Characterization of pseudorabies virus glycoprotein gII expressed by recombinant baculovirus.
The gene encoding the complete glycoprotein gII (homologue of gB of herpes simplex virus) of pseudorabies virus (PrV) was inserted into a baculovirus transfer vector, and a recombinant virus expressing gII was isolated. Three gII-related recombinant baculovirus-expressed peptides of 100, 60, and 45 to 50 kDa were detected with a polyclonal antibody against gII; these correspond to the authentic subunits gIIa and its cleavage products gIIb and gIIc, respectively. These proteins were subjected to N-terminal sequencing, and the results showed that the protease cleavage sites were identical to those of authentic gII. The expressed gII was shown to be transported to the surface of infected cells as judged by an indirect immunofluorescence test. Antibodies raised in mice immunized with the recombinant gII neutralized the infection of PrV in vitro. Mice inoculated with the recombinant gII were completely protected from lethal challenge with PrV.


Erratum: Efficacy and safety of icotinib in patients with brain metastases from lung adenocarcinoma [Corrigendum].
[This corrects the article on p. 2911 in vol. 9, PMID: 27274284.].


Event-related potentials recorded from the scalp and nasopharynx. II. N2, P3 and slow wave.
Scalp and nasopharyngeal recordings of the N2, P3 and slow wave components were compared in a target-detection task. The effects of probability, interstimulus interval, intensity, discrimination difficulty, attention, stimulus omission and modality were evaluated. Waves of opposite polarity to the scalp N2 and P3 components were recorded in the nasopharynx. The scalp and nasopharyngeal N2 components showed different patterns of variation across experimental conditions. These findings indicate that there are two different cerebral processes occurring at the latency of the scalp N2. The scalp and nasopharyngeal P3 components consistently covaried across conditions, suggesting a single underlying process. The slow wave was observed only in the scalp recordings.


Heparin coated decellularized xenogeneic small diameter vascular conduit for vascular repair with early luminal reendothelialization.
Small diameter vascular graft is a clinical need in cardiovascular disease (CAD) and peripheral atherosclerotic diseases (PAD). Autologous graft has limitations in availability and harvesting surgery. To make luminal surface modification with heparin coating in xenogeneic small diameter vascular graft. We constructed a conduit from decellularized human saphenous vein (HSV) matrices in small diameter vascular graft (< 0.8 mm diameter). Luminal surface modification was done with heparin coating for transplantation in the rat femoral artery. Biocompatibility of conduit was checked in Chorioallantoic Membrane (CAM) assay and in vivo. The blood flow rate in conduit grafts was measured, and immuno-histological analysis was performed. CAM assay and in vivo biocompatibility test showed cellular recruitment in the HSV scaffold. Heparin binding was achieved on the luminal surface. After three months of transplantation surgery neo-intimal layer was formed in the graft. The graft was patent for two weeks after surgery. There were no statistically differences between blood flow rate in graft (at proximal end 0.5 ± 0.01 m/s and at distal end 0.4 ± 0.01 m/s (n = 6)) and native artery (0.6 ± 0.1 m/second, (n = 3)). Biomarkers of endothelial cells, medial smooth muscle cells, and angiogenesis were observed in the transplanted graft. Our study demonstrates that xenogeneic decellularized vascular grafts with surface modification with heparin coating could be useful for the replacement of small diameter vessels.


The Teasing Questionnaire-Revised: measurement of childhood teasing in adults.
This study examined the reliability of the Teasing Questionnaire-Revised (TQ-R) and the relations between recalled childhood teasing and current psychological distress. Three hundred and three undergraduate college students were administered the TQ-R, Beck Depression Inventory-II, Brief Fear of Negative Evaluation Scale, Social Phobia and Anxiety Inventory, and UCLA Loneliness Scale. A sub-sample was administered the TQ-R two weeks later. Test-retest reliability of the TQ-R ranged from moderate to strong for the TQ-R scores. Internal consistency for the TQ-R scores ranged from acceptable to good. Intercorrelations among factors were moderate suggesting that the factors measure related but distinct teasing domains. The TQ-R Total Score and Appearance, Performance, and Social factors were related to later psychopathology with correlations of a moderate effect size. Implications of these findings and areas for future research are discussed.


Impact of minimal solid and micropapillary components on invasive lung adenocarcinoma recurrence.
The specific impacts of solid and micropapillary components on prognosis in lung adenocarcinoma remain unclear. Herein, we elucidated their distinct contributions to lung adenocarcinoma recurrence. Lung adenocarcinoma was classified into solid and micropapillary absent (S-M-); solid absent, micropapillary present (S-M+); micropapillary absent, solid present (S + M-); and solid and micropapillary present (S + M+). Cumulative incidence of recurrence (CIR) was calculated using competing risk analysis. Of 994 adenocarcinomas, 650 (65.4%) were classified as S-M-; 152 (15.3%), S-M+; 148 (14.9%), S + M-; and 44 (4.4%), S + M+. In total, 168 (16.9%) patients had recurrence; 16 (1.6%) died from other causes. S-M- had significantly lower CIR than other groups (S-M- vs. S-M+: P < 0.001, S-M- vs. S + M-: P < 0.001, S-M- vs. S + M+: P < 0.001); S + M- had significantly higher CIR than S-M+ (P = 0.002). These differences remained significant in multivariable analysis. In stage IA, S-M- had significantly lower CIR than other groups (S-M- vs. S-M+: P = 0.006, S-M- vs. S + M-: P < 0.001, S-M- vs. S + M+: P < 0.001); S + M- and S + M+ had significantly higher CIR than S-M+ (P = 0.005, P = 0.008, respectively). These differences remained significant in multivariable analysis. CIR was not significantly different between S + M- and S-M+ subgroups. The presence of solid or micropapillary component (≥1%) was an independent risk factor for CIR; patients with solid component alone had a higher CIR than those with micropapillary component alone. In IA lung adenocarcinoma, patients with both solid and micropapillary components had a higher CIR than those with micropapillary component alone; the proportion of solid or micropapillary component was not associated with CIR.


Pedagogical strategies to teach bachelor students evidence-based practice: A systematic review.
The aim of this study is to review international scientific articles about pedagogical strategies to teach nursing students at bachelor degree evidence-based practice (EBP). A literature review including peer reviewed, original, empirical articles describing pedagogical interventions aimed at teaching bachelor's degree nursing students EBP in the period 2004-2014. Theories of discretion, knowledge transfer and cognitive maturity development are used as analytical perspectives. The main challenge teaching evidence based practice is that the students fail to see how research findings contribute to nursing practice. The pedagogical strategies described are student active learning methods to teach the students information literacy and research topics. Information literacy is mainly taught according to the stages of EBP. These stages focus on how to elaborate evidence from research findings for implementation into nursing practice. The articles reviewed mainly use qualitative, descriptive designs and formative evaluations of the pedagogical interventions. Although a considerable effort in teaching information literacy and research topics, nursing students still struggle to see the relevance evidence for nursing practice. Before being introduced to information literacy and research topics, students need insight into knowledge transfer and their own epistemic assumptions. Knowledge transfer related to clinical problems should be the learning situations prioritized when teaching EBP at bachelor level. Theoretical perspectives of cognitive maturity development, knowledge transfer and discretion in professional practice give alternative ways of designing pedagogical strategies for EBP. More research is needed to develop and test pedagogical strategies for EBP in light of these theories.


In vitro analysis of the proliferative capacity and cytotoxic effects of ex vivo induced natural killer cells, cytokine-induced killer cells, and gamma-delta T cells.
Recent studies have focused on the significant cytotoxicity of natural killer (NK) cells, cytokine-induced killer (CIK) cells, and gamma-delta (γδ) T cells in tumor cells. Nevertheless, the therapeutic features of these cell types have not been compared in the literature. The aim of this study was to evaluate the feasibility of activation and expansion of NK, CIK, and γδ T cells from cancer patients in vitro, and to clarify the differences in their antitumor capacities. NK, CIK, and γδ T cells were induced from the peripheral blood mononuclear cells of 20 cancer patients by using specific cytokines. Expression of CD69, NKG2D, CD16, granzyme B, perforin, IFN-γ, and IL-2 was measured by flow cytometry. Cytokine production and cytotoxicity were analyzed by enzyme-linked immunosorbent assay and Calcein-AM methods. NK cell proliferation was superior to that of CIK cells, but lower than that of γδ T cells. NK cells had a much stronger ability to secrete perforin, granzyme B, IFN-γ, and IL-2 than did CIK and γδ T cells, and imparted significantly higher overall cytotoxicity. Expanded NK cells from cancer patients are the most effective immune cells in the context of cytokine secretion and anti-tumor cytotoxicity in comparison to CIK and γδ T cells, making them an optimal candidate for adoptive cellular immunotherapy.


The relationship between delayed hypersensitivity response, nutritional status and clinical outcome in surgical patients referred for nutritional support.
Delayed hypersensitivity responses to recall antigens were measured in 125 surgical patients referred for nutritional assessment and support. On initial testing 57 patients were skin test positive and 68 were anergic each of these patient groups being closely matched in terms of surgical conditions. There was a mortality of 4 in the skin test positive group and 26 in the anergic group. The anergic patients were significantly older and in biochemical and anthropometric terms were in poorer nutritional status than the skin test positive group. Of 33 anergic patients who were repeat tested, 15 remained anergic and 18 converted to a positive response. Conversion from anergy to a positive response was not associated with changes in the measured indices of nutritional status and did not improve clinical outcome. The value of repeat skin testing is therefore in doubt.


Cell proliferation inhibitors and apoptosis promoters.
Cancer is characterised by uncontrolled proliferation and prolonged cell survival. In some cases, tumour formation is the result from aberrant activity of various cell-cycle regulators leading to chromosome instability or from alteration of the apoptosis pathway. Ovarian cancer is an entity in which cell-cycle alterations are common. P53, a key regulator of checkpoint G1, is frequently altered in high-grade serous ovarian cancer. Targeting cell-cycle regulators will lead to mitotic catastrophe and cell death in these tumours. Promoting apoptosis is another target that is gaining interest in ovarian cancer. In this review, the most relevant evidence of clinical studies in ovarian cancer with compounds targeting cell cycle or promoting apoptosis is summarised.


Cross-infection prevention, basic hygiene practices and education within nursing and health care in Latvia: a Swedish-Latvian practice development project.
The primary aim of this practice development project was to explore the level of knowledge of nursing and medical staff at the Infection Clinic at Liepaja regarding the spread of infectious diseases. Arrangements were also made for some of the Latvian health care staff to visit the Infection Clinic in Gothenburg to increase their knowledge about basic hygiene and to enable them to study the research in this area. Later we were able to formulate this new knowledge into written guidelines. The theoretical education started with questions regarding staffs expertise in preventing the spread of infections. Areas covered were handwashing, hand disinfection, use of disposable gloves and protective clothing. This revealed a need for development of both theoretical and practical knowledge in this area. However, hygiene practices improved after the theoretical education and the visits to the Infection Clinic in Gothenburg. On our return visit to Liepaja dispensers of liquid soap together with hand disinfectants were evident at every wash basin on the unit. Disposable gloves were also routinely used for the dressing of wounds and invasive procedures. Furthermore, disposable coats and masks were used when caring for highly infectious patients. The key cultural differences were the lack of nursing documentation and the relative absence of a dialogue directly between the nurse and the patient.


Selenourea and thiourea derivatives of chiral and achiral enetetramines: Synthesis, characterization and enzyme inhibitory properties.
A series of chiral and achiral cyclic seleno- and thiourea compounds bearing benzyl groups on N-atoms were prepared from enetetramines and appropriate Group VI elements in good yields. All the synthesized compounds were characterized by elemental analysis, FT-IR, 1H NMR and 13C NMR spectroscopy, and the molecular and crystal structures of (R,R)-4b and (R,R)-5b were confirmed by the single-crystal X-ray diffraction method. These assayed for their activities against metabolic enzymes acetylcholinesterase, butyrylcholinesterase, and α-glycosidase. These selenourea and thiourea derivatives of chiral and achiral enetetramines effectively inhibit AChE and BChE with IC50 values in the range of 3.32-11.36 and 1.47-9.73 µM, respectively. Also, these compounds inhibited α-glycosidase enzyme with IC50 values varying between 1.37 and 8.53 µM. The results indicated that all the synthesized compounds exhibited excellent inhibitory activities against mentioned enzymes as compared with standard inhibitors. Representatively, the most potent compound against α-glycosidase enzyme, (S,S)-5b, was 12-times more potent than standard inhibitor acarbose; 7b and 8a as most potent compounds against cholinesterase enzymes, were around 5 and 13-times more potent than standard inhibitor tacrine against achethylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively.


Functional outcome and economic burden of operative management of patellar fractures: the pivotal role of onerous implants.
The complication rate following operative treatment of patellar fractures remains high and is associated with a poor functional outcome. The primary goal of this study was to evaluate our functional outcome of patellar fracture osteosynthesis and define strategies to improve the outcome. The healthcare costs and utilization were calculated. All demographic, clinical, radiographic variables and hospital-related costs of 111 patients with 113 surgically treated patellar fractures between January 2005 and December 2014 were analyzed. Fractures were grouped as either simple or complex. Functional outcome was assessed using Knee Injury and Osteoarthritis Outcome Score (KOOS). There were 67 simple fractures (59.3%) and 46 complex fractures (40.7%). The overall complication rate was 48.7%, including 19.5% implant-related complications. In 69 patients (61.1%), implants were removed. The outcome was rather poor, with considerable impairment in all KOOS subscales with the knee-related quality of life rated worst (median 62.5, IQR 37.5-81.25). Poor outcome correlated significantly with complex patellar fractures and extensive tension-band constructs. The operative treatment of patellar fractures was associated with a high complication rate, functional impairment and reduced quality of life. Complex patellar fractures and extensive tension-band constructs were identified as the main determinants of poor outcome and increased economic burden due to higher reinterventions rates. Strategies to reduce complications and improve outcome should focus on less onerous implants.


The National Partnership to Improve Dementia Care and Hospital Readmission Among Skilled Nursing Facility Residents.
The National Partnership to Improve Dementia Care in Nursing Homes (i.e., the National Partnership) was launched in March 2012. Using national Medicare, Minimum Data Set, and Nursing Home Compare data in CY 2010-2014, we examined changes in hospital readmissions for older post-acute skilled nursing facility (SNF) residents with Alzheimer's disease or related dementias (ADRD) following the National Partnership. Using residents without ADRD as reference group to control for concurrent policy and SNF quality changes, we estimated linear probability models to examine the relationship between readmissions and the National Partnership for residents with ADRD, and also stratified the analysis by quality of SNFs. We found a decreasing trend in hospital readmissions over time. The risk of readmissions in residents with ADRD decreased additional 0.3 percentage-points (p < .01) after the launch of the National Partnership. This relationship varied across SNFs with different quality, as it was stronger in high-quality compared to low-quality SNFs.


Three-dimensional computed tomographic angiography with computed tomographic colonography for laparoscopic colorectal surgery.
To prospectively correlate the preoperative vessel anatomy in three-dimensional computed tomographic angiography with computed tomographic colonography (3D-CTA with CTC) with that in laparoscopic surgery for colorectal cancer. The study protocol was approved by our institutional review board. The study population consisted of 101 patients with colon cancer who underwent 3D-CTA with CTC between June 2016 and January 2018. Two radiologists assessed the branching patterns of sigmoid arteries (SAs) and right colonic artery (RCA), the position between the ileocolic artery (ICA) and superior mesenteric vein (SMV), and the existence of an accessory middle colonic artery (aMCA). The vessel anatomy on 3D-CTA with CTC was correlated with that of intraoperative findings. Ninety-eight examinations (97.0%) were technically successful. Between preoperative and intraoperative vessel anatomy, the branching patterns of SAs were concordant in all 29 cases with rectosigmoid and descending colon cancer. The branching patterns of RCA and the position between the ICA and SMV were completely concordant in 32 cases of cecal and ascending colon cancer. No aMCA was identified either intraoperatively or by imaging analysis. 3D-CTA with CTC guided the surgeons to determine the resection margin of the relevant vessels for laparoscopic colorectal surgery.


A phylogeny of the schoenoid sedges (Cyperaceae: Schoeneae) based on plastid DNA sequences, with special reference to the genera found in Africa.
Despite its large size (about 700 species), the australy-centred sedge tribe Schoeneae has received little explicit phylogenetic study, especially using molecular data. As a result, generic relationships are poorly understood, and even the monophyly of the tribe is open to question. In this study, plastid DNA sequences (rbcL, trnL-trnF, and rps16) drawn from a broad array of Schoeneae are analysed using Bayesian and parsimony-based approaches to infer a framework phylogeny for the tribe. Both analytical methods broadly support the monophyly of Schoeneae, Bayesian methods doing so with good support. Within the schoenoid clade, there is strong support for a series of monophyletic generic groupings whose interrelationships are unclear. These lineages form a large polytomy at the base of Schoeneae that may be indicative of past radiation, probably following the fragmentation of Gondwana. Most of these lineages contain both African and non-African members, suggesting a history of intercontinental dispersal. The results of this study clearly identify the relationships of the African-endemic schoenoid genera and demonstrate that the African-Australasian genus Tetraria, like Costularia, is polyphyletic. This pattern is morphologically consistent and suggests that these genera require realignment.


Competency versus hours: an examination of a current dilemma in nurse education.
In Europe student nurses have to work within a framework of curriculum hours, the regulations governing which were determined almost three decades ago. European Higher Education institutions involved in the delivery of nurse education are constrained by this European Union legislation that harks back to an era of apprenticeship rather than modern day educational approaches. This article describes the background to current educational practices and discusses the conflict between legal requirements, enshrined in professional regulations and the realities of competency driven educational philosophy.


A 36-year-old lady with type three female genital mutilation (Infibulation) - its long-term complications: a case report and literature review.
Female genital mutilation comprises all procedures involving the partial or total removal of female external genitalia or other injury to the female external organs, whether for religious, cultural or other non-therapeutic reasons. The impact of female genital mutilation is diverse, including physical, social and psychological impact. We report a case of a 36-year-old woman with type three female genital mutilation who did not seek medical treatment due to lack of awareness that there was treatment for it, and use this case as an entry point to comprehensively review literature regarding long-term complications associated with female genital mutilation and its impact on women's quality of life. We present a case of a 36-year-old single nulligravida lady with type three female genital mutilation who had presented with difficulty with urination since childhood. She had difficulty with menstruation since her menarche, and she had never had sexual intercourse. She never sought treatment, but recently went to hospital after she heard of a young lady who had the same problem in her neighborhood who was treated surgically and got married. On external genitalia examination, there was no clitoris, no labia minora, and labia majora were fused to each other with a healed old scar between them. There was a 0.5 cm by 0.5 cm opening below the fused labia majora near to the anus through which urine was dribbling. De-infibulation was done. Six months after the procedure, she was married and at that moment she was pregnant. The physical, sexual, obstetrics and psychosocial consequences of female genital mutilation are neglected issues. The improvement of women's socio-cultural status in combination with planning programs to enhance their information and awareness as well as trying to change the cultural and religious leaders' viewpoints regarding this procedure is essential to reducing female genital mutilation and its burden on women's health.


[How to evaluate BPH-related SBAUs in clinical practice and research?]
To describe the useful explorations in the clinical evaluation of the symptoms of the lower urinary tract symptoms possibly related to BPH (LUTS/BPH), and to list the information necessary to allow an evaluation of an instrumental or surgical intervention in the treatment of the hypertrophy and benign prostatic obstruction. Bibliographic research in English using the European, American and French recommendations on the evaluation of BPH, supplemented by a Pubmed search. A number of systematic investigations into the evaluation of a man with LUTS/BPH include interrogation, clinical examination with rectal examination, urinalysis, flowmeter and post-micturition residual volume. The voiding catalog is necessary to understand the mechanism of a nocturia. PSA has a triple potential of interest: evaluation of the risk of progression, evaluation of the prostatic volume and diagnosis of a cancer of the prostate. Creatinine is needed only when chronic retention is observed and before surgery. Urethrocystoscopy is essential in case of hematuria, suspicion of stenosis of the urethra or bladder tumor. Ultrasound for evaluation of prostate volume is essential before surgery, and may be helpful in guiding the decision to prescribe a 5 alpha reductase inhibitor. No non-invasive technique has proven its possible substitution for pressure flow studies when indicated. When a researcher is considering evaluating a surgical or instrumental treatment for BPH, preoperative, perioperative and follow-up parameters are expected from readers to get a fair idea of the technique being evaluated. LEVEL OF EVIDENCE 5: Consensus d'experts.


Release of immunoreactive substance P in the brain stem upon stimulation of the cranial dura mater with low pH - inhibition by the serotonin (5-HT1) receptor agonist CP 93,129.
1. The therapeutical benefit of serotonin (5-HT1) receptor agonists in the treatment of migraine headache has been attributed to their inhibitory effect on the release of pro-inflammatory neuropeptides from trigeminal afferents within the cranial meninges. The effect of 5-HT1 receptor agonists on the release of neuropeptides from central afferent terminals has not been examined so far. In the present study in the rat we therefore measured the effect of the 5-HT1B receptor agonist CP 93,129 on the stimulation-evoked release of immunoreactive substance P (ir-SP) in the spinal trigeminal nucleus. 2. To measure release of ir-SP, microprobes coated with antibody to substance P were inserted into the medulla oblongata at the level of the obex. The ipsilateral parietal dura mater encephali was exposed and stimulated with acid phosphate buffered Tyrode solution (pH 5.8). This chemical stimulus increased the release of ir-SP in the medullary dorsal horn. 3. Systemic (i.v.) administration of CP 93,129 (460 nmol kg(-1)) prior to stimulation suppressed the stimulation-evoked increase of release of ir-SP. Local administration of CP 93,129 (10 microM) to the dorsal surface of the medulla had no significant inhibitory effect on the release. 4. It is concluded that systemically applied 5-HT1 receptor agonists reduce the stimulation-evoked release of substance P from the central endings of meningeal afferents in the spinal trigeminal nucleus (medullary dorsal horn). This inhibitory effect may contribute to the antinociceptive effect of 5-HT1 receptor agonists in migraine.


Chemical, Enantioselective, and Sensory Analysis of a Cholinesterase Inhibitor Essential Oil from Coreopsis triloba S.F. Blake (Asteraceae).
The fresh leaves of Coreopsis triloba S.F. Blake, collected at Cerro Villonaco in Loja, Ecuador, were investigated with respect to their essential oil (EO). The chemical composition was determined qualitatively through gas chromatography coupled with mass spectrometry (GC-MS) and quantitatively by gas chromatography coupled with flame ionization (GC-FID), using relative response factors (RRF) based on the enthalpy of combustion. The essential oil contained between 92.5% and 93.4% of monoterpene hydrocarbons, with (E)-β-ocimene being the main component (35.2-35.9%), followed by β-phellandrene (24.6-25.0%), α-pinene (15.3-15.9%), myrcene (10.9-11.0%), sabinene (2.2-2.4%), (Z)-β-ocimene (1.5%), and germacrene D (1.2-1.3%). The enantiomeric distribution of α-pinene, β-pinene, limonene, and germacrene D was also determined. The main components responsible for the aroma were identified through aroma extract dilution analysis (AEDA), a gas chromatography-olfactometry (GC-O) based technique, being α-pinene, β-pinene (0.6%), terpinolene (0.1%), α-copaene (0.1-0.3%), β-phellandrene, and (E)-4,8-dimethyl-1,3,7-nonatriene (0.1-0.2%) the main olfactory constituents according to the decreasing factor of dilution (FD) order. The biological tests showed IC50 inhibition values of 42.2 and 6.8 µg/mL for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively.


Effects of long-term catheter implantation on the contractile and histological properties of the canine bladder.
In beagles, a bladder catheter was surgically implanted and subvesical obstruction was artificially introduced. After 3 months a striking reduction in detrusor contractility measured in vitro was observed, which was associated with a presumptive reduction in the concentration of acetylcholinesterase in the muscle cells and a probable reduction in the mean cell size. In this model the contribution of the catheter to the changes is greater than that of the subvesical obstruction.


Quantification of diadenosine polyphosphates in blood plasma using a tandem boronate affinity-ion exchange chromatography system.
Endogenous diadenosine polyphosphates (Ap(n)As) have been associated with a variety of biological effects but quantifying their concentration in blood is difficult. We report on the development of a tandem affinity-ion exchange high-performance liquid chromatography (HPLC) system that employs boronate affinity upstream of ion exchange chromatography for automated rapid (45-min) resolution and extraction of Ap(n)As from human plasma. This system obviates previous requirements for multiple column separations and handling steps, so it is ideally set up for time- and cost-efficient screening of blood samples for Ap(n)A pharmacokinetic and biodistribution studies.


Radioimmunoassay of 5-hydroxymethyl-2'-deoxyuridine.
5-Hydroxymethyl-2'-deoxyuridine is an antileukemic thymidine analogue. It is also a well known thymidine-derivative in DNA exposed to ionizing irradiation. We report the production and characterization of specific rabbit anti-5HmdUrd antisera. The antisera were used for the radioimmunological measurement of 5HmdUrd. The radioimmunoassay was capable of quantitating 2 pmol of 5 HmdUrd per tube corresponding to 0.2 mumol/l in a 10 microliter plasma sample. A good correlation between the results obtained with the radioimmunoassay and HPLC was demonstrated when the methods were applied to the measurement of plasma levels of 5HmdUrd in mice receiving experimental chemotherapy.


Levamisole-Induced Leukoencephalopathy in Russia: Analysis of 30 Cases.
The study aims to raise medical specialists' awareness regarding the severity of possible complications of levamisole administration, and demonstrate the role of accurate medical history collection in a differential diagnosis. Levamisole, an anthelmintic drug with immunomodulatory effects, has long been used worldwide till the early 2000s, when its association with demyelinating leukoencephalopathy was established. However, in the developing countries, it is still widely used for the prevention and treatment of helminthic invasion in humans. The actual prevalence of levamisole-induced multiple inflammatory leukoencephalopathy (LEV-induced MIL) in Russia remains unknown, and therefore, the study of its frequency and characteristics is indisputably important. The objective of this study is to determine the clinical features and MRI findings of levamisole- induced MIL in the Russian population, and to analyse the frequency of diagnostic errors at the initial assessment. A single-center retrospective analysis of total 30 patients who were diagnosed with LEV- induced MIL and attended the Research Center of Neurology was conducted. Inclusion criteria were 1) clinically: acute or subacute polysymptomatic onset of neurological disturbances, 2) MRI: multifocal demyelinating lesion with no evidence of dissemination in time, 3) anamnestic data: levamisole exposure from 2 to 8 weeks before symptoms onset as well as monophasic disease course (absence of relapses according to follow up assessments up to 3 years). Clinically, presentation with constitutional symptoms including headache, fever, fatigue and myalgia, focal motor disturbances and dysarthria prevailed in our cohort. On the brain MRI, multiple foci of demyelination with simultaneous gadolinium enhancement were observed. The link between neurological symptoms and levamisole intake has often been detected only during follow- up assessments. Patients were most often misdiagnosed with acute disseminated encephalomyelitis, stroke and multiple sclerosis. In most cases, LEV-induced MIL was successfully treated with intravenous corticosteroids and/or plasma exchange (PLEX), however, residual neurologic symptoms were preserved in some patients. Additionally, two detailed clinical cases of patients being initially misdiagnosed are presented in the article. The differential diagnosis remains difficult for suspected cases of LEV-induced MIL that could lead to delayed therapy initiation, and consequently incomplete recovery. Growing evidence suggests that a single administration of levamisole even in low doses might potentially lead to severe neurological deficit or death. Therefore, changes in medication management policies are required in order to prevent the uncontrolled use of levamisole.


Current issues in Kawasaki disease.
The most important clinical aspect of Kawasaki disease is the cardiovascular problems. This article reports on the cardiovascular spectrum in acute Kawasaki disease, analysis of myocardial infarction and fatal cases, a follow-up study on the natural history of coronary artery lesions, long-term cardiovascular problems including premature atherosclerosis, problems in the adult cardiology and the treatment of acute Kawasaki disease. The etiology and pathogenesis of this disease are still unknown. Current hypotheses and leading studies on the etiology and the pathogenesis of Kawasaki disease are also reviewed.


Transmembrane AMPA receptor regulatory protein regulation of competitive antagonism: a problem of interpretation.
Synaptic AMPA receptors are greatly influenced by a family of transmembrane AMPA receptor regulatory proteins (TARPs) which control trafficking, channel gating and pharmacology. The prototypical TARP, stargazin (or γ2), shifts the blocking ability of several AMPAR-selective compounds including the commonly used quinoxalinedione antagonists, CNQX and NBQX. Stargazin's effect on CNQX is particularly intriguing as it not only apparently lowers the potency of block, as with NBQX, but also renders it a partial agonist. Given this, agonist behaviour by CNQX has been speculated to account for its weaker blocking effect on AMPAR-TARP complexes. Here we show that this is not the case. The apparent effect of stargazin on CNQX antagonism can be almost entirely explained by an increase in the apparent affinity for l-glutamate (l-Glu), a full agonist and neurotransmitter at AMPAR synapses. Partial agonism at best plays a minor role but not through channel gating per se but rather because CNQX elicits AMPAR desensitization. Our study reveals that CNQX is best thought of as a non-competitive antagonist at glutamatergic synapses due to the predominance of non-equilibrium conditions. Consequently, CNQX primarily reports the proportion of AMPARs available for activation but may also impose additional block by receptor desensitization.


Diterpenoids and phenylethanoid glycosides from the roots of Clerodendrum bungei and their inhibitory effects against angiotensin converting enzyme and α-glucosidase.
Abietane derivatives, bungnates A, B, 15-dehydrocyrtophyllone A and 15-dehydro-17-hydroxycyrtophyllone A, and two phenylethanoid glycosides, bunginoside A and 3″,4″-di-O-acetylmartynoside, together with nine known abietane derivatives and fourteen known phenylethanoid glycosides, were isolated from dried roots of Clerodendrum bungei. Their structures were determined on the basis of detailed spectroscopic analyses and acidic hydrolysis. The absolute configuration of bunginoside A was established from analysis of CD data. Selected compounds were evaluated for inhibitory effects against angiotensin converting enzyme (ACE) and α-glucosidase. 15-Dehydrocyrtophyllone A showed an ACE inhibitory effect, and verbascoside, leucosceptoside A and isoacteoside exhibited strong inhibitory capacity against α-glucosidase.


The association between cigarette smoking and DSM-IV nicotine dependence among first year college students.
This study was undertaken to evaluate the association between cigarette smoking behavior and DSM-IV nicotine dependence. Drawing on a sample of first year college students selected for representation across a continuum of smoking behavior, current DSM-IV nicotine dependence criteria were assessed among participants reporting any smoking in the preceding week on a web-based survey protocol. Logistic regression and receiver operator characteristic analyses were used to estimate the overall concordance between smoking and DSM-IV nicotine dependence. Relationships were supported between both quantity and frequency of smoking in the past week and DSM-IV nicotine dependence showing higher prevalence of dependence at higher levels of use (p<0.05). While the highest prevalence of nicotine dependence was seen among those reporting the most frequent and heavy smoking, a substantial number of participants reporting daily and/or heavy smoking did not meet criteria for nicotine dependence. Conversely, nicotine dependence was seen among a subgroup of participants reporting relatively low levels of non-daily smoking. Diagnostic concordance was found to be moderate for both quantity and frequency and was not improved by combining information from these two indices. Aside from confirming DSM-IV nicotine dependence at relatively low levels of smoking, these results may be used to inform research aimed at identifying samples of nicotine dependent youth across the range of smoking levels.


Prognostic value of myeloperoxidase in patients with peripheral artery disease.
The involvement of myeloperoxidase in the production of dysfunctional high-density lipoproteins and oxidised biomolecules leads to oxidative stress in the blood vessel endothelium. This prospective cohort study aimed to examine the prognostic value of myeloperoxidase in patients with peripheral artery disease in relation to major adverse cardiac events (MACEs), target lesion revascularisation, and major adverse limb events (MALEs) and its association with multi-bed vascular disease, which is defined as any combination of the following: peripheral artery disease and coronary artery disease. Myeloperoxidase levels were measured in patients with peripheral artery disease and coronary artery disease during angiography. A total of 94 patients were analysed and followed up regarding their MACEs, target lesion revascularisation, and MALEs from August 2016 until February 2019. Among patients with peripheral artery disease, the rates of MACE and mortality were higher in patients with high myeloperoxidase levels than in those with low myeloperoxidase levels; the myeloperoxidase levels were 3.68 times higher in these patients (p < 0.0001). Patients with peripheral artery disease and coronary artery disease (multi-bed vascular disease) had higher myeloperoxidase levels than those with only peripheral artery disease and only coronary artery disease (one-bed vascular disease). Peripheral artery disease patients with higher myeloperoxidase levels had significantly higher rates of limb ischaemia, requiring further revascularisation than those with low myeloperoxidase levels. High myeloperoxidase levels suggest poor outcomes and are associated with MACE and limb ischaemia. Our findings indicated that myeloperoxidase levels could become a prognostic marker and may be used in conjunction with other methods for risk stratification in patients with peripheral artery disease and multi-bed vascular disease.


GABAA sodium independent receptor sites in a strain of rats presenting generalized non-convulsive seizures.
The role of gamma-aminobutyric acid (GABA), a major inhibitor neurotransmitter in the central nervous system (CNS), is well established in the genesis and the control of epilepsies. The purpose of this work was to study the binding parameters of the Na(+)-independent GABA receptors in the brain of a strain of rats presenting spontaneous generalized non-convulsive seizures. The high- and low-affinity binding sites were evaluated in cerebral cortex, cerebellum, and hippocampus using [3H]muscimol. No significant modification was observed for the Bmax and the Kd of high-affinity binding sites, although a slight decrease of Bmax was noted in the three brain areas in rats with seizures. Concerning the low-affinity binding sites, significant decreases were observed in the values of Bmax in the cortex, cerebellum, and hippocampus of animals with spontaneous seizures, without modification of Kd values. Such changes could be considered to be involved in some of the physiological and behaviour activities observed in this strain of rats.


Structural features related to hydrolytic activity against ceftazidime of plasmid-mediated SHV-type CAZ-5 beta-lactamase.
Tryptic peptides of the novel ceftazidimase CAZ-5 were sequenced by manual Edman degradation and aligned according to strong homology (more than 98%) with SHV-1 and SHV-2 beta-lactamase sequences. CAZ-5 differed from SHV-1 by five amino acid substitutions. Unusually high activity of CAZ-5 towards ceftazidime was imputed to substitution of a Lys for a Glu at position 214 of the mature protein.


SOX9 expression is a general marker of basal cell carcinoma and adnexal-related neoplasms.
SOX9 is a transcription factor that fulfills multiple functions during development. In the hair follicle SOX9 is expressed in the outer layer of the epithelial sheath, and the hair stem cell compartment. Recent data suggest that Sox9 acts as a downstream target of the Sonic hedgehog (Shh) pathway. Activation of the Shh pathway is a major cause of cutaneous basal cell carcinoma (BCC). Here we test whether activation of SOX9 is a general feature of BCC, or whether it could be used as a biomarker to better define subtypes of these skin tumors. In addition we investigated SOX9 expression in other skin epidermal tumors. Tumors sections were stained with hematoxylin & eosin (H&E). SOX9 activation was determined by immunofluorescence. SOX9 activation was observed in all subtypes of BCC tested. Staining was heterogeneous and could be detected among the basaloid cells of the palisading cell layer as well as in the tumour nest. SOX9 expression was detected in all adnexal tumors analyzed and absent in Bowen's disease and Merkel tumor. SOX9 expression is a general feature of BCC and adnexal skin neoplasms, suggesting a contribution of SOX9 to the pathogenesis of these tumors.


Development of techniques for the detection of blood doping in sport.
Increased performance after blood transfusion was first demonstrated 40 years ago, but the technique did not create attention until the early 1970s when it was dubbed 'blood doping' by the media. The procedure can increase both maximal oxygen uptake (VO2max) and performance in endurance sports. It was forbidden by the International Olympic Committee (IOC) after the 1984 Olympics, despite the fact that no methods had been devised for unequivocal detection. There are 2 types of blood transfusions: either from a matching donor (heterologous transfusion) or reinfusion of the subject's own blood (autologous transfusion). While the subject's haemoglobin normalise, blood can be stored in commercially available blood bags for 4 to 5 weeks in a 'blood bank' (+4 degrees C), or as frozen erythrocytes with a storage time up to several years. A blood doping procedure, independent of transfusion type, induces some pronounced physiological changes. A desired effect of blood doping is the increased total red blood cell mass leading to increments in haemoglobin, which after successfully induced blood doping is in the magnitude of at least 10%. In addition, storing of blood leads to a constant decline in RBC count due to the limited life span of the RBC (haemolysis). Thereby, serum iron and bilirubin levels will increase and reach maximal levels within the first day. Haemolysis is more accentuated after storing of blood in a blood bank than in the frozen state. The regulation of RBC formation is mediated through a negative feed-back mechanism via the glucoprotein hormone erythropoietin.(ABSTRACT TRUNCATED AT 250 WORDS)


Labor market effects of intrauterine exposure to nutritional deficiency: Evidence from administrative data on Muslim immigrants in Denmark.
This paper examines whether nutritional disruptions experienced during the stage of fetal development impair an individual's labor market productivity later in life. We consider intrauterine exposure to the month of Ramadan as a natural experiment that might cause shocks to the inflow of nutrients essential for fetal development. Specifically, we use administrative data from Denmark to investigate the impact of exposure to Ramadan in utero on labor market outcomes of adult Muslim males, including employment status, annual salary, hourly wage rate, and hours of work. Our findings indicate that potential exposure to nutritional disruptions during a critical stage of fetal development is likely to have scarring effects on the fetus expressed as poor labor market outcomes later in life. Specifically, exposure to Ramadan around the 7th month of gestation results in a lower likelihood of employment and, to a lesser extent, a lower salary, and reduced labor supply. For example, the 7th month intrauterine exposure to Ramadan is associated with a 2.6 percentage points reduction in the likelihood of employment among Muslim males. We do not find an impact on the wage rate. Finally, we also document suggestive evidence that these results may partially be driven by increased disability and to a lesser extent by poor educational attainment among those who were exposed to Ramadan during this particular period in utero.


Harsh and Inconsistent Parental Discipline Is Associated With Altered Cortical Development in Children.
A growing body of evidence suggests that parenting behaviors may affect child mental health via altering brain development. There is a scarcity of research, however, that has investigated associations between parenting behavior and brain structure using longitudinal magnetic resonance imaging. This study aimed to investigate associations between parenting behaviors and structural brain development across the transition from childhood to adolescence. Participants were 246 children who provided 436 magnetic resonance imaging datasets covering the age range from 8 to 13 years. Parents (94% mothers) completed self-report measures of parenting behavior, and both children and parents reported on child mental health. Factor analysis was used to identify dimensions of parental behavior. Linear mixed-effects models investigated associations between parenting behaviors and age-related change in cortical thickness and surface area and subcortical volume. Mediation models tested whether brain changes mediated associations between parenting behaviors and changes in internalizing/externalizing symptoms. Hypothesized associations between parenting and amygdala, hippocampal, and frontal trajectories were not supported. Rather, higher levels of parent harsh/inconsistent discipline were associated with decreases in surface area in medial parietal and temporal pole regions and reduced cortical thinning in medial parietal regions. Some effects were present in female but not male children. There were no associations between these neurodevelopmental alterations and symptoms. This study provides insight into the links between parenting behavior and child neurodevelopment. Given the functions of implicated regions, findings may suggest that parental harsh/inconsistent discipline affects the development of neural circuits subserving sensorimotor and social functioning in children.


Reciprocal serotonergic connections between the hamster median and dorsal raphe nuclei.
The median (MnR), but not the dorsal (DR) raphe, sends a serotonergic projection to the suprachiasmatic (SCN) nucleus. Stimulation of either nucleus by electrode or serotonin agonist yields equivalent effects on circadian rhythmicity. This and other evidence suggests the existence of a functional serotonergic pathway from the DR to the MnR that may participate in circadian rhythm regulation. The present investigation was designed to identify such a connection. Tract tracer studies revealed cells in the DR that project to the MnR, as well as cells in the MnR that project to the DR. Double label immunofluorescence methods demonstrated that some of the cells projecting from either nucleus to the other contain serotonin immunoreactivity. The results support the existence of a reciprocal pathway between the DR and MnR that is at least partially serotonergic.


A phase II study evaluating axitinib in patients with unresectable, recurrent or metastatic head and neck cancer.
Axitinib is an oral, potent, small molecule tyrosine kinase inhibitor with selective inhibition of VEGFR 1,2, 3, as well as inhibition of potential downstream effectors of the EGFR pathway. Given the upregulation of EGFR and VEGFR in head and neck squamous cell carcinoma, treatment with axitinib holds promise as a rational targeted therapy. Patients with unresectable, recurrent or metastatic head and neck squamous cell carcinoma were included in this open label, single arm, phase II trial. Primary endpoint was 6 month progression free survival. All patients received single agent axitinib with planned dose escalation based on tolerability. A planned interim efficacy analysis was performed after enrollment of 30 patients. Forty-two patients were registered, 30 were evaluable. While treatment was well-tolerated with no severe bleeding events, only 19 patients were able to achieve full planned dose. The best overall response rate was 6.7% (two partial responses) with a disease control rate of 76.7%. Median progression free survival was 3.7 months (95% Confidence Interval (CI): 3.5-5.7) and overall survival was 10.9 months (95% CI: 6.4-17.8). Exploratory analysis demonstrated that patients with a smaller sum of diameter of target lesions experienced improved response rates, and better progression-free and overall survival. Treatment with single agent axitinib should be considered due to acceptable toxicity profile and favorable median overall survival compared to standard therapies.


Design and performance evaluation of a photocatalytic reactor for indoor air disinfection.
Since COVID-19 pandemic, indoor air quality control has become a priority, and the development of air purification devices effective for disinfecting airborne viruses and bacteria is of outmost relevance. In this work, a photocatalytic device for the removal of airborne microorganisms is presented. It is an annular reactor filled with TiO2-coated glass rings and irradiated internally and externally by UV-A lamps. B. subtilis spores and vegetative cells have been employed as model biological pollutants. Three types of assays with aerosolized bacterial suspensions were performed to evaluate distinct purification processes: filtration, photocatalytic inactivation in the air phase, and photocatalytic inactivation over the TiO2-coated rings. The radiation distribution inside the reactor was analysed by performing Monte Carlo simulations of photon absorption in the photocatalytic bed. Complete removal of a high load of microorganisms in the air stream could be achieved in 1 h. Nevertheless, inactivation of retained bacteria in the reactor bed required longer irradiation periods: after 8 h under internal and external irradiation, the initial concentration of retained spores and vegetative cells was reduced by 68% and 99%, respectively. Efficiency parameters were also calculated to evaluate the influence of the irradiation conditions on the photocatalytic inactivation of bacteria attached at the coated rings.


Food competition in captive female sooty mangabeys (Cercocebus torquatus atys).
We studied the social and foraging behavior of two captive groups of sooty mangabeys under two different spatial food situations. These food conditions were clumped (food was placed in a box) and dispersed (food was dispersed over the entire enclosure). In each group five adult females and two adult males were observed. As a criterion for food competition, individual differences in the relative food intake were used. Adult female mangabeys had a linear, stable, and unidirectional dominance hierarchy. Access to food was rank dependent among females only under clumped food distribution, as current models of the evolution of primate social systems predict. However, feeding success appeared to be mediated not by female but by male agonistic behavior toward females. High-ranking females received relatively less aggression from males and could, therefore, stay and feed longer in the feeding area. Male tolerance of higher-ranking females seems to mediate female feeding success under restricted food resources. The establishment of a special relationship with a high-ranking male might, therefore, be a strategy to get better access to food. This study demonstrates that female competition for access to food should not be analyzed separately from male influences on females and suggests that a more integral role of males in socioecological models of the evolution of primate social systems should be considered.


Two initiator-like elements are required for the combined activation of the human apolipoprotein C-III promoter by upstream stimulatory factor and hepatic nuclear factor-4.
Human apoC-III (-890/+24) promoter activity is strongly activated by hepatic nuclear factor (HNF)-4 through its binding to the proximal (-87/-72) element B. This site overlaps the binding site for an activity that we identified as the ubiquitously expressed upstream stimulatory factor (USF) (Ribeiro, A., Pastier, D., Kardassis, D., Chambaz, J., and Cardot, P. (1999) J. Biol. Chem. 274, 1216-1225). In the present study, we characterized the relationship between USF and HNF-4 in the activation of human apoC-III transcription. Although USF and HNF-4 binding to element B is mutually exclusive, co-transfection experiments in HepG2 cells surprisingly showed a combined effect of USF and HNF-4 in the transactivation of the (-890/+24) apoC-III promoter. This effect only requires the proximal region (-99/+24) of the apoC-III promoter and depends neither on USF binding to its cognate site in element B nor on a USF-dependent facilitation of HNF-4 binding to its site. By contrast, we found by electrophoretic mobility shift assay and footprinting analysis two USF low affinity binding sites, located within the proximal promoter at positions -58/-31 (element II) and -19/-4 (element I), which are homologous to initiator-like element sequence. Co-transfection experiments in HepG2 cells show that a mutation in element II reduces 2-fold the USF transactivation effect on the proximal promoter of apoC-III and that a mutation in element I inhibits the combined effect of USF and HNF-4. In conclusion, these initiator-like elements are directly involved in the transactivation of the apoC-III promoter by USF and are necessary to the combined effect between USF and HNF-4 for the apoC-III transcription.


Scaffold development using selective laser sintering of polyetheretherketone-hydroxyapatite biocomposite blends.
In tissue engineering (TE), temporary three-dimensional scaffolds are essential to guide cell proliferation and to maintain native phenotypes in regenerating biologic tissues or organs. To create the scaffolds, rapid prototyping (RP) techniques are emerging as fabrication techniques of choice as they are capable of overcoming many of the limitations encountered with conventional manual-based fabrication processes. In this research, RP fabrication of solvent free porous polymeric and composite scaffolds was investigated. Biomaterials such as polyetheretherketone (PEEK) and hydroxyapatite (HA) were experimentally processed on a commercial selective laser sintering (SLS) RP system. The SLS technique is highly advantageous as it provides good user control over the microstructures of created scaffolds by adjusting the SLS process parameters. Different weight percentage (wt%) compositions of physically mixed PEEK/HA powder blends were sintered to assess their suitability for SLS processing. Microstructural assessments of the scaffolds were conducted using electron microscopy. The results ascertained the potential of SLS-fabricated TE scaffolds.


Three-dimensional breathhold SSFP coronary MRA: a comparison between 1.5T and 3.0T.
To assess the feasibility of three-dimensional breathhold coronary magnetic resonance angiography (MRA) at 3.0T using the steady-state free precession (SSFP) sequence, and quantify the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) gains of coronary MRA from 1.5T to 3.0T using whole-body and phased-array cardiac coils as the signal receiver. Eight healthy volunteers were scanned on 1.5T and 3.0T whole-body systems using the SSFP sequence. Numerical simulations were performed for the SSFP sequence to optimize the flip angle and predict signal enhancement from 1.5T to 3.0T. Coronary artery images were acquired with the whole-body coil in transmit-receive mode or transmit-only with phased-array cardiac coil receivers. In vivo studies of the same volunteer group at both field strengths showed increases of 87% in SNR and 83% in CNR from 1.5T to 3.0T using a whole-body coil as the signal receiver. The corresponding increases using phased-array receivers were 53% in SNR and 92% in CNR. However, image quality at 3.0T was more variable than 1.5T, with increased susceptibility artifacts and local brightening as the result of increased B(0) and B(1) inhomogeneities. Coronary MRA at 3.0T using a three-dimensional breathhold SSFP sequence is feasible. Improved SNR at 3.0T warrants the use of coronary MRA with faster acquisition and/or improved spatial resolution. Further investigations are required to improve the consistency of image quality and signal uniformity at 3.0T.


Evaluation of electrochemical quartz crystal microbalance based sensor modified by uric acid-imprinted polypyrrole.
Uric acid-imprinted polypyrrole-based (MIP(UA)-Ppy) electrochemical quartz crystal microbalance sensor (EQCM) was developed. Experiments and theoretical calculations were focused on molecular interactions between uric acid molecule and: i) polypyrrole imprinted by uric acid (MIP(UA)-Ppy) ii) polypyrrole film without any molecular imprints (NIP-Ppy). Resonant frequency differences during electrochemical deposition of MIP(UA)-Ppy and NIP-Ppy films were observed and were attributed to the phenomenon of molecule capture within formed Ppy matrix. EQCM-resonators modified by MIP-Ppy showed the following advantages: selectivity, qualitative response, cost-effectiveness, and simple procedure. The selectivity of MIP(UA)-Ppy was tested by the replacement of uric acid in the PBS solution with several different concentrations of caffeine and glucose. Langmuir isotherm based molecular adsorption model was applied to evaluate the interaction of MIP(UA)-Ppy with uric acid. From experimental results calculated the standard Gibbs free energy of association (ΔGa) of uric acid with MIP(UA)-Ppy is -16.4 ± 2.05 kJ/mol and with NIP-Ppy is -13.3 ± 8.56 kJ/mol ΔG values illustrate that the formation of uric acid complex with MIP(UA)-Ppy is thermodynamically more favourable than that for complexation with NIP-Ppy.


LncRNA ASAP1-IT1 enhances cancer cell stemness via regulating miR-509-3p/YAP1 axis in NSCLC.
Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide, and cancer stem cell is responsible for the poor clinical outcome of NSCLC. Previous reports indicated that long noncoding RNAs (lncRNAs) play important roles in maintaining cancer stemness, however, the underlying mechanisms remain unclear. This study investigates the role of ASAP1 Intronic Transcript 1 (ASAP1-IT1) in cancer cell stemness of NSCLC. The expression of ASAP1-IT1, microRNA-509-3p (miR-509-3p) and apoptosis-/stemness-related genes was analyzed by qRT-PCR in NSCLC tissues, cancer cells and spheres of cancer stem cells. Knockdown of ASAP1-IT1 or overexpression of miR-509-3p in NSCLC cells by infection or transfection of respective plasmids. Sphere formation and colony formation were used to detect NSCLC stem cell-like properties and tumor growth in vitro. Luciferase reporter assays, RNA immunoprecitation (RIP) and qRT-PCR assays were used to analyze the interaction between lncRNA and miRNA. The expression of expression of regulated genes of ASAP1-IT1/miR-509-3p axis was evaluated by qRT-PCR and Western blot. The NSCLC xenograft mouse model was used to validate the role of ASAP1-IT1 in NSCLC stemness and tumor growth in vivo. ASAP1-IT1 was up-regulated in NSCLC tissues, cancer cells, and in spheres of A549-derived cancer stem cells. Downregulation of ASAP1-IT1 or overexpression of miR-509-3p significantly decreased cell colony formation and stem cell-like properties of A549-dereived stem cells with decreased expression of stem cell biomarkers SOX2, CD34, and CD133, and suppressing the expression of cell growth-related genes, Cyclin A1, Cyclin B1, and PCNA. Furthermore, knockdown of ASAP1-IT1 or overexpression of miR-509-3p repressed tumor growth in nude mice via reducing expression of tumorigenic genes. ASAP1-IT1 was found to interact with miR-509-3p. Moreover, overexpression of ASAP1-IT1 blocked the inhibition by miR-509-3p on stem cell-like properties and cell growth of A549-dereived stem cells both in vitro and in vivo. Finally, the level of YAP1 was regulated by ASAP1-IT1 and miR-509-3p. YAP1-involved ASAP1-IT1/miR-509-3p axis promoted NSCLC progression by regulating cancer cell stemness, and targeting this signaling pathway could be is a promising therapeutic strategy to overcome NSCLC stemness.


In vivo and in vitro anti-inflammatory activity evaluation of Lebanese Cannabis sativa L. ssp. indica (Lam.).
Cannabis sativa L. is an aromatic annual herb belonging to the family Cannabaceae and it is widely distributed worldwide. Cultivation, selling, and consumption of cannabis and cannabis related products, regardless of its use, was prohibited in Lebanon until April 22, 2020. Nevertheless, cannabis oil has been traditionally used unlawfully for many years in Lebanon to treat diseases such as arthritis, diabetes, cancer and few neurological disorders. The present study aims to evaluate the phytochemical and anti-inflammatory properties of a cannabis oil preparation that is analogous to the illegally used cannabis oil in Lebanon. Dried Cannabis flowers were extracted with ethanol without any purification procedures to simulate the extracts sold by underground dealers in Lebanon. GC/MS was performed to identify chemical components of the cannabis oil extract (COE). In vivo anti-inflammatory effect of COE was evaluated by using carageenan- and formalin-induced paw edema rat models. TNF-α production were determined by using LPS-activated rat monocytes. Anti-inflammatory markers were quantified using Western blot. Chemical analysis of COE revealed that cannabidiol (CBD; 59.1%) and tetrahydrocannabinol (THC; 20.2%) were found to be the most abundant cannabinoids.Various monoterpenes (α-Pinene, Camphene, β-Myrecene and D-Limonene) and sesquiterpenes (β-Caryophyllene, α-Bergamotene, α-Humelene, Humulene epoxide II, and Caryophyllene oxide) were identified in the extract. Results showed that COE markedly suppressed the release of TNF-α in LPS-stimulated rat monocytes. Western blot analysis revealed that COE significantly inhibited LPS-induced COX-2 and i-NOS protein expressions and blocked the phosphorylation of MAPKs, specifically that of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 MAPK. COE displayed a significant inhibition of paw edema in both rat models. Histopathological examination revealed that COE reduced inflammation and edema in chronic paw edema model. The current findings demonstrate that COE possesses remarkable in vivo and in vitro anti-inflammatory activities which support the traditional use of the Lebanese cannabis oil extract in the treatment of various inflammatory diseases including arthritis.


Towards reducing DBP formation potential of drinking water by favouring direct ozone over hydroxyl radical reactions during ozonation.
When ozonation is employed in advanced water treatment plants to produce drinking water, dissolved organic matter reacts with ozone (O3) and/or hydroxyl radicals (OH) affecting disinfection byproduct (DBP) formation with subsequently used chlorine-based disinfectants. This study presents the effects of varying exposures of O3 and •OH on DBP concentrations and their associated toxicity generated after subsequent chlorination. DBP formation potential tests and in vitro bioassays were conducted after batch ozonation experiments of coagulated surface water with and without addition of tertiary butanol (t-BuOH, 10 mM) and hydrogen peroxide (H2O2, 1 mg/mg O3), and at different pH (6-8) and transferred ozone doses (0-1 mg/mg TOC). Although ozonation led to a 24-37% decrease in formation of total trihalomethanes, haloacetic acids, haloacetonitriles, and trihaloacetamides, an increase in formation of total trihalonitromethanes, chloral hydrate, and haloketones was observed. This effect however was less pronounced for samples ozonated at conditions favoring molecular ozone (e.g., pH 6 and in the presence of t-BuOH) over •OH reactions (e.g., pH 8 and in the presence of H2O2). Compared to ozonation only, addition of H2O2 consistently enhanced formation of all DBP groups (20-61%) except trihalonitromethanes. This proves that •OH-transformed organic matter is more susceptible to halogen incorporation. Analogously, adsorbable organic halogen (AOX) concentrations increased under conditions that favor •OH reactions. The ratio of unknown to known AOX, however, was greater at conditions that promote direct O3 reactions. Although significant correlation was found between AOX and genotoxicity with the p53 bioassay, toxicity tests using 4 in vitro bioassays showed relatively low absolute differences between various ozonation conditions.


The use of basic life support skills by hospital staff; what skills should be taught?
To assess the frequency of use of basic life support (BLS) skills among hospital staff of all disciplines. Postal survey of 9600 teaching hospital staff. 3807 respondents from all disciplines. Frequency of attendance, and the use of BLS skills, at patients with cardiopulmonary arrest. Most respondents reported having attended BLS training previously: 27.9% in the prior 6 months; 24.5% 6-12 months previously; 17.1% over 1 year ago; and 11.5% over 2 years ago. 17.1% reported never having received BLS training. 1.9% gave no valid response. Nearly half of all respondents had never attended a cardiopulmonary arrest. Among those most likely to have attended, i.e. qualified nursing and medical staff, the median frequency of attendance was less than once per year. Ventilation delivered using a pocket mask or bag-valve-mask was reported by 9.4 and 29.2% of respondents, respectively. Less than 7% reported the use of mouth-to-mouth ventilation. Only among qualified nursing (8.8%) and medical (24.7%) staff did this proportion exceed 5%. The vast majority of non-qualified nursing staff (84.9%), allied health professionals (86%) and administrative and clerical staff (98%) had used neither chest compressions nor mouth-to-mouth ventilation. Some skills taught during BLS training are used infrequently in the in-hospital situation. The likelihood of attendance at arrest events and of the use of BLS skills is extremely low among some identified professional groups. BLS skills teaching should be targeted at those groups most likely to actually use them in order to make best use of the resources available.


High cell density alters the ratio of type III to I collagen synthesis by fibroblasts.
HUMAN fibroblasts in culture synthesise both type I and type III collagen(1), with type I accounting for 70-90% of the total(2). In culture, the rates at which these proteins are synthesised is constant and apparently rather rigidly controlled(3). However, the proportions of these collagens differs in cells cultured with increased amounts of serum (increased type III/I)(4) as well as in cells obtained from patients with certain diseases. Cells from patients with the Ehlers-Danlos type IV syndrome make little or no type III collagen(5,6), whereas cells from patients with osteogenesis imperfecta have an increased type III/I (refs 7, 8). We have found that cells from some patients with systemic sclerosis (scleroderma), have a reduced type III/I ratio. However, as previously reported, these cells grew to a lower density than control cells(9). We report here that normal fibroblasts from human and guinea pig skin produce proportionally more type III collagen at high cell density, probably because of a reduction in the synthesis of type I collagen.


Rescue and transmission of a replication-defective variant of moloney murine leukemia virus.
We have described a clone of mouse cells, termed "8A," which appears to be infected with a replication-defective variant of Moloney murine leukemia virus (MuLV) (Rein et al., J. Virol. 25:146-156, 1978). Clone 8A cells release virus particles which do not form plaques in the standard XC test. However, approximately 10(2) particles per ml of clone 8A supernatant do form plaques in a modified XC test (the "complementation plaque assay"), in which the assay cells are coinfected with the XC-negative, nondefective amphotropic MuLV as well as the test virus. Superinfection of clone 8A cells themselves with amphotropic MuLV results in the production of approximately 10(5), rather than approximately 10(2), particles per ml which register in the complementation plaque assay. This increase is due to the rescue of replication-defective ecotropic MuLV from clone 8A cells by amphotropic MuLV since (i) this ecotropic MuLV can only form XC plaques in cells which are coinfected with amphotropic MuLV; and (ii) it is possible to transmit this defective variant, rescued from superinfected clone 8A cells, to a fresh clone of normal mouse cells. The time course of production of the rescued MuLV particles by superinfected clone 8A cells is virtually identical to that of rescue from these cells of murine sarcoma virus. Amphotropic MuLV superinfection of "NP-N" cells, which contain a "non-plaque-forming" variant of N-tropic MuLV (Hopkins and Jolicoeur, J. Virol. 16:991-999, 1975), also increases the titer of particles registering in the complementation plaque assay; thus, NP-N cells, like clone 8A cells, contain a rescuable defective variant of ecotropic MuLV.


Chromosomes 17 and 22 involved in marker formation in neurofibrosarcoma in von Recklinghausen disease. A cytogenetic and in situ hybridization study.
We describe the cytogenetic findings in a recurrent neurofibrosarcoma in a patient with nonfamilial von Recklinghausen disease. The composite karyotype was: 40,Y,-X,+dic r(X;20)(:Xp22.2----q26::20p13----q13:), -1, +der(1)t(1;3) (p21;p24),-3,-4,-5,+der(5) t(5;?)(q31;?),-9,-9,+der(9)t(3;9)(q21 or q13;p24 or p22), -11,+der(11)t(11;?)(q22.2;?), -17,+der(17)t(17; 22;?)(q21;q13.1;?), -20, -21, -22, -22, +der(22)t(17; 22;?)(q21;q13.1;?),t(2;10)(q37;q22). The derivative chromosomes were demonstrated at the 500 band level. Chromosomes 17 and 22 were shown to be involved in an unbalanced three-way translocation: t(17;22;?)(q21;q13.1;?). This event was confirmed by in situ hybridization, using two probes mapped to chromosome 17. Hill H is a probe derived from the novel oncogene TRE and is located at 17q12-22. The second probe, derived from the granulocyte colony-stimulating factor (G-CSF), is located at 17q11-q21. The rearrangement between chromosomes 17 and 22 showed breakpoints similar or close to the gene loci for neurofibromatosis 1 (NF-1) and NF-2. Based on our observations we recommend that genetic studies on NF-1 tumors include both gene sites (NF-1 and NF-2) rather than focus on one gene locus.


Conditional deletion of nonmuscle myosin II-A in mouse tongue epithelium results in squamous cell carcinoma.
To investigate the contribution of nonmuscle myosin II-A (NM II-A) to early cardiac development we crossed Myh9 floxed mice and Nkx2.5 cre-recombinase mice. Nkx2.5 is expressed in the early heart (E7.5) and later in the tongue epithelium. Mice homozygous for deletion of NM II-A (A(Nkx)/A(Nkx)) are born at the expected ratio with normal hearts, but consistently develop an invasive squamous cell carcinoma (SCC) of the tongue (32/32 A(Nkx)/A(Nkx)) as early as E17.5. To assess reproducibility a second, independent line of Myh9 floxed mice derived from a different embryonic stem cell clone was tested. This second line also develops SCC indistinguishable from the first (15/15). In A(Nkx)/A(Nkx) mouse tongue epithelium, genetic deletion of NM II-A does not affect stabilization of TP53, unlike a previous report for SCC. We attribute the consistent, early formation of SCC with high penetrance to the role of NM II in maintaining mitotic stability during karyokinesis.


Ommatidia of blow fly, house fly, and flesh fly: implication of their vision efficiency.
This work aims to elucidate the number of ommatidia or facets (the outwardly visible units of each ommatidium) for compound eyes in blow flies [Chrysomya megacephala (F.), Chrysomya rufifacies (Macquart), Chrysomya nigripes (Aubertin), Lucilia cuprina (Wiedemann)], house flies (Musca domestica L.), and flesh flies (Liosarcophaga dux Thomson) by manual counts of the corneal spreads. The head of the fly in each species was soaked in 20% potassium hydroxide solution at room temperature for 7 days, and the clear compound eye was dissected into six small parts, each of which was placed onto a slide and flattened using a coverslip. Images of each part were obtained using a microscope connected to a computer. The printed images of each part were magnified, and the total number of ommatidia per eye was manually counted. For males, the mean number of ommatidia was statistically different among all flies examined: L. dux (6,032) > C. rufifacies (5,356) > C. nigripes (4,798) > C. megacephala (4,376) > L. cuprina (3,665) > M. domestica (3,484). Likewise, the mean number of facets in females was statistically different: L. dux (6,086) > C. megacephala (5,641) > C. rufifacies (5,208) > C. nigripes (4,774) > L. cuprina (3,608) > M. domestica (3433). Scanning electron microscopy analysis of adult flies revealed the sexual dimorphism in the compound eye. Male C. megacephala had large ommatidia in the upper two thirds part and small ommatidia in the lower one third part, whereas only small ommatidia were detected in females. Dense postulate appearance was detected in the external surface of the corneal lens of the ommatidia of C. megacephala, C. rufifacies, and C. nigripes, while a mix of dense postulate appearance and variable groove array length was detected in L. cuprina and M. domestica. The probable functions of ommatidia are discussed with reference to other literature.


A Structured Quality Improvement Educational Curriculum Increases Surgical Resident Involvement in QI Processes.
Patient safety and quality improvement (QI) processes are vitally important to healthcare systems. Training and experience in QI processes are mandated by the Accreditation Council for Graduate Medical Education (ACGME) for general surgery residents. The execution and efficacy of these training programs in residencies have thus far been inconsistent. The purpose of this study was to assess the effectiveness of our surgical residency's QI educational program. We instituted a formalized QI educational program for all residents in our academic general surgery residency program from 2018 to 2019. The curriculum included didactics, online educational resources, peer-group collaboration, and faculty mentorship. Residents performed a self-assessment survey of their knowledge, skill, and comfort levels with QI processes before and after the program using a 10-point Likert scale. The number of QI projects conducted, presented, and subsequently prepared for publication was enumerated. The ACGME resident survey program results regarding resident involvement in QI processes before and after program implementation were compared. After 1 year of the program, residents demonstrated significant increases in average self-assessed knowledge of QI processes (6.4 vs. 4.0, p < 0.05), knowledge of local QI resources (5.4 vs. 3.3, p < 0.05), and confidence in their ability to develop and implement a QI project (6.3 vs. 3.9, p < 0.05). The average number of QI projects each resident participated in the year preceding the program vs. during the program increased from 0.4 to 1.8 (p < 0.05). Ten of 26 residents (38%) reported no direct involvement in a QI project the preceding year before the QI program implementation, while 26/26 (100%) of residents reported direct involvement in at least 1 QI project during the implementation year. Residency program ACGME survey results regarding resident participation in QI increased from 86% (just below the national average of 87%) before the development of the QI program to 97% after program implementation. Implementation of a formalized, structured quality improvement education program for surgery residents significantly increased residents' participation in QI projects, as well as increasing their confidence in their knowledge and skillset to perform QI processes. The residency program's ACGME resident survey results regarding resident involvement in QI also improved during program implementation.


Rainbow trout (Oncorhynchus mykiss) possess two insulin-encoding mRNAs that are differentially expressed.
Insulin (INS) plays a critical role in the growth, development, and metabolism of vertebrates. In this study, two unique cDNAs that encode preproinsulin were isolated, cloned and sequenced from the endocrine pancreas (Brockmann body) of rainbow trout. One 592-bp cDNA (INS 1) encodes a 105-amino acid protein and the other 587-bp cDNA (INS 2) encodes a 107-amino acid protein. The sequences share 93% nucleotide identity and 91.4% deduced amino acid identity. Quantitative real-time PCR revealed that the two INS-encoding mRNAs were differentially expressed, both in terms of distribution among tissues as well as in terms of abundance within selected tissues of juvenile trout. Both INS 1 and INS 2 mRNAs were detected in pancreas, adipose tissue, pyloric cecum, and brain; however, only INS 1 mRNA was detected in upper and lower intestine and pituitary. In all cases where INS 1 and INS 2 were co-expressed, INS 1 was more abundant. INS 1 and INS 2 also were differentially expressed in various body regions (head, body, and tail) during embryonic development. Both INS 1 and INS 2 mRNAs were detected early in development (29 days post-fertilization), but their expression declined as development proceeded (through 90 days post-fertilization); in most cases, unlike the situation in juveniles, INS 2 mRNA was more abundant than INS 1 mRNA in embryos. These findings contribute to our understanding of the evolution, distribution, and function of INS.


Publisher Correction: Process calculi may reveal the equivalence lying at the heart of RNA and proteins.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


A complete durable response of vaginal clear cell carcinoma with pembrolizumab: A case report.
Primary clear cell adenocarcinoma of the vagina represents a rare form of cancer historically correlated with in-utero diethylstibestrol (DES) exposure. Mainstay treatment modalities include surgery, radiation, and chemotherapy. There has been a growing interest in immunotherapy in the field of oncology. KEYNOTE 826 demonstrated that patients with persistent, recurrent, or metastatic cervical cancer including patients who had adenocarcinoma showed improved progression and overall survival by the addition Pembrolizumab to chemotherapy plus or minus bevacizumab. To date, there are no documented cases using pembrolizumab as adjuvant treatment for active or recurrent vaginal clear cell adenocarcinoma. We present a case of a young patient with recurrent vaginal clear cell carcinoma who showed a complete and durable response to Pembrolizumab.


The role of calcium-sensing receptor and signalling pathways in the pathophysiology in two in vitro models of malignant hypercalcemia: the rat rice H-500 Leydig testis cancer and prostate cancer (PC-3) cells. Expression and regulation of pituitary tumor transforming gene in Leydig testis cancer and astrocyte and astrocytoma cells.
The calcium-sensing receptor (CaR) is a seven transmembrane receptor incorporated into the cell membrane that is sensitive to extracellular calcium and other cations. The finding that the CaR is expressed on cancer cells has opened the door to a new understanding of the role of extracellular calcium as a promalignant stimulus through the CaR and its signaling apparatus as demonstrated in this thesis. I found, in a model of humoral hypercalcemia of malignancy (HHM), that stimulation of the CaR worsens the promalignant features of the testicular H-500 Leydig cancer cells that were used in my studies. The CaR upregulated the release of parathyroid hormone-related peptide (PTHrP), the main mediator of hypercalcemia in HHM. The growth rate of the tumor was also increased by stimulation of the CaR, as DNA synthesis and protection against apoptosis were enhanced. The oncogene, pituitary tumor-transforming gene (PTTG), was found to be upregulated by the CaR in the H-500 cells, whereas calcium had no effect on PTTG expression in the U-87 astrocytoma cell line, but other proproliferative agents did upregulate PTTG in the U-87 cells. This makes PTTG a potential marker of malignancy and a therapeutic target in cancer, where the CaR is promalignant. Nitric oxide synthase (NOS) exists in three isoforms, and I found that the CaR upregulated the inducible NOS but not the two other isoforms. This upregulation was accompanied by an increased production of NO. NO has been shown to be potentially promalignant, although such a role was not established in the H-500 cells. Therefore, the CaR stimulates several promalignant features in the H-500 cells. In turn, blocking these effects by targeting a proximal downstream signaling molecule of the CaR may be a future clinical approach, since blocking the CaR might have too many adverse effects on calcium homeostasis. In conclusion, the CaR plays diverse roles in cancer-acting as an inhibitor of cell proliferation in the colon crypt cells giving rise to colon cancer but as a promalignant receptor in most other cancer types, including Leydig cell cancers.


Novel GTP-binding proteins in plasma membranes and zymogen granule membranes from rat pancreas and in pancreatic AR 4-2J cell membranes.
Photoaffinity labelling with [alpha-32P]GTP allowed to detect a 54 kDa GTP-binding protein in rat pancreatic plasma membranes and in pancreatic AR 4-2J cell membranes. Like the 42 and 48 kDa Gs alpha subunits and the 41 kDa Gi alpha subunit, this protein was absent from zymogen granule membranes. Contrastingly, a new 28 kDa GTP-binding protein (detected by [alpha-32P]GTP binding on immobilized proteins) and a 25 kDa protein (ADP-ribosylated by botulinum toxin D) were found in all three membrane preparations. This is to our knowledge the first report on GTP-binding proteins in zymogen granule membranes.


CircRNA_102179 promotes the proliferation, migration and invasion in non-small cell lung cancer cells by regulating miR-330-5p/HMGB3 axis.
Non-small cell lung cancer (NSCLC) accounting for 85 % of all lung cancer was one of the main causes of death worldwide. In this study, we investigated the role of circRNA_102179 in NSCLC development. The levels of circRNA_102179 in NSCLC tissues and cell lines were determined by quantitative real-time PCR assay (qRT-PCR). CCK8 and colony formation assays were applied to explore the effect of circRNA_102179 on the growth of NSCLC cells in vitro. Transwell assay was utilized to analyze the impact of circRNA_102179 on the migration and invasion of NSCLC cells. Target prediction and luciferase reporter assay were used to identify the interacting miRNA of circRNA_102179. The interaction among circRNA_102179/ miR-330-5p/HMGB3 was further validated by colony formation and Transwell invasion assays. Finally, the mouse xenograft NSCLC model was used to explore the role of circRNA_102179 in the tumor growth of NSCLC cells in vivo. CircRNA_102179 was overexpressed in NSCLC tissues and cells compared with normal lung tissues and human bronchial epithelial cells (HBEs). The down-regulation of circRNA_102179 markedly reduced the proliferation, migration, and invasion of NSCLC cells. Moreover, down-expression of circRNA_102179 significantly increased the level of miR-330-5p/HMGB3 in NSCLC cells. Further functional experiments indicated that over-expression of miR-330-5p reversed the inhibitory effect of circRNA_102179 on NSCLC cells growth, migration, and invasion. Our results reveal that circRNA_102179 facilitates the proliferation, migration, and invasion of NSCLC cell via modulating miR-330-5p/ HMGB3 axis in NSCLC cells.


Spectrometric study of tautomeric and protonation equilibria of o-vanillin Schiff base derivatives and their complexes with Cu(II).
Electronic absorption and emission properties of a series of Schiff bases derived from 2-hydroxy-3-methoxybenzaldehyde and 2-aminopyridine, 2,3-diaminopyridine, 2,6-diaminopyridine, or 3-aminomethylpyridine were studied in solvents of different polarities. The interconversion of the enolimine to the ketoamine tautomeric form was observed for compound 1, 6-methoxy-2-(3-pyridylmethyliminomethyl)phenol, and the corresponding equilibrium constant was estimated in several solvents. Protonation constants of all the investigated compounds were determined spectrophotometrically in the methanol/water 1/4 system. The effect of copper(II) ions on absorption and on the emission spectra of these ligands was examined in the buffered dioxane/water 1/1 system (pH 5.8). Strong complexation of Cu(II) and formation of a 1:1 complex were observed for the bis-Schiff base derived from 2,3-diaminopyridine. The complex of copper(II) with compound 1 was isolated and characterized by elemental analysis, magnetic susceptibility measurement, UV-vis and IR spectrometry.


How does thought-action fusion relate to responsibility attitudes and thought suppression to aggravate the obsessive-compulsive symptoms?
Comprehensive cognitive theories of obsessive compulsive disorder (OCD) propose that clinical obsessions and compulsions arise from specific sorts of dysfunctional beliefs and appraisals, such as inflated sense of responsibility, thought-action fusion (TAF), and thought suppression. The present study aimed to examine the mediator roles of responsibility and thought suppression between TAF and obsessive-compulsive symptoms. Specifically, it aimed to explore the relative effects of TAF factors (i.e. morality and likelihood) on inflated sense of responsibility and on thought suppression to increase the obsessive qualities of intrusions. Two hundred and eighty-three Turkish undergraduate students completed a battery of measures on responsibility, thought suppression, TAF, OC symptoms, and depression. A series of hierarchical regression analyses, where depressive symptoms were controlled for, indicated that TAF-morality and TAF-likelihood follow different paths toward OC symptoms. Although TAF-morality associated with inflated sense of responsibility, TAF-likelihood associated with thought suppression efforts, and in turn these factors increased OC symptoms. These findings provide support for the critical role of sense of responsibility and thought suppression between the relationship of TAF and OC symptoms. Findings were discussed in line with the literature.


Surface coating with cyclic RGD peptides stimulates osteoblast adhesion and proliferation as well as bone formation.
The physiological inertness of synthetic implant materials often results in insufficient implant integration and limited acceptance of implants in tissues. After implantation the implant surface is often separated from the surrounding healthy and regenerating tissue, for example by a fibrous capsule. To avoid this host-versus-graft reaction, a strong mechanical contact between tissue and implant must be ensured. An enhanced contact between graft and the surrounding tissue can be provided by coating the implant with cell-adhesive molecules. The highly active and alpha(v)beta(3)- and alpha(v)beta(5)-integrin-selective peptide c(-RGDfK-) (f=D-phenylalanine) was functionalized with various linker molecules containing an acrylamide end group by using the lysine side chain of c(-RGDfK-). The acrylamide group can be used to bind the peptide covalently to poly(methyl methacrylate) (PMMA) surfaces. The coated surfaces effectively bind to murine osteoblasts as well as human osteoblasts in vitro when a minimum distance of 3.5 nm between surface and the constrained RGD sequence is provided. In contrast to osteoblasts in cell suspension, surface-bound osteoblasts show no apoptosis but proliferate by a factor of 10 over a 22 d period. Coating of inert implant surfaces with highly active and alpha(v)-selective peptides affords a marked improvement in osteoblast binding over current technologies. In vivo studies show that peptide-coated PMMA pellets implanted into the patella groove of rabbits are integrated into the regenerating bone tissue faster and more strongly than uncoated pellets.


Transluminal angioplasty of peroneal artery branches in diabetics: initial technical experience.
The present study aimed to report the technical feasibility of percutaneous transluminal angioplasty (PTA) of obstructed or insufficient collateral branches (anterior and posterior perforating branches) from distal peroneal to foot arteries in diabetic patients with chronic critical limb ischemia (CLI) and chronic noncrossable occlusion of the anterior and posterior tibial arteries. Twenty-four diabetic CLI patients (age, 67 +/- 8 years; 87% males) undergoing collateral PTA were included. Baseline clinical angiographic and follow-up data were retrospectively reviewed. Collateral PTA was associated with a concomitant PTA of other sites in 21 (83%) cases. In 15 cases the treated collateral linked the peroneal with the plantaris communis; in 9 cases, the peroneal with the dorsalis pedis. Angiographic results of collateral PTA were good in 13 cases (<30% residual stenosis), whereas the result was considered moderate (30%-49% residual stenosis) in the remaining cases. Neither perforation nor acute occlusion of the treated collaterals or other relevant complications were observed. Mean follow-up was 32 +/- 17 months. Major amputation was necessary for two (8.3%) patients. Cumulative limb salvage rates at 2 and 4 years were 96% and 87%, respectively. In conclusion, this initial experience shows that PTA of the collateral branches from distal peroneal to foot arteries is a feasible technique. Future studies are required to define the clinical role of this novel approach.


Treatment-Resistant Late-Life Depression: A Review of Clinical Features, Neuropsychology, Neurobiology, and Treatment.
Major depression is common in older adults (≥ 60 years of age), termed late-life depression (LLD). Up to 30% of these patients will have treatment-resistant late-life depression (TRLLD), defined as depression that persists despite two adequate antidepressant trials. TRLLD is challenging for clinicians, given several etiological factors (eg, neurocognitive conditions, medical comorbidities, anxiety, and sleep disruption). Proper assessment and management is critical, as individuals with TRLLD often present in medical settings and suffer from cognitive decline and other marks of accelerated aging. This article serves as an evidence-based guide for medical practitioners who encounter TRLLD in their practice.


Effect of instrument diameter on the depth of penetration of fiberoptic sigmoidoscopes.
Newer fiberoptic sigmoidoscopes tend to have smaller diameter insertion shafts than older models. The extent to which this diameter affects how deeply an instrument can be inserted into the colon and the frequency with which sigmoidoscopes of different diameters could reach more proximal areas of the colon was evaluated. Instrument diameter did not influence the length of the sigmoidoscope shaft that could be introduced into the patient. However, when fully inserted to 60 cm, the 12-mm diameter sigmoidoscopes viewed significantly less of the sigmoid and descending colon than did the 16-mm diameter sigmoidoscopes. This lesser degree of anatomic depth of penetration has direct implications for the diagnostic capabilities of smaller diameter instruments.


Development and use of the Australian reproductive genetic carrier screening decision aid.
Reproductive genetic carrier screening (RGCS) may be offered to all individuals and couples, regardless of family history or ethnicity. "Mackenzie's Mission" (MM) is an Australian RGCS pilot study, evaluating the offer of couple-based screening for ~1300 genes associated with around 750 autosomal and X-linked recessive childhood-onset conditions. Each member of the couple makes an individual decision about RGCS and provides consent. We developed a decision aid (RGCS-DA) to support informed decision-making in MM, suitable for couples who were either non-pregnant or in early pregnancy. A Delphi approach invited experts to review values statements related to various concepts of RGCS. Three review rounds were completed, seeking consensus for relevance and clarity of statements, incorporating recommended modifications in subsequent iterations. The final RGCS-DA contains 14 statements that achieved Delphi consensus plus the attitude scale of the measure of informed choice. This was then evaluated in cognitive talk aloud interviews with potential users to assess face and content validity. Minimal wording changes were required at this stage. After this process, the RGCS-DA was piloted with 15 couples participating in MM who were then interviewed about their decision-making. The RGCS-DA prompted discussion within couples and facilitated in depth consideration of screening. There was reassurance when values aligned and a sense of shared decision-making within the couple. This RGCS-DA may become a very useful tool in supporting couples' decision making and contribute to RGCS being feasible for scaled-up implementation.


Endocavitary irradiation for rectal cancer and villous adenomas.
Endocavitary irradiation has been used for rectal adenocarcinoma and villous adenoma at St. Joseph's Hospital, Milwaukee, Wisconsin since 1978. The 52 patients treated since that time include 32 patients with adenocarcinoma, 19 patients with villous adenoma, and 1 patient with an adenomatous polyp and associated atypia. The average age of these patients (70.5 years) was a full decade older than the average age of all rectal cancer patients. The treatment was administered by a superficial contact machine with most patients receiving 80 Gy over four treatments in a period of 1.5 months. The overall local recurrence rate was 24% in the cancer group and 32% in the villous adenoma group. The 1-, 2-, and 3-year determinate disease-free survival rates were 90.4%, 78.6%, 74.2% and 80.4%; 60.3%, 45.2% for invasive adenocarcinoma and villous adenoma patients, respectively. There was no mortality and very little morbidity associated with the treatment. It is concluded that endocavitary irradiation is an effective alternative to surgery for the treatment of rectal cancer in selected cases. However, villous adenomas do not respond as well. Better results may be obtained for this group of patients by higher doses than were used in this study.


Different degree of intervention in 6-month weight-loss support and arterial stiffness: Secondary analysis of a randomized controlled trial.
Weight reduction by lifestyle modification (i.e., low-calorie diet and/or exercise) decreases arterial stiffness in overweight or obese individuals. We previously demonstrated that weight loss differs depending on the degree of intervention in weight-loss support in a randomized controlled trial (UMIN000001259). However, the effect of different degrees of intervention on arterial stiffness remains unclear. A total of 188 middle-aged men and women with overweight or obesity (51 ± 7 years, BMI: 29.0 ± 3.2 kg/m2) participated in the 6-month trial wherein they were assigned to a low (LI, n = 63), moderate (MI, n = 62), or high intensive intervention (HI, n = 63) group. Initially, one motivational lecture on weight loss was provided to all three groups, whereas educational materials (textbooks, notebooks, and a pedometer) were provided to groups MI and HI. Additionally, the HI group participated in a series of group-based sessions. Body weight and arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV) were measured at 0, 3, and 6 months. Six-month weight loss was greater in the order of HI, MI, and LI groups. The interventions reduced baPWV in all groups, and the reduction was not significantly different among the groups (114.3 ± 16.3, 82.6 ± 15.2, and 98.8 ± 90.4 cm/s, respectively). In overweight or obese individuals, different degrees of intervention in weight-loss support affect body weight; however, the extent to which arterial stiffness improves does not differ among support programs.