Cytomorphological evaluation of non-haematopoietic malignancies metastasizing to the bone marrow.
Bone marrow (BM) is one of the rare but important site of metastasis of solid tumors. The key steps of metastasis include invasion, intravasation, circulation, extravasation, and colonization. Tumor cells may express some adhesion molecules that promote the transmigration to the marrow space and link them to the marrow stroma with subsequent engraftment. It is important to detect the bone marrow metastasis for initial clinical staging, therapeutic selection, prognostic risk stratification, assessment of response to therapy and predicting relapse. Prognosis of non-hematopoietic malignancies with BM metastasis is dismal. Due to occulting and atypical clinical manifestations, bone marrow metastases can be easily missed or misdiagnosed, leading to higher mortality rates. The important factors on which the prognosis of patients with bone marrow metastases depends are primary tumor site, performance status, platelet count, and therapeutic regimens (systemic chemotherapy or palliative/supportive care). Further, in cases with BM metastasis with unknown primary sites, misdiagnosis can lead to delayed initiation of therapy and increased mortality. BM metastasis is seen in less than 10% of patients with metastatic cancer and is common in lung, breast or prostate carcinoma. Bone marrow metastasis can be presented as the initial presentation with hematological changes and may be misdiagnosed as a primary haematopoietic disorder. Leucoerythoblastic blood picture is the most common peripheral blood smear finding indicating BM metastasis, may be an indicator of associated BM fibrosis. Bone marrow aspiration and biopsy with immunohistochemistry (IHC) is an easy, cost effective and gold standard method of detection of BM metastasis. BM biopsy is superior to bone marrow aspirate for detection of metastasis. Morphology of metastatic cells is as per the primary site of tumor. Immunohistochemistry is a useful adjunct to morphology in reaching a definitive diagnosis even in case with carcinoma unknown primary (CUP) and also in diagnosing case of unsuspected malignancies. Though bone marrow is not among the most common site of involvement in CUP, which are liver, bone, lymph nodes and lung. But BM, if involved, the site of origin is determined using the immunohistochemistry panel applied to the metastatic deposits based on the morphology The aim of the review is to discuss the hematological findings of non-haematopoietic malignancies metastasizing to the bone marrow, emphasizing on histomorphology with IHC and its significance in establishing primary diagnosis in clinically unsuspected cases.


Participant views on involvement in a trial of social recovery cognitive-behavioural therapy.
The PRODIGY trial (Prevention of long term social disability amongst young people with emerging psychological difficulties, ISRCTN47998710) is a pilot trial of social recovery cognitive-behavioural therapy (SRCBT). The PRODIGY qualitative substudy aimed to (a) explore individual experiences of participating in the pilot randomised, controlled trial (recruitment, randomisation, assessment) and initial views of therapy, and (b) to explore perceived benefits of taking part in research v. ethical concerns and potential risks. Qualitative investigation using semi-structured interviews with thematic analysis. Analysis revealed participant experiences around the key themes of acceptability, disclosure, practicalities, altruism and engagement. Participants in both trial arms perceived themselves as gaining benefits from being involved in the study, above and beyond the intervention. This has implications for the design of future research and services for this client group, highlighting the importance of being flexible and an individualised approach as key engagement tools.


The development of multiple reaction monitoring assays for liver-derived plasma proteins.
There is wide interpatient variability in toxicity to chemotherapeutic drugs and a lack of routine clinical tests for prospectively identifying patients at risk of developing toxicity from chemotherapy. An empirically driven MS strategy has been developed to monitor liver-derived plasma proteins as potential biomarkers of early toxicity. Multiple reaction monitoring (MRM) has been used to assess 46 candidate peptides from 18 liver-derived proteins. Following an iterative process of assay design, optimisation and assessment we selected 29 MRM assays (median CV 4.6%, range 1.2-11.6%) and monitored changes in levels of plasma proteins from a small number of colorectal cancer (CRC) patients undergoing chemotherapy. We demonstrated MRM assay robustness, and show that patients undergo minor elevation in plasma proteins when profiled on Day 3 of the chemotherapeutic regime. The MRM assays were in general agreement with 2-D DIGE-based quantitation from the same patient samples. The data supports the application of MRM-based methods as facile, highly reproducible, medium-throughput techniques that warrant expanded investigation for clinical utility in identifying patients at risk of developing chemotoxicity.


[Ultrastructure of the inner surface of the aorta of mature and old animals].
In the experiments, performed on 12 white rats and 8 rabbits, by means of scanning electron microscopy of the native preparations and in a number of cases with use of silver nitrate impregnation, the internal surface structure has been studied in the aortal membrane of mature and old animals. At ageing the integrity and continuity of the endothelial monolayer is preserved, on the surface local intimal pits, craters and microdefects appear, adhesiveness of endothelium to leucocytes increases. Orientation of the intimal folds is disturbed. The type of the senescent remodeling in the endothelial layer revealed predisposes to development of atherosclerosis.


Scale-invariant quantum anomalous Hall effect in magnetic topological insulators beyond the two-dimensional limit.
We investigate the quantum anomalous Hall effect (QAHE) and related chiral transport in the millimeter-size (Cr(0.12)Bi(0.26)Sb(0.62))₂Te₃ films. With high sample quality and robust magnetism at low temperatures, the quantized Hall conductance of e²/h is found to persist even when the film thickness is beyond the two-dimensional (2D) hybridization limit. Meanwhile, the Chern insulator-featured chiral edge conduction is manifested by the nonlocal transport measurements. In contrast to the 2D hybridized thin film, an additional weakly field-dependent longitudinal resistance is observed in the ten-quintuple-layer film, suggesting the influence of the film thickness on the dissipative edge channel in the QAHE regime. The extension of the QAHE into the three-dimensional thickness region addresses the universality of this quantum transport phenomenon and motivates the exploration of new QAHE phases with tunable Chern numbers. In addition, the observation of scale-invariant dissipationless chiral propagation on a macroscopic scale makes a major stride towards ideal low-power interconnect applications.


Ventricular fibrillation in a patient with tachycardia-induced cardiomyopathy after liver transplantation.
We report a case of atrial fibrillation-related tachycardia induced cardiomyopathy and ventricular fibrillation after liver transplantation in a 41-year-old man with end-stage liver failure. Atrial fibrillation and congestive heart failure occurred postoperatively. Cardiac arrests due to ventricular fibrillation occurred 6 months after the operation with subsequent implantations of an implantable cardioverter-defibrillator. Ventricular arrhythmias did not recur during the 18 months after normalization of heart functions with guideline-directed medical treatments.


Dysregulation of axogenesis in the antennal nervous system of the embryonic grasshopper Schistocerca gregaria.
The antennal nervous system of the grasshopper Schistocerca gregaria features two parallel axon tracts each established early in embryogenesis by discrete pairs of pioneer neurons located at the antennal tip and whose growth cones contact so-called base pioneers en route to the brain. Here we present two antennal phenotypes in which a stereotypic dysregulation of axogenesis in a given tract is observed when only the base pioneer associated with that pathway is missing, consistent with a role for this cell type in guided axogenesis. Dysregulation involves defasciculation and aberrant navigation by pioneer axons resulting in a missing or depleted primordial antennal nerve to the brain. The dysregulated phenotypes reveal that axogenesis in each pathway is regulated independently. Previously unseen discrepancies in the navigational decisions made by pioneer neurons which derive sequentially from the same mother cell demonstrate that these progeny have separate identities. Possible mechanisms for the dysregulated phenotypes are considered.


Patient and Caregiver Adjustment to Hematopoietic Stem Cell Transplantation: a Systematic Review of Dyad-Based Studies.
The aims of this study were to identify and systematically evaluate studies published from 2005-2017 that took a dyadic approach to assessing or intervening upon hematopoietic cell transplant (HCT) recipients and their informal caregivers. Our search yielded 20 studies. Regarding sample demographic characteristics, most participants were Caucasian and most caregivers were related to the patient by marriage. Regarding design characteristics, 18 studies were quantitative and two were qualitative; five were cross-sectional, ten were longitudinal, one was experimental, and four were interventional. Most outcomes were psychosocial and the interventions were largely psycho-educational in nature. Large variation in quality of the studies emerged (six were rated as low quality, seven as adequate, and seven as high quality). Understudied populations include racial/ethnic minorities and same-sex couples. More work is needed to understand functioning during survivorship and impacts on patient medical outcomes, and to truly leverage the dyad to optimize individual- and relationship-level adjustment.


Hypercoagulation and fibrinolysis in oral sub-mucous fibrosis.
In seven out of seven patients suffering from oral submucous fibrosis (OSMF), we detected circulating molecules that are immunologically similar to fibrinogen (MISFI), as suggested by the hemagglutination inhibition studies using the FDP Kit (Wellcome) and by paracoagulation tests such as serial dilution protamine tests. The ethanol gelation test was positive in three of the seven patients. Cryofibrinogen developed in six of the seven patients within three to six days of incubation of plasma samples at 4 degrees C. Plasma kept at 37 degrees C did not develop any fibrous or amorphous precipitate. In OSMF, fibrinogen, fibrinogen intermediates, and fibrin degradation products deserve further scrutiny, as this may help define the etiology of OSMF which is, so far, obscure.


Ultrastructure and molecular composition of the central filament body in hydrozoan cnidocils.
The cnidocils of hydrozoan nematocytes contain modified microtubular axonemes and a cross-striated central filament body. Filament body and axonemal microtubules are interconnected by cross-bridges or are directly attached to one another. Structure and molecular composition of the central filament body was analyzed by means of electron microscopy and immunological techniques. The spindle-like, cross-striated filament body is composed of less than 4 nm thick subfibers. Each unit of its periodical striation pattern is approximately 19 nm broad and comprises subzones with different electron densities. Pure filament bodies are obtainable by a lysis of isolated cnidocils in detergent- and EDTA-containing buffers. The filament body is soluble in 5 mM dithioerythritol (DTE) or 1 M urea. Its structure is stabilized by high concentrations of Na+ or K+ (0.5 M both). Intermediate states of assembly can be induced by 1 mM DTE in lysis buffer which causes the filament bodies to spread into subfibers. CFB43, a monoclonal antibody against filament body protein reacts with a 33 kDa protein in Hydra. Like a polyclonal antibody against SF-assemblin, the protein forming cross-striated system I fibers in unicellular green algae, the antibody cross-reacts with a 36 kDa protein obtained from the unicellular organism Tetrahymena. In immunogold labeling experiments, CFB43 binds to the central filament body in Hydra and recognizes an epitope on the striated rootlets associated with the basal bodies of Tetrahymena. Our results indicate that the central filament body of hydrozoan cnidocils is composed of a protein with properties similar to those of SF-assemblin. In combination with microtubules, the filament body seems to participate in the formation of a stiff mechanical backbone within the cnidocils.


Genetic characterization and functional analysis of the GID1 gibberellin receptors in Arabidopsis.
We investigated the physiological function of three Arabidopsis thaliana homologs of the gibberellin (GA) receptor GIBBERELLIN-INSENSITIVE DWARF1 (GID1) by determining the developmental consequences of GID1 inactivation in insertion mutants. Although single mutants developed normally, gid1a gid1c and gid1a gid1b displayed reduced stem height and lower male fertility, respectively, indicating some functional specificity. The triple mutant displayed a dwarf phenotype more severe than that of the extreme GA-deficient mutant ga1-3. Flower formation occurred in long days but was delayed, with severe defects in floral organ development. The triple mutant did not respond to applied GA. All three GID1 homologs were expressed in most tissues throughout development but differed in expression level. GA treatment reduced transcript abundance for all three GID1 genes, suggesting feedback regulation. The DELLA protein REPRESSOR OF ga1-3 (RGA) accumulated in the triple mutant, whose phenotype could be partially rescued by loss of RGA function. Yeast two-hybrid and in vitro pull-down assays confirmed that GA enhances the interaction between GID1 and DELLA proteins. In addition, the N-terminal sequence containing the DELLA domain is necessary for GID1 binding. Furthermore, yeast three-hybrid assays showed that the GA-GID1 complex promotes the interaction between RGA and the F-box protein SLY1, a component of the SCF(SLY1) E3 ubiquitin ligase that targets the DELLA protein for degradation.


Pinealectomy does not affect the healing of experimental colonic anastomoses.
Gastrointestinal system anastomoses, especially colonic anastomoses, have significant morbidity and mortality despite recent technical improvements. Besides regulating the circadian rhythm, the pineal gland and its main neurohormone product melatonin have widespread actions in the organism. The purpose of this study was to investigate the effects of pinealectomy on the healing of colonic anastomoses. One hundred male albino Wistar rats were used in this study. The rats were separated into three groups: control, pinealectomy, and sham groups. In the control group, only colonic resection and anastomoses were performed. Following pinealectomy, colonic anastomosis was performed 2 weeks later on one half and 2 months later on the other half of the pinealectomy group. Only craniotomy was performed on the sham group, and the rats were separated and evaluated like the pinealectomy group. Colonic anastomoses were evaluated on postanastomotic day 3 and 7 by measuring the bursting pressure and the hydroxyproline levels in the anastomotic segments. There was no difference in the bursting pressure measurements between the groups on both postoperative day 3 and 7. Although hydroxyproline levels were different between groups on both postanastomotic days 3 and 7, it has been observed that neither normal nor anastomotic hydroxyproline levels influenced the anastomotic bursting pressure measurements. The percent deviation from the normal values was compared in the anastomotic segments, and no differences were found regarding the bursting pressure and hydroxyproline levels. It was concluded that pinealectomy has no effect on the healing of colonic anastomoses.


Overview of iron metabolism in health and disease.
Iron is an essential element for numerous fundamental biologic processes, but excess iron is toxic. Abnormalities in systemic iron balance are common in patients with chronic kidney disease and iron administration is a mainstay of anemia management in many patients. This review provides an overview of the essential role of iron in biology, the regulation of systemic and cellular iron homeostasis, how imbalances in iron homeostasis contribute to disease, and the implications for chronic kidney disease patients.


Alpha erythropoietin in the management of anaemia of prematurity: a report of three cases in Nigeria.
Anaemia of prematurity is a common problem encountered in most special care baby units warranting often repeated blood transfusions with its inherent dangers. We present three patients in Nigeria who were very low birth weight premature babies on whom recombinant erythropoietin was used as an efficient replacement for blood transfusions. All three patients showed a progressive drop in haemoglobin concentration from the first to the sixth to eight week of life with development of heamic murmurs and insignificant reticulocyte responses, and were planned for transfusion therapy. The parents of all the patients strongly refused transfusion therapy (one on religious grounds) warranting the use of recombinant erythropoietin to which there was a significant response in all three patients with elevation of haemoglobin concentration, PCV, and reticulocyte counts, and obviating the planned transfusions. No significant side effects were also noticed. We suggest further controlled trials to establish this mode of therapy.


Police response time to road crashes in south-east of Iran.
To investigate post-crash time management by police. The retrospective study comprised data related to all road traffic crashes from March 2009 to March 2010 in Sistan and Baluchistan province of Iran. Data was retrieved from the standard national form designed for road traffic crashes completed by police officers present at the scene. SPSS 15 was used for statistical analysis. The median time for police to be informed in the total 2442 accidents was 10 minutes and the police response time was 15-20 minutes for non-fatal cases, while the corresponding duration for fatal cases was 15 minutes and 30 minutes (p < 0.001). Police arrival was not dependent on road condition (p=0.178). Police arrival at the crash scene was beyond the average response time by Emergency Medical Services in Iran. It is vital to provide quicker ways of informing the police and to have more police stations along the highways.


Choroidal infarction in a glaucoma patient with Flammer syndrome: a case report with a long term follow-up.
We present a long term follow-up of a young female patient with choroidal infarction, primary open angle glaucoma and Flammer syndrome. The patient had no classical risk factors for vascular occlusions, except for the presence of Flammer syndrome. The essential feature of this syndrome is primary vascular dysregulation, sometimes including vasospasm. The vessels of affected people respond more intensely to a number of stimuli, such as coldness or emotional stress. Any organ can be involved, including parts of the eye. The dense autonomic innervation of the choroidal vessels predisposes them particularly to vasospasms. The patient was originally referred to our centre because of a deep unilateral paracentral scotoma with the presumptive diagnosis of a normal tension glaucoma. The discrepancy between the visual field defect and the optic nerve head morphology, however, led us to a vascular evaluation by a simultaneous fluorescein/indocyanine green angiography. This revealed an antecedent choroidal infarction that explained the visual field scotoma and the retinal nerve fibre layer defect in the corresponding area. During the follow-up period of 11 years, the patient also developed bilateral glaucomatous optic neuropathy despite a well-controlled intraocular pressure. We hypothesise that in the patient presented here, the Flammer syndrome contributed to both the acute unilateral choroidal infarction and to the chronic development of bilateral glaucomatous optic neuropathy.


Qualitative and quantitative analysis of amino acids by capillary electrophoresis-electrospray ionization-tandem mass spectrometry.
We describe a method to identify and quantify amino acids using capillary electrophoresis-electrospray ionization-triple-quadrupole tandem mass spectrometry (CE-ESI-MS/MS). Amino acids, including physiological amino acids, were first separated by CE under acidic pH conditions and then detected by MS/MS. To efficiently introduce the whole sample into the capillary, no electrical potential was applied to the electrospray probe until running electrophoresis. The position of the electrosprayer with respect to the MS capillary entrance drastically affected sensitivity and generation of cluster ions. MS/MS with multiple reaction monitoring (MRM) detection was performed to obtain sufficient selectivity and sensitivity. Under optimized CE-MS/MS conditions, the minimum detectable levels for 32 free amino acids normally found in proteins and other physiological amino acids were between 0.1 and 14 micromol/L with pressure injection of 50 mbar for 3 s (3 nL) at a signal-to-noise ratio of 3. For most amino acids, this constitutes a severalfold increase in sensitivity compared to CE-MS. The relative standard deviations (% RSD) for all amino acids were better than 0.4% for migration times and between 1.4% and 8.6% for peak areas (n = 10). Since amino acids exhibited characteristic MS/MS spectra, this approach is useful for the simultaneous, selective, quantitative, and reproducible analysis of amino acids in physiological and biological samples that contain various kinds of matrices. The power of the method was demonstrated by analyzing amino acids in human urine.


Blistering disease: insight from the hemidesmosome and other components of the dermal-epidermal junction.
The hemidesmosome is a specialized transmembrane complex that mediates the binding of epithelial cells to the underlying basement membrane. In the skin, this multiprotein structure can be regarded as the chief adhesion unit at the site of the dermal-epidermal junction. Focal adhesions are additional specialized attachment structures located between hemidesmosomes. The integrity of the skin relies on well-assembled and functional hemidesmosomes and focal adhesions (also known as integrin adhesomes). However, if these adhesion structures are impaired, e.g., as a result of circulating autoantibodies or inherited genetic mutations, the mechanical strength of the skin is compromised, leading to blistering and/or tissue inflammation. A particular clinical presentation emerges subject to the molecule that is targeted. None of these junctional complexes are simply compounds of adhesion molecules; they also play a significant role in signalling pathways involved in the differentiation and migration of epithelial cells such as during wound healing and in tumour invasion. We summarize current knowledge about hereditary and acquired blistering diseases emerging from pathologies of the hemidesmosome and its neighbouring proteins as components of the dermal-epidermal junction.


High-frequency pulsed electron-electron double resonance spectroscopy on DNA duplexes using trityl tags and shaped microwave pulses.
Accurate distances between two trityl paramagnetic tags site-specifically attached to DNA duplexes were measured by pulsed electron-electron double resonance spectroscopy at 180 and 260 GHz microwave frequencies. Up to a threefold increase in the sensitivity of 260 GHz PELDOR measurements was achieved by using shaped broad-band microwave pulses.


Learning in dental education.
Learning in dental education has long been a subject of academic research. There are different types of student learning which directly or indirectly contribute to the learning outcomes. In this paper, the various classifications of different types of learning; superficial, deep, individual, collaborative and resource-based learning are explored. In order to achieve the learning objectives, different teaching methods such as group-work, rôle-play and problem-based learning are employed. The types of resources used in present day teaching are diverse and multiple: such as print-based, computer-based technologies and audio-visual technologies. In order to assess the effectiveness of such teaching, different methods of assessment have been adopted for use in higher education. In the context of good teaching in higher education, there are a number of constraints placed upon the individual and the institution. These constraints are discussed and recommendations made whereby they may be overcome.


Mitochondrial superoxide production and MnSOD activity after exposure to agonist and antagonists of ionotropic glutamate receptors in hippocampus.
Competitive glutamate receptor antagonists APV and CNQX were injected with kainate unilaterally into CA3 region of the rat hippocampus. They both expressed sufficient neuroprotection in the sense of decreasing superoxide production and increasing MnSOD levels, but with differential effect in mechanisms and time dynamics. Our findings suggest that NMDA and AMPA/kainate receptors are differentially involved in superoxide production, and they also impose different neuroprotective effects on the induction of MnSOD activity in hippocampus.


Patient and Provider Perspectives on Communication About Body Image With Adolescents and Young Adults With Cystic Fibrosis.
This mixed-methods study examined perspectives of adolescents and young adults (AYAs) with cystic fibrosis (CF) and health care providers on body image communication. Interviews and questionnaires were completed by 20 AYAs and 28 providers. Although 85% of patients reported they had never had a body image conversation with a health care provider, 74% of providers reported discussing this topic with patients. Patients and providers described body image as an important issue, which should be discussed comfortably and supportively. However, patients often preferred to discuss body image as a distinct topic, separate from physical health, whereas providers preferred integrating body image conversations within weight- and health-based discussions. Body image is an important topic for AYAs with CF that often goes unaddressed or addressed in ways that are less preferred by patients. Providers should reduce barriers to effective communication about this important topic, particularly through increased awareness of AYA preferences.


Differential regulation of mouse and human Mu opioid receptor gene depends on the single stranded DNA structure of its promoter and α-complex protein 1.
The Mu opioid receptor (MOR) mediates various functions of opioid-induced analgesia, euphoria and respiratory depression, and is a major target of opioid analgesics. Understanding of MOR gene expression among species is important for understanding its analgesic function in humans. In the current study, the polypyrimidine/polypurine (PPy/u) region, a key element of MOR gene expression, was compared in humans and mice. The mouse PPy/u element is highly homologous to its human element (84%), and the mouse MOR (mMOR) reporter drives luciferase activity 35-fold more effectively than the human MOR (hMOR) reporter. The structural study of reporter plasmids using S1 nuclease indicates that the mouse PPy/u element has a particular conformational structure, namely a single-stranded DNA (ssDNA) region that promotes strong promoter activity. DNA electrophoretic mobility shift assays demonstrated that the recombinant α-complex protein 1 (α-CP1) is capable of binding to a single-stranded mouse PPy/u sequence. Furthermore, plasmid-expressing α-CP1 activated the expression of a luciferase reporter when cotransfected with a single-stranded (p336/306) construct. In addition, the α-CP1 gene induced the mMOR gene in mouse neuronal cells and did not induce the human neuronal MOR gene. The current study demonstrates that α-CP1 functions as a transcriptional activator in the mMOR gene, but does not function in the hMOR gene due to species-specific structural differences. The differences in human and mouse MOR gene expression are based on α-CP1 and the ssDNA structure of the MOR promoter. The MOR gene is species-specifically regulated, as the PPy/u element adopts a unique species-specific conformation and α-CP1 recruitment.


Dipole-LUMO/dipolarophile-HOMO controlled asymmetric cycloadditions of carbonyl ylides catalyzed by chiral Lewis acids.
We have found the first successful example of reverse-electron-demand dipole-LUMO/dipolarophile-HOMO controlled cycloaddition reactions between carbonyl ylides, which were generated from o-methoxycarbonyl-alpha-diazoacetophenone and their acyl derivatives as precursors, and vinyl ether derivatives with high levels of asymmetric induction (97-77% ee) using chiral 2,6-(oxazolinyl)pyridine-Eu(III) or binaphthyldiimine-Ni(II) complexes as chiral Lewis acid catalysts.


Application of pyramided traits against Lepidoptera in insect resistance management for Bt crops.
Since initial launch of insect protected transgenic crops, the most effective strategy to manage the potential for target pests to evolve resistance has been the use of a single mode of action with "high dose" and structured refuge. However, the effectiveness of this strategy is limited if mortality of certain pests does not reach "high dose" criteria, inconsistent implementation of refuges and non-rare resistance alleles. More recently, several pyramided trait products, which include multiple modes of action against key target pests, have been developed. These products offer the potential for dramatically improved resistance management with smaller refuges and less dependence on high mortality of susceptible and heterozygous insects and rare resistance alleles. We show that products such as SmartStax and PowerCore offer compelling resistance management benefits compared with single mode of action products and allow for the option of products containing refuge seed mixtures rather than structured refuges to effectively delay resistance. We conclude that all stakeholders, including technology developers, growers, crop advisors, extensions services and regulatory authorities should continue to encourage the development, deployment and adoption of pyramided trait products for improved pest management and improved resistance management.


Role of palliative resection of the primary tumour in advanced pancreatic and small intestinal neuroendocrine tumours: A systematic review and meta-analysis.
This study aimed to evaluate the impact on overall survival following palliative surgery to remove the primary lesion in unresectable metastatic small intestinal (SI-NET) and pancreatic neuroendocrine tumours (P-NET). A systematic review of the literature and meta-analysis was performed. MEDLINE and Embase databases were searched to identify articles comparing patients undergoing palliative primary tumour resection without metastatectomy vs. no resection. Relevant articles were identified in accordance with PRISMA guidelines. The primary outcome was overall survival. Included studies were evaluated for heterogeneity and publication bias. 13 studies met the inclusion criteria, of which 6 presented data suitable for meta-analysis. No randomised controlled trials were identified. Analysis of pooled multivariate hazard ratios demonstrated significantly longer overall survival in patients undergoing resection of both P-NETs (HR 0.43; 95% CI: 0.34-0.57, p < 0.001) and SI-NETs (HR 0.47; 95% CI: 0.35-0.55, p = 0.007). The increase in median survival in patients treated surgically relative to non-surgically ranged from 14 to 46 months in P-NET, and 22-112 months in SI-NET. The number needed to treat in order that one additional patient was alive at five years, ranged from 3.0 to 4.2, and 1.7 to 7.7 respectively. Meta-analysis demonstrates that palliative resection of primary SI-NETs and P-NETs in the setting of unresectable metastatic disease can increase survival. Although these results should be interpreted with caution due to potential selection and publication bias, the data supports consideration of surgery, particularly in patients with low tumour burdens and good functional status.


Nanoplatelet interactions in the presence of multivalent ions: The effect of overcharging and stability.
The stability of colloidal dispersions in the presence of multivalent ions depends strongly on the electrostatic interactions between the suspended particles. Of particular interest are colloidal particles having dimensions in the nanometric range and with an anisotropic shape due to its high surface area per unit mass, for example clay, which has the key characteristic of a negatively charged surface, surrounded by an oppositely charged rim. In this study, we investigate the interactions in nanoplatelet dispersions for the model system of Laponite® clay with addition of mono- and multivalent salt. Molecular dynamics simulations with enhanced umbrella sampling have been utilised in combination with the experimental techniques of zeta-potential measurements, dynamic light scattering, and transmission electron microscopy. It was observed that tactoid formation and tactoidal dissolution due to overcharging occur upon the addition of trivalent salt. The overcharging effect was captured from calculated potential of mean force and confirmed from the zeta-potential, which changed sign from negative to positive when increasing the stoichiometric charge-ratio between the positive salt ions and the clay. Consequently, the gained information could provide useful physical insight of nanoplatelet interactions in the presence of multivalent ions.


The Effects of an Integrated Community Case Management Strategy on the Appropriate Treatment of Children and Child Mortality in Kono District, Sierra Leone: A Program Evaluation.
Integrated community case management (iCCM) aims to reduce child mortality in areas with poor access to health care. iCCM was implemented in 2009 in Kono district, Sierra Leone, a postconflict area with high under-five mortality rates (U5MRs). We evaluated iCCM's impact and effects on child health using cluster surveys in 2010 (midterm) and 2013 (endline) to compare indicators on child mortality, coverage of appropriate treatment, timely access to care, quality of care, and recognition of community health workers (CHWs). The sample size was powered to detect a 28% decline in U5MR. Clusters were selected proportional to population size. All households were sampled to measure mortality and systematic random sampling was used to measure coverage in a subset of households. We used program data to evaluate utilization and access; 5,257 (2010) and 3,649 (2013) households were surveyed. U5MR did not change significantly (4.54 [95% confidence interval [CI]: 3.47-5.60] to 3.95 [95% CI: 3.06-4.83] deaths per 1,000 per month (P = 0.4)) though a relative change smaller than 28% could not be detected. CHWs were the first source of care for 52% (2010) and 50.9% (2013) of children. Coverage of appropriate treatment of fever by CHWs or peripheral health units increased from 45.5% [95% CI: 39.2-52.0] to 58.2% [95% CI: 50.5-65.5] (P = 0.01); changes for diarrhea and pneumonia were not significant. The continued reliance on the CHW as the first source of care and improved coverage for the appropriate treatment of fever support iCCM's role in Kono district.


The anterior ectosylvian sulcal auditory field in the cat: II. A horseradish peroxidase study of its thalamic and cortical connections.
The thalamic and cortical projections to acoustically responsive regions of the anterior ectosylvian sulcus were determined by identifying retrogradely labelled cells after physiologically guided iontophoretic injections of horseradish peroxidase. The medial division of the medial geniculate nucleus, the intermediate division of the posterior nuclear group, the principal division of the ventromedial nucleus, and the lateroposterior complex were consistently labelled after these injections, although each animal showed slightly different patterns of labelling. The suprageniculate nucleus and the lateral and medial divisions of the posterior nuclear group were also labelled in most experiments. The cortex of the suprasylvian sulcus was the most consistently and densely labelled cortical region; each experiment showed a slightly different pattern of labelling throughout the suprasylvian sulcus, with an overall tendency for greater labelling in the ventral (lateral) bank of the middle region of the sulcus. Other cortical regions labelled less consistently included the anterior ectosylvian sulcus itself, the insular cortex of the anterior sylvian gyrus, and the posterior rhinal sulcus. In three experiments the contralateral cortex was examined and a small number of labelled cells was located in the anterior ectosylvian and suprasylvian sulci. Input from extralemniscal auditory thalamus is compatible with previously described auditory response properties of anterior ectosylvian sulcus neurons. The results also confirm the presence of input from visual and multimodal regions of thalamus and cortex, and therefore support claims of overlap of modalities within the sulcus. This overlap, as well as input from motor regions, suggests that the anterior ectosylvian sulcal field serves a sensorimotor role.


X-ray absorption near edge structure and first-principles spectral investigations of cationic disorder in MgAl2O4 induced by swift heavy ions.
Cationic disorder in the MgAl2O4 spinel induced by swift heavy ions was investigated using the X-ray absorption near edge structure. With changes in the irradiation fluences of 200 MeV Xe ions, the Mg K-edge and Al K-edge spectra were synchronously changed. The calculated spectra based on density function theory indicate that the change in the experimental spectra was due to cationic disorder between Mg in tetrahedral sites and Al in octahedral sites. These results suggest a high inversion degree to an extent that the completely random configuration is achieved in MgAl2O4 induced by the high density electronic excitation under swift heavy ion irradiation.


Stressed Liver and Muscle Call on Adipocytes with FGF21.
Fibroblast growth factor 21 (FGF21) is an emerging regulator of local and systemic metabolic homeostasis. Treatment with pharmacological levels of FGF21 alleviates obesity and associated metabolic diseases including diabetes. However, beyond anti-obesogenic effects, the normal roles and underlying mechanisms of FGF21 as an endocrine hormone remain unclear. A recent wave of studies has revealed that FGF21 is a stress-induced endocrine factor in liver, muscle, and other tissues that targets adipose tissue and adipocytes through the FGFR1-betaKlotho complex. Adipose tissues and adipocytes within diverse tissues respond with metabolites and adipokine signals that affect functions of body tissues systemically and cells within the local microenvironment adjacent to adipocytes. Normally this is to prevent impaired tissue-specific function and damage to diverse tissues secreting FGF21 in response to chronic stress. Therefore, diverse stressed tissues and the adipose tissue and adipocytes constitute a beneficial endocrine and paracrine communication network through FGF21. Here we attempt to unify these developments with beneficial pharmacological effects of FGF21 on obesity in respect to inter-organ stress communication and mechanisms.


Strong hierarchically porous monoliths by pulsed current processing of zeolite powder assemblies.
Binderless hierarchically porous monoliths have been produced from silicalite-1 and ZSM-5 zeolite powders by a rapid and facile powder processing method where the zeolite powders are assembled in a graphite die and subjected simultaneously to a compressive pressure and a pulsed current. Pulsed current processing (PCP) or, as it is commonly called, spark plasma sintering, enables rapid thermal processing of zeolite powder assemblies with heating and cooling rates at 100 degrees C/minute or more, which results in the formation of strong powder bodies without any addition of secondary binders. Nitrogen adsorption measurements show that it is possible to form strong zeolite monoliths by PCP that maintain between 85 and 95% of the surface area of the as-received silicalite-1 and ZSM-5 powders. Line-broadening analysis of X-ray powder diffraction data by the Rietveld method and high-resolution electron microscopy showed that the formation of strong interparticle bonds is associated with a local amorphization reaction at the interfacial contact points between the zeolite particles. The PCP-treated binderless ZSM-5 monoliths display a high selectivity in xylene isomer separation.


Myasthenia gravis: the specificities of skeletal muscle and thymus antibodies.
Antibodies against skeletal muscle antigens and against thymic myoid cells were examined in sera from 40 patients with myasthenia gravis (MG). Using an indirect immunofluorescence technique, antibodies against the surface of muscle cells were found in 23 sera, and antibodies against muscle cell cross-striations in 28 sera. Antibodies against thymic myoid cells were found in 27 sera, stained cells also occurring in fetal thymus from 14 weeks of gestation and in hyperplastic thymus from MG patients. Sera which stained myoid cells also stained muscle cell cross-striations. Sera from all the 20 patients with thymoma contained antibodies to a citric acid extract of skeletal muscle (CAE) as detected by indirect haemagglutination, whereas sera from 20 comparable patients without thymoma did not contain CAE antibodies. The myoid cell antibodies could be absorbed by homogenized muscle, but not by CAE-coated sheep erythrocytes. Different antibody patterns are seen among different MG patients; close associations were found between cross-striational and myoid cell antibodies, and between CAE-antibodies and a thymoma.


Evaluation of oxidative stress in seminal plasma of adolescents with varicocele.
Varicocele, defined by a dilation of efferent testicular veins, is the most commonly identifiable, surgically correctable lesion associated with male-factor infertility, starts at puberty and causes a progressive decline in fertility potential. The pathophysiology of infertility caused by this disease is still poorly understood, but it is suggested that the main mechanism is oxidative stress. Therefore, the aim of this study was to verify if the varicocele is associated with changes in enzymatic antioxidant mechanisms and seminal plasma lipid peroxidation levels in adolescents. We recruited 90 adolescents that were divided into control (C; n = 27); varicocele and normal semen (VNS; n =46); varicocele and altered semen (VAS; n =17). Seminal and serum levels of lipid peroxidation were quantified by thiobarbituric acid reactive substances (TBARS). Seminal plasma antioxidant profile was evaluated by the activities of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). The VAS group had increased lipid peroxidation levels when compared to the other groups. The levels of serum lipid peroxidation and activities of the enzymes SOD and GPx did not differ between groups. CAT was undetectable by the method used. In conclusion, in adolescents with varicocele and altered semen analysis, there is an increase in seminal lipid peroxidation levels compared to adolescents with varicocele and without seminal change and adolescents without evident varicocele. However, the observed oxidative stress is not caused by a decrease in superoxide dismutase and glutathione peroxidase activities, which did not differ between adolescents with and without evident varicocele. Varicocele, defined by a dilation of efferent testicular veins, is the most commonly identifiable, surgically correctable lesion associated with male-factor infertility, starts at puberty and causes a progressive decline in fertile potential. There is still much that is not understood regarding how exactly it affects semen quality, but most studies agree that oxidative stress, which is defined as excessive amounts of free radicals in relation to antioxidant defense, is an important mechanism. In this study, we aimed to verify if the varicocele is associated with changes in antioxidant defense and semen oxidation in 90 adolescents with and without varicocele. In adolescents with varicocele and abnormal semen, there is an increase in semen oxidation compared to controls or to the group with varicocele and normal semen quality. Our results can help to understand how varicocele leads to infertility in adolescents, identifying changes in oxidative activity in semen, since the onset of varicocele and before damage to sperm production can be detected.


[Civil and criminal responsibility of epileptics].
Since the new Penal Code has come into force, certain sections have been altered, such as those dealing with exculpatory circumstances, and as specialists treating patients with possible mental changes, we should be aware that section 20 now takes the place of the former section 8. The situation of the epileptic with regard to civil and criminal responsibility, has hardly changed. This is not surprising in view of current clinico-therapeutic knowledge. Epileptic patients are legally able to testify, inherit etc. and also have the obligation to compensate for damage they have caused. An attempt is made to define the immunity from prosecution of epileptics in accordance with non-static criteria, and to use a mixed biological-mental formula, which would make it possible to discover whether there was an alteration or anomaly of mental state at the time of the criminal offence, which would mean that the patient was unable to understand the unlawfulness of his action, or to act in accordance with such understanding. The deed itself is considered, without labelling illnesses or persons, seeking a simple definition of immunity from prosecution. The epileptic is immune from prosecution during a full attack, whilst during the rest of the time each case has to be decided individually. We emphasize the necessity of 'declassifying' epilepsy as a typical endogenous psychosis, which puts these patients into the group of the insane, although this term is no longer included in the new legal code.


Stem cells as therapy for hearing loss.
One of the greatest challenges in the treatment of inner-ear disorders is to find a cure for the hearing loss that is caused by the loss of cochlear hair cells or spiral ganglion neurons. The recent discovery of stem cells in the adult inner ear that are capable of differentiating into hair cells, as well as the finding that embryonic stem cells can be converted into hair cells, raise hope for the future development of stem-cell-based treatment regimens. Here, we propose different approaches for using stem cells to regenerate the damaged inner ear and we describe the potential obstacles that translational approaches must overcome for the development of stem-cell-based cell-replacement therapies for the damaged inner ear.


An ultrastructural study of the renal medulla in experimental acute pyelonephritis.
Experimental acute pyelonephritis was produced in rats by a combination of intravenous administration of Escherichia coli, strain IMRU-54, and temporary unilateral mechanical ureteral obstruction. Structural alterations of the renal medulla were studied by light and electron microscopy. Major cellular alterations occurred in the vasa recta. Tubular and interstitial cells demonstrated minimal alterations after the brief period of acute inflammation. Polymorphonuclear leukocytes within tubular lumina contained structures resembling E. coli in nonprotoplasts-like form. Numerous protoplast-like organisms, to the exclusion of any other structural forms, were detected within the interstitium of the inner medulla. Nonprotoplast-like structures resembling E. coli were rarely observed in interstitium of the inner medulla. Following relief of ureteral obstruction, clearance of acute inflammation was rapid. In conclusion, hemoatogenous acute pyelonephritis induced by E. coli, IMRU-54, is able to inflict cytological and ultrastructural damage to structural elements of the inner and outer medulla of rats. Vasa recta incurred prominent alterations in endothelia and basement membranes, whereas tubular epithelia and interstitial cells had relatively good structural preservation. The data suggest that intravenously administered E. coli is capable to revert to a protoplast-like structure in the inner medulla.


Systematic Review of Intrapartum Fetal Heart Rate Spectral Analysis and an Application in the Detection of Fetal Acidemia.
It is fundamental to diagnose fetal acidemia as early as possible, allowing adequate obstetrical interventions to prevent brain damage or perinatal death. The visual analysis of cardiotocography traces has been complemented by computerized methods in order to overcome some of its limitations in the screening of fetal hypoxia/acidemia. Spectral analysis has been proposed by several studies exploring fetal heart rate recordings while referring to a great variety of frequency bands for integrating the power spectrum. In this paper, the main goal was to systematically review the spectral bands reported in intrapartum fetal heart rate studies and to evaluate their performance in detecting fetal acidemia/hypoxia. A total of 176 articles were reviewed, from MEDLINE, and 26 were included for the extraction of frequency bands and other relevant methodological information. An open-access fetal heart rate database was used, with recordings of the last half an hour of labor of 246 fetuses. Four different umbilical artery pH cutoffs were considered for fetuses' classification into acidemic or non-acidemic: 7.05, 7.10, 7.15, and 7.20. The area under the receiver operating characteristic curve (AUROC) was used to quantify the frequency bands' ability to distinguish acidemic fetuses. Bands referring to low frequencies, mainly associated with neural sympathetic activity, were the best at detecting acidemic fetuses, with the more severe definition (pH ≤ 7.05) attaining the highest values for the AUROC. This study shows that the power spectrum analysis of the fetal heart rate is a simple and powerful tool that may become an adjunctive method to CTG, helping healthcare professionals to accurately identify fetuses at risk of intrapartum hypoxia and to implement timely obstetrical interventions to reduce the incidence of related adverse perinatal outcomes.


[4 years' experience with combined hormonal treatment of cryptorchism].
86 patients aged 9 months to 15 years (means = 4.8) having 102 cryptorchid testes were treated with either LHRH nasal spray or with a combination of LHRH and HCG. The immediate success rate after the termination of treatment was 74%. The follow-up showed that 65% of the testes were still descended after the critical period had elapsed. An open processus vaginalis was found in 74% (20/27) while pathological changes of the epididymis (64%) (7/11) and testis "reflexus" (48%) (13/27) were frequently encountered in unsuccessfully treated patients. Furthermore, the above grouping of patients displayed typical histological changes associated with cryptorchidism, namely an impaired number of germ cells (0.14 S/T median values) and atrophy of the Leydig cells. In almost all of the patients classified as treated unsuccessfully, there was a definite improvement in the position of the gonad, thus facilitating subsequent surgery.


Human-in-the-Loop Optimization of Shared Autonomy in Assistive Robotics.
In this paper, we propose a mathematical framework which formalizes user-driven customization of shared autonomy in assistive robotics as a nonlinear optimization problem. Our insight is to allow the end-user, rather than relying on standard optimization techniques, to perform the optimization procedure, thereby allowing us to leave the exact nature of the cost function indeterminate. We ground our formalism with an interactive optimization procedure that customizes control sharing using an assistive robotic arm. We also present a pilot study that explores interactive optimization with end-users. This study was performed with 17 subjects (4 with spinal cord injury, 13 without injury). Results show all subjects were able to converge to an assistance paradigm, suggesting the existence of optimal solutions. Notably, the amount of assistance was not always optimized for task performance. Instead, some subjects favored retaining more control during the execution over better task performance. The study supports the case for user-driven customization and provides guidance for its continued development and study.


Plasmodium falciparum gene encoding a protein similar to the 78-kDa rat glucose-regulated stress protein.
Genes homologous to heat shock protein 70 have been described in parasitic protozoa. It has been proposed that they may be important to the parasite as it moves from the vertebrate host at 37 degrees C to the insect. We now describe a genomic DNA clone isolated from Plasmodium falciparum that encodes a protein similar in sequence to a mammalian heat shock-related protein, the 78-kDa glucose-regulated protein of rat and hamster. The gene is expressed during the erythrocytic stage in both asexual and sexual parasites (RNA blot analysis) and a 72-kDa protein is immunoprecipitated from erythrocytic stage parasites. Importantly, the sequence of the clone is similar to the canonical sequence at the carboxyl termini of glucose-regulated proteins of mammals that determines their localization within endoplasmic reticulum. Since the parasite sequence has only three (Asp-Glu-Leu) of the four carboxyl-terminal amino acids, its location and its function within the parasite remain to be determined.


Monascus secondary metabolites monascin and ankaflavin inhibit activation of RBL-2H3 cells.
Monascus-fermented products have been used as dietary food and traditional medicine due to their beneficial effects on circulation and digestive systems in Asia for thousands of years. Besides, monascin and ankaflavin, secondary metabolites from Monascus-fermented products, have proven anti-inflammatory and immunomodulatory effects. In previous research, monascin and ankaflavin ameliorated ovalbumin-induced airway allergic reaction often used as a type I allergy asthma model. Additionally, mast cells play critical roles in type I allergy. Therefore, RBL-2H3 cells were used as the mast cell model to determine whether the improving effects on asthma of monascin and ankaflavin came from influencing mast cells. PMA and ionomycin are common activators of mast cells because they stimulate the main signaling molecules during mast cell activation. Forty micromolar monascin and ankaflavin inhibited PMA/ionomycin-induced mast cell degranulation and TNF-α secretion through suppressing the phosphorylation of PKC and MAPK family ERK, JNK, and p38. Consequently, monascin and ankaflavin affected the activation of mast cells and may have the potential to improve type I allergy.


Reversible DNA compaction by sulfite reductase regulates transcriptional activity of chloroplast nucleoids.
The transcriptional activity of nucleoids changes during plastid development, presumably due to the morphological and molecular differences of the nucleoids. Pea chloroplast nucleoids have an abundant 70-kDa protein identified as sulfite reductase (SiR) that can compact DNA. Using an in vitro transcription assay, we show here that heparin increased the transcriptional activity of chloroplast nucleoids with concomitant release of SiR. Using a fluorometric method we developed for analyzing DNA compaction, we found that the fluorescence intensity of chloroplast DNA stained with 4',6-diamidino-2-phenylindole was decreased by the addition of SiR and increased by the subsequent addition of heparin. Addition of exogenous SiR increased the compaction of isolated nucleoids, and the addition of heparin relaxed it. SiR effectively repressed the in vitro transcription activity of nucleoids and counteracted the activation by heparin. These results suggest that SiR regulates the transcriptional activity of chloroplast nucleoids through changes in DNA compaction.


Alcohol-Treated Porous PTFE Substrate for the Penetration of PTFE-Incompatible Hydrocarbon-Based Ionomer Solutions.
For a mechanically tough proton exchange membrane, a composite membrane incorporated with a porous polymer substrate is of great interest to suppress the ionomer swelling and to improve the dimensional stability and mechanical strength of the ionomers. For the composite membranes, good impregnation of substrate-incompatible ionomer solution into the substrate pores still remains one of the challenges to be solved. Here, we demonstrated a facile process (surface treatment with solvents compatible with both substrate and the ionomer solution) for the fabrication of the composite membranes using polytetrafluoroethylene (PTFE) as a porous substrate and poly(arylene ether sulfone) (SPAES) as a hydrocarbon-based (HC) ionomer. Appropriate solvents for the surface treatment were sought through the contact angle measurement, and it was found that alcohol solvents effectively tuned the surface property of PTFE pores to facilitate the penetration of the SPAES/N-methyl-2-pyrrolidone (NMP) solution into ∼300 nm pores of the substrate. Using this simple alcohol treatment, the SPAES/NMP contact angle was reduced in half, and we could fabricate the mechanically tough PTFE/HC composite membranes, which were apparently translucent and microscopically almost void-free composite membranes.


Identification of a new endogenous metabolite and the characterization of its protein interactions through an immobilization approach.
The emerging field of global mass-based metabolomics provides a platform for discovering unknown metabolites and their specific biochemical pathways. We report the identification of a new endogenous metabolite, N(4)-(N-acetylaminopropyl)spermidine and the use of a novel proteomics based method for the investigation of its protein interaction using metabolite immobilization on agarose beads. The metabolite was isolated from the organism Pyrococcus furiosus, and structurally characterized through an iterative process of synthesizing candidate molecules and comparative analysis using accurate mass LC-MS/MS. An approach developed for the selective preparation of N(1)-acetylthermospermine, one of the possible structures of the unknown metabolite, provides a convenient route to new polyamine derivatives through methylation on the N(8) and N(4) of the thermospermine scaffold. The biochemical role of the novel metabolite as well as that of two other polyamines: spermidine and agmatine is investigated through metabolite immobilization and incubation with native proteins. The identification of eleven proteins that uniquely bind with N(4)-(N-acetylaminopropyl)spermidine, provides information on the role of this novel metabolite in the native organism. Identified proteins included hypothetical ones such as PF0607 and PF1199, and those involved in translation, DNA synthesis and the urea cycle like translation initiation factor IF-2, 50S ribosomal protein L14e, DNA-directed RNA polymerase, and ornithine carbamoyltransferase. The immobilization approach demonstrated here has the potential for application to other newly discovered endogenous metabolites found through untargeted metabolomics, as a preliminary screen for generating a list of proteins that could be further investigated for specific activity.


Land mines in the field: a modest proposal for improving the craft of qualitative health research.
In this commentary, the authors encourage a renewed enthusiasm for attention to quality criteria in qualitative health research by poking fun at what they understand to be patterns and themes emerging from data collected in their respective extensive "fieldwork" experiences within the genre. Conceptualizing some of the particularly problematic interpretive turns as land mines in the field (or, alternatively, missteps in the dance, cracks in the pottery, wrong turns in the journey, weeds in the garden, or dropped stitches in the quilt), they challenge researchers' collective relationship to both factual and metaphoric empirical claims. With a warning to those unaccustomed to self-deprecating humor, the authors challenge all to pay serious heed to what does and does not constitute rigorous, high-quality, empirical science within the qualitative tradition.


Petroleum pitch-based porous aromatic frameworks with phosphonate ligand for efficient separation of uranium from radioactive effluents.
Porous aromatic frameworks with structural/pore controllability and rigid skeletons present a series of emerging materials for solid phase extraction. However, the complicated monomers or noble metal catalyst, and cumbersome synthetic strategies result in high-cost engineering application of porous aromatic frameworks. Herein, a simple synthetic strategy of porous aromatic frameworks with phosphonate is reported for efficient separation of uranium from radioactive effluents, and petroleum pitch, a low-cost and widely available material, was used as the building block. 4-Vinylbenzylphosphonic acid diethyl ester monomer is introduced to chelate uranium and to improve the aqueous dispersibility of sorbents. The phosphonate functionalized PPAFs take 40 min to achieve adsorption equilibrium, and the maximum sorption capacity reaches 147 mg U/g at pH 1.0. PPAFs exhibit good selectivity over various competing ions and excellent radioresistance in acidic solution. Besides, PPAFs remain almost 100% sorption efficiency and intact structure over 5 sorption-desorption cycles with alkaline eluent. This work not only applies a low-cost material for uranium extraction, but a new idea for the utilization of waste and recycling of resources.


Local adaptation along smooth ecological gradients causes phylogeographic breaks and phenotypic clustering.
Coalescent theory has provided a basis for evolutionary biologists to build sophisticated methods for inferring population history from variation in genetic markers, but these methods leave out a major conceptual cornerstone of modern evolutionary theory: natural selection. I provide the first quantitative analysis of the effects of selection on genealogical patterns in a continuously distributed population in which the selective optimum for a trait linked to the marker varies gradually and continuously across the landscape. Simulations show that relatively weak selection for local adaptation can lead to strong phylogeographic structure, in which highly divergent genealogical groups (i.e., clades) are geographically localized and differentially adapted, and dramatically increased standing variation (e.g., coalescence time) compared to neutral expectations. This pattern becomes more likely with increasing population size and with decreasing dispersal distances, mutation rates, and mutation sizes. Under some conditions, the system alternates between a nearly neutral behavior and a behavior in which highly divergent clades are locally adapted. Natural selection on markers commonly used in phylogeographic studies (such as mitochondrial DNA) presents a major challenge to the inference of biogeographic history but also provides exciting opportunities to study how selection affects both between- and within-species biodiversity.


Growth factors and corneal epithelium.
Regeneration of corneal epithelium following injury is essential for visual rehabilitation. A limited number of approaches are available for treating patients who fail to heal epithelial injuries adequately. The presence of specific receptors for epidermal growth factor (EGF) on epithelial cells suggests that this potent mitogen may play a role in normal epithelial wound healing. Topical application of biosynthetic human EGF significantly accelerated epithelial regeneration in primates following epikeratophakia surgery. Epidermal growth factor alone and with fibronectin accelerated epithelial regeneration of rabbits following mild alkali burns. Since prolonged exposure of cells to EGF is necessary to induce mitosis, the dynamics of EGF in the eye and with various lenses was studied. When applied in methylcellulose-based eye drops, 90% of the EGF was lost from tear film within 10 min, while a small amount (10%) remained associated with conjuctival tissue. Soft contact lenses or epikeratophakia lenticles took up substantial amounts of EGF (50 micrograms) and released 85% of the EGF within 24 h, with a half-life of 4 h in vitro. Epidermal growth factor did not diffuse through corneas or lenticles and did not promote epithelial downgrowth along sutures in primate corneas. These results suggest that biosynthetic growth factors may be useful in the treatment of some epithelial injuries.


Homeless youth and their exposure to and involvement in violence while living on the streets.
The purpose of this research were to explore homeless youths' histories of exposure to violence, perpetration of violence, and fear of violent victimization, and to examine the extent to which these constructs are associated with demographic variables. A sample of 432 youth (between 13 and 23 years old) who were homeless or at imminent risk for homelessness were sampled from both service and street sites. The percentage of youth who reported exposure to each type of violence was calculated. Multiple regression analyses were used to examine differences in the risk of exposure to violence across gender, ethnicity, age, and length of time homeless. Respondents reported a high rate of exposure to violence. Female respondents reported levels of exposure to violence that were as high as those reported by males. Females were more likely to report having been sexually assaulted and fearing victimization, and tended to be less likely to report perpetrating violence. With a few exceptions, ethnic identity was not a significant predictor of exposure to violence or fear of victimization. Age tended to be inversely associated with risk of exposure to violence. Length of time homeless was not associated with fear of victimization. Homeless youth are at high risk for exposure to a variety of forms violence as both witnesses and victims. The overall rates of exposure to violence and patterns of association with demographic variables are significantly higher than those reported in national samples of adolescents.


Functional Bandaging in Children with Idiopathic Toe-Walking.
Idiopathic toe-walking (ITW) is a persistent gait pattern with no known etiology characterized as premature heel rise or no heel contact. We investigated the effects of functional bandaging in children with ITW on heel contact during stance phase and on gait quality. Nineteen children aged 4 to 16 years with ITW and ten age-matched healthy children were included in the study. Elastic adhesive bandages were applied to children with ITW to assist with dorsiflexion. Before bandaging (T0) and immediately (T1) and 1 week (T2) after initial bandaging, the initial contact, loading response, and midstance subphases of gait were analyzed using light pressure sensors and the Edinburgh Visual Gait Score (EVGS). Ten age-matched children with typical gait participated for comparison in T0. The data were analyzed with Friedman and Wilcoxon signed rank tests for within-group comparisons and Mann-Whitney U tests for between-group comparisons. In T0, for the ITW group, no heel contact was observed during stance. In T1, all of the participants achieved heel contact at initial contact and loading response and 56.8% at midstance. In T2, all of the heels continued contact at initial contact and loading response and 54.3% at midstance. The EVGS significantly improved. The Friedman test showed that there were noteworthy improvements between T0-T1 and T0-T2 in video-based observational gait analysis and EVGSs (P < .001), although no difference was found between T1-T2 in video-based observational gait analysis (P = .913) and EVGSs (P = .450). In children with ITW, dorsiflexion assistive functional bandaging was an effective tool to help achieve heel contact on the ground and improve walking quality for a short period after application. Further studies with longer follow-up and larger sample sizes are required to confirm the long-term therapeutic effects of this promising functional bandaging.


Portal vein embolization stimulates tumour growth in patients with colorectal cancer liver metastases.
Portal vein embolization (PVE) can facilitate the resection of previously unresectable colorectal cancer (CRC) liver metastases. Bevacizumab is being used increasingly in the treatment of metastatic CRC, although data regarding its effect on post-embolization liver regeneration and tumour growth are conflicting. The objective of this observational study was to assess the impact of pre-embolization bevacizumab on liver hypertrophy and tumour growth. Computed tomography scans before and 4 weeks after PVE were evaluated in patients who received perioperative chemotherapy with or without bevacizumab. Scans were compared with scans obtained in a control group in which no PVE was administered. Future liver remnant (FLR), total liver volume (TLV) and total tumour volume (TTV) were measured. Bevacizumab was discontinued ≥ 4 weeks before PVE. A total of 109 patients and 11 control patients were included. Portal vein embolization induced a significant increase in TTV: the right lobe increased by 33.4% in PVE subjects but decreased by 34.8% in control subjects (P < 0.001), and the left lobe increased by 49.9% in PVE subjects and decreased by 33.2% in controls (P= 0.022). A total of 52.8% of the study group received bevacizumab and 47.2% did not. There was no statistical difference between the two chemotherapy groups in terms of tumour growth. Median FLR after PVE was similar in both groups (28.8% vs. 28.7%; P= 0.825). Adequate liver regeneration was achieved in patients who underwent PVE. However, significant tumour progression was also observed post-embolization.


Towards new paradigms for the treatment of hypobaric decompression sickness.
Altitude induced (hypobaric) decompression sickness (DCS) has long been treated with ground level oxygen and U.S. Navy Treatment Tables 5 and 6. These treatment tables originate from surface excursion diving and, when implemented, require significant resource allocation. Although they are effective treatment regimens, these tables were not developed for treating hypobaric DCS which has an etiology similar to saturation diving DCS. In this review, different treatment options for hypobaric DCS are presented. These options include more aggressive use of ground level oxygen and treatment tables using a maximum pressure of 2 atmospheres (ATA). Specific attention is given to USAF Table VIII, an experimental hypobaric DCS treatment-table, and space suit overpressurization treatment. This paradigm shift for DCS treatment is based on a projected increase in hypobaric DCS treatment from exposure to low pressure during several operational conditions: cruise flight in the next generation aircraft (e.g., F-22); high altitude, unpressurized flight by special operations forces; and the extraordinary amount of extravehicular activity (EVA) required to construct the international space station. Anticipating the need to treat DCS encountered during these and other activities, it is proposed that 2 ATA or less hyperbaric oxygen (HBO) treatment conjoined with new collapsible chamber technology can be used to address these issues in a safe and cost effective fashion.


Evaluation of a commercial IgE ELISA in comparison with IgA and IgM ELISAs, IgG avidity assay and complement fixation for the diagnosis of acute toxoplasmosis.
A panel of sera from patients with known case histories representative of acute toxoplasmosis (primarily lymphadenopathy, n = 106), latent toxoplasmosis (asymptomatic, n = 368) and negative samples (n = 54) was used to evaluate the capacity of five serological tests to differentiate among patients with acute or latent toxoplasmosis and non-infected individuals. Positive IgA, IgE and IgM ELISA results and low IgG avidity and complement fixation test (CFT) titres of >or=256 were considered to be indicative of acute toxoplasmosis. The most sensitive methods were IgM ELISA (98.1%) and CFT (97.1%), albeit with low specificity (65.0% and 64.5%, respectively) and positive predictive values (43.3% and 42.7%, respectively). IgG avidity assay and IgE ELISA had the highest specificity (97.7% and 91.7%, respectively) and the highest positive predictive values (89.4% and 75.6%, respectively). The best association between serological results and clinical findings was obtained with IgE ELISA (86%, as expressed via Youden's index). In a subset of 259 samples categorised by the period between the onset of clinical symptoms and sampling, >50% of patients had enlarged lymph nodes for <4 months, despite a broad range of differences. However, IgM remained positive for 12-18 months, IgA for 6-9 months and IgE for 4-6 months. IgG avidity remained low for a maximum of 4 months, after which avidity increased despite the persistence of enlarged lymph nodes and a positive IgE assay. Detection of IgE appears to be a highly specific test for confirming the acute nature of Toxoplasma infections that have been detected by other sensitive methods.


Biodegradable Hollow Mesoporous Organosilica Nanotheranostics for Mild Hyperthermia-Induced Bubble-Enhanced Oxygen-Sensitized Radiotherapy.
Alleviation of tumor hypoxia has been the premise for improving the effectiveness of radiotherapy, which hinges upon the advanced delivery and rapid release of oxygen within the tumor region. Herein, we propose a "bubble-enhanced oxygen diffusion" strategy to achieve whole tumor oxygenation for significant radiation enhancement based on the "bystander effect". Toward this end, sub-50 nm CuS-modified and 64Cu-labeled hollow mesoporous organosilica nanoparticles were constructed for tumor-specific delivery of O2-saturated perfluoropentane (PFP). Through the aid of PFP gasification arising from NIR laser-triggered mild hyperthermia, simultaneous PET/PA/US multimodality imaging and rapid oxygen diffusion across the tumor can be achieved for remarkable hypoxic radiosensitization. Furthermore, the multifunctional oxygen-carrying nanotheranostics also allow for other oxygen-dependent treatments, thus greatly advancing the development of bubble-enhanced synergistic therapy platforms.


Clinical outcomes associated with blenderized tube feedings in adults: A systematic review.
Nearly half a million individuals in the United States are dependent on enteral nutrition to meet their nutrition needs. Public interest in blenderized tube feeding (BTF) has increased over the past decade; however, medical professionals indicate a lack of knowledge about these products and their effects. The purpose of this review is to analyze clinical outcomes in adults who use a BTF formula as their primary nutrition source. A literature search was conducted in PubMed, Scopus, and CINAHL using search terms "adult," "enteral nutrition," "tube feeding," "BTF," blenderized," "blended," "homemade," and "pureed." Nine studies met the inclusion criteria and were analyzed in the review. Under close monitoring, BTF does not pose a higher risk for deterioration in anthropometric measurements. Furthermore, BTF use is consistently associated with improvements in diarrhea. As such, clinicians should consider the use of these formulas in the acute care or rehabilitation settings. Additional research is needed in patients with diverse clinical backgrounds in free-living communities. Larger populations sizes and longer intervention time frames are crucial to providing statistically significant results needed to strengthen the quality of evidence on this topic.


Assessing knowledge of antimicrobial stewardship.
The Scottish Antimicrobial Prescribing Group (SAPG) is a national clinical multidisciplinary forum that coordinates and delivers antimicrobial stewardship (AS). This work includes ensuring health professionals have the necessary knowledge to contribute to improving the use of antimicrobials and to develop and implement education resources if required. The SAPG undertook a survey to scope the current understanding and learning needs among nurses and midwives in a range of care settings across Scotland. This article reports on the results, which have been used to help develop a dedicated AS education programme for this group of health professionals.


Liver gene expression during chronic dietary iron overload in rats.
To clarify the pathogenesis of hepatic iron toxicity, we investigated the effect of chronic dietary iron overload on the expression of several genes in rat liver. After 10 wk of iron treatment, when only minor histological features of liver damage were appreciable, the level of pro-alpha 2(I)-collagen mRNA was already higher than in control liver and increased further at 30 wk of treatment. Also, the relative amount of L ferritin subunit mRNA was enhanced early by iron load and was even more elevated at the latest time point considered, whereas neither H ferritin subunit nor transferrin mRNA levels were affected by iron treatment. In contrast, after chronic iron treatment, no variations were found in the steady-state level of mRNAs transcribed from liver-specific and preferentially expressed genes (albumin, alpha-fetoprotein, apolipoprotein A-1), growth-related genes (c-myc, c-Ha-ras and c-fos) and stress-induced genes (heat shock protein 70). These results suggest that chronic dietary iron overload in rats can specifically activate target genes in the liver (i.e., L ferritin and procollagen) in the absence of either histological signs of severe liver damage or alterations in differentiated liver functions.


Specific antibody response after in vivo antigenic stimulation in systemic lupus erythematosus.
Several in vitro studies have demonstrated a polyclonal B cell response to antigenic stimulation in patients with systemic lupus erythematosus (SLE). To determine if this polyclonal response occurs in vivo, 18 patients with SLE were antigenically stimulated with the pneumococcal vaccine Pneumovax . Mean antibody response to immunization was the same in SLE and normal control subjects. Although elevated antibody levels to several viruses were present in SLE subjects preimmunization, these levels did not change postimmunization. Total immunoglobulin levels, immune complex levels, and antiblood group B antibody levels did not change in SLE patients after immunization. Antiblood group A titers rose in both SLE patients and normals due to a media contaminant in the Pneumovax . Thus, SLE patients appear to have a specific antibody response to antigenic stimulation with pneumococcal polysaccharide. Polyclonal activation as seen in vitro in SLE may be more restricted in vivo.


Hydrodynamism and its influence on the reproductive condition of the edible sea urchin Paracentrotus lividus.
Despite the large body of work published in the last two decades on the reproduction of the sea urchin Paracentrotus lividus, the reproductive aspects linked to hydrodynamic conditions and their influence on gonad production remain poorly understood. The present paper aims to evaluate the effect of hydrodynamism on the reproductive cycle of P. lividus. Variability in the gonadosomatic index (GSI) of P. lividus was estimated seasonally from 2007 to 2008 at two shallow sub-littoral flat basaltic areas at Ustica Island (Western Mediterranean). GSI was higher in the sites characterized by low hydrodynamism than in those with high hydrodynamism. Results also suggest a possible role for hydrodynamism in triggering processes of resource limitation (food shortage), probably by interfering with P. lividus feeding activity.


Defining Predictors of Future Academic Productivity in Plastic Surgery Residency.
Research is a valued component of applications to plastic surgery residency. No prior studies have explored factors associated with increased resident research productivity. This study aims to compare the academic productivity levels of plastic surgery residency graduates based on their pre- and postresidency experiences. Residents graduating in 2019 and 2020 were identified from integrated programs. Metrics collected included the number of publications in medical school and residency. Descriptive statistics were completed along with linear regressions to evaluate the impact of these on academic productivity. A total of 221 residents from the classes of 2019 and 2020 were included. Most residents completed fellowship (75.9%) although less than half went on to academic practice (42.3%). Approximately one in five residents obtained secondary degrees (17.4%). Subjects averaged 3.15 (N = 208, SD = 4.51) publications while in medical school and 8.1 publications during residency (N = 209, SD = 10.0). For h-index calculated at the end of residency, having dedicated medical school research time was the only statistically significant factor (coefficient = 2.96, P = 0.002). Plastic surgery residents published more often as first authors and overall during residency than medical school, indicating increased research involvement and leadership. The present study builds upon prior studies by confirming the importance of dedicated medical school research time and its lasting impact. Understanding the associations of academic factors with increased research productivity in residency is relevant for both applicants and programs evaluating residency candidates.


Feasibility and Acceptability of a Mobile Technology Intervention to Support Postabortion Care (The FACTS Study Phase II) After Surgical Abortion: User-Centered Design.
Human-centered design is a methodology that applies an iterative participatory process that engages the end-user for whom an innovation or intervention is designed for from start to end. There is general evidence to support the use of human-centered design for development of tools to affect health behavior, but specifically for family planning provision. This study is part two of a three-phase study that uses a user-centered design methodology which uses the findings from Phase I to design, develop, and test a digital health solution to support follow-up after an induced surgical abortion. The objectives for this study were to: (1) develop a Web-based intervention based on preferences and experiences of women who underwent an abortion as measured in the formative phase of the Feasibility and Acceptability of a Mobile Technology Intervention to Support Postabortion Care Study; (2) conduct usability testing of the intervention to determine user-friendliness and appropriateness of the intervention; and (3) finalize a beta version of the Web-based intervention for pilot testing. The study design was based on the "development-evaluation-implementation" process from the Medical Research Council Framework for Complex Medical Interventions. This study is in Phase II of III and is based on user-centered design methodology. Phase I findings demonstrated that women engage with technology to assist in clinical care and they preferred a comprehensive website with email or text notifications to support follow-up care. In Phase II we collaborated with family planning experts and key stakeholders to synthesize evidence from Phase I. With them and a development partner we built a prototype. Usability testing was completed with 9 participants using a validated System Usability Scale. This was then used to refine the intervention for Phase III pilot study. This study was approved by the local Ethics board. We developed a comprehensive Web-based tool called myPostCare.ca, which includes: Post-Procedure Care, Emotional Well-Being Tool, Contraception Explorer, Sexual Health, Book an Appointment, and Other Resources. Additionally, over the course of a month after the procedure, automatic email notifications were sent to women as a form of virtual follow-up support, directing them to myPostCare.ca resources. The Web-based tool was refined based on usability testing results. This study demonstrated that user-centered design is a useful methodology to build programs and interventions that are women-centered, specifically for abortion care.


Digital evaluation of nasal changes induced by rapid maxillary expansion with different anchorage and appliance design.
Scientific evidence showed that rapid maxillary expansion (RME) affects naso-maxillary complex, increasing nasal width and volume. This study aimed to evaluate nasal changes induced by rapid maxillary expansion with different anchorage and appliance design by using low dose and cone beam computed tomography. A total of 44 patients (20 males, mean age 8y 8 m ± 1y 2 m; 24 females mean age 8y 2 m ± 1y 4 m) were included in the investigation and divided into three groups according to the appliance: Hyrax-type expander anchored to permanent teeth, modified Hyrax-type expander anchored to deciduous teeth, modified Haas-type expander anchored to deciduous teeth. Maxillary expansion was performed until overcorrection and the expander was passively kept in situ for 7 months at least. All patients had three-dimensional imaging before expansion (T0) and after the retention period (T1). Nasal floor width, nasal wall width, maxillary inter-molar width were measured by means of Mimics software. The paired sample t-test was employed to assess the significance of the differences between the time points; the analysis of variance test (ANOVA) was used to compare differences between groups. The statistical analysis revealed significant differences between T0 and T1 for each recorded measurement in each group; no significant differences were found by comparing groups. Rapid maxillary expansion produces a significant skeletal transverse expansion of nasal region in growing patients. No significant differences in nasal effects are expected when the appliance is anchored onto deciduous teeth, with or without the palatal acrylic coverage.


Interfacial Activity of Starch-Based Nanoparticles at the Oil-Water Interface.
Understanding the interfacial activity of polysaccharide nanoparticles adsorbed at oil-water interfaces is essential and important for the application of these nanoparticles as Pickering stabilizers. The interfacial properties of starch-based nanospheres (SNPs) at the interface of an n-hexane-water system were investigated by monitoring the interfacial tension at different bulk concentrations. The three-phase contact angle (θ) and the adsorption energy (ΔE) increased with increasing size and degree of substitution with octenyl succinic groups (OSA) in the particles. Compared with the OSA-modified starch (OSA-S) macromolecule, the SNPs effectively reduced the interfacial tension of the n-hexane-water system at a relatively higher concentration. These results and the method reported herein are useful for selecting and preparing polysaccharide nanoparticles as Pickering stabilizers for oil-water emulsions.


Failure of the Problem-Oriented Medical Paradigm and a Person-Centered Alternative.
Our problem-oriented approach to health care, though historically reasonable and undeniably impactful, is no longer well matched to the needs of an increasing number of patients and clinicians. This situation is due, in equal parts, to advances in medical science and technologies, the evolution of the health care system, and the changing health challenges faced by individuals and societies. The signs and symptoms of the failure of problem-oriented care include clinician demoralization and burnout; patient dissatisfaction and non-adherence; overdiagnosis and labeling; polypharmacy and iatrogenesis; unnecessary and unwanted end-of-life interventions; immoral and intolerable disparities in both health and health care; and inexorably rising health care costs. A new paradigm is needed, one that humanizes care while guiding the application of medical science to meet the unique needs and challenges of individual people. Shifting the focus of care from clinician-identified abnormalities to person-relevant goals would elevate the role of patients; individualize care planning; encourage prioritization, prevention, and end-of-life planning; and facilitate teamwork. Paradigm shifts are difficult, but the time has come for a reconceptualization of health and health care that can guide an overdue transformation of the health care system.


Goldenhar's syndrome associated with cardiac malformations.
A case of Goldenhar's syndrome associated with cardiac malformations such as single ventricle, atresia of pulmonary artery, and patent ductus arteriosus is described. The association of cardiac malformations with Goldenhar's syndrome is very rare and suggests that it is necessary to perform a careful clinical evaluation in this syndrome whether or not additional malformations may exist in visceral organs.


Plasticity of synaptopodin and the spine apparatus organelle in the rat fascia dentata following entorhinal cortex lesion.
Synaptopodin is an actin-associated molecule essential for the formation of a spine apparatus in telencephalic spines. To study whether synaptopodin and the spine apparatus organelle are regulated under conditions of lesion-induced plasticity, synaptopodin and the spine apparatus were analyzed in granule cells of the rat fascia dentata following entorhinal denervation. Confocal microscopy was employed to quantify layer-specific changes in synaptopodin-immunoreactive puncta densities. Electron microscopy was used to quantify layer-specific changes in spine apparatus organelles. Within the denervated middle and outer molecular layers, the layers of deafferentation-induced spine loss, synaptogenesis, and spinogenesis, the density of synaptopodin puncta and the number of spine apparatuses decreased by 4 days postlesion and slowly recovered in parallel with spinogenesis by 180 days postlesion. Within the nondenervated inner molecular layer, the zone without deafferentation-induced spine loss, a rapid loss of synaptopodin puncta and spine apparatuses was also observed. In this layer, spine apparatus densities recovered by 14 days postlesion, in parallel with plastic remodeling at the synaptic level and the postlesional recovery of granule cell activity. These data demonstrate layer-specific changes in the distribution of synaptopodin and the spine apparatus organelle following partial denervation of granule cells: in the layer of spine loss, spine apparatus densities follow spine densities; in the layer of spine maintenance, however, spine apparatus densities appear to be regulated by other signals.


Bardet-Biedl syndrome and retinitis punctata albescens in an isolated northern Canadian community.
Autosomal recessive inheritance of various conditions is well documented among inbreeding groups. In northern Canada inbreeding occurs in communities as a result of language and cultural uniqueness as well as geographic isolation. In one such community--Rae, in the Northwest Territories--two autosomal recessive disorders, the Bardet-Biedl syndrome and retinitis punctata albescens, are segregating. This report outlines the major clinical features of the disorders, establishes for both conditions the high frequency of the heterozygous carrier genotype in the community and suggests a possible way to reduce the likelihood of increased numbers of affected individuals in forthcoming generations.


Modelling and Characterization of Glial Fibrillary Acidic Protein.
Glial Fibrillary Acidic Protein (GFAP) is an intermediate-filament (IF) protein that maintains the astrocytes of the Central Nervous System in Human. This is differentially expressed during serological studies in inflamed condition such as Rheumatoid Arthritis (RA). Therefore, it is of interest to glean molecular insight using a model of GFAP (49.88 kDa) due to its crystallographic nonavailability. The present study has been taken into consideration to construct computational protein model using Modeller 9.11. The structural relevance of the protein was verified using Gromacs 4.5 followed by validation through PROCHECK, Verify 3D, WHAT-IF, ERRAT and PROVE for reliability. The constructed three dimensional (3D) model of GFAP protein had been scrutinized to reveal the associated functions by identifying ligand binding sites and active sites. Molecular level interaction study revealed five possible surface cavities as active sites. The model finds application in further computational analysis towards drug discovery in order to minimize the effect of inflammation.


A fast and accurate feature-matching algorithm for minimally-invasive endoscopic images.
The ability to find image similarities between two distinct endoscopic views is known as feature matching, and is essential in many robotic-assisted minimally-invasive surgery (MIS) applications. Differently from feature-tracking methods, feature matching does not make any restrictive assumption about the chronological order between the two images or about the organ motion, but first obtains a set of appearance-based image matches, and subsequently removes possible outliers based on geometric constraints. As a consequence, feature-matching algorithms can be used to recover the position of any image feature after unexpected camera events, such as complete occlusions, sudden endoscopic-camera retraction, or strong illumination changes. We introduce the hierarchical multi-affine (HMA) algorithm, which improves over existing feature-matching methods because of the larger number of image correspondences, the increased speed, and the higher accuracy and robustness. We tested HMA over a large (and annotated) dataset with more than 100 MIS image pairs obtained from real interventions, and containing many of the aforementioned sudden events. In all of these cases, HMA outperforms the existing state-of-the-art methods in terms of speed, accuracy, and robustness. In addition, HMA and the image database are made freely available on the internet.


Antitumor activity of cisplatin analogs against malignant ovarian tumor xenografts into nude mice.
The antitumor activity of new platinum analogs was studied at equitoxic doses to that of cisplatin (CDDP) in BALB/C nu-nu nude mice bearing xenografts of human ovarian malignant tumors. The following two tumor lines were used: OH-1 (serous cystadenocarcinoma) and MP-1 (mucinous cystadenoma, LPM). 1) Antitumor activity was determined for all agents from the T/C ratio for OH-1. In particular, 254-S and JM-8 were found to be much more active than the other agents. 2) Antitumor activity was determined with JM-8 from the abdominal diameter ratio for MP-1. Both JM-8 and CDDP yielded active responses which were evaluated by the CEA value. Therefore, JM-8 and CDDP were considered to be the most active agents for MP-1. 3) We evaluated the mean body weight loss of tumor bearing mice in order to study the side effects, and a great weight loss was observed with 254-S. 4) A large variety of effects were observed in the histological evaluation for the two tumor lines, and were thus difficult to discuss. Our findings suggest the necessity of individual chemotherapy for each histological type of ovarian malignant tumor.


1-(2,3-Dimeth-oxy-benzyl-idene)-2-(2,4-dinitro-phen-yl)hydrazine.
In the title compound, C(15)H(14)N(4)O(6), the dihedral angle between the aromatic rings is 3.7 (4)°. The nitro groups make dihedral angles of 6.0 (4) and 5.2 (4)° with the parent ring and are oriented at 6.0 (6)° with respect to each other. The meth-oxy groups are inclined at 54.0 (2) and 2.5 (3)° with respect to the benzene ring to which they are attached. In the crystal, mol-ecules are linked by weak C-H⋯O inter-actions. The mol-ecular conformation is consolidated by an intra-molecular N-H⋯O hydrogen bond.


Discerning the impact of personal and situational variables in risk perception of coronary heart disease.
Research into how people perceive risk has highlighted the interaction between the available information and personal variables and their impact on judgement. This study sought to identify demographic and health variables that influenced risk and the influence of individual risk assessment, dispositional optimism and negative affect on judgement. A total of 476 participants were asked to make risks judgements of 24 vignettes depicting hypothetical risk scenarios. The findings showed that while people are able to correctly recognise, in others, relevant risk factors for coronary heart disease, risk perception is likely to imply a personal consideration of the same risk factors in themselves.


DNA deletions in mild and severe Becker muscular dystrophy.
The DNA of 33 patients diagnosed as suffering from Becker muscular dystrophy (BMD) has been probed with cloned DNA sequences from Xp21, known to reveal DNA deletions in patients suffering from the more severe Duchenne muscular dystrophy (DMD). Two BMD cases showed clear deletions. A third case gave aberrant band sizes, which further analysis showed to be caused by a small deletion. This suggests that deletions in DXS164 occur approximately as frequently in BMD as they do in DMD. Of the two cases showing large deletions, one is at the severe end of the Becker clinical spectrum, whilst the other is a classical Becker-type dystrophy. The fact that loci defined by probes commonly deleted in classical DMD patients are also deleted in BMD patients of varying severity is strong additional evidence that these disorders are allelic, and further justifies the use of probes with defined linkage relationships to DMD also being used for counselling in BMD families.