESI) tandem mass spectrometric (MS) and matrix-assisted laser desorption/ionization (MALDI) MS methods in the condensed phase. The quantitative dependences were obtained on the twenty binary mixtures of the analytes and were further tested on the three trade fungicide products, containing mixtures of trifloxystrobin-tebuconazole and trifloxystrobin-propiconazole, as an emissive concentrate or water soluble granules of the active ingredients. The present methods provided sufficient sensitivity as reflected by the metrologic quantities, evaluating the concentration limit of detection (LOD) and quantification (LOQ), linear limit (LL), measurement accuracy and precision, true quantity value, trueness of measurement and more.


Macular pigment and lutein supplementation in choroideremia.
Choroideremia is an incurable X-linked retinal degeneration caused by mutations in the gene encoding Rab escort protein-1. A group of clinically defined and genotyped patients were studied to determine: (1) the degree of rod and cone dysfunction and structural abnormality in the central retina and the level of macular pigment; and (2) the response of macular pigment and foveal vision to a 6 month trial of supplementation with oral lutein (at 20 mg per day). Rod and cone-mediated function was measured with dark-adapted static perimetry; in vivo retinal structure was determined with optical coherence tomography; and macular pigment optical density was measured with heterochromatic flicker photometry. In this cohort of patients (ages 15-65 years), both rod- and cone-mediated central function declined with age as did central retinal thickness. Macular pigment levels did not differ between patients and male control subjects. Supplementation of oral lutein in a subset of patients led to an increase in serum lutein and macular pigment levels; absolute foveal sensitivity did not change. It is concluded that macular pigment density can be augmented by oral intake of lutein in patients with choroideremia. There was no short-term change in the central vision of the patients on the supplement, but long-term influences of lutein supplementation on disease natural history warrant further study.


A variant of the endothelial nitric oxide synthase gene (NOS3) associated with AMS susceptibility is less common in the Quechua, a high altitude Native population.
Endothelial nitric oxide synthase (eNOS) is a vascular enzyme that produces nitric oxide, a transient signaling molecule that by vasodilatation regulates blood flow and pressure. Nitric oxide is believed to play roles in both short-term acclimatization and long-term evolutionary adaptation to environmental hypoxia. Several laboratories, including ours, have shown that variants in NOS3 (the gene encoding eNOS) are overrepresented in individuals with altitude-related illnesses such as high altitude pulmonary edema (HAPE) and acute mountain sickness (AMS), suggesting that NOS3 genotypes contribute to altitude tolerance. To further test our hypothesis that the G allele at the G894T polymorphism in NOS3 (dbSNP number: rs1799983; protein polymorphism Glu298Asp) is beneficial in hypoxic environments, we compared frequencies of this allele in an altitude-adapted Amerindian population, Quechua of the Andean altiplano, with those in a lowland Amerindian population, Maya of the Yucatan Peninsula. While common in both populations, the G allele was significantly more frequent in the highlanders. Taken together, our data suggest that this variant in NOS3, which has been previously associated with higher levels of nitric oxide, contributes to both acclimatization and adaptation to altitude.


Cluster C personality disorder and recovery from major depression: 24-month prospective follow-up.
We investigated whether Cluster C personality disorder (CPD) is associated with recovery from depression. Changes in symptom scales in 30 patients with MD and CPD were compared with changes in 60 patients with MD alone over a 24-month follow-up period. Recovery of patients with MD and comorbid CPD was inferior to recovery of those with MD alone based on the Hamilton and Beck Depression Inventory (BDI) scales, and the SCL-90 total score. Only 18% of those with MD alone but 47% of those with CPD and MD met the criteria for major depression at the end of the 24-month follow-up. Multiple logistic regression analyses revealed an independent association between the lack of recovery (BDI score > 9 at 24 months) and the presence of CPD (OR 4.9, 95% CI 1.5-16.0). Moreover, the presence of CPD associated with the presence of major depression at 24 months (OR 4.2, 95% CI 1.4-12.2). The presence of CPD hinders the alleviation of depressive symptoms in major depression.


Repair of ventricular septal perforation with asymmetrical conical patch exclusion.
We report a case of repair of the postinfarction ventricular septal perforation (VSP), using an equine pericardium tailored in an asymmetrical conical shape for exclusion (modified sack technique) and an additional direct patch closure of VSP. An asymmetrical conical patch is easily sutured to the normal septum away from the VSP edge by using the longer part of the cone border. The postoperative left ventriculogram 1.5 months after surgery revealed a minor leakage from the patch to the excluded left ventricle. However, no residual left to the right shunt was found in calculation from the oxygen saturation in blood samples. Echocardiography 1 year after surgery showed no residual patch leakage at all. We suggest that this modified sack technique is a simple and easy method by which to exclude the VSP.


An Exploratory Study of Predictors of Relationship Commitment for Cisgender Female Partners of Transgender Individuals.
The current exploratory study investigates which variables predict commitment among cisgender women currently in a relationship with a transgender-identified partner. This study includes variables specific to gender diverse couples such as years in the relationship, amount of prior knowledge about transgender identity, and gender role beliefs. Also included are the general relationship factors of satisfaction, quality of alternatives, investment size, and the outcome variable of commitment, as described in the Investment Model of Commitment. Using convenience sampling from online support groups, the sample was n = 138 cisgender female partners. The findings of the regression analyses indicate one's personal resilience and the number of years in the relationship prior to transition are significantly related to partner commitment, with satisfaction mediating both associations. The longer a participant was in the relationship at the time of a gender transition of a partner, the less satisfaction they report, thus reducing commitment to the relationship. Additionally the more personal resilience a partner endorses, the higher the relationship satisfaction, and in turn, more commitment is reported. The results offer information about the important factors related to staying in relationships during and after a gender transition.


An MRI Hyperintense Acute Reperfusion Marker Is Related to Elevated Peripheral Monocyte Count in Acute Ischemic Stroke.
Blood-brain barrier (BBB) disruption detected on magnetic resonance imaging (MRI) in acute ischemic stroke as a hyperintense acute reperfusion marker (HARM) is associated with upregulation of matrix metalloproteinase-9 (MMP-9). Although activated leukocytes, including monocytes, are the main source of MMPs, limited data exist to support relationship between leukocyte activation and BBB disruption in patients with acute ischemic stroke. The goal of this study is to investigate the relationship between neutrophils, lymphocytes, and monocytes with BBB disruption detected as HARM (+) in patients with acute ischemic stroke. We conducted a retrospective analysis of prospectively collected data in patients who did not receive any reperfusion therapy with acute (<12 hours) ischemic stroke. MRI scans were obtained at baseline, 24 hours, and 5 days. HARM was evaluated on the 24-hour follow-up scan. Thirty-three patients were studied. HARM was detected in 27% of patients. Median volumes of baseline perfusion (mean transit time [MTT]) deficit (219.4 mL vs. 158.4 mL, P = .029) and DWI infarct growth at 24 hours (18.50 mL vs. .14 mL, P = .017), as well as the median absolute numbers (1 × 103 /mm3 ) of monocytes, were significantly higher in HARM (+) versus HARM (-) patients (0.9 vs. 0.6, p = 0.011). Increased monocyte count associated with HARM supports importance of systemic inflammation in BBB disruption in acute ischemic stroke.


pH-Dependent aggregation and disaggregation of native β-lactoglobulin in low salt.
The aggregation of β-lactoglobulin (BLG) near its isoelectric point was studied as a function of ionic strength and pH. We compared the behavior of native BLG with those of its two isoforms, BLG-A and BLG-B, and with that of a protein with a very similar pI, bovine serum albumin (BSA). Rates of aggregation were obtained through a highly precise and convenient pH/turbidimetric titration that measures transmittance to ±0.05 %T. A comparison of BLG and BSA suggests that the difference between pHmax (the pH of the maximum aggregation rate) and pI is systematically related to the nature of protein charge asymmetry, as further supported by the effect of localized charge density on the dramatically different aggregation rates of the two BLG isoforms. Kinetic measurements including very short time periods show well-differentiated first and second steps. BLG was analyzed by light scattering under conditions corresponding to maxima in the first and second steps. Dynamic light scattering (DLS) was used to monitor the kinetics, and static light scattering (SLS) was used to evaluate the aggregate structure fractal dimensions at different quench points. The rate of the first step is relatively symmetrical around pHmax and is attributed to the local charges within the negative domain of the free protein. In contrast, the remarkably linear pH dependence of the second step is related to the uniform reduction in global protein charge with increasing pH below pI, accompanied by an attractive force due to surface charge fluctuations.


An assessment of high risk sexual behaviour and HIV transmission among migrant oil workers in the Niger Delta area of Nigeria.
A cross--sectional behavioural survey undertaken amongst migrant oil-workers of an oil exploration outfit operating in the Niger-Delta of Nigeria with the aim of assessing the interplay of migrancy, high-risk sexual behaviour and HIV transmission. A total of 300 randomly selected migrant oil workers were assessed using structured questionnaires to evaluate key high - risk sexual behavioral parameters such as multiplicity of sexual partners, bisexuality (closet homosexuality), high grade sexual behaviour and lesbianism. Sampling period was two months with a control cohort of 200. The prevalence of high risk sexual behaviour (HRSB) amongst the migrant oil workers was found to be 7.7% while low-risk sexual behaviour (LRSB) was 92.3%. There was no record of HRSB in the control group. We did not also encounter any lesbian sexual orientation in this study. The distribution of HRSB amongst the migrant oil workers showed that the commonest variety was bisexuality (closet homosexuality) with 10(43.5%) followed by high-risk sexual behaviour 7(30.4%), while the least common was multiplicity of sexual partners with 6 (26.1%). Furthermore, majority of these individuals 19 (82.6%) were above the age of 35 years. The index of condom-use and acceptance was high. Here 14 (60.9%) found condom-use convenient while 13 (56.5%) regularly used the condom. This study confirms the existence of HRSB among migrant oil workers in the Niger delta. It is therefore advisable to focus interventionist and prevention programmes on this group which appear to be pivotal in the transmission and spread of HIV/AIDS in this environment.


Antitumor effect of the nucleoside analogs 2-chlorodeoxyadenosine and 2',2'-difluorodeoxycytidine on human hepatoma HepG2 cells.
Hepatocellular carcinoma is one of the most malignant tumors in the world. Although a wide range of therapeutic options is available, the efficacy of these methods and the prognosis of hepatocellular carcinoma are still very poor. The nucleoside analogs 2-chlorodeoxyadenosine (Cladribine, 2-CdA) and 2',2'-difluorodeoxycytidine (Gemcitabine, dFdC) have shown potent cytotoxic effects on various human tumor cell lines in vitro and marked therapeutic efficacy in the treatment of lymphoproliferative disorders and several solid tumors in vivo. In the present study we evaluated the antitumor effect of 2-CdA and dFdC on human hepatoma HepG2 cells. HepG2 cells were grown in the absence and presence of increasing concentrations of 2-CdA and dFdC. Antitumor activity was assessed by inhibition of cell growth, evaluated by counting cell numbers in a hemocytometer and by 3H-thymidine uptake, and by reduction of cell viability as determined by exclusion of 0.1% trypan blue. For rescue experiments, the natural pyrimidine deoxycytidine (dCyd) was added simultaneously or delayed. A strong antitumor activity was observed for both compounds. dFdC showed a more pronounced effect with an inhibition constant (IC50) of 3.98+/-0.03 nM in comparison to 2-CdA with an IC50 of 16.66+/-0.40 nM. Both drugs achieved their half-maximal antitumor activity after 31 h. With respect to dFdC, fractionated daily administrations showed a distinctly greater antitumor activity than a single transient administration. The cytotoxic effects of 2-CdA and dFdC were completely reversed by simultaneous addition of dCyd. In this paper we show strong antitumor effects of the nucleoside analogs 2-CdA and dFdC on the human hepatoma cell line HepG2. These findings suggest that both compounds, but in particular dFdC, are promising substances for further evaluations in the treatment of hepatocellular carcinoma.


Diagnostic Technology for Spine Pathology.
Diagnostic techniques for spinal pathologies have been developed in accordance with advances in technology. Accurate diagnosis of spinal pathology is essential for appropriate management of spinal diseases. Since the development of X-rays in 1895 and computed tomography (CT) in 1967, several diagnostic imaging modalities have been utilized for detecting spinal pathologies, including radiography, CT, magnetic resonance imaging, and radionuclide imaging. In addition to diagnostic imaging technologies, electrodiagnostic tests, including electromyography and nerve conduction studies, play a significant role as diagnostic tools, as spinal diseases are mostly profoundly associated with pathologies of the neural structures, such as the spinal cord and nerve root, and extent of injury at the structure cannot be adequately detected by conventional imaging techniques. In patient-specific treatment strategies, usage of diagnostic modalities is of great importance; thus, we should be aware of the basic details and approaches of the different diagnostic modalities. In this review, the authors discuss the details of the technologies that aid in the diagnosis of spinal pathologies.


Activity of extracts and alkaloids of thai Alstonia species against human lung cancer cell lines.
Methanol extracts of root barks of Alstonia macrophylla, A. glaucescens, and A. scholaris, collected from Thailand, have been assessed for cytotoxic activity against two human lung cancer cell lines, MOR-P (adenocarcinoma) and COR-L23 (large cell carcinoma), using the SRB assay. Significant cytotoxic activity was exhibited by the extract of A. macrophylla on both cell lines. Activity-directed fractionation led to the isolation of a novel indole alkaloid, O-methylmacralstonine, from the most active fraction of A. macrophylla along with four known alkaloids, talcarpine, villalstonine, pleiocarpamine, and macralstonine. Structure elucidation of the novel alkaloid was based on spectroscopic methods, especially 2D-NMR. The bisindole villalstonine was found to possess pronounced activity on both cell lines with an IC50 value less than 5 muM, but was about 10(3) times less potent than vinblastine sulphate. The monomeric alkaloid, talcarpine, was found to be inactive. Pleiocarpamine, O-methylmacralstonine and macralstonine were all considerably less active than villalstonine.


Terahertz spectroscopy of human skin tissue models with different melanin content.
Terahertz imaging has been proposed for burns and skin cancer identification. However, the role of melanocytes, melanosomes, melanin content and distribution in determining the terahertz optical properties of human skin has not been investigated. We use terahertz time domain spectroscopy to measure the optical properties of in vitro pigmented human skin tissue models from Asian, Black, and Caucasian donors. Spectra were collected at various time intervals and used to extract the absorption coefficient and index of refraction at terahertz frequencies. Our results indicate that the degree of cell differentiation and type of donor both contribute to the measured terahertz optical properties.


Frequency of corneal dystrophies on the basis of histopathology in surgically removed corneas.
To assess the frequency of corneal dystrophies on the basis of histopathology in surgically-removed corneas. The descriptive study was conducted at Foundation University Medical College, Islamabad, and Al Shifa Eye Hospital, Rawalpindi, Pakistan, from May to October 2011, and comprised post-keratoplasty corneal specimen irrespective of age and gender. The surgically-removed corneas were processed according to the standard guidelines of histopathological processing. The histopathological sections were examined for various corneal dystrophies. Data was recorded on a proforma and was analysed using SPSS 17. Of the 63 patients in the study, 12(19%) were diagnosed as having corneal dystrophies. In these 12 patients, 6(50%)were diagnosed as stromal corneal dystrophies and 5(42%)had posterior corneal dystrophies, and 1(8%)had anterior corneal dystrophy. Histopathological examination of corneas is a reliable method to diagnose and classify corneal dystrophies.


Frequent disruption of chromodomain helicase DNA-binding protein 8 (CHD8) and functionally associated chromatin regulators in prostate cancer.
Abnormal expression and function of chromatin regulators results in the altered chromatin structure seen in cancer. The chromatin regulator CTCF, its cofactor CHD8, and antagonistic paralogue BORIS have wide-ranging effects on gene regulation. Their concurrent expression and regulation was examined in benign, localized, and metastatic prostate cancer (PCa) arrays with extended follow-up using an automated quantitative imaging system, VECTRA. Epithelial staining was quantified and compared against a range of clinicopathologic variables. CHD8 expression was decreased in HGPIN, localized, and metastatic PCa compared to benign (P < .001). CHD8 promoter hypermethylation, assessed by Quantitative Pyrosequencing, occurred in over 45% of primary cancers in this population as well as the TGCA database. Treatment of cell lines with the demethylating agent 5-Aza-2'-deoxycytidine reinduced expression. An interesting dichotomy for CHD8 was observed within primary cancers, with higher nuclear protein expression associated with adverse clinical outcomes including extracapsular extension (P = .007), presence of metastases (P = .025) and worse PSA-recurrence free survival (P = .048). CHD8 outperformed Gleason score and predicted biochemical failure within intermediate grade prostate cancers. The BORIS/CTCF expression ratio increased in localized (P = .03) and metastatic PCa (P = .006) and was associated with higher Gleason score (P = .02), increased tumor volume (P = .02) and positive margins (P = .04). Per cell heterogeneity of expression revealed all protein expression to be more heterogeneous in cancerous tissue (both P < .001), especially high grade (P < .01). In the first detailed analysis in cancer, a marked loss of CHD8 expression and increased BORIS/CTCF ratio indicate frequent disruption of CTCF and its effector genes in PCa.


Clinicopathological significance of forkhead box protein A1 in breast cancer: A meta-analysis.
The aim of the present study was to investigate the associations between the expression of forkhead box protein A1 (FOXA1) and differential clinicopathological characteristics in breast cancer using a meta-analysis method. Eligible studies that investigated the correlation between FOXA1 expression and the clinical characteristics of breast cancer were collected through searching numerous databases, including PubMed, EMBASE, the Chinese National Knowledge Infrastructure and the VIP database. In total, eight studies were included in the meta-analysis. Following a systematic analysis, the expression of FOXA1 was found to be significantly associated with the estrogen receptor α status, the progesterone receptor status, lymph node metastasis and the histological grade in breast cancer. However, no statistically significant association was observed between FOXA1 expression and the human epidermal growth factor receptor-2 status in breast cancer patients.


The ability of 18F-choline PET/CT to identify local recurrence of prostate cancer.
To determine when 18F-choline PET/CT can truly identify local recurrence of prostate cancer. 1031 patients from 3 European centers underwent (18)F-choline PET/CT (FCH PET/CT) for recurrent disease; 131 subjects (12.7%) showed a positive FCH uptake in the prostatic gland or prostatic fossa. Median age was 72 years (range 48-87 years), and the median PSA level at the time of FCH PET/CT scan was 4.41 ng/mL (0.22-18.13 ng/mL). 45 patients (34.4%) had a Gleason score (GS) >7, and the residual subjects had a GS ≤ 7. The assessment of true or false-positive FCH PET/CT findings was made by magnetic resonance imaging (n = 34) and/or biopsy in 75/131 cases. A χ (2) test and a Z Kolmogorov-Smirnov test were used to assess the correlation between clinical variables (age, PSA, GS, type of therapy) and FCH PET/CT findings. FCH PET/CT resulted truly positive (TP) for recurrent disease in the prostatic gland/fossa in 59/75 patients (79%) and falsely positive (FP) in 16 subjects (21%). The median value of PSA at the time of FCH PET/CT scan was higher in TP as compared to FP, although not statistically significant (4.76 vs. 3.04 ng/mL p > 0.05). Similarly, median age, GS categories, and the type of therapy were similar between the two groups (p > 0.05). However, when matching GS categories and PSA values, we found that the number of patients with TP findings were higher in the case of a PSA > 2 ng/mL, independently from the GS (ranging between 74% and 92%). Conversely, FP rate ranged between 50% and 65% in patients with a PSA ≤ 2 ng/mL, especially in the case of GS ≤ 7, whereas FP was around 25% in those with a GS >7 and PSA > 2 ng/mL. FCH PET/CT has a limited role in evaluation of prostatic gland/fossa recurrence, due to the physiological biodistribution of the radiopharmaceutical agent. However, in 70-90% of patients with a PSA >2 ng/mL, independently from GS, a focal FCH uptake is compatible with a true local recurrence.


Fracture resistance of teeth restored with dentin-bonded crowns.
While dentin-bonded crowns may hold esthetic advantages over metal-ceramic restorations, and minimal tooth preparation may also be appropriate, resistance to fracture of the restored unit is an important consideration. Dentin-bonded crowns were placed on standardized preparations in two groups of 10 maxillary premolar teeth in vitro. The preparations differed only in degree of taper. The restored specimens were subjected to compressive loading at 1 mm/min from a steel bar placed along the midline fissure. Mean fracture loads of 0.77 kN (6-degree taper) and 0.71 kN (8-degree taper) were recorded for the groups of prepared teeth, and a mean fracture load of 0.97 kN was obtained for a group of unprepared controls. Statistical analysis indicated that there was no significant difference between the fracture load of the 6-degree taper group and that of the sound control teeth.


Thiazole, oxadiazole, and carboxamide derivatives of artemisinin are highly selective and potent inhibitors of Toxoplasma gondii.
We have prepared 23 new dehydroartemisinin (DART) trioxane derivatives (11 thiazoles, 2 oxadiazoles, and 10 carboxamides) and have screened them for in vitro activity in the Toxoplasma lytic cycle. Fifteen (65%) of the derivatives were noncytotoxic to host cells (TD(50) > or = 320 microM). Eight thiazole derivatives and two carboxamide derivatives displayed effective inhibition of Toxoplasma growth (IC(50) = 0.25-0.42 microM), comparable in potency to artemether (IC(50) = 0.31 microM) and >100 times more inhibitory than the currently employed front-line drug trimethoprim (IC(50) = 46 microM). The thiazoles as a group were more effective than the other derivatives at inhibiting growth of extracellular as well as intracellular parasites. Unexpectedly, two thiazole trioxanes (5 and 6) were parasiticidal; both inhibited parasite replication irreversibly after parasite exposure to 10 microM of drug for 24 h, whereas the standard trioxane drugs artemisinin and artemether were not parasiticidal. Some of the new derivatives of artemisinin described here represent effective anti-Toxoplasma trioxanes as well as molecular probes for elucidating the mechanism of action of the DART class of artemisinin derivatives.


APOBEC3 activity promotes the survival and evolution of drug-tolerant persister cells during acquired resistance to EGFR inhibitors in lung cancer.
APOBEC mutagenesis is one of the most common endogenous sources of mutations in human cancer and is a major source of genetic intratumor heterogeneity. High levels of APOBEC mutagenesis are associated with poor prognosis and aggressive disease across diverse cancers, but the mechanistic and functional impacts of APOBEC mutagenesis on tumor evolution and therapy resistance remain relatively unexplored. To address this, we investigated the contribution of APOBEC mutagenesis to acquired therapy resistance in a model of EGFR-mutant non-small cell lung cancer. We find that inhibition of EGFR in lung cancer cells leads to a rapid and pronounced induction of APOBEC3 expression and activity. Functionally, APOBEC expression promotes the survival of drug-tolerant persister cells (DTPs) following EGFR inhibition. Constitutive expression of APOBEC3B alters the evolutionary trajectory of acquired resistance to the EGFR inhibitor gefitinib, making it more likely that resistance arises through de novo acquisition of the T790M gatekeeper mutation and squamous transdifferentiation during the DTP state. APOBEC3B expression is associated with increased expression of the squamous cell transcription factor ΔNp63 and squamous cell transdifferentiation in gefitinib-resistant cells. Knockout of ΔNp63 in gefitinibresistant cells reduces the expression of the p63 target genes IL1a/b and sensitizes these cells to the thirdgeneration EGFR inhibitor osimertinib. These results suggest that APOBEC activity promotes acquired resistance by facilitating evolution and transdifferentiation in DTPs, and suggest that approaches to target ΔNp63 in gefitinib-resistant lung cancers may have therapeutic benefit.


Characterizing the Performance of Denitrifying Bioreactors during Simulated Subsurface Drainage Events.
The need to mitigate nitrate export from corn and soybean fields with subsurface (tile) drainage systems, a major environmental issue in the midwestern United States, has made the efficacy of field-edge, subsurface bioreactors an active subject of research. This study of three such bioreactors located on the University of Illinois South Farms during their first 6 mo of operation (July-Dec. 2012) focused on the interactions of seasonal temperature changes and hydraulic retention times (HRTs), which were subject to experimental manipulation. Changes in nitrate, phosphate, oxygen, and dissolved organic carbon were monitored in influent and effluent to assess the benefits and the potential harmful effects of bioreactors for nearby aquatic ecosystems. On average, bioreactors reduced nitrate loads by 63%, with minimum and maximum reductions of 20 and 98% at low and high HRTs, respectively. The removal rate per unit reactor volume averaged 11.6 g NO-N m d (range, 5-30 g NO-N m d). Multiple regression models with exponential dependencies on influent water temperature and on HRT explained 73% of the variance in NO-N load reduction and 43% of the variance in its removal rate. Although concentrations of dissolved reactive phosphorus and dissolved organic carbon in the bioreactor effluent increased relative to the influent by an order of magnitude during initial tests, within 1 mo of operation they stabilized at nearly equal values.


Cytotoxic polyketides from the deep-sea-derived fungus Engyodontium album DFFSCS021.
Eight new chromones, engyodontiumones A-H (1-8), and three new phenol derivatives (9-11) together with eight known polyketides (12-19) were isolated from the deep-sea-derived fungus Engyodontium album DFFSCS021. Their structures were identified by extensive spectroscopic analysis. Compounds 8 and 16 showed significant selective cytotoxicity against human histiocytic lymphoma U937 cell line with IC50 values of 4.9 and 8.8 μM, respectively. In addition, this is the first time to report that 8, 15 and 16 had mild antibacterial activity against Escherichia coli and Bacillus subtilis, and 15 showed potent antilarval activity against barnacle Balanus amphitrite larval settlement.


Regional blood flow during isoflurane and halothane anesthesia.
Cardiac output distribution and regional blood flow in 18 dogs during isoflurane and halothane anesthesia were studied in dose-related fashion. Surgical preparation consisted of left thoracotomy and placement of catheters in the left atrium and aorta through a femoral artery. Regional blood flow was studied one week after surgical preparation using a microsphere technique at the three stages: awake, 1 MAC, and 2 MAC of inhalation anesthesia. At each stage of the experiment, two sets of microspheres (15- and 9-micron diameter), labeled with different isotopes, were used simultaneously. Both anesthetics increased cerebral blood flow, decreased blood flow through preportal area, and preserved renal blood flow. Isoflurane increased hepatic artery blood flow at both levels of anesthesia, while halothane preserved the flow during 1 MAC and decreased it at 2 MAC. Apparently, isoflurane provided better oxygenation to the liver than halothane. Myocardial blood flow was increased during isoflurane (despite decrease in blood pressure and cardiac output) and decreased during halothane anesthesia. Isoflurane appears to be a coronary vasodilator with potential beneficial (improvement in myocardial blood supply) as well as hazardous ("steal effect") effects on the heart.


Attention control in middle childhood: relations to psychopathological symptoms and threat perception distortions.
The present study examined the construct of attention control, which is an important aspect of effortful control, in a sample of non-clinical children aged between 9 and 13 years. Results demonstrated that attention control was associated with a broad range of psychopathological complaints, including symptoms of anxiety, aggression, depression, and ADHD. As predicted, lower levels of attention control were accompanied by higher levels of these symptoms. Further, attention control was also negatively related to threat perception distortions, which indicates that children who display low levels of this regulative temperament factor are more prone to such cognitive biases. Third, when controlling for neuroticism, attention control remained significantly (negatively) associated with symptoms of anxiety, depression (child report only), and ADHD. The correlations between attention control and threat perception distortions largely disappeared when the influence of neuroticism was partialled out. Only the link between attention control and anxious interpretations of ambiguous vignettes survived this correction. Finally, no evidence was found for the hypothesised mediating role of cognitive distortions on the relation between temperament factors and psychopathological symptoms.


Poly(Lactic Acid)-Based Nanobiocomposites with Modulated Degradation Rates.
In the field of biodegradable polymers such as poly(Lactic Acid) (PLA), it is quite well known that their kinetics of hydrolysis strongly depend on the pH of the hydrolyzing medium. The idea explored during this study focused on PLA, is the addition of additives that are able to control the pH of water when it diffuses inside the polymer. For instance, acids (i.e. succinic acid, also used as food additive) are bio- and eco- friendly additives that are able to play this role. In order to control the release of these molecules and their dispersion inside the polymer, their intercalation in biocompatible nanofillers like layered double hydroxides (LDH) is here considered. The additives have been dispersed in the polymer by melt compounding, commonly used in the plastic industry. Several composites of PLA (4032D) and LDH intercalated with organic acids (succinic, fumaric, and ascorbic acid) have been obtained by an extrusion process. From all extruded materials, PLA films obtained by compression molding were then subjected to hydrolysis tests. The results showed that the mentioned molecules, dispersed in the polymer, are able to control the rate of hydrolysis, and experimental results show an increase of degradation time for samples containing LDH-organic acid (in particular with LDH-succinic acid), making such hybrid additives an appropriate and efficient solution for PLA.


Interplay of Fli-I and FLAP1 for regulation of beta-catenin dependent transcription.
Beta-catenin mediates Wnt/wingless signaling and transcriptional activation by lymphocyte enhancer binding factor 1/T cell factor (LEF1/TCF) proteins with the assistance of multiple coregulators, including positive cofactors like p300/CBP and negative cofactors like HDACs. We previously demonstrated that a developmentally essential protein, Flightless-I (Fli-I), serves as a coactivator for nuclear receptor-mediated transcription. To further understand the action mechanism of Fli-I, we investigated the functional roles of Fli-I and Fli-I leucine rich repeat associated protein 1 (FLAP1) in transcriptional activation by beta-catenin and LEF1/TCF. beta-catenin-dependent transcription was activated by exogenous FLAP1 but inhibited by Fli-I. Reduction of endogenous FLAP1 levels compromised transcriptional activation by LEF1/TCF, beta-catenin and the p160 coactivator GRIP1. FLAP1 interacted directly with beta-catenin, GRIP1 and p300 and enhanced their activity. Furthermore, FLAP1 was strongly synergistic with p300 in supporting transcriptional activation by beta-catenin and LEF1/TCF, but Fli-I disrupted the synergy of FLAP1 with p300 and beta-catenin. Thus the opposing effects of Fli-I and FLAP1 may be a key regulatory mechanism for beta-catenin and LEF1/TCF-mediated transcription and thus for Wnt signaling, and some mutations of Fli-I may result in developmental defects, such as the flightless phenotype of Drosophila, by causing dysregulation of the Wnt/beta-catenin pathway.


Primary Health Care Evaluation: the view of clients and professionals about the Family Health Strategy.
to evaluate the attributes of primary health care as for access; longitudinality; comprehensiveness; coordination; family counseling and community counseling in the Family Health Strategy, triangulating and comparing the views of stakeholders involved in the care process. evaluative research with a quantitative approach and cross-sectional design. Data collected using the Primary Care Assessment Tool for interviews with 527 adult clients, 34 health professionals, and 330 parents of children up to two years old, related to 33 family health teams, in eleven municipalities. Analysis conducted in the Statistical Package for Social Sciences software, with a confidence interval of 95% and error of 0.1. the three groups assessed the first contact access - accessibility with low scores. Professionals evaluated with a high score the other attributes. Clients assigned low score evaluations for the attributes: community counseling; family counseling; comprehensiveness - services rendered; comprehensiveness - available services. the quality of performance self-reported by the professionals of the Family Health Strategy is not perceived or valued by clients, and the actions and services may have been developed inappropriately or insufficiently to be apprehended by the experience of clients.


Improvements in diagnostic tools for early detection of psoriatic arthritis.
Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease characterized by a wide clinical spectrum. The early diagnosis of PsA is currently a challenging topic. Areas covered: The literature was extensively reviewed for studies addressing the topic area "diagnosis of psoriatic arthritis". This review will summarize improvements in diagnostic tools, especially referral to the rheumatologist, the role of patient history and clinical examination, laboratory tests, and imaging techniques in getting an early and correct diagnosis of PsA. Expert commentary: Due to the heterogeneity of its expression, PsA may be easily either overdiagnosed or underdiagnosed. A diagnosis of PsA should be taken into account every time a patient with psoriasis or a family history of psoriasis shows peripheral arthritis, especially if oligoarticular or involving the distal interphalangeal joints, enthesitis or dactylitis. Magnetic resonance imaging and ultrasonography are useful for diagnosing PsA early, particularly when isolated enthesitis or inflammatory spinal pain occur.


[Congenital dacryocystocele: presentation and treatment].
To report the presentation, complications, and treatment strategies for infants with congenital dacryocystocele. We performed a retrospective chart review of all patients presenting with dacryocystoceles to Beijing Children's Hospital between 2007 and 2011. Thirty-one patients (33 eyes) were identified, presenting at a median age of 10 days of life. Twenty-four (72.72%) patients presented with cellulitis or dacryocystitis and required systemic antibiotics. Two (6.45%) patients presented with respiratory compromise. Resolution occurred with conservative treatment for 6 eyes, but 27 (81.82%) required surgical intervention. All 27 eyes received probing, and 20 (74.07%) were successful. The other 7 eyes required marsupialization of an intranasal cyst. Although congenital dacryocystoceles may resolve with conservative measures, many become infected and require systemic antibiotic treatment, and most require surgical intervention. Referral in the early neonatal period can aid in timely intervention before complications such as infection occur.


The Influence of Blood Pressure on Fetal Aortic Distensibility: An Animal Validation Study.
Aortic distension waveforms describe the change in diameter or cross-sectional area over the cardiac cycle. We aimed to validate the association of aortic fractional area change (AFAC) with blood pressure (BP) in a fetal lamb model. Four pregnant ewes underwent open fetal surgery under general anesthesia at 107-120 gestational days. A 4-Fr catheter was introduced into the fetal femoral artery and vein, or the carotid artery and jugular vein. The thoracic aorta was imaged using real-time ultrasound; AFAC was calculated using offline speckle tracking software. Measurements of invasive BP and AFAC were obtained simultaneously and averaged over 10 cardiac cycles. BP was increased by norepinephrine infusion and the association of aortic distensibility with BP was assessed. Baseline measurements were obtained from 4 lambs, and changes in aortic distensibility with increasing BP were recorded from 3 of them. A positive correlation was found between AFAC and systolic BP (r = 0.692, p = 0.001), diastolic BP (r = 0.647, p = 0.004), mean BP (r = 0.692, p = 0.001), and BP amplitude (r = 0.558, p = 0.016) controlled for heart rate. No association was found between BP and maximum or minimum aortic area. AFAC provides a quantifiable measure of aortic distensibility and correlates with systolic BP, diastolic BP, mean BP, and BP amplitude in a fetal lamb model.


Studies on the effect of different inhibitors of arachidonic acid metabolism on glyceryltrinitrate-induced relaxation and cGMP elevation in bovine vascular tissue.
This study was performed in order to investigate the possible involvement of arachidonic acid metabolites in the mediation of glyceryltrinitrate (GTN)-induced relaxation in isolated bovine mesenteric artery (BMA) and vein (BMV) and in bovine coronary artery (BCA). Concentration-effect curves for GTN were established on the different types of vessels, precontracted with 2.5 microM phenylephrine (BMA) or K+-depolarization (BMV and BCA), in the presence or absence of different inhibitors of the arachidonic acid metabolism. The used inhibitors of arachidonic acid metabolism were: 10 microM quinacrine (a phospholipase A2 inhibitor), 100 microM acetylsalicylic acid, 20 microM indomethacin (cyclooxygenase inhibitors), 3 mM tranylcypromine (inhibitor of PGI2 synthesis), 50 microM nordihydroguairetic acid and 40 microM BW 755C (lipoxygenase inhibitors). In addition, SKF 525A (10 microM) was tested on BMA; this agent is considered to block the cytochrome P450-dependent monooxygenase pathway. The effect on the endogenous levels of cyclic nucleotides after treatment with some of the inhibitors were also measured. Quinacrine and acetylsalicylic acid had no statistical significant effect (P greater than 0.05) on the pD2-value for GTN-induced relaxation in BMA, BMV and BCA. The results obtained with indomethacin were very variable. This drug was almost completely without effect on the GTN induced relaxation in BCA. In BMA a significant potentiation of the relaxant response was obtained (P = 0.002), while in BMV a significant inhibition was seen (P = 0.049).(ABSTRACT TRUNCATED AT 250 WORDS)


Transcriptional pattern of 21-hydroxylase gene (P-450C21) during embryonic development, before, and after birth in mice as determined by in situ hybridization.
21-Hydroxylase is a member of the P-450 superfamily of genes involved in the biosynthesis of cortisol and aldosterone in the adrenal cortex. Congenital adrenal hyperplasia, a well-characterized disease, originates from a lack of this enzyme. We present in this report an in situ hybridization study aimed at detecting 21-hydroxylase activity during murine development, from mid gestation to adulthood. Our results demonstrate that even during the embryonic period the adrenal cortex is the only major site of transcription of this enzyme, which is detectable beginning at embryonic day 14. In addition, a peculiar topographical pattern of transcriptional activity, characteristic of the stage of differentiation of the gland, could be drawn. Using a computer-assisted method, we were able to quantitate the relative transcription level at each stage of development. A steady increase in the level of transcription was demonstrated throughout embryonic life to birth, with a drop during the prepubertal period and a final rise at adult age. The possible physiological significance of our findings is discussed.


Prothrombotic effects and clinical implications of third-generation oral contraceptives use.
Although the use of oral contraceptives has been frequently associated with an increased risk of thromboembolic events, definitive prothrombotic mechanisms have not so far been fully elucidated. The aim of our investigation was the evaluation of the activities of antithrombin, protein C, protein S and the resistance to activated protein C in 137 healthy users of third-generation oral contraceptives and in 170 healthy women who were not consuming oral contraceptives. Women on oral contraceptives showed a marked prothrombotic pattern, characterized by reduced activities of antithrombin and protein S, and increased resistance to activated protein C. Nearby 50% of oral contraceptive users displayed activities of protein S below the lower value of the reference range (controls, 10%; P < 0.001). No significant differences were observed between two progestagens (desogestrel or gestodene) on the coagulation parameters tested. We believe that, due to the adverse effect on haemostasis, the administration of third-generation oral contraceptives should be carefully considered in women carrying prothrombotic abnormalities.