A novel prognostic signature of immune-related lncRNA pairs in lung adenocarcinoma.
Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, but the prognosis of LUAD patients remains unsatisfactory. Here, we retrieved the RNA-seq data of LUAD cohort from The Cancer Genome Atlas (TCGA) database and then identified differentially expressed immune-related lncRNAs (DEirlncRNAs) between LUAD and normal controls. Based on a new method of cyclically single pairing along with a 0-or-1 matrix, we constructed a novel prognostic signature of 8 DEirlncRNA pairs in LUAD with no dependence upon specific expression levels of lncRNAs. This prognostic model exhibited significant power in distinguishing good or poor prognosis of LUAD patients and the values of the area under the curve (AUC) were all over 0.70 in 1, 3, 5 years receiver operating characteristic (ROC) curves. Moreover, the risk score of the model could serve as an independent prognostic factor for patients with LUAD. In addition, the risk model was significantly associated with clinicopathological characteristics, tumor-infiltrating immune cells, immune-related molecules and sensitivity of anti-tumor drugs. This novel signature of DEirlncRNA pairs in LUAD, which did not require specific expression levels of lncRNAs, might be used to guide the administration of patients with LUAD in clinical practice.


Molecular and circulatory expression of insulin growth factors in Indian females with advanced cervical cancer.
Recent studies have demonstrated an association between insulin growth factor (IGF) and insulin growth factor binding protein-3 (IGFBP-III) serum levels and increased risk for various cancers. However, little information is available on clinical implications of the IGF system in Indian patients with cervical cancer. This study explored associations by analyzing their expression profiles in cervical cancer cases. Totals of 50 patients with advanced cervical cancer and 40 healthy controls were enrolled. Human papillomavirus (HPV) and cervical biopsy sample were obtained from all participating women. Circulatory levels were estimated by ELISA and the tissue expression was assessed using RT-PCR and Western blotting. Levels of IGF-I and II showed significant increase whereas IGFBP-III showed significant decline in all patients as compared to controls. Spearman correlation analysis between IGFs and HPV status showed significant correlations. We demonstrated elevated circulating levels and tissue expression of IGF-I and IGF-II in advancer cancer cervix patients, as compared with controls, with a converse trend being apparent for IGFBP-III. In future, associations of the IGF system and clinical outcome of cervical cancer patients in post treatment samples might point to significance in disease mapping as a prognostic marker after validation with a larger patient series.


Association between number of parathyroid glands identified during total thyroidectomy and functional parathyroid preservation.
Systematic identification of all 4 parathyroid glands has been recommended during total thyroidectomy (TT); however, it is unclear whether this strategy necessarily translates into optimized functional parathyroid preservation. We wished to investigate the association between number of parathyroids identified intraoperatively during TT, and incidence of incidental parathyroidectomy, and postoperative hypoparathyroidism. Retrospective review of prospectively maintained database of 511 consecutive patients undergoing TT at an academic teaching hospital. The association between number of parathyroid glands identified intraoperatively and incidence of biochemical hypocalcaemia (defined as any calcium < 2 mmol/L n first 48 h after surgery), symptomatic hypocalcaemia; permanent hypoparathyroidism (defined as any hypocalcaemia or need for calcium or vitamin D > 6 months after surgery), and incidental parathyroidectomy, was investigated. The association between number of parathyroid glands visualized and postoperative parathyroid hormone (PTH) levels was investigated in a subset of 454 patients. Patients in whom a greater number of parathyroids had been identified had a significantly higher incidence of biochemical and symptomatic hypocalcaemia, and significantly lower postoperative PTH levels, than patients with fewer glands identified. There were no significant differences in incidence of permanent hypoparathyroidism or incidental parathyroidectomy. On multivariate analysis, malignancy, Graves disease, and identification of 3-4 parathyroids were independent predictors of biochemical hypocalcaemia. For symptomatic hypocalcaemia, identification of 2-4 parathyroids, and identification of 3-4 parathyroids, were significant. Systematic identification of as many parathyroid glands as possible during TT is not necessary for functional parathyroid preservation.


[Antihypertensive therapy in arterial occlusive disease].
Patients with hypertension requiring therapy frequently present with concurrent peripheral vascular disease (PVD). This situation must be taken into account for an optimum antihypertensive treatment. In general, in patients with PVD only a cautious and gradual lowering of the blood pressure is recommended, since the decrease in poststenotic perfusion pressure may accentuate the symptoms of occlusive disease. In intermittent claudication--the most frequent manifestation of occlusive disease beta--receptor blockers today are no longer considered to be contraindicated. In the presence of critical ischemia of the legs (pain at rest and/or necroses) beta blockers should only be given with extreme caution. The agents of choice are calcium antagonists, ACE -inhibitors as well as alpha blockers and some newer vasodilating substances (e.g. Carvedilol). Conventional diuretics show disadvantages. An slightly elevated blood pressure in critical leg ischemia helps to improve the poststenotic perfusion of the affected limb. Antihypertensive treatment should not be instituted in patients whose systolic blood pressure is lower than 160 mmHg.


[The mode of recurrence of esophageal cancer after surgical treatment--autopsy study].
The results of clinical examinations, operative findings and autopsy findings of 113 patients submitted to esophagectomy were evaluated in terms of their correlations. Tumor was absent in 45 patients at autopsy. Of the remaining 68 cases, lymphnode metastases were present in 56 cases, metastases to the distant organs in 39, pleural and/or peritoneal disseminations in 15, direct extensions into the adjacent structures in 31, involvement of anastomotic site in 11 and intramural metastases to the esophagus and/or stomach in 9 cases. Lymphnode metastases were noted in autopsied cases even though death occurred shortly after surgery. Sixteen of these 51 patients had lymphnode metastases, 9 in the paratracheal or parabronchial , 6 in the abdominal, 5 in the supraclavicular and 4 in the posterior mediastinal nodes. Tracheobronchial tree and thoracic aorta were the commonest neighboring organs affected by direct extension. Local recurrences were noticed most frequently in cases where carcinoma extended to the deep border of the surgically resected specimens. Local recurrences were suppressed in those who received preoperative irradiation. The results suggested a possibility of improving the survival rate by 4% by combined resection, 10% by extended radical lymphnode dissection and 19% by both procedures.


[Tumors of brain middle line. Report on 12 cases (author's transl)].
A study is made of 12 cases with median supratentorial expansive processes. Six of them were in the 3rd ventricle; two in septum pellucidum and corpus callosum; and four in the pineal and mesencephalum. They are not very frequent processes. From the clinical point of view, they present a picture of endocraneal hypertension with rapid evolution. There are also other signs of important diagnostic value, which varied according to the location. We emphasize the value of the encephalography and the angiography for diagnosis. The E.E.G. studies gave only prognostic data. The clinical course was different in every case. It was better when the tumor was extirpated with or without ventriculo-peritoneal shunt. The most severe evolution as observed in the cases who had the tumor in the posterior part of the 3rd ventricle.


Effects on fertility of rabbits after active immunization with rat testicular cytochrome ct.
A Male rabbit was immunized with rat testicular cytochrome (Cyt) ct and mated with normal, unimmunized females. The matings resulted in abnormal pregnancies: no offspring or stillborn or undersized liveborn offspring weighing 25-30 gm each. Another unusual observation was that fur-pulling behavior, normally exhibited by pregnant female rabbits at the end of the gestational period, was absent in all of these pregnancies. Therefore, immunization of a normal rabbit with testicular cyt ct appeared to interfere with physiological and behavioral aspects of pregnancy in normal female rabbits. The immunological basis of these findings remains to be determined.


Understanding spatial patterns of poaching pressure using ranger logbook data to optimize future patrolling strategies.
Poaching is driving many species toward extinction, and as a result, lowering poaching pressure is a conservation priority. This requires understanding where poaching pressure is high and which factors determine these spatial patterns. However, the cryptic and illegal nature of poaching makes this difficult. Ranger patrol data, typically recorded in protected area logbooks, contain information on patrolling efforts and poaching detection and should thus provide opportunities for a better understanding of poaching pressure. However, these data are seldom analyzed and rarely used to inform adaptive management strategies. We developed a novel approach to making use of analog logbook records to map poaching pressure and to test environmental criminology and predator-prey relationship hypotheses explaining poaching patterns. We showcase this approach for Golestan National Park in Iran, where poaching has substantially depleted ungulate populations. We digitized data from >4800 ranger patrols from 2014 to 2016 and used an occupancy modeling framework to relate poaching to (1) accessibility, (2) law enforcement, and (3) prey availability factors. Based on predicted poaching pressure and patrolling intensity, we provide suggestions for future patrol allocation strategies. Our results revealed a low probability (12%) of poacher detection during patrols. Poaching distribution was best explained by prey availability, indicating that poachers target areas with high concentrations of ungulates. Poaching pressure was estimated to be high (>0.49) in 39% of our study area. To alleviate poaching pressure, we recommend ramping up patrolling intensity in 12% of the national park, which could be achievable by reducing excess patrols in about 20% of the park. However, our results suggest that for 27% of the park, it is necessary to improve patrolling quality to increase detection probability of poaching, for example, by closing temporal patrolling gaps or expanding informant networks. Our approach illustrates that analog ranger logbooks are an untapped resource for evidence-based and adaptive planning of protected area management. Using this wealth of data can open up new avenues to better understand poaching and its determinants, to expand effectiveness assessments to the past, and, more generally, to allow for strategic conservation planning in protected areas.


In vitro reconstitution of yeast tUTP/UTP A and UTP B subcomplexes provides new insights into their modular architecture.
Eukaryotic ribosome biogenesis is a multistep process involving more than 150 biogenesis factors, which interact transiently with pre-ribosomal particles to promote their maturation. Some of these auxiliary proteins have been isolated in complexes found separate from the ribosomal environment. Among them, are 3 large UTP subcomplexes containing 6 or 7 protein subunits which are involved in the early steps of ribosome biogenesis. The composition of the UTP subcomplexes and the network of binary interactions between protein subunits have been analyzed previously. To obtain further insights into the structural and biochemical properties of UTP subcomplexes, we established a heterologous expression system to allow reconstitution of the yeast tUTP/UTP A and UTP B subcomplexes from their candidate subunits. The results of a series of reconstitution experiments involving different combinations of protein subunits are in good agreement with most of the previously observed binary interactions. Moreover, in combination with additional biochemical analyses, several stable building blocks of the UTP subcomplexes were identified. Based on these findings, we present a refined model of the tUTP/UTP A and UTP B architecture.


Alterations in the Global Proteome and Phosphoproteome in Third Generation EGFR TKI Resistance Reveal Drug Targets to Circumvent Resistance.
Lung cancer is the leading cause of cancer mortality worldwide. The treatment of patients with lung cancer harboring mutant EGFR with orally administered EGFR tyrosine kinase inhibitors (TKI) has been a paradigm shift. Osimertinib and rociletinib are third-generation irreversible EGFR TKIs targeting the EGFR T790M mutation. Osimertinib is the current standard of care for patients with EGFR mutations due to increased efficacy, lower side effects, and enhanced brain penetrance. Unfortunately, all patients develop resistance. Genomic approaches have primarily been used to interrogate resistance mechanisms. Here we characterized the proteome and phosphoproteome of a series of isogenic EGFR-mutant lung adenocarcinoma cell lines that are either sensitive or resistant to these drugs, comprising the most comprehensive proteomic dataset resource to date to investigate third generation EGFR TKI resistance in lung adenocarcinoma. Unbiased global quantitative mass spectrometry uncovered alterations in signaling pathways, revealed a proteomic signature of epithelial-mesenchymal transition, and identified kinases and phosphatases with altered expression and phosphorylation in TKI-resistant cells. Decreased tyrosine phosphorylation of key sites in the phosphatase SHP2 suggests its inhibition, resulting in subsequent inhibition of RAS/MAPK and activation of PI3K/AKT pathways. Anticorrelation analyses of this phosphoproteomic dataset with published drug-induced P100 phosphoproteomic datasets from the Library of Integrated Network-Based Cellular Signatures program predicted drugs with the potential to overcome EGFR TKI resistance. The PI3K/MTOR inhibitor dactolisib in combination with osimertinib overcame resistance both in vitro and in vivo. Taken together, this study reveals global proteomic alterations upon third generation EGFR TKI resistance and highlights potential novel approaches to overcome resistance. SIGNIFICANCE: Global quantitative proteomics reveals changes in the proteome and phosphoproteome in lung cancer cells resistant to third generation EGFR TKIs, identifying the PI3K/mTOR inhibitor dactolisib as a potential approach to overcome resistance.


Teaching consultation-liaison psychotherapy: assessment of adaptation to medical and surgical illness.
Little has been written about teaching consultation-liaison inpatient psychotherapy to residents or other trainees. Resident interviews at completion of consultation-liaison training identified learning needs. In response, the authors created a seminar series and modified it reiteratively eight times. In this approach, the primary task of consultation-liaison psychotherapy assessment is to determine the success of a patient's adaptation to hospitalization, and to identify obstacles to adaptation. Selected determinants of adaptation are reviewed and organized as individual factors and intrahospital and extrahospital environmental factors. This provides a viable means of organizing and integrating disparate bodies of knowledge for the student. The teaching model awaits empirical validation as a tool that enhances teaching and patient care outcomes.


Scientific research, stakeholders, and policy: continuing dialogue during research on radionuclides on Amchitka Island, Alaska.
It is increasingly clear that a wide range of stakeholders should be included in the problem formulation phase of research aimed at solving environmental problems; indeed the inclusion of stakeholders at this stage has been formalized as an integral part of ecological risk assessment. In this paper, we advocate the additional inclusion of stakeholders in the refinement of research methods and protocols and in the execution of the research, rather than just at the final communication and reporting phase. We use a large study of potential radionuclide levels in marine biota around Amchitka Island as a case study. Amchitka Island, in the Aleutian Island Chain of Alaska, was the site of three underground nuclear tests (1965-1971). The overall objective of the biological component of the study was to collect a range of marine biota for radionuclide analysis that could provide data for assessing current food safety and provide a baseline for developing a plan to monitor human and ecosystem health in perpetuity. Stakeholders, including regulators (State of Alaska), resource trustees (US Fish and Wildlife Service, State of Alaska), representatives of the Aleut and Pribilof Island communities, the Department of Energy (DOE), and others, were essential for plan development. While these stakeholders were included in the initial problem formulation and approved science plan, we also included them in the refinement of protocols, selection of bioindicators, selection of a reference site, choice of methods of collection, and in the execution of the study itself. Meetings with stakeholders resulted in adding (or deleting) bioindicator species and tissues, prioritizing target species, refining sampling methods, and recruiting collection personnel. Some species were added because they were important subsistence foods for the Aleuts, and others were added because they were ecological equivalents to replace species deleted because of low population numbers. Two major refinements that changed the research thrust were (1) the inclusion of Aleut hunters and fishers on the biological expedition itself to ensure that subsistence foods and methods were represented, and (2) the addition of a fisheries biologist on a NOAA research trawler to allow sampling of commercial fishes. Although the original research design called for the collection of biota by Aleut subsistence fishermen, and by a commercial fishing boat, the research was modified with continued stakeholder input to actually include Aleuts and a fisheries biologist on the expeditions to ensure their representation. The inclusion of stakeholders during the development of protocols and the research itself improved the overall quality of the investigation, while making it more relevant to the interested and affected parties. Final responsibility for the design and execution of the research and radionuclide analysis rested with the researchers, but the process of stakeholder inclusion made the research more valuable as a source of credible information and for public policy decisions.


Placental transfer of tyrosine kinase inhibitors used for chronic myeloid leukemia treatment.
Both favorable pregnancy outcomes and fetal abnormalities have been associated with the use of tyrosine kinase inhibitors (TKIs) during pregnancy. The placental transfer of TKIs in humans is poorly understood. We observed women with chronic myeloid leukemia who used imatinib or nilotinib during the late pregnancy stages. The newborns had no birth abnormalities. We evaluated the drug concentrations in maternal blood, umbilical cord blood, and placental samples collected during labor. We found limited placental transfer of the TKIs. The fetal/maternal concentration ratio ranged from 0.5 to 0.58 for nilotinib and from 0.05 to 0.22 for imatinib. The placental/maternal ratio was higher for imatinib than for nilotinib. Theoretical pharmacokinetic modeling of passive placental crossing was insufficient to predict the in vivo data because the calculated fetal/maternal ratio was close to 1 for both drugs. We propose that active placental transport contributes to fetal protection against TKI exposure during pregnancy.


VUV to IR Emission Spectroscopy and Interferometry Diagnostics for the European Shock Tube for High-Enthalpy Research.
The European Shock Tube for High-Enthalpy Research is a new state-of-the-art facility, tailored for the reproduction of spacecraft planetary entries in support of future European exploration missions, developed by an international consortium led by Instituto de Plasmas e Fusão Nuclear and funded by the European Space Agency. Deployed state-of-the-art diagnostics include vacuum-ultraviolet to ultraviolet, visible, and mid-infrared optical spectroscopy setups, and a microwave interferometry setup. This work examines the specifications and requirements for high-speed flow measurements, and discusses the design choices for the main diagnostics. The spectroscopy setup covers a spectral window between 120 and 5000 nm, and the microwave interferometer can measure electron densities up to 1.5 × 1020 electrons/m3. The main design drivers and technological choices derived from the requirements are discussed in detail herein.


Enantioselective Modulatory Effects of Naringenin Enantiomers on the Expression Levels of miR-17-3p Involved in Endogenous Antioxidant Defenses.
Naringenin is a flavanone present in citrus fruit as a mixture of chiral isomers. The numerous biological properties attributed to this compound include antioxidant and anti-inflammatory activities, even though the molecular mechanisms of these remain unknown. This study aims to evaluate the effects of racemic and enantiomeric naringenin on the expression levels of miR-17-3p, miR-25-5p and relative mRNA targets, to elucidate the mechanisms underlying these antioxidant and anti-inflammatory properties. Caco-2 cells, a well characterized in vitro model which mimics the intestinal barrier, were treated with subtoxic concentrations of racemate and enantiomers. The expression levels of miR-17-3p and miR-25-5p were determined by Real-Time PCR and were found to be decreased for both miRNAs. miR-17-3p behavior was in agreement with the increased levels of target mRNAs coding for two antioxidant enzymes, manganese-dependent superoxide dismutase (MnSOD) and glutathione peroxidase 2 (GPx2), while expression levels of miR-25-5p were not in agreement with its target mRNAs, coding for two pro-inflammatory cytokines, Tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6). These results lead to the conclusion that naringenin could exert its antioxidant activity through epigenetic regulation operated by miRNAs, while anti-inflammatory activity is regulated by other miRNAs and/or mechanisms.


Nasopharyngeal cryptococcosis in a cat: interlaboratory variation in cryptococcal antigen assay test results.
An indoor-only 6-year-old spayed female domestic cat was evaluated for a history of stertorous respiration. Skull radiographs revealed increased soft tissue density within the caudal aspect of the left nasal cavity. CT and rhinoscopy revealed a mass lesion in the choana, plus a smaller lesion, nearly completely occluding flow through the nasal passages. Rhinoscopy was used to collect a biopsy specimen from a fleshy, tan-yellow mass visualized in the caudal nasopharynx. Histopathology was diagnostic for Cryptococcus species infection and systemic antifungal therapy with fluconazole was initiated. Following a series of discordant results, serum samples were submitted to a veterinary diagnostic laboratory that utilized a cryptococcal antigen latex agglutination system with pretreatment of serum with pronase. Twenty-three months after the initial diagnosis, the cat's serum cryptococcal antigen titer declined to 1:5 and the cat has responded well to continuing treatment. This case illustrates challenges associated with discordant test results for cryptococcal antigen among laboratories. Discordancies may be due to differences in assay design, or the underlying disease state itself, or whether serum is pre-treated with pronase; with some tests relying on the training and experience of the operator if the cryptococcal antigen detection test requires a subjective interpretation. It also resolves some confusion in the literature related to the assay types available and terminology used to describe them, and emphasizes the importance of considering cryptococcosis as an important differential for cats with upper respiratory signs, without nasal discharge, even if the cat is kept exclusively indoors.


A comprehensive and user-friendly framework for 3D-data visualisation in invertebrates and other organisms.
Methods for 3D-imaging of biological samples are experiencing unprecedented development, with tools such as X-ray micro-computed tomography (μCT) becoming more accessible to biologists. These techniques are inherently suited to small subjects and can simultaneously image both external and internal morphology, thus offering considerable benefits for invertebrate research. However, methods for visualising 3D-data are trailing behind the development of tools for generating such data. Our aim in this article is to make the processing, visualisation and presentation of 3D-data easier, thereby encouraging more researchers to utilise 3D-imaging. Here, we present a comprehensive workflow for manipulating and visualising 3D-data, including basic and advanced options for producing images, videos and interactive 3D-PDFs, from both volume and surface-mesh renderings. We discuss the importance of visualisation for quantitative analysis of invertebrate morphology from 3D-data, and provide example figures illustrating the different options for generating 3D-figures for publication. As more biology journals adopt 3D-PDFs as a standard option, research on microscopic invertebrates and other organisms can be presented in high-resolution 3D-figures, enhancing the way we communicate science.


Therapeutic Effects of Topical Application of Lycium barbarum Polysaccharide in a Murine Model of Dry Eye.
To evaluate the safety and efficacy of Lycium barbarum polysaccharide (LBP) eye drops in a murine model of dry eye disease (DED). Six- to eight-week-old female C57BL/6 mice were subjected to a combination of desiccating stress (DS) and topical benzalkonium chloride (BAC) to induce DED. Five microliters of LBP eye drops (0.625, 2.5, or 12.5 mg/ml) or PBS was applied topically 3 times per day for 10 days to subsequently test their efficacy. Tear secretion, tear breakup time (TBUT), corneal irregularity, and corneal fluorescein staining scores were measured on days 3 and 10 after treatment. The expression of tumor necrosis factor-alpha (TNF-α) in the cornea was assessed by quantitative (q) RT-PCR on days 10. The ocular irritation of LBP eye drops of corresponding concentrations was evaluated on 10- to 12-week-old female Sprague-Dawley rats. Compared with PBS-treated groups, mice treated with 0.625, 2.5, and 12.5 mg/ml LBP showed a significant improvement in the clinical signs of DED in a dose-dependent manner, including corneal epithelial integrity, corneal regularity, and tear production, as well as significant inhibition of inflammatory cell infiltration and TNF-α expression levels in the cornea. All corresponding concentrations of LBP eye drops revealed no obvious ocular irritation. Topical application of LBP could ameliorate dry eye in a murine model of DED without obvious ocular irritation.


Synergy between histone deacetylase inhibitors and DNA-damaging agents is mediated by histone deacetylase 2 in colorectal cancer.
Previous studies have associated the overexpression of histone deacetylase 2 (HDAC2) and the presence of TP53 mutations with the progression to advanced stage drug resistant colorectal cancer (CRC). However, the mechanistic link between HDAC2 expression and the TP53 mutational status has remained unexplored. Here, we investigated the function of HDAC2 in drug resistance by assessing the synergistic effects of DNA-targeted chemotherapeutic agents and HDAC inhibitors (HDACis) on two TP53-mutated colorectal adenocarcinoma CRC cell lines (SW480 and HT-29) and on the TP53-wild type carcinoma cell line (HCT116 p53+/+) and its TP53 deficient sub-line (HCT116 p53-/-). We showed that in the untreated SW480 and HT-29 cells the steady-state level of HDAC2 was low compared to a TP53-wild type carcinoma cell line (HCT116 p53+/+). Increased expression of HDAC2 correlated with drug resistance, and depletion by shRNA sensitised the multi-drug resistance cell line HT-29 to CRC chemotherapeutic drugs such as 5-fluorouracil (5-FU) and oxaliplatin (Oxa). Combined treatment with the HDACi suberoylanilide hydroxamic acid plus 5-FU or Oxa reduced the level of HDAC2 expression, modified chromatin structure and induced mitotic cell death in HT-29 cells. Non-invasive bioluminescence imaging revealed significant reductions in xenograft tumour growth with HDAC2 expression level reduced to <50% in treated animals. Elevated levels of histone acetylation on residues H3K9, H4K12 and H4K16 were also found to be associated with resistance to VPA/Dox or SAHA/Dox treatment. Our results suggest that HDAC2 expression rather than the p53 mutation status influences the outcome of combined treatment with a HDACi and DNA-damaging agents in CRC.


ANCA-Associated Vasculitis Pathogenesis: A Commentary.
The ANCA-associated vasculitides are a group of small vessel vasculitides characterized by autoantibodies recognizing the neutrophil cytoplasmic antigens PR3 and MPO. We examine the current clinical and molecular immunology understanding of ANCA-associated vasculitides and discuss the current needs in our understanding of the pathogenic mechanisms of these rare diseases. The majority of efforts to understand the pathogenesis of these diseases have focused on dissecting neutrophil biology because the neutrophil is the primary expressor of ANCA autoantigens. However, a number of important genetic, clinical, and cellular biology observations suggest that attempts to understand the pathogenesis of ANCA vasculitides should move away from emphasis on the role of the neutrophil and instead re-focus on the potential role of other immune cell mediators. Whether or not neutrophils are the key determinant of ANCA-associated vasculitis pathogenesis should be revisited in detail. A neutrophil-centric view of the pathogenesis of these diseases cannot fully account for important genetic, clinical, and cellular biology observations that implicate important and under-appreciated roles for monocytes and T cells. Refocusing on these findings will likely lead to new discovery of novel therapeutic targets and the identification of clinically useful biomarkers for disease activity.


Clinical and economic impact of drug eluting beads in transarterial chemoembolization for hepatocellular carcinoma.
Drug eluting beads (DEBs) theoretically improve the efficacy and safety of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). Nonetheless, their economic profile has not been assessed. Our retrospective before/after study aimed to compare efficacy, safety and economic profile of two strategies of TACE without (Period 1) or with the possibility of using DEBs (Period 2). All HCC patients treated by TACE in our hospital between March 2006 and May 2013 were included. Economic analyses were performed from the French Public Health Insurance point of view according to the French Diagnosis-Related Group prospective payment system and from the analytic accountability. One hundred and sixty-one patients were included. Median time to treatment failure and overall survival were 13.1 and 23.8 months in Period 1 vs. 14.1 and 30.2 months in Period 2 (P = 0.45 and P = 0.40). Mean hospital durations and tariffs were 14.9 ± 7.7 days and € 11 472 ± 5901 in Period 1 vs. 12.4 ± 8.4 days and € 7654 ± 4625 in Period 2 (P = 0.03 and P < 10(-4) ). The possibility of using DEBs did not improve the prognosis in HCC patients treated by TACE. Nonetheless, it had a better medico-economic profile.


[The epidemic of smallpox in Guangdong Province and its prevention and treatment in the Republican period].
During the Republican period, the smallpox broke out in high frequency almost annually in Guangdong. In response to infectious diseases, the Guangdong government established the Health Administration and institutions for infectious disease's prevention and treatment, and prepared smallpox vaccine by themselves. In order to grasp the situation of the epidemic, related institutions collected epidemic data weekly, monthly, and annually with the statistics reported regularly. Meanwhile, infectious disease hospital was established for smallpox patients. Harbor quarantine put smallpox as a key target of inspection. With the joint effort of the government and social organizations, massive "vaccination campaigns" was organized to promote vaccination, in which children, students and young people were the main subjects for inoculations. Prevention knowledge and anti-epidemic concept towards smallpox have been actively publicized and improved by media.


Depression in older adults: a meta-synthesis.
Depression in older adults is often overlooked and dismissed as a part of aging. A body of knowledge-both quantitative and qualitative-has developed on the topic of depression in older adults. Meta-analyses and systematic reviews have been used to synthesize the quantitative findings of studies, and our research seeks to synthesize the qualitative studies that have been conducted on elders' experience with depression. Thirteen studies met inclusion criteria, and 4 major themes were extracted: experiences, causes, recovery, and barriers to treatment. These themes are detailed and their implications for practice are explored.


The ethical and clinical practice of disclosing raw test data: addressing the ongoing debate.
Neuropsychologists are prone to having raw test data requested by colleagues, clients, and attorneys. Although questions of when and to whom neuropsychologists should release raw test data have been debated for years, uncertainty about how to address requests for raw test data persists. Although contradictions within and between ethical and legal guidelines exist, general bioethical principles, most ethical and professional guidelines, and federal copyright law support the responsibility of practitioners to maintain the security of neuropsychological tests, including raw test data. Neuropsychologists are best served by taking a proactive approach regarding the manner in which requests for raw test data are addressed. The purpose of this article is to provide the information necessary to make informed decisions regarding the release of raw test data; however, each neuropsychologist must ultimately choose to pursue a course of action that is simply ethically acceptable or one that is ethically preferable.


The Added Value of SARC-F to Prescreening Using FRAX for Hip Fracture Prevention in Older Community Adults.
To examine the potential added value of a simple 5-item questionnaire for sarcopenia screening (SARC-F) to the Fracture Risk Assessment Tool (FRAX) for hip fracture risk prediction, in order to identify at-risk older adults for screening with dual-energy x-ray absorptiometry (DXA). A prospective cohort study. Two thousand Chinese men and 2000 Chinese women aged 65 years or older were recruited from local communities and were prospectively followed up for about 10 years. Areal bone mineral density (BMD) of hip and lumbar spine were measured by DXA at baseline. Ten-year FRAX probability of hip fracture was calculated using the baseline risk factors. Information from the baseline questionnaire was extracted to calculate a modified SARC-F score. The independent predictive values of SARC-F and FRAX questionnaire were evaluated using multivariate survival analysis. The added predictive values of SARC-F to FRAX for pre-DXA screening were examined. During the follow-up, 63 (3.2%) men and 69 (3.5%) women had at least 1 incident hip fracture. SARC-F had an independent value of FRAX for hip fracture risk prediction, with an adjusted hazard ratio [95% confidence interval (CI)] of 1.24 (1.02, 1.52) and 1.15 (0.99, 1.13) in men and women, respectively. Compared with using FRAX, using SARC-F in conjunction with FRAX made the sensitivity for prediction rise from 58.7% to 76.2% in men and from 69.6% to 78.3% in women, with a nondecreased area under receiver operating characteristic curve of 0.67. Prescreening using FRAX in conjunction with SARC-F could save more than half of the DXA assessment than with no prescreening. SARC-F is associated with a modest increase in hip fracture risk, especially in men. Conjoint evaluation for sarcopenia in addition to FRAX screening may help identify older adults at higher risk of hip fracture for more intensive screening and/or preventive interventions.


Social Robots in Applied Settings: A Long-Term Study on Adaptive Robotic Tutors in Higher Education.
Learning in higher education scenarios requires self-directed learning and the challenging task of self-motivation while individual support is rare. The integration of social robots to support learners has already shown promise to benefit the learning process in this area. In this paper, we focus on the applicability of an adaptive robotic tutor in a university setting. To this end, we conducted a long-term field study implementing an adaptive robotic tutor to support students with exam preparation over three sessions during one semester. In a mixed design, we compared the effect of an adaptive tutor to a control condition across all learning sessions. With the aim to benefit not only motivation but also academic success and the learning experience in general, we draw from research in adaptive tutoring, social robots in education, as well as our own prior work in this field. Our results show that opting in for the robotic tutoring is beneficial for students. We found significant subjective knowledge gain and increases in intrinsic motivation regarding the content of the course in general. Finally, participation resulted in a significantly better exam grade compared to students not participating. However, the extended adaptivity of the robotic tutor in the experimental condition did not seem to enhance learning, as we found no significant differences compared to a non-adaptive version of the robot.


[Long-term survival of patients with hypertension treated in general practice or at a specialized hypertension clinic. A 21-year observation study of 831 patients with hypertension].
This article is based on a study first published in Blood Pressure. After an initial diagnostic and therapeutic assessment at a specialized hypertension clinic, 831 patients with primary hypertension were during a 15-year period allocated to continuing managing care either by their general practitioner or by the hypertension clinic. Survival was assessed in the two groups: general practice (n = 437, 223 males, 214 females) and specialized hypertension clinic (n = 394, 208 males, 186 females). Median observation times for both groups were 11 years. There were no significant differences between the groups concerning age at entry, pretreatment clinical status, pretreatment blood pressure or treated blood pressure level before allocation. Judged by a Cox' regression model, no difference in survival between the two groups could be registered. The leading cause of death in both groups was ischemic heart disease. Our results indicate that after the initial diagnostic assessment and adjustment of treatment, managing care in a specialized hypertension clinic offers no advantage concerning survival compared to managing care in general practice.


[A retrospective study comparing the clinical efficacy of laparoscopic cryoablation and partial nephrectomy for renal cell carcinoma].
To compare the clinical outcomes of laparoscopic cryoablation (LCA) and laparoscopic partial nephrectomy (LPN) in the treatment of renal cell carcinoma (RCC). Between April 2005 and March 2009, 47 patients were treated with minimally invasive nephron sparing surgery (LPN or LCA) for RCC. The LCA group included 18 selected primary RCC cases (14 men and 4 women, mean age 63 years). There were 6 tumors located in the left, 11 located in the right and 1 located bilaterally. The maximum diameter of tumors was 1.5 - 5.0 cm (mean: 2.9 cm). The LPN group included 29 renal tumors patients (19 men and 10 women, mean age 61 years). The maximum diameter of tumors in this group was 2.0 - 4.5 cm (mean: 2.8 cm). Changes of hemoglobin (Hb), erythrocyte sedimentation rate (ESR), serum creatinine (SCr) and glomerular filtration rate (GFR) after operations were compared between LCA group and LPN group. The operative time, average intra-operative bleeding volume, postoperative hospital stay and incidence of postoperative complications of the 2 groups were analyzed and compared. The 2 surgical procedures were both successful. There was no significant change of Hb, ESR, SCr and GFR after operations in LCA group and LPN group (P > 0.05). The operative time was (94 ± 29) min and (146 ± 45) min in LCA group and LPN group, respectively. The average estimated blood loss was (37 ± 20) ml and (274 ± 69) ml. The postoperative hospital stay was (4 ± 2) d and (10 ± 2) d. These differences between the 2 groups were significant (P < 0.01). No laparoscopic operative complications were noted in LCA group. Follow-up magnetic resonance imaging (MRI) at 1, 3, and 6 months identified the punched-out, nonenhancing, spontaneously resorbing, renal cryolesion. LCA group had completed a minimum follow-up of 6 months (mean 16, range 6 to 21 months). No evidence of local or port-site recurrence was found, and no patient developed metastatic disease. 3 - 36 months' (mean 20 months) follow-up showed no recurrence of tumors or metastatic disease in LPN group. LCA for RCC is an accurate and effective intervention with a relatively low incidence of complications, and is superior to LPN in operative time, intraoperative bleeding volume and postoperative recovery.


Development and Validation of the Relational Needs Satisfaction Scale.
The aim of the research was the development of a new scale for measuring the satisfaction of relational needs. In the first study, we developed 269 items based on Erskine's description of eight relational needs. Five experts evaluated the items, and then they were pilot-tested on a sample of 221 participants. Using principal component analysis, we found five components related to five relational needs: authenticity, support and protection, having an impact, shared experience, and initiative from the other. In the second study, the Relational Needs Satisfaction Scale was tested on a sample of 255 participants and further refined with the help of factor analysis. The final version of the scale consists of 20 items and measures overall relational needs satisfaction and the five dimensions of relational needs. The reliability of the overall score was excellent, while subscales had acceptable to good reliability. The relational needs satisfaction positively and significantly correlates with the secure attachment style, self-compassion, higher satisfaction with life, and better well-being. In the third study, we confirmed both the five-factor model and the hierarchical model on the sample of 354 participants. We proposed that the hierarchical model is more congruent with the theoretical model, as all five dimensions of relational needs are aspects of one general dimension of relational needs satisfaction. The scale can be used in both psychotherapy and counseling and research related to different fields of psychology.


Monitoring performance in thyroidectomy: cumulative sum analysis of outcomes.
Cumulative sum (CUSUM) analysis gives visual feedback on performance. It requires agreed benchmarks to compare binary outcomes. This process has not previously been applied to thyroidectomy. The objective of this study was to determine if CUSUM analysis can be employed to give feedback on performance of thyroidectomy. A literature review to define the CUSUM analysis key performance indicators for thyroidectomy was performed. The key performance indicators for thyroid surgery were hematoma (return to theater for evacuation), hypocalcemia (corrected calcium <2.0 mmol/L), and vocal cord palsy (postoperative hoarseness with nasal endoscopic confirmation). Pre- and postoperative laryngoscopy was not routinely performed by all surgeons. Permanent was defined as duration longer than 6 months. A prospective audit of 216 patients undergoing thyroidectomy between January 2003 and December 2006 at the Geelong Hospital was completed. CUSUM charting of outcomes was performed after agreeing by consensus the boundaries of acceptable and unacceptable performance. Aggregate analysis of outcomes demonstrated acceptable performance across all clinical indicators. The incidence of temporary/permanent hypocalcemia and vocal cord palsy were 24%/2.6% and 3.2%/0.65%, respectively. About 1.39% of patients required evacuation of hematoma. CUSUM plotting of outcomes demonstrated acceptable performance. There is some variation of how standard outcome indicators for thyroidectomy are measured in the literature. A prospective audit using aggregate outcomes and CUSUM analysis has demonstrated that the performance of thyroid surgery at the Geelong Hospital was acceptable. These indicators and our methods of analysis could be used to monitor the performance of thyroid surgery at other hospitals.


Kinetic Selectivity of Olefin Metathesis Catalysts Bearing Cyclic (Alkyl)(Amino)Carbenes.
The evaluation of ruthenium olefin metathesis catalysts 4-6 bearing cyclic (alkyl)(amino)carbenes (CAACs) in the cross-metathesis of cis-1,4-diacetoxy-2-butene (7) with allylbenzene (8) and the ethenolysis of methyl oleate (11) is reported. Relative to most NHC-substituted complexes, CAAC-substituted catalysts exhibit lower E/Z ratios (3:1 at 70% conversion) in the cross-metathesis of 7 and 8. Additionally, complexes 4-6 demonstrate good selectivity for the formation of terminal olefins versus internal olefins in the ethenolysis of 11. Indeed, complex 6 achieved 35 000 TONs, the highest recorded to date. CAAC-substituted complexes exhibit markedly different kinetic selectivity than most NHC-substituted complexes.


Electron-Electron Cross-Relaxation and Spectral Diffusion during Dynamic Nuclear Polarization Experiments on Solids.
Recently it has been shown that experimental electron-electron double resonance (ELDOR) spectra of amorphous glasses containing free radicals with inhomogeneously broadened electron paramagnetic resonance (EPR) spectra can be analyzed using a set of coupled rate equations for the electron polarizations of frequency bins composing these spectra, named the eSD (electron spectral diffusion) model. The rate matrix defining these equations has elements depending on the microwave, the spin-lattice relaxation rates and on eSD rate constants responsible for polarization exchange. In this study, we show that in addition to the static dipolar flip-flop terms in the Hamiltonian a zero-quantum electron cross-relaxation mechanism can be responsible for the polarization exchange process in our samples. This conclusion was reached by calculating the EPR lineshapes of a system of 11 coupled electrons exposed to microwave irradiation using an eigenstate population rate equation derived from the spin density vector rate equation in Liouville space. These equations involve all terms of the Hamiltonian and in addition rate constants representing longitudinal relaxation and cross-relaxation mechanisms as well as MW irradiation. The results of these calculations are compared with the results obtained from the eSD model.


Progress towards the understanding of the GABAA receptor structure.
The GABA receptor of mammalian brain is a ligand-gated channel protein with allosteric binding sites for the benzodiazepines and barbiturate drugs. The receptor is an acidic oligomeric membrane glycoprotein and it has been purified to homogeneity from bovine cerebral cortex, bovine cerebellum and rat cerebral cortex by benzodiazepine affinity chromatography. In each case, extraction and purification with the zwitterionic detergent CHAPS and exogenous phospholipid has demonstrated the coexistence of GABA, benzodiazepine and cage convulsant ligand binding sites on a single protein complex; in addition the allosteric interactions between these sites are preserved in the isolated protein. The receptor has a heterologous structure that is conserved at the subunit level between the aforementioned mammalian species and brain regions. SDS-PAGE has shown that the receptor consists of two subunits, alpha (Mr 53000) and beta (Mr 57000) present in equal stoichiometry. A model consistent with the determination of the molecular weight of the native protein, i.e., Mr 230,000, is that of a tetramer alpha 2 beta 2. [3H]Flunitrazepam and [3H]muscimol have been employed as photoaffinity labels to map the benzodiazepine and GABA binding polypeptides respectively. Polyclonal and monoclonal antibodies have been raised to the native bovine GABAA receptor and these have been employed for the further characterisation of the receptor protein.


Ischemic preconditioning treatment of astrocytes transfers ischemic tolerance to neurons.
Ischemic preconditioning (IPC) represents a potential therapy against cerebral ischemia. While our group has previously shown IPC to induce neuroprotection through various pathways, the role of astrocytes in supporting IPC-induced neuroprotection has not been extensively studied. Astrocyte-derived lactate has gained attention as a potential soluble mediator through which astrocytes could impart ischemic tolerance to neurons. Therefore, the goal of this study was to determine if i) IPC-treatment of astrocytes alone could transfer ischemic tolerance to neurons; ii) if IPC-treatment of astrocytes increases lactate production; and if iii) exogenous lactate administration to neurons could induce neuroprotection against lethal ischemia in vitro. For this purpose, a co-culture system was used and modified from a previous method. This system allows astrocytes and neurons to be separated by a physical barrier, while allowing secreted substances from either cell type to interact with each other. Oxygen-glucose deprivation was used as a model of cerebral ischemia and IPC in cultured rodent astrocytes and neurons. Neurons incubated with IPC-treated astrocytes were significantly protected against lethal ischemic injury compared to neurons incubated with sham-treated astrocytes. In addition, IPC-treatment of astrocytes significantly increased lactate secretion into the extracellular media. Finally, exogenous lactate administration can significantly attenuate cell death in neuronal cultures following exposure to lethal OGD. Our results suggest that IPC-treatment of astrocytes alone can transfer ischemic tolerance to neurons. In addition, the ability of IPC to increase lactate production in astrocytes suggest that lactate could represent a neuroprotective agent to protect neurons against lethal ischemic injury.


Genetic parameters for the weights and yields of carcass cuts in Chianina cattle.
Chianina is the tallest and heaviest beef cattle breed in the world and 1 of the most appreciated breeds on the Italian meat market. A selection program focused on improving Chianina carcass quality could provide a further economic advantage to Chianina breeders. However, the current European carcass scoring system [i.e., the SEUROP (S=superior, E=excellent, U= very good, R=good, O=fair, and P=poor) grid] is not suitable for use in selective breeding programs; methods based on carcass cuts would be much more efficient. Here, the genetic parameters of weights and yields (percentage of carcass weight) of the main commercial cuts were estimated on 842 Chianina carcasses (heifers and bullocks) using a mixed model that takes into account the fixed effects of herd, year of slaughter, and sex and the random additive effect of the animal; the carcass weight was also considered in cuts yield. The average carcass weights were 492.6 ± 86.52 kg (males) and 312.1 ± 68.74 kg (females), and the largest cut was the round, with a weight of 58.6 ± 19.35 kg and yield of 24.4 ± 1.28% in males and 40.2 ± 17.59 kg and 25.3 ± 1.41% in females. The variability in cut weight was greater than that in yield percentage. The cut weight heritabilities ranged from 0.74 (chuck) to 0.21 (short plate) whereas the yield heritabilities ranged from 0.88 (loin) to 0.40 (brisket). The genetic correlations were generally high and positive between weights; correlation values with yields were lower and could be positive or negative. These findings suggest that a selection program to improve the carcass quality of Chianina beef using cuts data could potentially achieve good results.


Quantitative densitometry from the point of view of information theory.
The process of quantitative densitometry is analyzed with methods developed in information theory. It is shown that the steps involved in densitometry, e.g. gel staining, mechanical, optical and electronic processing, as well as all the steps of data processing, can be viewed as communication channels. The factors affecting both the relevant and irrelevant part of the total information passed through these channels are discussed in the consistent frame provided by information theory. This view leads to a unifying context for analyzing the performance of quantitative densitometers.


The integration of new therapies and radiation in the management of ovarian cancer.
New biologic information has led to a therapeutic program in Stage III ovarian cancer that considers the whole peritoneal cavity the tumor-bearing region and that uses intraperitoneal administration of ovarian cancer antiserum, intraperitoneal P-32, delayed split abdominal irradiation, and chemotherapy. The survival for those patients completing irradiation was 85%. Forty-nine patients with advanced (Stage III, IV, or recurrent) ovarian cancer have been treated with combinations of the present agents. Twenty-two patients have received intraperitoneal ovarian cancer antiserum without significant toxicity. Extensive staging has been a requirement for initial evaluation and includes maximal surgical resection, omentectomy, TAH and BSO, nodal biopsies, and peritoneal cytology. Nineteen patients had 5-mm nodules or less residual disease and were treated with colloidal P-32, abdominal irradiation, and chemotherapy; five of these patients received intraperitoneal antiserum before cytotoxic therapy. The four-year cumulative survival is 84%, and the disease-free survival 43%. A randomized prospective study is now examining the value of antiserum therapy. New experimental data from our laboratory indicate 1) the value of 2/3 biomarkers (alpha globulin and free secretory protein) in following patients for remission of disease and 2) the probability of the development of more effective antiserum with high specific titer. Studies of the radiosensitivity of ovarian cancer indicate the tumor was not different from other solid tumors. Our studies indicate the role of radiation therapy as a cytoreductive agent should be integrated in multimodality therapy and that the immune system offers new possibilities in amplifying therapeutic results.


Highly Sensitive MoS2 Humidity Sensors Array for Noncontact Sensation.
Recently, 2D materials exhibit great potential for humidity sensing applications due to the fact that almost all atoms are at the surface. Therefore, the quality of the material surface becomes the key point for sensitive perception. This study reports an integrated, highly sensitive humidity sensors array based on large-area, uniform single-layer molybdenum disulfide with an ultraclean surface. Device mobilities and on/off ratios decrease linearly with the relative humidity varying from 0% to 35%, leading to a high sensitivity of more than 104 . The reversible water physisorption process leads to short response and decay times. In addition, the device array on a flexible substrate shows stable performance, suggesting great potential in future noncontact interface localization applications.


Predicting the perceived sound quality of frequency-compressed speech.
The performance of objective speech and audio quality measures for the prediction of the perceived quality of frequency-compressed speech in hearing aids is investigated in this paper. A number of existing quality measures have been applied to speech signals processed by a hearing aid, which compresses speech spectra along frequency in order to make information contained in higher frequencies audible for listeners with severe high-frequency hearing loss. Quality measures were compared with subjective ratings obtained from normal hearing and hearing impaired children and adults in an earlier study. High correlations were achieved with quality measures computed by quality models that are based on the auditory model of Dau et al., namely, the measure PSM, computed by the quality model PEMO-Q; the measure qc, computed by the quality model proposed by Hansen and Kollmeier; and the linear subcomponent of the HASQI. For the prediction of quality ratings by hearing impaired listeners, extensions of some models incorporating hearing loss were implemented and shown to achieve improved prediction accuracy. Results indicate that these objective quality measures can potentially serve as tools for assisting in initial setting of frequency compression parameters.


A validated stability-indicating ultra performance liquid chromatography method for the determination of potential process-related impurities in eplerenone.
A simple, sensitive, and accurate stability-indicating analytical method has been developed and validated using ultra high performance liquid chromatography. The developed method is used to evaluate the related substances of eplerenone (EP). The degradation behavior of EP under stress conditions was determined, and the major degradants were identified by ultra high performance liquid chromatography with tandem mass spectrometry. The chromatographic conditions were optimized using an impurity-spiked solution, and the samples, generated from forced degradation studies. The resolution of EP, its potential impurities, and its degradation products was performed on a Waters UPLC BEH C18 column (50 × 2.1 mm, 1.7 μm) by linear gradient elution using a mobile phase consisting of 10 mmol/L ammonium acetate adjusted to pH 4.5, methanol and acetonitrile. A photo-diode array detector set at 245 nm was used for detection. The flow rate was set at 0.3 mL/min. The procedure had good specificity, linearity (0.02-3.14 μg/mL), recovery (96.1-103.9%), limit of detection (0.01-0.02 μg/mL), limit of quantitation (0.03-0.05 μg/mL), and robustness. The correction factors of the process-related substances were calculated.


[The effect of the blood pressure lowering effect of bopindolol (Sandonorm) in patients with mild and moderate hypertension].
The effect of a once a day dose one or one and a half mg bopindolol on mild to moderate hypertensive patients was studied. During the treatment the changes in blood pressure, heart rate, serum triglyceride, cholesterin, HDL cholesterin were examined. The drug was given as monotherapy to 9 previously untreated patients with a mean blood pressure of 163/102 mm Hg. 12 patients, who had received a combination therapy including beta-blocking agents, were treated with bopindolol instead of the previously taken beta-blockers. The initial mean blood pressure of this group was 140/80 mm Hg. The patients' age was between 35 and 72. The observation period was 12 months. The cardiac performance was examined by bicycle ergometry. On the base of the results the authors think that bopindolol is effective in blood pressure lowering both in mono- and combination therapy, and it doesn't increase the level of blood lipids. No side-effects were observed. The results of the bicycle ergometry indicated better cardiac performance. Because of its long duration of action it is important to emphasize that bopindolol in a once a day dose of one or one and a half mg is effective in the treatment of mild to moderate hypertensive patients.


Histopathological assessment of metastasis.
In spite of advances in the fields of immunohistochemistry and molecular biology, in clinical practice much of the assessment of metastases still relies on light microscopy using conventional histological stains. This is not so much a reflection of a reluctance by histopathologists to adopt new techniques, but more an indication that for most malignancies an enormous amount of useful prognostic data can be gained from relatively unsophisticated assessment of tissues, and that many of the strongest studies of prognostic factors in malignancy predate the era of molecular diagnostics. Although it is undoubtedly true that newer techniques have added prognostic information in the assessment of many tumors, and many, such as the measurement of estrogen receptor status in breast cancer, could be considered routine, a skilled assessment of the morphology of the tissues still provides the fundamental basis of assessing prognosis in the vast majority of cases.


[How to express results of 24-hour gastric pH measurement? Choice of a mode of expression in 27 healthy subjects].
Twenty-four hour intragastric acidity was studied in 27 healthy subjects (mean age = 29 yrs) by continuous recording in standardized conditions. Data obtained were expressed according to several analytical methods as used extensively elsewhere. In our study, there was a wide discrepancy in results from one subject to another. The use of median values of pH was more appropriate than mean values to express half-hour acidity levels for 24 hours. The median value of H+ concentration is recommended as well. The median value of pH varied from 1 to 4.8 with a slight rise during the second half of the night. During the postprandial period, increase of pH values was prolonged over 2 h 30 in 50 p. 100 of subjects. Profile of pH allowed to demonstrate the distribution of pH value without excluding the extreme values. Both periodicity of pH measurement (30 or 60 min) and parameters used to quantify acidity (percentage of time or pH value at or below threshold values) did not modify results. As measured over a 24 hours period, the percentage of time (mean +/- SEM) at or below pH 1.5 and 3.5 was 54 +/- 3 p. 100 and 85 +/- 2 p. 100, respectively. Daytime and night-time profiles were similar. Mean 24 h H+ concentration (mean +/- SEM) was 47 +/- 35 mmol/l, with, once again, similarity between day and night-time values. The mean 24 h pH values underestimated true acidity with respect to median values.(ABSTRACT TRUNCATED AT 250 WORDS)


NMDA antagonist inhibits the extracellular signal-regulated kinase pathway and suppresses cancer growth.
Glutamate antagonists limit the growth of human cancers in vitro. The mechanism of anticancer action of NMDA antagonists is not known, however. In this article, we report that the NMDA antagonist dizocilpine inhibits the extracellular signal-regulated kinase 1/2 pathway, an intracellular signaling cascade that is activated by growth factors and controls the proliferation of cancer cells. Dizocilpine reduces the phosphorylation of cAMP-responsive element binding protein, suppresses the expression of cyclin D1, up-regulates the cell cycle regulators and tumor suppressor proteins p21 and p53, and increases the number of lung adenocarcinoma cells in the G(2) and S phases of the cell cycle. Silencing of the tumor suppressor protein p21 abolishes antiproliferative action of dizocilpine. Consistent with inhibition of the extracellular signal-regulated kinase 1/2-signaling cascade, dizocilpine reverses the stimulation of proliferation induced by epidermal, insulin, and basic fibroblast growth factors in lung adenocarcinoma cells. Furthermore, dizocilpine prolongs the survival of mice with metastatic lung adenocarcinoma and slows the growth of neuroblastoma and rhabdomyosarcoma in mice. These findings reveal the mechanism of antiproliferative action of dizocilpine and indicate that it may be useful in the therapy of human cancers.


[The influence of inhaled glucocorticoids on the growth of asthmatic children].
In this paper general characteristic of the growing process of children is described. Various factors may modify this process including genetic predisposition, environmental factors, diseases, diet, and drugs. Asthmatic children present growth retardation, however without significant influence on final height. Low and moderate doses of inhaled glycocorticosteroids have no significant effects on growth. The results of short, medium and long term studies are discussed.


Gene expression profiling in pulmonary hypertension.
The application of functional genomics toward the investigation of complex medical conditions has moved from a futuristic dream to a medical reality in less then a decade. The ability to examine the expression level of thousands of genes simultaneously has opened the door for entirely new approaches toward experimental observation and discovery. The resulting data from these genomic studies is being collected at an unprecedented scale. This wealth of data can present its own obstacles in terms of analysis. However, as new and more powerful means of examining these experiments are developed, medical science is reaping significant benefit. The power of microarray gene expression analysis has been directed at a diverse and complex array of diseases. As will be discussed in this article, the investigation of pulmonary hypertension has already benefited greatly from the application of this technology.


Is there a standard of care for eccentric viewing training?
A study was conducted to determine the current Department of Veterans Affairs (VA) standard of practice for eccentric viewing (EV) training. EV training is the process of teaching patients to realign the visual image away from a diseased foveal/macular region onto healthier retina. Optometrists and Visual Skills Instructors at all VA blind rehabilitation centers (BRCs) and VICTORS (vision impairment centers to optimize remaining sight) programs were asked to rate preference for EV prescription criteria, evaluation, and training techniques. Responses were received from 70% of BRCs and 67% of VICTORS. The respondents reported that all programs include EV training. The average minutes of training per patient varied from 20 minutes to nearly 24 hours, with instructors within a single center varying by as much as two orders of magnitude. Routinely, 82% of optometrists prescribe EV training, yet no consensus was found among these practitioners as to the criteria for selecting the best EV area. The results of this survey reveal an inconsistent standard of practice across VA centers and demonstrate the need for prospective studies of the efficacy, effectiveness, and cost-effectiveness of EV training.


Do we all agree on how to measure work engagement? Factorial validity of Utrecht Work Engagement Scale as a standard measurement tool - A literature review.
Work engagement as a predictor of health is an emerging concept in occupational science and the Utrecht Work Engagement Scale (UWES) is the most popular work engagement measurement tool. However, despite its popularity, the UWES is not free from controversy concerning its factorial validity. In this paper, 21 research studies on both UWES-9 and UWES-17 factorial validity within the confirmatory factor analysis (CFA) approach have been reviewed in order to answer the question as to which of the UWES factorial structures displays greater validity. The originally proposed threefactor structure of the UWES has been recognized as superior in 6 studies. In further 6 studies, the UWES structure with 1 general factor has been found to be superior. In 8 studies, the authors have concluded that the one- and three-factor structures could be considered equivalent. One study has failed to confirm either the one- or three-factor structure of the UWES. These ambiguous results from studies focusing on the UWES factorial validity are puzzling because they not only indicate a lack of validity for the UWES as a measurement tool but might also challenge the whole concept of work engagement as a three-factor structure of dedication, vigor and absorption. Int J Occup Med Environ Health 2017;30(2):161-175.


Repetition Priming Magnitude Depends on Affirmative Prime Responses: A Test of Two Congruity Explanations.
We conducted 2 experiments to evaluate the impact of positive prime responses on repetition priming effects while decoupling this impact from content congruity and specific evaluation operations. Our first experiment consisted of word-meaning comparison trials that required participants to evaluate synonyms or antonyms. A crossing of evaluation operation with semantic content allowed us to test the goal-content congruity hypothesis against the semantic congruity explanation for greater facilitation from positive response primes. Results suggested that operation-based priming is affected by goal-content congruity. A second experiment tested the observed effect of positive responses on repetition priming using mental rotation of irregular shapes, affording a test of the impact of congruity in evaluation goals and content in a nonverbal stimulus domain. Both experiments produced a pattern of results inconsistent with Schulman's (1974) semantic congruity account and instead implicated a different form of congruity that affects memory for prior operations rather than memory for semantic and episodic content.


Eyelid sebaceous gland carcinoma: Varied presentations and reconstruction outcome.
To analyze varying clinical presentations, histopathological features, and management outcome of sebaceous gland carcinoma (SGC) of the eyelid. We retrospectively reviewed medical records of 30 patients with histologically proven cases of SGC of eyelid treated at tertiary care hospital. Patients were in the age group of 28-80 years, among which 18 (60%) were females and 12 (40%) were males. Mean follow-up period was 29.83 ± 8.14 months. Six out of 30 cases were lost to follow-up; hence, only 24 cases were analyzed for reconstruction techniques and management outcome. Initial anatomic sites involved were upper eyelid (10 cases [33.33%]), lower eyelid (5 cases [16.66%]), both upper and lower eyelid (10 cases [33.33%]), and medial canthus (1 case [3.33%]). Orbital extension at presentation was present in 4 cases (13.33%) while metastasis to preauricular lymph nodes was seen in 1 case (3.33%). T2 was the most common category according to TNM staging (14, 58.33%). Reconstruction techniques included direct closure with or without cantholysis in 5 (20.83%), closure with Tenzel's semicircular flap in 2 (8.33%), Cutler Beard repair in 5 (20.83%), and Hughes's flap with either cheek advancement flap or full-thickness skin graft in 3 (12.5%). Both upper eyelid and lower eyelid repair were done in three (12.5%) cases and medial canthal repair in one (4.16%) case. Five (20.83%) cases underwent exenteration. On histopathological examination, 23 (95.83%) patients had localized tumors while only 1 (4.16%) patient had pagetoid invasion. Recurrence was observed in three (12.5%) cases. One (4.16%) case died subsequent to brain metastasis. SGC of eyelid may have varied presentations, but early diagnosis and consequent surgical therapy has good outcome and higher survival rate.


Cancer-associated fibroblasts promote cancer stemness by inducing expression of the chromatin-modifying protein CBX4 in squamous cell carcinoma.
The chromobox-containing protein CBX4 is an important regulator of epithelial cell proliferation and differentiation, and has been implicated in several cancer types. The cancer stem cell (CSC) population is a key driver of metastasis and recurrence. The undifferentiated, plastic state characteristic of CSCs relies on cues from the microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of the microenvironment that can influence the CSC population through the secretion of extracellular matrix and a variety of growth factors. Here we show CBX4 is a critical regulator of the CSC phenotype in squamous cell carcinomas of the skin and hypopharynx. Moreover, CAFs can promote the expression of CBX4 in the CSC population through the secretion of interleukin-6 (IL-6). IL-6 activates JAK/STAT3 signaling to increase ∆Np63α-a key transcription factor that is essential for epithelial stem cell function and the maintenance of proliferative potential that is capable of regulating CBX4. Targeting the JAK/STAT3 axis or CBX4 directly suppresses the aggressive phenotype of CSCs and represents a novel opportunity for therapeutic intervention.


Assessment of central, peripheral, and autonomic nervous system functions in vibrating tool operators: neuroelectrophysiological studies.
To evaluate the effects of vibrating tool operation (i.e., combined stressors of local vibration, noise, cold climate, and heavy work) on the central, peripheral, and autonomic nervous systems, the short-latency somatosensory and brain stem auditory evoked potentials (SSEP and BAEP), the distribution of sensory median nerve conduction velocities (DCV), conventional median nerve conduction velocities (NCV), and the electrocardiographic R-R interval variability (CVRR) were measured in three groups of male vibrating tool operators and age-matched male healthy adults. Two components of the CVRR reflecting parasympathetic activity (C-CVRSA) and sympathetic activity (C-CVMWSA) were also examined. In the first group of vibrating tool operators (15 chain saw operators), all parameters of DCV (V10-V90 velocities) and sensory and motor nerve conduction velocities of NCV were significantly slowed. All peak latencies of SSEP were significantly prolonged, while no significant differences were found in the interpeak latencies of SSEP. The N9 peak latency of SSEP was significantly related to total working days. In the second group of the operators (12 chain saw and 8 brush saw operators), the I-V interpeak and V peak latencies of BAEP were significantly prolonged in the 12 chain saw operators; the I-V interpeak latency of BAEP was significantly correlated with the working years in the 8 brush saw operators. In the third group of vibrating tool operators, i.e., 13 operators with a history of vibration-induced white finger (VWF group) and 11 operators without VWF (non-VWF group), both the CVRR and C-CVRSA were significantly reduced in the VWF group; only the CVRR was significantly reduced in the non-VWF group. Similarly, the faster velocities of DCV (V70, V80, and V90 velocities) were significantly slowed in both the VWF and non-VWF groups. In conclusion, it is suggested that vibrating tool operation affects the faster sensory and motor nerve fibers, the parasympathetic activity, and the auditory pathway from the acoustic nerve to the brain stem.


Regioselective aminolysis and hydrolysis of chiral 1,4-ferrocenyl diacetate.
The treatment of (1R,4R)-1,2-bis(phenylmethyl)ferrocenyl diacetate 2a with aqueous ammonium in THF/MeOH at room temperature for 18 h gave the single diastereomer of the (1R,4R,Sp)-1,2-acetoamido alcohol 4a with retention of the configuration. This result showed that the aminolysis occurred regioselectively at one side of the two acetates. Similarly, hydrolysis of the diacetate 2a at room temperature for 18 h occurred regio- and stereoselectively to give the optically active half-ester 10 in a good yield. The ease of the substitution may depend on the geometry of the two stereogenic centers. Only one of the acetoxy groups is suitably aligned for ionization (exo to the ferrocenyl group) to proceed efficiently; the aminolysis takes place smoothly by iron-assisted ionization, i.e., neighboring group participation. The leaving group on the second acetoxy group is not suitably aligned (endo to the ferrocenyl group) and also cannot undergo a conformational change for it to adopt the appropriate orientation for ionization to occur. This reaction is the first case of substitution in a chiral molecule in which a conformational difference between two leaving groups happened to affect the rate of aminolysis and hydrolysis at two stereogenic centers.


The use of myeloid hematopoietic growth factors in patients with HIV infection.
Hematologic abnormalities are frequent occurrences in patients with HIV infection. Myelosuppression in AIDS may be due to multiple factors and has significant impact on the treatment of HIV-infected individuals, as it is the major dose-limiting toxicity of a number of antimicrobial compounds and chemotherapy. Both granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) are hematopoietic hormones which effect myeloid progenitor cells and enhance the function of mature neutrophils. Clinical studies of the effects of these agents in patients with AIDS indicate that GM-CSF and G-CSF can increase the production of leukocytes in a dose-dependent fashion. This increase in leukocyte production may allow the continued administration of full doses of antiviral or other myelosuppressive medications in previously hematologically intolerant patients with AIDS. Investigations of the hematopoietic, virologic, and immunologic effects of these agents alone and in combination with other hematopoietins, cytokines, and chemotherapeutic agents will ultimately define their clinical utility in patients with HIV infection.


Germany/Australia index of sperm sex sortability in elephants and rhinoceros.
Flow cytometric sexing of spermatozoa followed by application in artificial insemination or in vitro fertilization provides a unique opportunity to predetermine the sex of offspring and might enhance the conservation management of endangered species in captivity such as the elephant and rhinoceros. To obtain an indication of the sortability of spermatozoa from these species, the relative DNA differences between X and Y chromosome bearing spermatozoa (fresh, frozen thawed, epididymal) from three rhinoceros species [white (Ceratotherium simum), black (Diceros bicornis), Indian (Rhinoceros unicornis)] and both elephant species, the Asian and the African elephant (Elephas maximus, Loxodonta Africana), were determined through separation of spermatozoa into X and Y chromosome bearing populations, using a modified high speed flow cytometer. The head profile areas of spermatozoa from all five species were measured using light microscopy. By multiplying the relative DNA differences and the head profile areas, the sperm sorting indices were calculated to be 47, 48 and 51 for white, black and Indian rhinoceros respectively. The calculated sorting index for the Asian elephant was 66. In the African elephant, we determined the highest sorting index of 76. These results indicate the practicability of flow cytometric sex sorting of spermatozoa from the tested rhinoceros species and both elephant species. The lower sorting indices in rhinos indicate that sex sorting of spermatozoa from the rhinoceros will be more challenging than in elephants.


Immune-enhancing activities of chondroitin sulfate in murine macrophage RAW 264.7 cells.
As a representative sulfated glycosaminoglycan (GAG), chondroitin sulfate (CS) has been reported playing vital roles in the immune response in vivo and in vitro. However, limited information is available about their immune-enhancing activity. This study was to achieve more precise understandings about the immuno-stimulating activity of CS. In in vitro experiments, CS was found to significantly promote the pinocytic, phagocytic activity and ROS production of RAW264.7 cells at the dose range of 100-1000 μg/mL compared with the untreated group (p < 0.05). Further experiments showed that CS could increase the secretion levels of NO, TNF-α, IL-6 and IL-10 via activating the corresponding mRNA expression in macrophages through the toll-like receptor 2 (TLR2). These results indicated that CS could function as an immunostimulator to enhance the immune responses and might be a potential candidate for application in immunological diseases or functional foods.


Conservation biology, genetically modified organisms, and the biosafety protocol.
Concerns have been raised regarding the potential adverse effects on biological diversity of the use of living modified organisms (LMOs, which are commonly known by similar terms such as genetically modified organisms). At the international level these concerns are addressed in part by an agreement known as the Cartagena Protocol on Biosafety and include potential toxic effects of insect-resistant crops on nontarget organisms and potential ecological effects of gene flow from modified crops, fish, microorganisms, or insects to wild species or counterparts. We reviewed the protocol's main provisions, including those dealing with risk assessment and risk management, decision making on imports, documentation accompanying shipments, and liability resulting from damages caused by LMOs. A medium-term program of work has been adopted by the parties, which includes the potential contribution of conservation biologists to delivering capacity building, developing risk assessment guidance, evaluating mechanisms of potential ecological damages from LMOs, and other issues. Conservation biologists and other experts have opportunities to influence the negotiations and implementation of the protocol by providing inputs at meetings, offering expertise to governments and organizations, and participating in or developing relevant projects and initiatives. Involvement of conservation biologists in the implementation and further development of the protocol would contribute to its effectiveness.


Some remarks on protein attribute prediction and pseudo amino acid composition.
With the accomplishment of human genome sequencing, the number of sequence-known proteins has increased explosively. In contrast, the pace is much slower in determining their biological attributes. As a consequence, the gap between sequence-known proteins and attribute-known proteins has become increasingly large. The unbalanced situation, which has critically limited our ability to timely utilize the newly discovered proteins for basic research and drug development, has called for developing computational methods or high-throughput automated tools for fast and reliably identifying various attributes of uncharacterized proteins based on their sequence information alone. Actually, during the last two decades or so, many methods in this regard have been established in hope to bridge such a gap. In the course of developing these methods, the following things were often needed to consider: (1) benchmark dataset construction, (2) protein sample formulation, (3) operating algorithm (or engine), (4) anticipated accuracy, and (5) web-server establishment. In this review, we are to discuss each of the five procedures, with a special focus on the introduction of pseudo amino acid composition (PseAAC), its different modes and applications as well as its recent development, particularly in how to use the general formulation of PseAAC to reflect the core and essential features that are deeply hidden in complicated protein sequences.


Role of Dispersive Fluorous Interaction in the Solvation Dynamics of the Perfluoro Group Containing Molecules.
Perfluoro group containing molecules possess an important self-aggregation property through the fluorous (F···F) interaction which makes them useful for diverse applications such as medicinal chemistry, separation techniques, polymer technology, and biology. In this article, we have investigated the solvation dynamics of coumarin-153 (C153) and coumarin-6H (C6H) in ethanol (ETH), 2-fluoroethanol (MFE), and 2,2,2-trifluoroethanol (TFE) using the femtosecond upconversion technique and molecular dynamics (MD) simulation to understand the role of fluorous interaction between the solute and solvent molecules in the solvation dynamics of perfluoro group containing molecules. The femtosecond upconversion data show that the time scales of solvation dynamics of C6H in ETH, MFE, and TFE are approximately the same whereas the solvation dynamics of C153 in TFE is slow as compared to that of ETH and MFE. It has also been observed that the time scale of solvation dynamics of C6H in ETH and MFE is higher than that of C153 in the same solvents. MD simulation results show a qualitative agreement with the experimental data in terms of the time scale of the slow components of the solvation for all the systems. The experimental and simulation studies combined lead to the conclusion that the solvation dynamics of C6H in all solvents as well as C153 in ETH and MFE is mostly governed by the charge distribution of ester moieties (C═O and O) of dye molecules whereas the solvation of C153 in TFE is predominantly due to the dispersive fluorous interaction (F···F) between the perfluoro groups of the C153 and solvent molecules.


[Personalized therapy in non-small cell lung cancer: from diagnosis to therapy].
Molecular targeted treatment, with broadening opportunities, plays an important role in the management of lung cancer patients, which renders molecular mapping of the tumor tissue crucial. In case of cytotoxic chemotherapy, there is no patient selection according to tissue biomarkers; however, there are expanding results that might help oncologists to use personalized chemotherapy in the near future. This may be of great importance when patients' age, performance status and/or co-morbidity make the applicability of chemotherapy uncertain. Nowadays, molecular targeted treatment gives hope mainly for patients with adenocarcinoma; however, promising therapeutic targets have already been outlined due to intensive research. In these days, we are experiencing a turbulent era of onco-pulmonology, which - despite all difficulties - gives hope for both patients and clinicians.


Muscles used for chest compression under static and transportation conditions.
Unstable conditions during ambulance transportation are not conducive to the performance of high-quality cardiopulmonary resuscitation by emergency medical technicians. The present study was conducted to clarify differences in the quality of chest compression and associated muscle activity between static and ambulance transportation conditions. Nine paramedic students performed chest compression for 5 minutes on the floor and during ambulance transportation. Compression rate and depth and success and error rates of chest compression were determined using the Resusci Anne manikin with a PC SkillReporting System (Laerdal Medical). Integrated electromyography (i-EMG) values of eight different muscles were also recorded bilaterally during the first and last 30 seconds of compression. There was no significant difference in compression rate per minute (p = 0.232) and depth of chest compression (p = 0.174) between the two conditions. The success rate was significantly lower under the ambulance transportation condition than under the static condition (p = 0.0161). Compared with those under the static condition, the total i-EMG values were significantly lower for the multifidus (p = 0.0072) and biceps femoris (p < 0.0001) muscles and significantly higher for the deltoid (p = 0.0032), pectoralis major (p = 0.0037), triceps brachii (p = 0.0014), vastus lateralis (p < 0.0001), and gastrocnemius (p = 0.0004) muscles under the ambulance transportation condition. Chest compression is performed mainly through flexion and extension of the hip joint while kneeling on the floor and through the elbow and shoulder joints while standing in a moving ambulance. Therefore, the low quality of chest compression during ambulance transportation may be attributable to an altered technique of performing the procedure.


Biological psychiatry: time for new paradigms.
Biological psychiatry has not yet produced clinically viable biomarkers for any of the major psychiatric diseases, and the past 25 years have not brought any fundamentally new biological treatment principles. I discuss reasons for this slow progress and suggest avenues for the development of biomarkers and the discovery of new treatment targets.


Phenotype-Environment Matching Predicts Both Positive and Negative Effects of Intraspecific Variation.
Natural populations can vary considerably in their genotypic and/or phenotypic diversity. Differences in this intraspecific diversity can have important consequences for contemporary ecological dynamics, but the direction and magnitude of these effects appear inconsistent across studies and systems. Here we proposed and tested the hypothesis that context-dependent ecological effects of altering phenotypic variance are predictable and arise from the relationship between a population's mean phenotype and the local environmental optimum. By factorially manipulating the mean and variance of a key host trait in environments with and without a lethal parasite, we demonstrate that increasing phenotypic variance can have beneficial effects for host populations (e.g., smaller disease epidemics) but only when the population's initial phenotype was poorly matched to the local environment. When phenotypes were initially well suited to environmental conditions, in contrast, greater phenotypic variance led to larger disease epidemics. Significant reductions in individual susceptibility occurred in both contexts over time, but the mechanisms leading to those reductions differed; strong selection was caused by either a suboptimal trait mean and insufficient trait variance or a near-optimal trait mean and too much trait variance. Increasing intraspecific variation is clearly not always beneficial for populations, instead producing predictable ecological and evolutionary effects that depend on environmental context and biological interactions.


Prevalence of chlamydial infection in patients with gonococcal urethritis.
Using a fluorescein labelled monoclonal antibody ("Microtrak") to identify Chalmydia elementary bodies in urethral smears, we detected Chlamydia trachomatis in 32 (26.67%) of 120 male patients after treatment of their gonococcal urethritis. Sixteen of these 32 patients (50%) had normal urethral smear. Only 16 (50%) of the patients yielding chlamydia would have received treatment in the absence of diagnostic service for chlamydial infection.


A convolution-superposition fluence model for the Siemens HD120 multi leaf collimator with application to a 3D VMAT dose engine.
Purpose. To construct a fast-calculating fluence modelfor the Siemens HD120 multi leaf collimator (MLC) using convolution-superposition techniques, and to develop a 3D VMAT dose engine using this fluence model. This work offers analternative to time-consuming open-source Monte Carlo simulations for thosedeveloping in-house dose-calculating software for research or clinical needs.Methods. EPID-acquired images of sweeping-window and sweeping-checker field profiles were used to commission transmission, 2 Dinterleaf leakage, and tongue-and-groove maps specific to the HD120 MLC. These maps, along with a 2D head-scattermodel were incorporated into a convolution-superposition algorithm to provide a fluence model for the HD120 MLC. This fluence model was used to develop a 3D VMAT dose engine, where 3D pre-computed 6MV dose kernels (EGSnrc) and a 3D fluence curvature-correction map were incorporatedto calculate 3D VMAT doses in a 22 cm diameter cylindrical phantom. Four VMAT patient plans witha large range of PTV sizes (36 cc to 604 cc) were chosen to test the fluence model and dose engine.Results. Excellent agreement was observed between the simulated commissioning fields and measured EPID-responses. 2D 2%/2 mm gamma analysis yielded a 98.9% pass rate for 1 cm, 2 cm, and 4 cm sweeping-window fields. 2D 2%/2mm gamma analysis for outer/inner MLC leaves yielded 89.1%/77.0% and 95.2%/91.1% pass rates from 1 cm and 2 cm sweeping-checker fields. Mean 3%/3 mm gamma analysis showed excellent agreement between our dose engine and Eclipse (Acuros) regardless of PTV size: 98.7% pass rate, with 95.1% pass rate in the high-dose volume. Fluence calculation times were13.6 seconds per dynamic MLC field and 1.4 minutes/arc for 3D VMAT dose on a standard PC. Conclusions. A fast-calculating convolution-superposition fluence model has been commissioned for the Siemens HD120 MLC and incorporatedinto a 3D VMAT dose engine. This work can be used to facilitate the development of fast in-house dose-calculating software.


Protective action of spermine and spermidine against photoinhibition of photosystem I in isolated thylakoid membranes.
The photo-stability of photosystem I (PSI) is of high importance for the photosynthetic processes. For this reason, we studied the protective action of two biogenic polyamines (PAs) spermine (Spm) and spermidine (Spd) on PSI activity in isolated thylakoid membranes subjected to photoinhibition. Our results show that pre-loading thylakoid membranes with Spm and Spd reduced considerably the inhibition of O2 uptake rates, P700 photooxidation and the accumulation of superoxide anions (O2(-)) induced by light stress. Spm seems to be more effective than Spd in preserving PSI photo-stability. The correlation of the extent of PSI protection, photosystem II (PSII) inhibition and O2(-) generation with increasing Spm doses revealed that PSI photo-protection is assumed by two mechanisms depending on the PAs concentration. Given their antioxidant character, PAs scavenge directly the O2(-) generated in thylakoid membranes at physiological concentration (1 mM). However, for non-physiological concentration, the ability of PAs to protect PSI is due to their inhibitory effect on PSII electron transfer.


Point-of-care ultrasound as a competency for general internists: a survey of internal medicine training programs in Canada.
Point-of-care ultrasound (POCUS) is increasingly used on General Internal Medicine (GIM) inpatient services, creating a need for defined competencies and formalized training. We evaluated the extent of training in POCUS and the clinical use of POCUS among Canadian GIM residency programs. Internal Medicine trainees and GIM Faculty at the University of Toronto were surveyed on their clinical use of POCUS and the extent of their training. We separately surveyed Canadian IM Program Directors and Division Directors on the extent of POCUS training in their programs, barriers in the implementation of POCUS curricula, and recommendations for POCUS competencies in IM. A majority of IM trainees (90/118, 76%) and GIM Faculty (15/29, 52%) used POCUS clinically. However, the vast majority of resident (111/117, 95%) and GIM Faculty (18/28, 64%) had received limited training. Of the Program Leaders surveyed, half (9/17, 53%) reported POCUS clinical use by their trainees; however only one quarter (4/16, 25%) reported offering formal curricula. Most respondents agreed that POCUS training should be incorporated into IM residency curricula, specifically for procedural guidance. A considerable discrepancy exists between the clinical use of POCUS and the extent of formal training among Canadian IM residents and GIM Faculty. We propose that formalized POCUS training should be incorporated into IM residency programs, GIM fellowships, and Faculty development sessions, and identify POCUS skills that could be incorporated into future IM curricula.


[A case of pleural malignant lymphoma associated with chronic tuberculous pyothorax].
We report a case of pleural malignant lymphoma associated with chronic tuberculous pyothorax. A 67-year-old male was hospitalized because of left lateral chest swelling and pain. He had suffered from pulmonary tuberculosis at the age of six and tuberculous pleurisy at the age of 24. We made a histologic diagnosis of malignant lymphoma diffuse large B-cell type. He was medicated THP-COP (THP, CY, VCR, PSL) therapy and his chest pain and swelling has improved gradually. From the view point of molecular biology, we detected Epstein-Barr virus (EBV) infection in the pyothorax wall. In conclusion, we should be more careful about medical examination in patients with EBV positive tuberculous pyothorax considering the complication of malignant lymphoma.


[Differential diagnosis of edemas].
Differential diagnosis of the various forms of edema certainly demands a wide range of experience. Up to 80% of cases can be diagnosed accurately on the basis of an exact case history and physical examination, a diagnosis which only needs to be confirmed by further tests. The rest of the cases require mechanical and laboratory tests which are, for the most part, very time consuming and costly.


[Primary bladder adenocarcinoma in a young girl].
We describe a case of primary adenocarcinoma of the bladder in an 18-year-old girl. She had no recurrence five years after operation. A young case is very rare because primary bladder adenocarcinoma are found mostly in old patients. We collected 86 cases of primary bladder adenocarcinoma in the Japanese literature, but found no case of a young patient in them. In the literature, epithelial bladder tumors in children have been reported to show good prognosis compared with adults.