Insulin/IGF-regulated size scaling of neuroendocrine cells expressing the bHLH transcription factor Dimmed in Drosophila.
Neurons and other cells display a large variation in size in an organism. Thus, a fundamental question is how growth of individual cells and their organelles is regulated. Is size scaling of individual neurons regulated post-mitotically, independent of growth of the entire CNS? Although the role of insulin/IGF-signaling (IIS) in growth of tissues and whole organisms is well established, it is not known whether it regulates the size of individual neurons. We therefore studied the role of IIS in the size scaling of neurons in the Drosophila CNS. By targeted genetic manipulations of insulin receptor (dInR) expression in a variety of neuron types we demonstrate that the cell size is affected only in neuroendocrine cells specified by the bHLH transcription factor DIMMED (DIMM). Several populations of DIMM-positive neurons tested displayed enlarged cell bodies after overexpression of the dInR, as well as PI3 kinase and Akt1 (protein kinase B), whereas DIMM-negative neurons did not respond to dInR manipulations. Knockdown of these components produce the opposite phenotype. Increased growth can also be induced by targeted overexpression of nutrient-dependent TOR (target of rapamycin) signaling components, such as Rheb (small GTPase), TOR and S6K (S6 kinase). After Dimm-knockdown in neuroendocrine cells manipulations of dInR expression have significantly less effects on cell size. We also show that dInR expression in neuroendocrine cells can be altered by up or down-regulation of Dimm. This novel dInR-regulated size scaling is seen during postembryonic development, continues in the aging adult and is diet dependent. The increase in cell size includes cell body, axon terminations, nucleus and Golgi apparatus. We suggest that the dInR-mediated scaling of neuroendocrine cells is part of a plasticity that adapts the secretory capacity to changing physiological conditions and nutrient-dependent organismal growth.


Multidimensional rehabilitation programs for adult cancer survivors.
To assess the effectiveness of multidimensional rehabilitation programs (MDRPs) in terms of maintaining or improving the physical and psychosocial well-being of adult cancer survivors.


Ia specificities on parental and hybrid cells of an I-A mutant mouse strain.
Splenic B cells and B cell blasts from the I-A mutant mouse strain B6.C-H-2bm12 were tested by serology with a series of new monoclonal anti-Iab antibodies. Four out of 5 of those monoclonal antibody-defined specificities that are determined by wild-type I-Ab antigens were undetectable on B6.C-H-2bm12 cells. Specificities both present and absent on mutant cells appear to be determinants on the same wild-type molecule, as indicated by sequential precipitation experiments with soluble H-2b antigens. The lack of expression of certain Ia specificities on mutant cells was found not to be the result of disparate control by the Xid gene, which was previously shown to control the expression of Ia.W39, another specificity absent in B6.C-H-2bm12 mice. Serologic testing of Ia specificities on cells and blasts from F1-hybrid mice suggested that the Iabm12 antigens are codominantly expressed, indicating a failure to detect trans regulation or complementation of the mutant phenotype. Another monoclonal antibody-defined Ia specificity dependent on the expression of the E beta polypeptide was normally expressed in B6.C-H-2bm12 mice. These data thus suggest that the lesion of these mutant mice occurred in the A alpha and/or A beta structural gene, resulting in the loss of several Ia specificities.


Revision of brief health literacy assessment scale among the older adults and its reliability and validity test.
The development and validation of the specific health literacy assessment tool for older adults is the basis for conducting the research on health literacy among older adults. The existing health literacy assessment scale for older adults in Chinese mainland has some limitations, such as too many items and poor compliance during the survey. It is necessary to develop or introduce simplified assessment tools to support large-scale surveys in the future. This study aims to modify the brief health literacy assessment scale compiled by Taiwan scholars, and to conduct the test for the reliability, validity and the measurement equivalence across gender in the older population in mainland China. From March to April 2021, 508 older adults from Jinan, Shandong Province, China were selected by cluster sampling method to conduct a questionnaire survey using the brief health literacy assessment scale and health-promoting lifestyle profile. After 4 weeks, 83 of them were selected for retesting. SPSS 25.0 statistical software was used for descriptive analysis, item analysis, exploratory factor analysis, correlation analysis, and reliability test, and Mplus 8.0 was used for confirmatory factor analysis and gender measurement equivalence test. Each item of the scale had good discrimination, and there were significant differences in the scores of each item between high score and low score groups (P<0.05), and the coefficient of correlation between the scores of each item and the total score was between 0.721 and 0.891. Exploratory factor analysis extracted a factor with a characteristic root greater than 1, and the cumulative variance interpretation amount was 67.94%. The confirmatory factor analysis showed that the single factor structure fit was good [χ2/df was 2.260, the Tucker-Lewis index was 0.973, the comparison fit index (CFI) was 0.982, and the root mean square error of approximation (RMSEA) was 0.071]. The multi-group confirmatory factor analysis results showed that the brief health literacy assessment scale's configural equivalence, weak equivalence, and strong equivalence models were all accepted. The comparison results of measurement equivalence models showed that the changes of RMSEA were less than 0.015, and the changes of CFI were less than 0.01, indicating that the brief health literacy assessment scale had measurement equivalence between different gender groups. Cronbach's α coefficient was 0.945, and the test-retest reliability was 0.946. The correlation coefficient between health literacy and health-promotion lifestyles was 0.557 (P<0.05). The brief health literacy assessment scale has good reliability, validity, and measurement equivalence across gender, and can be used as an effective measurement tool for the health literacy of the older people in Chinese mainland.


Radioiodinated branched-chain fatty acids: substrates for beta oxidation? Concise communication.
Branched-chain iodinated fatty acids have been proposed for use as myocardial imaging agents. Several omega- iodoalkyl and omega- iodoaryl beta-methyl branched fatty acids have been synthesized and tested in rats. Myocardial activity levels at t = 5 min are affected by chain length for both alkyl and aryl acids, with chain lengths of 16 carbons possessing higher levels of activity than shorter lengths. Branching significantly lowers heart-to-blood ratios relative to straight-chain analogs. The degree of branching also affects radioactivity levels. Monoalkylation at the beta-carbon does not reduce the levels for omega- iodoalkyl fatty acids, but dialkylation reduces the levels significantly. Branching in the omega- iodoaryl series of fatty acids altered the time course of activity in the myocardium from a level of activity decreasing with time for the straight-chain acid to an essentially constant level of activity for the branched analogs.


[Osteodensitometry in children and adolescents with inflammatory bowel disease].
To evaluate the quantity and severity of bone disorders in children and adolescents with inflammatory bowel diseases (IBD) and to examine the correlation to whole body growth. In this study 89 bone mineral density measurements were performed and retrospectively analyzed. Under consideration of growth retardation, over 65.2 % of the patients with Cohn's disease showed a reduced bone mineral density. Osteopenia/Osteoporosis is seldom seen in patients with ulcerative colitis, i. e., only 34.8 % showed a reduction in bone mineral density. Growth retardation and reduced bone mineral density are correlated. Patients with Cohn's disease and a body length below the 25th height percentile showed a reduced bone mineral density in 78.1 % of the cases. Patients with a body length below the 10th height percentile had a reduced bone mineral density in 83.3 % of the cases. These results demonstrate the value of osteodensitometric measurements in patients with chronic diseases, especially in children and adolescents with inflammatory bowel disease.


Trevathana noae, a new species of coral inhabiting barnacle (Cirripedia: Thoracica: Pyrgomatidae).
We describe a new species from the genus Trevathana Anderson, 1992, collected from the Cocos/Keeling Islands in the Indian Ocean. Trevathana noae sp. nov. is similar to other species of Trevathana by its external shell and opercular valve morphology. It is distinct from congeners in that the tergum has a distinct spur which lacks an internal tooth in adult specimens. A key to the known species of Trevathana is given.


Cervical cancer: are there potential new targets? An update on preclinical and clinical results.
According to international guidelines, treatment of cervical cancer (CC) consists of surgery in early stages and of chemoradiation in locally advanced disease. Metastatic disease is usually treated with palliative chemotherapeutic regimens, but cytostatic drugs present significant side effects and show limited activity. Thus, the discovery of new anticancer agents, interfering with molecular targets expressed by the tumor's microenvironment or by the tumor cell itself, represents a possible chance for the struggle against this tumor. The aim of this review is to report all targets that have been investigated in preclinical and clinical studies. We discuss these potential targets according to "targeted therapies" NCI classification. The most investigated molecular targets have been epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), both involved in CC etiopathogenesis. Studies with anti-angiogenetic agents showed encouraging clinical efficacy and acceptable toxicity. Other interesting results have been obtained by immunotherapeutic strategies. Since biological characteristics of CC, especially in recurrent disease, are still partially unknown, future studies are necessary to understand mechanisms involved in CC carcinogenesis, in order to give to patients the most tailored and efficient treatments.


Anisotropic and Multicomponent Nanostructures by Controlled Symmetry Breaking of Metal Halide Intermediates.
We propose and validate herein a solution-phase synthetic strategy relying on in situ photostimulation and reduction of metal-halide intermediates to yield complex anisotropic and multicomponent nanostructures. Exposure of AgBr nanoparticles to ultraviolet light and l-Arginine forms dimers composed of crystalline Ag and AgBr nanophases. The Ag nanoparticle nucleates at and grows from a single point on the surface of the AgBr phase and the interface connecting these phases is atomically sharp. The complex nanostructures are generated at greater than 80% yield and are highly monodisperse in morphology and in size. The high crystallinity of the nanophases arises from an apparent solid-solid crystallization process and is unusual considering the nearly 40% lattice mismatch between Ag and AgBr. Such structures may be used to interrogate photocatalytic mechanisms or to construct more complex materials.


Modulation of hepatic glutathione transferases isoenzymes in three bivalve species exposed to purified microcystin-LR and Microcystis extracts.
This study compares the role of hepatic cytosolic glutathione transferases (cGST) isoforms of three different bivalve species to a Microcystis aeruginosa extract and purified MC-LR exposure (both at 150 μg MC-LR L-1) for 24 h. Characterization and alterations of the cytosolic GST activities in Mytilus galloprovincialis, Ruditapes philippinarum and Corbicula fluminea were measured using four class-specific substrates and changes in individual GST isoforms expression were achieved by a subsequent two-dimensional electrophoresis analysis. Evaluation of cGST activity basal levels using the four class-specific substrates denoted quantitative differences between the three bivalves. Purified MC-LR did not induce any significant response from bivalves. On the other hand, cell extracts caused significant alterations according to bivalves and substrates. Among the three bivalves, only R. philippinarum showed a significant induction of cGST activity using generic 1-chloro-2,4-dinitrobenzene (CDNB) substrate. However, no significant alterations were detected in these clams by cell extracts using the other specific substrates. In contrast, C. fluminea revealed significant induction of cGST activity when using 3,4-dichloronitrobenzene (DCNB) and ethacrynic acid (EA). In M. galloprovincialis, cell extracts promoted a significant decrease of cGST activity when using EA substrate. Altered protein expression was quantitatively detected upon exposure to cell extracts for one spot in R. philippinarum and another for C. fluminea, both upregulated (2.0 and 8.5-fold, respectively) and identified as a sigma1-class GST in the case of the first. The results showed that the three bivalves presented specific adaptive biotransformation responses to MCs and other cyanobacteria compounds supported by the modulation of distinct cGST classes.


Interstitial lung disease in newborns.
The term 'interstitial lung disease' (ILD) refers to a group of disorders involving both the airspaces and tissue compartments of the lung, and these disorders are more accurately termed diffuse lung diseases. Although rare, they are associated with significant morbidity and mortality, with the prognosis depending upon the specific diagnosis. The major categories of ILD in children that present in the neonatal period include developmental disorders, growth disorders, surfactant dysfunction disorders, and specific conditions of unknown etiology unique to infancy. Whereas lung histopathology has been the gold standard for the diagnosis of ILD, as many of the disorders have a genetic basis, non-invasive diagnosis is feasible, and characteristic clinical and imaging features may allow for specific diagnosis in some circumstances. The underlying mechanisms, clinical, imaging, and lung pathology features and outcomes of ILD presenting in newborns are reviewed with an emphasis on genetic mechanisms and diagnosis.


The European Pharmacopoeia.
In defining a pharmacopoeia as an instrument for the quality control of medicines in the public health field, the author illustrates the origin, history and development of the European Pharmacopoeia since the Brussels Treaty in 1948. 20 countries are now applying the European Pharmacopoeia standards; they are based on an international Convention, which is a sort of law-making and institutional treaty.


The influence of context on the success of adoptive breastfeeding: developing countries and the west.
It is commonly believed that adoptive mothers in developing countries are more successful breastmilk producers than women in the west. A review of published research supports this assertion. However, an examination of the practice of adoptive breastfeeding in developing countries and in the west via the literature reveals differences that may explain the variation in success. Adoptive mothers in developing countries may have greater milk production than mothers in the west because they are more knowledgeable about breastfeeding, practice frequent breastfeeding, remain in close physical contact with their children and live in cultures that are supportive of breastfeeding. They also have reproductive and breastfeeding histories that may make breastfeeding easier, though they are less likely to have pharmaceutical galactagogues available. Adoptive mothers in the west should be encouraged to maximise their milk supply by emulating the mothering styles of women in developing countries and developing a strong support network for breastfeeding. It may be that most adoptive mothers are physically capable of producing sufficient breastmilk for their child but that in the west, sociocultural factors act as preventatives.


Effect of factors inhibiting HLA-DR antibodies before transplantation on kidney graft survival.
Blood transfusions administered before renal allografts are known to enhance graft survival. Among alternative hypotheses proposed to explain this effect, one of the most attractive is the possible induction of antiidiotypic antibodies directed against the specific antigen-binding site of donor-specific antibodies. In order to determine if such blocking antibodies are generated after blood transfusions, serial serum samples obtained before transplantation from 44 kidney recipients were analyzed for the development of HLA-DR alloantisera inhibitory activity by a microcytotoxicity inhibition assay. A significant correlation was found between the presence of inhibitory factors before transplantation and prolonged graft survival. However a clear relation between the development of inhibitory factors and the administration of transfusions could not be established. In addition the sera of 36 patients were studied for the presence of circulating immune complexes (CIC) before grafting. The presence of CIC was clearly associated with that of inhibitory factors, and with a prolonged graft survival. Thus these studies provide support for the development of blocking (possibly antiidiotypic) antibodies to anti-MHC in human renal graft recipients.


Production of green fluorescent protein transgenic embryonic stem cells using the GENSAT bacterial artificial chromosome library.
Transgenic green fluorescent protein (GFP) reporter embryonic stem (ES) cells are powerful tools for studying gene regulation and lineage choice during development. Here we present a rapid method for the generation of ES cells expressing GFP under the control of selected genes. Bacterial artificial chromosomes (BACs) from a previously constructed GFP transcriptional fusion library (Gene Expression Nervous System Atlas [GENSAT]) were modified for use in ES cells, and multiple BAC transgenic ES cell lines were generated. Specific GFP expression in transgenic cell lines was confirmed during neural differentiation marking neural stem cells, neuronal precursors, and glial progeny by Hes5, Dll1, and GFAP, respectively. GFP was dynamically regulated in ES cell progeny in response to soluble factors that inhibit Notch signaling and a factor that directs astroglial fate choice. Our protocols provide a simple and efficient strategy to utilize the whole GENSAT BAC library to create hundreds of novel fluorescent cell lines for use in ES cell biology.


Seizures and antiepileptic drugs: does exposure alter normal brain development?
Seizures and antiepileptic drugs (AEDs) affect brain development and have long-term neurological consequences. The specific molecular and cellular changes, the precise timing of their influence during brain development, and the full extent of the long-term consequences of seizures and AEDs exposure have not been established. This review critically assesses both the basic and clinical science literature on the effects of seizures and AEDs on the developing brain and finds that evidence exists to support the hypothesis that both seizures and antiepileptic drugs influence a variety of biological process, at specific times during development, which alter long-term cognition and epilepsy susceptibility. More research, both clinical and experimental, is needed before changes in current clinical practice, based on the scientific data, can be recommended.


Epigenetic profiling and mRNA expression reveal candidate genes as biomarkers for colorectal cancer.
Colorectal cancer (CRC) is characterized by DNA methylation, which is associated with genomic instability and tumor initiation. As an important epigenetic regulation, DNA methylation can be used as a potential therapeutic target for CRC. In our study, we downloaded DNA methylation profiles (GSE17648 and GSE29490) and RNA sequencing microarray data (GSE25070 and GSE32323) from the Gene Expression Omnibus (GEO) database. As a result, 14 aberrantly methylated differentially expressed genes (DEGs) were screened according to the different criteria. We further validated these DEGs in The Cancer Genome Atlas (TCGA) database and obtained Pearson's correlation coefficient (COR) for the relationship between gene expression and DNA methylation. Three candidate genes (SOX9, TCN1, and TGFBI) with COR greater than 0.3 were screened out as Hub genes. The receiver operating characteristic result indicated that SOX9 and TGFBI effectively serve as biomarkers for the early diagnosis of CRC. Furthermore, the potential prognosis of the Hub genes for CRC patients was evaluated. Only TGFBI, which is regulated by methylation, can predict patient disease-free survival. Additionally, we examined the methylation level of the Hub genes in CRC cells in the Cancer Cell Line Encyclopedia database. Considering that methylation status tends to be highly modified on CpG islands in tumorigenesis, we screened the CpG island methylation of TGFBI based on the TCGA database and verified its diagnostic value in the GEO database. Our result revealed two Hub genes (TCN1 and TGFBI) whose aberrant expressions were regulated by DNA methylation. Additionally, we uncovered the hypermethylation of TGFBI on CpG islands and its clinical value in the diagnosis of CRC.


Indications and expectations for neuropsychological assessment in epilepsy surgery in children and adults.
In our first paper in this series (Epilepsia 2015; 56(5): 674-681), we published recommendations for the indications and expectations for neuropsychological assessment in routine epilepsy care. This partner paper provides a comprehensive overview of the more specialist role of neuropsychological assessment in the pre and postoperative evaluation of epilepsy surgery patients. The paper is in two parts. The first part presents the framework for the mandatory role of neuropsychologists in the presurgical evaluation of epilepsy surgery candidates. A preoperative neuropsychological assessment should be comprised of standardised measures of cognitive function in addition to wider measures of behavioural and psychosocial function. The results from the presurgical assessment are used to: (1) establish a baseline against which change can be measured following surgery; (2) provide a collaborative contribution to seizure characterization, lateralization and localization; (3) provide evidence-based predictions of cognitive risk associated with the proposed surgery; and (4) provide the evidence base for comprehensive preoperative counselling, including exploration of patient expectations of surgical treatment. The second part examines the critical role of the neuropsychologist in the evaluation of postoperative outcomes. Neuropsychological changes following surgery are dynamic and a comprehensive, long-term assessment of these changes following surgery should form an integral part of the postoperative follow-up. The special considerations with respect to pre and postoperative assessment when working with paediatric populations and those with an intellectual disability are also discussed. The paper provides a summary checklist for neuropsychological involvement throughout the epilepsy surgery process, based on the recommendations discussed.


Antioxidants with proven efficacy and elastin-conserving vitamin C-A new approach to free radical defense.
This paper describes the background research and validation related to the formulation of a novel antioxidant product. Two defined outcomes were sought. Firstly, a combined efficacy of antioxidant ingredients in quenching free oxygen radicals. Secondly, the investigation into whether a vitamin C derivative sodium salt was elastin conserving in contrast to current vitamin C/l-ascorbic acid variations that have been reported to negatively affect elastin constitution and regeneration. A leading l-ascorbic acid antioxidant available on the market was compared with the experimental new product in two studies. In the first experiment, the products were compared to assess their antioxidant properties. The evaluated products TOPICAL ANTIOXIDANT 1 and TOPICAL ANTIOXIDANT 2 were applied to human skin cultures (25-30 mg/cm2 ) for a total of 72 h of treatment and exposed to oxidative stress. The generation of free radicals was semi-quantitatively assessed by measuring the fluorescence intensity of the deacetylation and oxidation of the probe dichlorofluorescein diacetate (DCFH-DA). In the second experiment, an ex vivo skin model (derived from patients undergoing facelift procedures) was used to assess elastin preservation. Three skin explants were topically subjected to the two formulations daily for 7 days. The skin was then prepared and fixed for immunofluorescent assessment after staining with CD44 and tropoelastin antibodies. Images were then analyzed using ImageJ. A full description of the different components selected for the new formulation is presented. In the first study, the experimental formulation performed with absolute equivalence to the comparator in its radical quenching capacity; both showed extremely effective antioxidant function. In the second study, the comparator negatively affected the existing elastin with areas of breakdown and diminished staining. In contrast, the new formulation showed good conservation of healthy elastin in all sections demonstrating elastin preservation. A new antioxidant formulation was carefully designed with multiple actives that show an equivalent antioxidant capacity to a leading product on the market. More importantly, the vitamin C component shows direct elastin conservation and improvement as opposed to the comparator, which had negative effects on elastin preservation. This is in keeping with little-known literature reports on vitamin C and its negative effects on elastin and validates the use of a sodium salt derivative, which appears to have protective effects on elastin. These findings support the overall regenerative extracellular matrix changes seen with TriHex® technology in other products.


Unusual polyamines in slime molds Physarum polycephalum and Dictyostelium discoideum.
We analyzed the cellular contents of not only major polyamines but also minor polyamines in slime molds Physarum polycephalum and Dictyostelium discoideum. The presence of putrescine and spermidine in either plasmodia or myxamoebae of these molds as major polyamines was confirmed. In addition to these polyamines, appreciable amounts of 1,3-diaminopropane were detected in P. polycephalum and D. discoideum. Cadaverine and sym-homospermidine were detected in P. polycephalum even when the slime mold was cultured in a chemically defined growth medium. Spermine was not detected when these molds were grown in synthetic media. Other "unusual" polyamines such as norspermidine, norspermine, thermospermine, aminopropylcadaverine, and canavalmine were not detected in either mold.


Simultaneous determination of seven hydrophilic bioactive compounds in water extract of Polygonum multiflorum using pressurized liquid extraction and short-end injection micellar electrokinetic chromatography.
Polygoni Multiflori Radix, He-Shou-Wu in Chinese, is a widely used traditional Chinese medicine. Clinically, water decoction is the major application form of He-Shou-Wu. Therefore, simultaneous determination of bioactive compounds in water extract is very important for its quality control. A pressurized liquid extraction and short-end injection micellar electrokinetic chromatography (MEKC) were first developed for simultaneous determination of seven hydrophilic bioactive compounds in water extract of He-Shou-Wu. The influence of parameters, such as pH, concentration of phosphate, SDS and HP-β-CD, capillary temperature and applied voltage, on the analysis were carefully investigated. Optimum separation was obtained within 14 min by using 50 mM phosphate buffer containing 90 mM SDS and 2% (m/v) HP-β-CD (pH 2.5) at 15 kV and 20°C. All calibration curves showed good linearity (R2>0.9978) within test ranges. The overall LOD and LOQ were lower than 2.0 μg/mL and 5.5 μg/mL, respectively. The RSDs for intra- and inter-day of seven analytes were less than 3.2% and 4.6%, and the recoveries were 97.0%-104.2%. The validated method was successfully applied to the analysis of He-Shou-Wu samples, which is helpful for its quality control.


Bilateral metastasis to the retina, choroids and optic nerve from breast cancer: a clinicopathological case.
A 39-year-old Asian woman, with a known history of breast cancer, presented with a gradual onset of painless reduction in vision in both eyes. Examination revealed visual acuity of counting fingers in the right eye and light perception in the left. There were subretinal lesions in the posterior poles of both eyes and retinal detachment in the left eye. Later she developed left proptosis and restriction in left ocular movement, most likely to be caused by metastatic extraocular spread. She subsequently died from disseminated metastatic disease. Histopathological examination confirmed tumor cells infiltrating the choroids, retina and optic nerve in both eyes. The tumor cells were arranged in lobular fashion and stained positively with Periodic Acid Schiff, suggesting the primary to be lobular adenocarcinoma type. Choroidal metastatic disease is common but bilateral retinal and optic nerve involvement with extraocular spread from breast cancer is rare.


Elevated temperature and tyrosine iodination aid in the crystallization and structure determination of an antifreeze protein.
Production and refolding of recombinant Choristoneura fumiferana antifreeze protein (CfAFP) leads to a disulfide-bonded product containing dynamic conformational microheterogeneity. Difficulties in the crystallization of this protein arising from its microheterogeneity were overcome by screening of crystallization conditions at various temperatures and finally using a temperature of 318 K to obtain diffraction-quality crystals. In addition, heavy-atom derivatization of this protein required the iodination of a specific tyrosine residue, leading to the successful single anomalous scattering (SAS) structure determination. The techniques of higher temperature screening, to reduce dynamic conformational microheterogeneity, and defined tyrosine iodination, for specific heavy-atom incorporation, are methods which can be employed with other proteins to aid in structure determination.


Description and evaluation of a clerkship in International Health and Medicine.
In 1998 Ben-Gurion University, in collaboration with Columbia University, inaugurated the first medical school with the express purpose of training students in International Health and Medicine (IHM). The highlight of the program is the two-month clerkship in IHM. The purpose of this paper is to describe the IHM clerkship and report the preliminary results of an evaluation. To evaluate the impact of the clerkship on the students' attitudes and knowledge of IHM, the students were asked to complete a previously validated self-assessment questionnaire before and after the clerkship. Ninety-six students participated in the IHM clerkship in the first 3 years. The mean age of the students was 29.4 +/- 4 and 53% were female. Comparison of the student's answers before their departure and after their return showed a significant difference in 5 of 64 items on the questionnaire. There was also a significant increase in the overall scores of the female students but no change in the scores of the male students pre- and post-clerkship. Our results show that students who completed the clerkship modestly increased their knowledge of some aspects of IHM as measured by the survey. Further studies on the long-term impact of IHM experiences are needed in parallel with efforts to increase medical students' exposure to IHM.


Partial suppression of the phenotype of Escherichia coli K-12 dnaG mutants by some I-like conjugative plasmids.
Three I-like conjugative plasmids, ColIdrd1, R144drd3, and R64drd11, which are derepressed for functions involved in conjugation, were found to suppress at least partially the phenotype of temperature-sensitive dnaG mutants of Escherichia coli K-12, as judged from the kinetics of deoxyribonucleic acid synthesis at elevated temperature in newly formed and established plasmid-containing strains. In contrast, the corresponding wild-type plasmids and three F-like derepressed conjugative plasmids, F101, R100drd1, and R1drd16, all failed to suppress. Suppression is presumably caused by a different plasmid-determined function from that which promotes survival of ultraviolet-irradiated bacteria, because both the wild-type I-like plasmids and their drd mutants protected irradiated bacteria. One possible interpretation of these results is that the product of a gene carried by certain I-like plasmids can substitute for the bacterial dnaG gene product during ongoing deoxyribonucleic acid replication.


Mechanistic basis of differential cellular responses of phosphatidylinositol 3,4-bisphosphate- and phosphatidylinositol 3,4,5-trisphosphate-binding pleckstrin homology domains.
Phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) are lipid second messengers that regulate various cellular processes by recruiting a wide range of downstream effector proteins to membranes. Several pleckstrin homology (PH) domains have been reported to interact with PtdIns(3,4)P2 and PtdIns(3,4,5)P3. To understand how these PH domains differentially respond to PtdIns(3,4)P2 and PtdIns(3,4,5)P3 signals, we quantitatively determined the PtdIns(3,4)P2 and PtdIns(3,4,5)P3 binding properties of several PH domains, including Akt, ARNO, Btk, DAPP1, Grp1, and C-terminal TAPP1 PH domains by surface plasmon resonance and monolayer penetration analyses. The measurements revealed that these PH domains have significant different phosphoinositide specificities and affinities. Btk-PH and TAPP1-PH showed genuine PtdIns(3,4,5)P3 and PtdIns(3,4)P2 specificities, respectively, whereas other PH domains exhibited less pronounced specificities. Also, the PH domains showed different degrees of membrane penetration, which greatly affected the kinetics of their membrane dissociation. Mutational studies showed that the presence of two proximal hydrophobic residues on the membrane-binding surface of the PH domain is important for membrane penetration and sustained membrane residence. When NIH 3T3 cells were stimulated with platelet-derived growth factor to generate PtdIns(3,4,5)P3, reversible translocation of Btk-PH, Grp1-PH, ARNO-PH, DAPP1-PH, and its L177A mutant to the plasma membrane was consistent with their in vitro membrane binding properties. Collectively, these studies provide new insight into how various PH domains would differentially respond to cellular PtdIns(3,4)P2 and PtdIns(3,4,5)P3 signals.


Effect of liandouqingmai recipe on quality of life and inflammatory reactions of patients with coronary heart disease.
To observe the effect of Liandouqingmai recipe (Chinese herbal medicine compound preparation) on the quality of life (QOL) and inflammatory reaction of patients with coronary heart disease (CHD). A total of 101 CHD patients were randomized into two groups: treatment group (n = 45) receiving standard treatment for CHD plus Liandouqingmai recipe, and control group (n = 56) receiving standard treatment only. The control group contained 16 normal healthy subjects. Changes in hs-C-reactive protein (CRP), peripheral blood leucocytes (PBL), and interleukin (IL)-6 and IL-10 levels were measured. The Seattle Angina Questionnaire (SAQ) was used to determine patient QOL before and after treatment for 2 weeks. Before treatment, SAQ scores [physical limitation (PL), angina stability (AS), angina frequency (AF), treatment satisfaction (TS), and disease perception (DP)] were not statistically different between groups. After treatment, AS and DP levels of controls were significantly increased compared with the other groups, while PL,AS, AF, TS, and DP levels of the treatment group were significantly increased compared with controls. Treatment group SAQ scores (PL, AS, AF, TS, and DP) were significantly higher than for controls. CHD patient IL-6 and IL-10 levels were significantly higher than controls. Before treatment, mean levels of IL-6, hs-CRP and PBL of the two groups were not statistically different. After treatment, mean levels of IL-6, IL-10, hs-CRP and PBL of the two groups were significantly decreased compared with their before treatment values, and levels of IL-6, hs-CRP, and PBL of the treatment group were lower than controls. Although mean IL-10 levels of both groups decreased, there was no significant difference in between-group and in-roup comparisons before and after treatment. Mean levels of IL-6 and IL-10 in the normal group were lower than in CHD patients. SAQ scores of QOL were negatively associated with the inflammatory index (IL-6/IL-10), and there was a significant negative association of IL-10 with AS (r = - 0.15, P < 0.05). Inflammatory reactions in CHD patients are related to angina status. Coadministration of CHD standard treatment and Liandouqingmai recipe increased patient SAQ scores by decreasing IL-6, IL-10, hs-CRP, and PBL levels in CHD patients, which might inhibit endothelial inflammation to improve patient QOL.


Facile Synthesis of Azetidine Nitrones and Diastereoselective Conversion into Densely Substituted Azetidines.
An electrocyclization route to azetidine nitrones from N-alkenylnitrones was discovered that provides facile access to these unsaturated strained heterocycles. Reactivity studies showed that these compounds undergo a variety of reduction, cycloaddition, and nucleophilic addition reactions to form highly substituted azetidines with excellent diastereoselectivity. Taken together, these transformations provide a fundamentally different approach to azetidine synthesis than traditional cyclization by nucleophilic displacement and provide novel access to a variety of underexplored strained heterocyclic compounds.


DNA barcoding reveals novel insights into pterygophagy and prey selection in distichodontid fishes (Characiformes: Distichodontidae).
DNA barcoding was used to investigate dietary habits and prey selection in members of the African-endemic family Distichodontidae noteworthy for displaying highly specialized ectoparasitic fin-eating behaviors (pterygophagy). Fin fragments recovered from the stomachs of representatives of three putatively pterygophagous distichodontid genera (Phago, Eugnathichthys, and Ichthyborus) were sequenced for the mitochondrial gene co1. DNA barcodes (co1 sequences) were then used to identify prey items in order to determine whether pterygophagous distichodontids are opportunistic generalists or strict specialists with regard to prey selection and, whether as previously proposed, aggressive mimicry is used as a strategy for successful pterygophagy. Our findings do not support the hypothesis of aggressive mimicry suggesting instead that, despite the possession of highly specialized trophic anatomies, fin-eating distichodontids are opportunistic generalists, preying on fishes from a wide phylogenetic spectrum and to the extent of engaging in cannibalism. This study demonstrates how DNA barcoding can be used to shed light on evolutionary and ecological aspects of highly specialized ectoparasitic fin-eating behaviors by enabling the identification of prey species from small pieces of fins found in fish stomachs.


Patients' help-seeking experiences and delaying in breast cancer diagnosis: A qualitative study.
To identify the influencing factors in help-seeking behavior by comparing delayers with non-delayers in Japanese female patients with breast cancer. This is a descriptive qualitative study. A total of 21 female patients with breast cancer (nine delayers and 12 non-delayers) who were at least 3 months to 5 years postdiagnosis were recruited from two hospitals in Okinawa, Japan. Semistructured interviews were carried out and the results were analyzed by using a qualitative inductive approach. The comparison between the delayers and non-delayers showed eight barriers to help-seeking behavior that were unique to the delayers: (i) the appearance of symptoms that cannot be definitely linked to breast cancer; (ii) anxiety and fear; (iii) the necessity to prioritize the immediate needs of daily life; (iv) non-disclosure of the situation; (v) the view that medical care is a nuisance; (vi) a desire to surrender to the natural course of things; (vii) confidence that they would not develop cancer; and (viii) inaccessibility of medical facilities. A common trigger for help-seeking that was identified in both the delayers and the non-delayers was the presence of other persons who encouraged seeking a provider evaluation. The barriers to help-seeking that were found in this study (namely, the emotional reaction and difficult living conditions) are common worldwide. The Japanese patients with breast cancer in the sample tended to emphasize their relationship with family and friends in their help-seeking behavior, which is a common content in Japanese and other Asian cultures. Therefore, health professionals should assess the social conditions of their patients.


Mosaic methylation of the repeat unit of the human ribosomal RNA genes.
The pattern of methylation in human genes for 18S and 28S ribosomal RNA has been investigated using methylation-sensitive restriction enzymes. We find that the transcribed region of the repeat unit is predominantly unmethylated, in agreement with previous studies. In contrast the non-transcribed spacer, which makes up the majority of the 43 kb repeat unit, is highly methylated in blood cell DNA. The boundaries between methylated and non-methylated domains appear to be relatively sharp, and occur approximately 1.5 kb upstream of the 5' edge of the proximal promoter and approximately 1.0 kb downstream of the 3' end of the transcribed region. A small proportion of all repeat units are methylated throughout the transcribed region, and may represent silent genes. The coincidence between the methylation pattern, the transcription pattern and other features of the repeat unit has implications for our understanding of the mechanism by which patterns of DNA methylation are generated.


Effects of airflow and work load on cardiovascular drift and skin blood flow.
Cardiovascular drift (CVD) can be defined as a progressive increase in heart rate (HR), decreases in stroke volume (SV) and mean arterial pressure (MAP), and a maintained cardiac output (Q) during prolonged exercise. To test the hypothesis that the magnitude of CVD would be related to changes in skin blood flow ( SkBF ), eight healthy, moderately trained males performed 70-min bouts of cycle ergometry in a 2 X 2 assortment of airflows (less than 0.2 and 4.3 m X s-1) and relative work loads (43.4% and 62.2% maximal O2 uptake). Ambient temperature and relative humidity were controlled to mean values of 24.2 +/- 0.8 degrees C and 39.5 +/- 2.4%, respectively. Q, HR, MAP, SkBF , skin and rectal temperatures, and pulmonary gas exchange were measured at 10-min intervals during exercise. Between the 10th and 70th min during exercise at the higher work load with negligible airflow, HR and SkBF increased by 21.6 beats X min-1 and 14.0 ml X 100 ml-1 X min-1, respectively, while SV and MAP decreased by 16.4 ml and 11.3 mmHg. The same work load in the presence of 4.3 m X s-1 airflow resulted in nonsignificant changes of 7.6 beats X min-1, 4.0 ml X (100 ml-1 X min)-1, -2.7 ml, and -1.7 mmHg for HR, SkBF , SV, and MAP. Since nonsignificant changes in HR, SkBF , SV, and MAP were observed at the lower work load in both airflow conditions, the results emphasize that CVD occurs only in conditions which combine high metabolic and thermal circulatory demands.(ABSTRACT TRUNCATED AT 250 WORDS)


Correlation between Serum Levels of 3,3',5'-Triiodothyronine and Thyroid Hormones Measured by Liquid Chromatography-Tandem Mass Spectrometry and Immunoassay.
For measuring serum 3,3',5'-triiodothyronine (rT3) levels, radioimmunoassay (RIA) has traditionally been used owing to the lack of other reliable methods; however, it has recently become difficult to perform. Meanwhile, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has recently been attracting attention as a novel alternative method in clinical chemistry. To the best of our knowledge, there are no studies to date comparing results of the quantification of human serum rT3 between LC-MS/MS and RIA. We therefore examined the feasibility of LC-MS/MS as a novel alternative method for measuring serum rT3, thyroxine (T4), and 3,5,3'-triiodothyronine (T3) levels. Assay validation was performed by LC-MS/MS using quality control samples of rT3, T4, and T3 at 4 various concentrations which were prepared from reference compounds. Serum samples of 50 outpatients in our department were quantified both by LC-MS/MS and conventional immunoassay for rT3, T4, and T3. Correlation coefficients between the 2 measurement methods were statistically analyzed respectively. Matrix effects were not observed with our method. Intra-day and inter-day precisions were less than 10.8% and 9.6% for each analyte at each quality control level, respectively. Intra-day and inter-day accuracies were between 96.2% and 110%, and between 98.3% and 108.6%, respectively. The lower limit of quantification was 0.05 ng/mL. Strong correlations were observed between the 2 measurement methods (correlation coefficient, T4: 0.976, p < 0.001; T3: 0.912, p < 0.001; rT3: 0.928, p < 0.001). Our LC-MS/MS system requires no manual cleanup operation, and the process after application of a sample is fully automated; furthermore, it was found to be highly sensitive, and superior in both precision and accuracy. The correlation between the 2 methods over a wide range of concentrations was strong. LC-MS/MS is therefore expected to become a useful tool for clinical diagnosis and research.


Appropriateness of Empirical Antibiotic Therapy in Hospitalized Patients with Bacterial Infection: A Retrospective Cohort Study.
The incidence of inappropriate and excessive empirical antibiotic therapy is unclear. The aim of this study was to determine the prevalence of different empirical antibiotic therapy prescriptions, related factors, and outcomes in hospitalized patients with bacterial infection. A retrospective cohort study was performed and patients with bacterial infection who were admitted between October 1, 2019, and September 30, 2020, were included. Multivariable analysis was performed by the logistic regression model. A total of 536 (42.6%) of the 1257 included patients received inappropriate empirical antibiotic therapy (IEAT), and 368 (29.3%) patients received appropriate but unnecessarily broad-spectrum empirical antibiotic therapy (AUEAT). MDRO (adjusted OR 2.932 [95% CI 2.201~3.905]; p < 0.001) and fever on admission (adjusted OR 0.592 [95% CI 0.415~0.844]; p = 0.004) were correlates of IEAT; sepsis (adjusted OR 2.342 [95% CI 1.371~3.999]; p = 0.002), age (adjusted OR 1.019 [95% CI 1.008~1.030]; p < 0.001), MDRO (adjusted OR 0.664 [95% CI 0.469~0.941]; p = 0.021), and urinary tract infection (adjusted OR 0.352 [95% CI 0.203~0.611]; p < 0.001) were correlates of AUEAT. Patients who received AUEAT were more likely to have a poor prognosis (63 [17.8%] vs 101 [27.4%]; p = 0.002). Both IEAT (median [IQR], 24,971 [13,135-70,155] vs 31,489 [14,894-101,082] CNY; p = 0.007) and AUEAT (median [IQR], 24,971 [13,135-70,155] vs 30,960 [16,475-90,881] CNY; p = 0.002) increased hospital costs. 45.3% (570/1257) of patients were infected with MDRO and 62.9% of them received IEAT. Inappropriate and excessive empirical antibiotic use was widely prevalent among hospitalized patients. Either inappropriate or excessive use of antibiotics may increase the burden of healthcare costs, the latter of which may be associated with poor prognosis. Clinicians need to be more judicious in choosing antibiotic(s). The MDRO epidemic was severe, especially in patients who received IEAT. It is imperative to take effective measures to improve the current situation of antibiotic abuse and antimicrobial resistance.


Quality of spirometry tests and pulmonary function changes among industrial company workers in Iran: a two-year before-and-after study following an intensive training intervention.
Quality improvement, standardisation of spirometry testing, and interpretation of results are critically important in the occupational setting. To determine the quality of spirometry tests and pulmonary function changes in two consecutive years among the personnel of an industrial company. This study was performed in an oil refinery in Iran in 2011. Data on 1,004 male personnel were evaluated before and after a training course conducted according to the National Institute for Occupational Safety and Health guidelines. American Thoracic Society/European Respiratory Society guidelines were used for assessment of the acceptability and repeatability criteria. The most common error in the first year of evaluation was forced vital capacity >6 seconds or a 1 second plateau. Acceptability and proper interpretation significantly improved after the course (p<0.05), but repeatability did not change significantly (p>0.05). The results of this study show that the validity and quality of spirometric tests conducted in the studied company in Iran were unacceptable, but these improved significantly after the training intervention. The study demonstrated the lack of a systematic guideline for conducting spirometry and interpreting the results in the occupational setting in Iran, and emphasises the need for a nationwide programme to improve the quality of spirometry tests in this setting.


Alteration of the migratory behavior of UV-induced regulatory T cells by tissue-specific dendritic cells.
UV radiation-induced regulatory T cells (UV-Treg) inhibit the sensitization but not the elicitation of contact hypersensitivity when injected i.v. Because UV-Treg express the lymph node homing receptor CD62 ligand, upon i.v. injection they migrate into the lymph nodes but not into the periphery and therefore inhibit sensitization but not elicitation. We tried to modify the migratory behavior of UV-Treg with the aim to get them into the periphery and thereby to suppress the effector phase of immune reactions. Because the tissue selective homing of T effector cells is determined by tissue-specific dendritic cells (DC), we attempted to reprogram the migratory behavior of UV-Treg by DC. 2,4-Dinitrofluorobencene (DNFB)-specific UV-Treg coincubated with epidermal Langerhans cells (LC) blocked the elicitation upon i.v. injection into DNFB-sensitized mice. In contrast, i.v. injection of UV-Treg not incubated with LC did not inhibit the ear challenge. The same negative effect was observed for UV-Treg coincubated with DC from bone marrow, spleen, or lymph nodes. This effect was not due to different maturation stages as checked by MHC class II expression of the different DC types. Incubation with LC but not with bone marrow-derived DC down-regulated the expression of CD62 ligand on UV-Treg. Accordingly, CFDA-SE labeled UV-Treg coincubated with LC were found in the ears but not in the lymph nodes upon i.v. injection. This finding shows that the migratory behavior can be reprogrammed by tissue-specific DC and may have input on strategies trying to use Treg not only for the prevention but also for the treatment of immune-mediated diseases.


Crystal structure of ICAM-2 reveals a distinctive integrin recognition surface.
Recognition by integrin proteins on the cell surface regulates the adhesive interactions between cells and their surroundings. The structure of the 'I' domain that is found in some but not all integrins, has been determined. However, the only integrin ligands for which structures are known, namely fibronectin and VCAM-1, are recognized by integrins that lack I domains. The intercellular adhesion molecules ICAM-1, 2 and 3 are, like VCAM-1, members of the immunoglobulin superfamily (IgSF), but they are recognized by an I domain-containing integrin, lymphocyte-function-associated antigen 1 (LFA-1, or CD11a/CD18). Here we present the crystal structure of the extracellular region of ICAM-2. The glutamic acid residue at position 37 is critical for LFA-1 binding and is proposed to coordinate the Mg2+ ion in the I domain; this Glu 37 is surrounded by a relatively flat recognition surface and lies in a beta-strand, whereas the critical aspartic acid residue in VCAM-1 and fibronectin lie in protruding loops. This finding suggests that there are differences in the architecture of recognition sites between integrins that contain or lack I domains. A bend between domains 1 and 2 of ICAM-2 and a tripod-like arrangement of N-linked glycans in the membrane-proximal region of domain 2 may be important for presenting the recognition surface to LFA-1. A model of ICAM-1 based on the ICAM-2 structure provides a framework for understanding its recognition by pathogens.


Effects of temperature, and dietary magnesium and nickel levels on magnesium and nickel concentrations during the moult-cycle in Oniscus asellus (Porcellionidae, Isopoda, Crustacea).
Mean magnesium concentrations in intermoult Oniscus asellus, caged at 20 degrees C for 10 days, ranged from 1,059.15 +/- 51.9 ppm on diets containing 10 ppm nickel, to 6,827.6 +/- 314.1 ppm on a mixture of 500 ppm magnesium + 10 ppm nickel. Mean nickel concentrations ranged from 89.4 +/- 4.3 ppm on diets containing 500 ppm magnesium, to 314.0 +/- 14.8 ppm on a mixture of 500 ppm magnesium + 10 ppm nickel. At 30 degrees C, magnesium tissue concentrations ranged from 4,149.8 +/- 153.5 ppm on diets with 10 ppm nickel to 12,602.6 +/- 529.3 ppm on 500 ppm magnesium. Nickel concentrations at 30 degrees C varied from 156.8 +/- 6.7 in isopods in the control to 490.5 +/- 23.5 ppm on those on 500 ppm magnesium + 10 ppm nickel. Magnesium in intermoult isopods was mainly stored in other tissues, including the exoskeleton, and nickel in the hepatopancreas. Differences in both magnesium and nickel concentrations between males and females were not significant. Magnesium and nickel concentrations in postmoult isopods, on the average, amounted to 367.6 +/- 16.5 ppm and 18.7 +/- 0.7 ppm, respectively, at 20 degrees C, and 369.9 +/- 16.3 ppm and 30.9 +/- 1.3 ppm, respectively, at 30 degrees C. Differences between males and females, and between various treatments were not significant at P greater than 0.01. It is suggested that both hepatopancreas and other tissues, including the exoskeleton, are used as sinks to get rid of excessive tissue magnesium and nickel during the moult-cycle.


Indoor air pollution from biomass combustion and acute respiratory illness in preschool age children in Zimbabwe.
Reliance on biomass for cooking and heating exposes many women and young children in developing countries to high levels of air pollution indoors. This study investigated the association between household use of biomass fuels for cooking and acute respiratory infections (ARI) in preschool age children (<5 years) in Zimbabwe. Analysis is based on 3559 children age 0-59 months included in the 1999 Zimbabwe Demographic and Health Survey (ZDHS). Children who suffered from cough accompanied by short, rapid breathing during the 2 weeks preceding the survey were defined as having suffered from ARI. Logistic regression was used to estimate the odds of suffering from ARI among children from households using biomass fuels (wood, dung, or straw) relative to children from households using cleaner fuels (liquid petroleum gas [LPG]/natural gas, or electricity), after controlling for potentially confounding factors. About two-thirds (66%) of children lived in households using biomass fuels and 16% suffered from ARI during the 2 weeks preceding the survey interview. After adjusting for child's age, sex, birth order, nutritional status, mother's age at childbirth, education, religion, household living standard, and region of residence, children in households using wood, dung, or straw for cooking were more than twice as likely to have suffered from ARI as children from households using LPG/natural gas or electricity (OR = 2.20; 95% CI: 1.16, 4.19). Household use of high pollution biomass fuels is associated with ARI in children in Zimbabwe. The relationship needs to be further investigated using more direct measures of smoke exposure and clinical measures of ARI.


Superficial angiomyxoma of the external ear not associated with Carney's complex: a case report.
Superficial angiomyxomas are rare tumours and multiple tumours occurring in the external ear are invariably associated with Carney's complex. In the present study, a solitary superficial angiomyxoma was found in a 20 year old lady; and there was no evidence of any of the components of Carney's complex at the time of presentation or at the end of 2 years of follow-up, after the surgical excision of the tumour.


[Long-Term Complete Response following Chemotherapy for Advanced Gastric Cancer in an Elderly Patient].
A 78-year-old man was diagnosed with HER2-positive advanced gastric cancer, cT3N2M1(LYM: #16a1, 16b1), cStage ⅣB, after being referred for anemia. The lesion was deemed unresectable, and first-line chemotherapy was initiated using S-1, cisplatin(CDDP), and trastuzumab(T-mab). After 2 courses of chemotherapy, the patient developed febrile neutropenia( Grade 3). At this point, the lesion showed partial response(PR), and chemotherapy was continued using oral S-1 as a single agent. After 3 months of S-1 monotherapy, the para-aortic lymph node metastases showed a complete response (CR). S-1 monotherapy was continued without major adverse events for 2 years, and the patient is presently alive and well 6 years after obtaining clinical CR. This may suggest that S-1 is a safe and effective treatment for unresectable advanced gastric cancer in elderly patients.


Association of body mass index with physical function and health-related quality of life in adults with arthritis.
Arthritis and obesity, both highly prevalent, contribute greatly to the burden of disability in US adults. We examined whether body mass index (BMI) was associated with physical function and health-related quality of life (HRQOL) measures among adults with arthritis and other rheumatic conditions. We assessed objectively measured BMI and physical functioning (six-minute walk, chair stand, seated reach, walking velocity, hand grip) and self-reported HRQOL (depression, stiffness, pain, fatigue, disability, quality of life-mental, and quality of life, physical) were assessed. Self-reported age, gender, race, physical activity, and arthritis medication use (covariates) were also assessed. Unadjusted and adjusted linear regression models examined the association between BMI and objective measures of functioning and self-reported measures of HRQOL. BMI was significantly associated with all functional (Ps ≤ 0.007) and HRQOL measures (Ps ≤ 0.03) in the unadjusted models. Associations between BMI and all functional measures (Ps ≤ 0.001) and most HRQOL measures remained significant in the adjusted models (Ps ≤ 0.05); depression and quality of life, physical, were not significant. The present analysis of a range of HRQOL and objective measures of physical function demonstrates the debilitating effects of the combination of overweight and arthritis and other rheumatic conditions. Future research should focus on developing effective group and self-management programs for weight loss for people with arthritis and other rheumatic conditions (registered on clinicaltrials.gov: NCT01172327).


Closure of mitral paravalvular defects without performing an arteriovenous loop: a case series of fourteen patients.
The arteriovenous (AV) loop is recommended when further support is needed during paravalvular leak (PVL) closure. We report the feasibility and safety of mitral PVL closure without constructing an AV loop, based on a single-centre experience. Fourteen patients with mitral valve replacement (MVR) who had New York Heart Association (NYHA) class III-IV dyspnoea or NYHA class II symptoms with significant haemolytic anaemia caused by severe or moderate-to-severe paravalvular regurgitation and who underwent transcatheter PVL closure (TPVLC) between May 2014 and February 2017 were enrolled. In total, 15 PVL procedures and 19 device deployments were performed. The patients had one (n = 10), three (n = 1) or four (n = 1) devices for closure at the time of the procedure; one patient had two devices from two procedures at different times with different access ways. Nineteen devices (10 (66.6%) via transseptal access; 4 (26.6%), transapical access; and 1 (6.6%), retrograde access) were deployed successfully without making an AV loop. The TPVLC is a less invasive and effective alternative to surgery in symptomatic patients with significant PVLs and high operational risks. The success rates are satisfactory, with improving techniques and devices. Procedural success without using an AV loop can be achieved with reduced costs, fluoroscopic times and complications.


Analysis of Maternal Near Miss at Tertiary Level Hospitals, Ahmedabad: A Valuable Indicator for Maternal Health Care.
Complications during pregnancy and childbirth remain a leading cause of illness and death among women of reproductive age in India. In the recent years, the concept of the WHO maternal near miss (MNM) has been adopted by the tertiary level hospitals as it has an added advantage of offering a large number of cases for intervention and for the evaluation of the maternal healthcare being provided by the health-care system. In the present study, near miss criterion-based audit of MNM cases and maternal death (MD) cases, based on the WHO near miss approach and MD, was conducted from the record section of the four tertiary level hospitals. In the present study, the WHO MNM approach was adopted to assess the quality of maternal healthcare in tertiary level hospitals. Retrospective secondary data analysis from the records of record section and maternity wards pertaining to June 2015-May 2016, of the hospitals of Ahmedabad city, was conducted from January 2016 to November 2017. The total number of live births of all the four hospitals under surveillance was 21,491. Severe maternal outcome cases were 326, of which 247 (75.8%) were of MNM cases and 79 (24.2%) were of MD. MNM mortality ratio was found to be 3.13:1. Eclampsia (29.45%) followed by preeclampsia (25.46%) and severe postpartum hemorrhage (22.39%) were the leading causes of potentially life-threatening conditions. Above finding suggests the development of a comprehensive framework for the assessment of MNM and further improvement in the quality of maternal health care.


Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial: Study protocol for a randomized controlled trial.
Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. While the primary injury results from the initial bleeding cannot currently be influenced, secondary injury through vasospasm and delayed cerebral ischemia worsens outcome and might be a target for interventions to improve outcome. To date, beside the aneurysm treatment to prevent re-bleeding and the administration of oral nimodipine, there is no therapy available, so novel treatment concepts are needed. Evidence suggests that inflammation contributes to delayed cerebral ischemia and poor outcome in SAH. Some studies suggest a beneficial effect of anti-inflammatory glucocorticoids, but there are no data from randomized controlled trials examining the efficacy of glucocorticoids. Therefore, current guidelines do not recommend the use of glucocorticoids in SAH. The Fight INflammation to Improve outcome after aneurysmal Subarachnoid HEmorRhage (FINISHER) trial aims to determine whether dexamethasone improves outcome in a clinically relevant endpoint in SAH patients. FINISHER is a multicenter, prospective, randomized, double-blinded, placebo-controlled clinical phase III trial which is testing the outcome and safety of anti-inflammatory treatment with dexamethasone in SAH patients. In all, 334 patients will be randomized to either dexamethasone or placebo within 48 h after SAH. The dexamethasone dose is 8 mg tds for days 1-7 and then 8 mg od for days 8-21. The primary outcome is the modified Rankin Scale (mRS) at 6 months, which is dichotomized to favorable (mRS 0-3) versus unfavorable (mRS 4-6). The results of this study will provide the first phase III evidence as to whether dexamethasone improves outcome in SAH.


A Dual-Band Multilayer InSe Self-Powered Photodetector with High Performance Induced by Surface Plasmon Resonance and Asymmetric Schottky Junction.
A dual-band self-powered photodetector (SPPD) with high sensitivity is realized by a facile combination of InSe Schottky diode and Au plasmonic nanoparticle (NP) arrays. Comparing with pristine InSe devices, InSe/Au photodetectors possess an additional capability of photodetection in visible to near-infrared (NIR) region. This intriguing phenomenon is attributed to the wavelength selective enhancement of pristine responsivities by hybridized quadrupole plasmons resonance of Au NPs. It is worth pointing out that the maximum of enhancement ratio in responsivity reaches up to ∼1200% at a wavelength of 685 nm. In addition, owing to a large Schottky barrier difference formed between active layer and two asymmetric electrodes, the responsivities of dual-band InSe/Au photodetector could reach up to 369 and 244 mA/W at the wavelength of 365 and 685 nm under zero bias voltage, respectively. This work would provide an additional opportunity for developing multifunctional photodetectors with high performance based on two-dimensional materials, upgrading their capacity of photodetection in a complex environment.


Transarterial embolization of a hepatic arteriovenous malformation in an infant using Onyx: a case report and review of the differential diagnosis imaging findings.
Hepatic arteriovenous malformations are rare congenital lesions associated with significant morbidity and mortality, most commonly from high output cardiac failure. Efficient diagnosis and treatment demands an interdisciplinary approach, and the interventional radiologist plays a pivotal role in both. Imaging is important for diagnostic accuracy and treatment planning, and transcatheter embolization has become an established primary therapy. We report the clinical and imaging findings of a rare hepatic arteriovenous malformation in an infant presenting with high-output cardiac failure and pulmonary artery hypertension that was successfully treated by transarterial embolization using Onyx.


A review on recent advances in LED-based non-thermal technique for food safety: current applications and future trends.
Light-emitting diodes (LEDs) is an eco-friendly light source with broad-spectrum antimicrobial activity. Recent studies have extensively been conducted to evaluate its efficacy in microbiological safety and the potential as a preservation method to extend the shelf-life of foods. This review aims to present the latest update of recent studies on the basics (physical, biochemical and mechanical basics) and antimicrobial activity of LEDs, as well as its application in the food industry. The highlight will be focused on the effects of LEDs on different types (bacteria, yeast/molds, viruses) and forms (planktonic cells, biofilms, endospores, fungal toxin) of microorganisms. The antimicrobial activity of LEDs on various food matrices was also evaluated, together with further analysis on the food-related factors that lead to the differences in LEDs efficiency. Besides, the applications of LEDs on the food-related conditions, packaged food, and equipment that could enhance LEDs efficiency were discussed to explore the future trends of LEDs technology in the food industry. Overall, the present review provides important insights for future research and the application of LEDs in the food industry.


H2Mab-77 is a Sensitive and Specific Anti-HER2 Monoclonal Antibody Against Breast Cancer.
Human epidermal growth factor receptor 2 (HER2) plays a critical role in the progression of breast cancers, and HER2 overexpression is associated with poor clinical outcomes. Trastuzumab is an anti-HER2 humanized antibody that leads to significant survival benefits in patients with HER2-positive metastatic breast cancers. In this study, we developed novel anti-HER2 monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses. Initially, we expressed the full length or ectodomain of HER2 in LN229 glioblastoma cells and then immunized mice with ectodomain of HER2 or LN229/HER2, and performed the first screening by enzyme-linked immunosorbent assays using ectodomain of HER2. Subsequently, we selected mAbs according to their efficacy in flow cytometry (second screening), Western blot (third screening), and immunohistochemical analyses (fourth screening). Among 100 mAb clones, only three mAbs reacted with HER2 in Western blot, and clone H2Mab-77 (IgG1, kappa) was selected. Finally, immunohistochemical analyses with H2Mab-77 showed sensitive and specific reactions against breast cancer cells, warranting the use of H2Mab-77 to detect HER2 in pathological analyses of breast cancers.


Unveiling the Concentration-Dependent Grain Growth of Perovskite Films from One- and Two-Step Deposition Methods: Implications for Photovoltaic Application.
In order to achieve high-efficiency perovskite solar cells, understanding both the crystal structure and the optoelectronic properties of perovskite layers is of importance. This paper uses crystallization analysis and the modeling study of two different perovskite deposition methods (two- and one-step methods) and thereby shows that the one-step method embodies a film formation process that is dominated by crystal growth, while the dominant mechanism of the two-step procedure is nucleation. Our data based on experimental and theory shows that the one-step recipe is superior in terms of morphology control, and, hence, reproducibility, compared to the two-step recipe.


Synthesis of haptens for development of antibodies to alkylphenols and evaluation and optimization of a selected antibody for ELISA development.
The development of an enzyme-linked immunosorbent assay (ELISA) based on polyclonal antibodies for a class of endocrine disrupting compounds, 4-nonylphenol, is described. The parent molecule was derivatized at the ortho position of the free phenolic hydroxyl group to obtain the hapten, NP1, and it was conjugated with keyhole limpet hemocyanin, which was used as an immunogen. Four antisera were generated and screened against three coating antigens. The most sensitive ELISA from the screening tests (antiserum NP03As, 1/1000, and coating antigen NP1-BSA, 1 microg/mL) was further optimized and characterized. The influence of various physicochemical factors (organic solvent, pH, ion strength) was investigated. Methanol as the additive organic solvent was found to be the best organic solvent for the ELISA, with optimal sensitivity observed at a concentration of 5%. The ELISA parameters were changed at more acidic or basic pH values, whereas higher ionic strengths strongly suppressed the I(50) value and the maximum absorbance. The most sensitive ELISA for 4-nonylphenol exhibited an I(50) value of 38.6 +/- 5.5 microg/L, with a dynamic range from 12 to 350 microg/L, and the lower limit of detection was 7.7 +/- 1.3 microg/L. The optimized ELISA displayed no significant cross-reaction against the parent compounds, nonylphenol ethoxylates, degradation products, carboxylates, and bisphenol A, except in 4-octylphenol.


Independent measurement of ampicillin and cloxacillin in mixtures.
A simplified method of assaying mixtures of ampicillin and cloxacillin is presented. The method consists of cylinder-plate assays of appropriately diluted samples in three assay systems in which: (i) cloxacillin is measured, utilizing agar seeded with a penicillinase-producing Staphylococcus aureus; (ii) ampicillin is measured after the greatest dilution practicable, by use of agar seeded with Sarcina lutea; and (iii) the proportion of activity found in the second assay that remains after treatment with staphylococcal penicillinase is determined on agar seeded with S. lutea. The error was 4% or less when each system was run in quadruplicate, except when there was 10 or more times as much cloxacillin as ampicillin, in which case the greatest error was 12%. Mixtures of methicillin with benzylpenicillin or with ampicillin can also be quantitated by this method.


Sonochemical synthesis of MOF-5.
High quality MOF-5 crystals of 5-25 mum in size were prepared for the first time using a sonochemical method in substantially reduced synthesis time (ca. 30 min) compared with conventional solvothermal synthesis (24 h).


Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle.
Vx-770 (Ivacaftor), a Food and Drug Administration (FDA)-approved drug for clinical application to patients with cystic fibrosis (CF), shifts the paradigm from conventional symptomatic treatments to therapeutics directly tackling the root of the disease: functional defects of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel caused by pathogenic mutations. The underlying mechanism for the action of Vx-770 remains elusive partly because this compound not only increases the activity of wild-type (WT) channels whose gating is primarily controlled by ATP binding/hydrolysis, but also improves the function of G551D-CFTR, a disease-associated mutation that abolishes CFTR's responsiveness to ATP. Here we provide a unified theory to account for this dual effect of Vx-770. We found that Vx-770 enhances spontaneous, ATP-independent activity of WT-CFTR to a similar magnitude as its effects on G551D channels, a result essentially explaining Vx-770's effect on G551D-CFTR. Furthermore, Vx-770 increases the open time of WT-CFTR in an [ATP]-dependent manner. This distinct kinetic effect is accountable with a newly proposed CFTR gating model depicting an [ATP]-dependent "reentry" mechanism that allows CFTR shuffling among different open states by undergoing multiple rounds of ATP hydrolysis. We further examined the effect of Vx-770 on R352C-CFTR, a unique mutant that allows direct observation of hydrolysis-triggered gating events. Our data corroborate that Vx-770 increases the open time of WT-CFTR by stabilizing a posthydrolytic open state and thereby fosters decoupling between the gating cycle and ATP hydrolysis cycle. The current study also suggests that this unique mechanism of drug action can be further exploited to develop strategies that enhance the function of CFTR.


Facilely Tuning the First-Shell Coordination Microenvironment in Iron Single-Atom for Fenton-like Chemistry toward Highly Efficient Wastewater Purification.
Precisely identifying the atomic structures in single-atom sites and establishing authentic structure-activity relationships for single-atom catalyst (SAC) coordination are significant challenges. Here, theoretical calculations first predicted the underlying catalytic activity of Fe-NxC4-x sites with diverse first-shell coordination environments. Substituting N with C to coordinate with the central Fe atom induces an inferior Fenton-like catalytic efficiency. Then, Fe-SACs carrying three configurations (Fe-N2C2, Fe-N3C1, and Fe-N4) fabricate facilely and demonstrate that optimized coordination environments of Fe-NxC4-x significantly promote the Fenton-like catalytic activity. Specifically, the reaction rate constant increases from 0.064 to 0.318 min-1 as the coordination number of Fe-N increases from 2 to 4, slightly influencing the nonradical reaction mechanism dominated by 1O2. In-depth theoretical calculations unveil that the modulated coordination environments of Fe-SACs from Fe-N2C2 to Fe-N4 optimize the d-band electronic structures and regulate the binding strength of peroxymonosulfate on Fe-NxC4-x sites, resulting in a reduced energy barrier and enhanced Fenton-like catalytic activity. The catalytic stability and the actual hospital sewage treatment capacity also showed strong coordination dependency. This strategy of local coordination engineering offers a vivid example of modulating SACs with well-regulated coordination environments, ultimately maximizing their catalytic efficiency.


A dosimetric comparison of two high-dose-rate brachytherapy planning systems in cervix cancer: standardized template planning vs. computerized treatment planning.
High-dose-rate brachytherapy is an important component of the curative treatment for cervical cancer. Some institutions use standardized template planning (STP), based on a precalculated table of dose rates, instead of computerized treatment planning (CTP), based on digitized orthogonal X-ray films. STP can be used as a backup check in case of computer hardware malfunction, and/or as a way to minimize treatment planning time. We performed a dosimetric comparison of STP and CTP to determine dose differences at point A and the International Commission on Radiation Units and Measurements Report 38 bladder and rectal reference points. We retrospectively reviewed the treatment plans of 62 patients (135 applications) treated with a tandem and two ovoids using the CTP method. For each of these plans, we calculated the dwell times required to deliver the same prescription dose had STP been used. We also used the planning computer to vary tandem and ovoid geometry and develop a table of dose rates based on geometric parameters. The mean dose at point A was 7.6 Gy using CTP, increasing to 8.4 Gy when the STP approach was used (p<0.05). The mean doses at the International Commission on Radiation Units and Measurements Report 38 bladder and rectal points were both 4.5 Gy with CTP and increased to 4.9 and 5.0 Gy, respectively using STP (p<0.05). Our table of dose rates showed significant dose rate dependency on the applicators geometry. Our study shows that if the STP approach had been used, a significantly higher dose would have been delivered, and that STP tables accounting for differences in implant geometry should be carefully considered.


Conformational restraints revealing bioactive beta-bend structures for halpha CGRP8-37 at the CGRP2 receptor of the rat prostatic vas deferens.
1. The main aim of this study was to identify putative beta-bends and the role of the N- and C-terminus in the CGRP receptor antagonist halpha CGRP8-37, which was measured against halpha CGRP inhibition of twitch responses in the rat prostatic vas deferens. 2. With a bend-biasing residue (proline) at position 16 in halpha CGRP8-37 (10(-5) M) an inactive compound was produced, while alanine at the same position retained antagonist activity (apparent pKB 5.6+/-0.1 at 10(-5) M). Proline at position 19 within halpha CGRP8-37 (10(-5) M) was an antagonist (apparent pKB 5.8+/-0.1). 3. Incorporation of a bend-forcing structure (beta-turn dipeptide or BTD) at either positions 19,20 or 33,34 in halpha CGRP8-37 (10(-5) M) antagonized halpha CGRP responses (apparent pKB 6.0+/-0.1 and 6.1+/-0.1, respectively). Replacement by BTD at both positions 19,20 and 33,34 within halpha CGRP8-37 competitively antagonized responses to halpha CGRP (pA2 6.2; Schild plot slope 1.0+/-0.1). 4. Halpha CGRP8-37 analogues (10(-5) M), substituted at the N-terminus by either glycine8, or des-NH2 valine8 or proline8 were all antagonists against halpha CGRP (apparent pKB 6.1+/-0.1, 6.5+/-0.1 and 6.1+/-0.1, respectively), while halpha CGRP8-37 (10(-5) M) substituted in three places by proline8 and glutamic acid10,14 was inactive. 5. Replacement of the C-terminus by alanine amide37 in halpha CGRP8-37 (10(-5) M) failed to antagonize halpha CGRP responses. 6. Peptidase inhibitors did not alter either the agonist potency of halpha CGRP or the antagonist affinities of halpha CGRP8-37 BTD19,20 and 33,34 and halpha CGRP8-37 Gly8 (against halpha CGRP responses). 7. In conclusion, two beta-bends at positions 18-21 and 32-35 are compatible with high affinity by BTD and is the first approach of modelling the bioactive structure of halpha CGRP8-37. Further, the N-terminus of halpha CGRP8-37 is not essential for antagonism, while the C-terminus interacts directly with CGRP receptor binding sites of the rat vas deferens.


Plasminogen activator inhibitor-1 inhibits factor VIIa bound to tissue factor.
A growing body of experimental evidence supports broad inhibitory and regulatory activity of plasminogen activator inhibitor 1 (PAI-1). The present study was designed to investigate whether PAI-1 inhibits factor (F) VIIa complexed with tissue factor (TF), a well-known procoagulant risk factor. The ability of PAI-1 to inhibit FVIIa-TF activity was evaluated in both clotting and factor X (FX) activation assays. PAI-1 and its complex with vitronectin inhibit: (i) clotting activity of FVIIa-TF (PAI-1(IC50) , 817 and 125 nm, respectively); (ii) FVIIa-TF-mediated FX activation (PAI-1(IC50) , 260 and 50 nm, respectively); and (iii) FVIIa bound to TF expressed on the surface of stimulated endothelial cells (PAI-1(IC50) , 260 and 120 nm, respectively). The association rate constant (k(a)) for PAI-1 inhibition of FVIIa-TF was determined using a chromogenic assay. K(a) for PAI-1 inhibition of FVIIa bound to relipidated TF is 3.3-fold higher than that for FVIIa bound to soluble TF (k(a) = 0.09 ± 0.01 and 0.027 ± 0.03 μm(-1) min(-1), respectively). Vitronectin increases k(a) for both soluble and relipidated TF by 3.5- and 30-fold, respectively (to 0.094 ± 0.020 and 2.7 ± 0.2 μm(-1) min(-1)). However, only a 3.5- to 5.0-fold increase in the acylated FVIIa was observed on SDS PAGE in the presence of vitronectin for both relipidated and soluble TF, indicating fast formation of PAI-1/vitronectin/FVIIa/relipidated TF non-covalent complex. Our results demonstrate potential anticoagulant activity of PAI-1 in the presence of vitronectin, which could contribute to regulation of hemostasis under pathological conditions such as severe sepsis, acute lung injury and pleural injury, where PAI-1 and TF are overexpressed.


Capacity needs assessment and challenges for multisectoral implementation of nutrition in Burkina Faso: A guide for the formulation of a capacity development plan.
Achieving nutritional goals depends on individual, organisational and environmental capacities. The aim of this study was to analyse and identify capacity gaps among the coordination platforms and networks, and the key technical institutions related to nutrition in Burkina Faso for a capacity development plan formulation. Using the new Nutrition Capacity Framework developed by the United Nations Network, information were collected using the Nutrition Stakeholder Mapping and Analysis tool, and the Checklist for Capacity Areas. Capacity needs were analysed in terms of Human resource and infrastructure, functional, organisational, coordination and partnership, and financial and resource mobilisation. Limited human resource capacity in nutrition was highlighted in most cases by the structures, and the nutrition coordination structure and more than 4/5 of the technical structures are faced with the unavailability of working materials, tools and basic Internet connection. Only 10 among the 30 structures have a unit or service for exchange on nutrition, and only three of them have integrated nutrition actions. Shortfalls were noted in terms of functional, facilitation, communication and advocacy skills, as well as a weak diversification of resource mobilisation strategies. The use of the analytical framework helped to identify the gaps and to propose paths for capacity development. Efforts need to be strengthened, intensified, coordinated, monitored, evaluated and funded.


Reassuring data on the cardiovascular risk in adults with X-linked hypophosphatemia receiving conventional therapy.
X-linked hypophosphatemia (XLH) is a rare genetic disorder that results in increased plasma levels of FGF23. Several studies have demonstrated a direct association between FGF-23 and cardiovascular mortality in cohorts of patients with chronic renal failure. However, in patients with XLH, studies on the cardiovascular impact of the disease are rare, with contradictory results. The aim was to assess whether the disease led to an increased cardiovascular risk. We conducted a single-centre retrospective observational study on a local cohort of XLH adult patients. The primary endpoint was a composite endpoint of the frequency of LVH or presence of high blood pressure. Our secondary objectives were to assess echocardiographic, pulse wave velocity and central blood pressure data as other markers of CV health. Independently of this cohort, tissue sodium content with MRI was studied in 2 XLH patients before and after burosumab. 22 patients were included. Median serum phosphate was 0.57 [0.47 - 0.72] mmol/l, FGF23 94 pg/L [58 - 2226]. Median blood pressure was 124 [115-130]/68 [65-80] mmHg, with only 9% of patients hypertensive. A majority of patients (69%) had no left ventricular hypertrophy (LVH), only one had LV mass >100 g/m² and 25% of patients had LV remodeling. Pulse wave velocity was normal in all patients. No differences in skin and muscle sodium content were observed before and after burosumab in the two patients who underwent sodium MRI. We found no elevated risk of developing hypertension or LVH in patients with XLH.


Photoinhibition - a historical perspective.
Photoinhibition is a state of physiological stress that occurs in all oxygen evolving photosynthetic organisms exposed to light. The primary damage occurs within the reaction center of Photosystem II (PS II). While irreversible photoinduced damage to PS II occurs at all light intensities, the efficiency of photosynthetic electron transfer decreases markedly only when the rate of damage exceeds the rate of its repair, which requires de novo PS II protein synthesis. Photoinhibition has been studied for over a century using a large variety of biochemical, biophysical and genetic methodologies. The discovery of the light induced turnover of a protein, encoded by the plastid psbA gene (the D1 protein), later identified as one of the photochemical reaction center II proteins, has led to the elucidation of the underlying mechanism of photoinhibition and to a deeper understanding of the PS II 'life cycle.'


Rare case of venous tumour thrombus from acinic cell carcinoma of the parotid gland.
Head and neck tumour thrombus is a rare pathology and at present there are no reported cases of tumour thrombus secondary to acinic cell carcinoma of the parotid gland. We report a case of an 81-year-old man with an acinic cell carcinoma of the left parotid and an intravenous tumour thrombus extending from the retromandibular vein into the internal jugular vein. This case also highlights the importance of radiological imaging in the management of tumour thrombus.


Use of 504 plans for children and youth with disabilities: nursing application.
Section 504 of the Rehabilitation Act of 1973 for students with disabilities in elementary and secondary school settings specifies that students with disabilities must not be discriminated against because of their disabilities; therefore, the school is required to provide the necessary accommodations to assure this does not occur. The school plans for making educational accommodations for students with disabilities when their condition adversely affects their ability to learn are known as 504 plans. This article provides information about the history of 504 plans; requirements for primary, secondary, and post-secondary settings; and how nurses can be involved. Nurses can have an important role in schools and clinical settings in developing 504 plans.


Risk factors for lymphatic metastasis of malignant bone and soft-tissue tumors: a retrospective cohort study of 242 patients.
Metastasis to the lymph nodes is relatively rare in malignant bone and soft-tissue tumors, and its risk factors remains unknown, except for tumors of the lymphogenous histotype, including rhabdomyosarcoma, epithelioid sarcoma, and clear cell sarcoma. The purpose of this study was to identify the risk factors for lymph node metastasis of malignant bone and soft-tissue tumors. We retrospectively reviewed 242 patients with malignant bone and soft-tissue tumors. The predictors of interest for the risk of lymph node metastasis included age, sex, histopathological diagnosis, location(s) of the primary tumor(s), local recurrence, residual tumor(s), and the size of the primary tumors. To identify the risk factors for lymph node metastasis, Cox regression analyses were performed. Among the 242 patients with malignant bone and soft-tissue tumors in the current study, 60, 29, and 28 were detected to have lung, lymph node, and bone metastases, respectively. In the univariate analyses, the lymphogenous histotype and a primary tumor invading the subcutis were the risk factors for lymph node metastasis. In the multivariate analysis, the lymphogenous histotype (P < 0.01) and a primary tumor in the subcutis (P < 0.01) remained significantly associated with a higher risk of lymph node metastasis with 5.15 and 3.48 of hazard ratios, respectively. Lymph node metastasis was detected in malignant bone and soft-tissue tumors more frequently than that has been previously reported, and the risk factors for lymph node metastasis were the lymphogenous histotype and primary tumors invading the subcutis.


Characterization of infectious bronchitis virus isolates by slot blot hybridization.
We used slot blot hybridization of the hypervariable regions of the S1 subunit of spike peplomer gene to identify and characterize infectious bronchitis virus (IBV) strains. Template DNA was created from six reference strain IBVs of different serotypes and immobilized on a nitrocellulose membrane. We synthesized digoxigenin-labeled probes from reference and unknown field viruses and hybridized them to template DNA. All reference strains could be distinguished and isolates identified by serotype if they were at least 95% identical to a reference strain. This slot blot hybridization procedure was specific and reproducible, and strain typing was consistent with the S1 sequencing of the IBV genome. This study thus provides a simple and rapid method for typing of IBV.


Using the 6-min walk test to assess the clinical response to mepolizumab and conventional therapy in severe eosinophilic asthma.
Severe asthma limits exercise to avoid respiratory symptoms. The objective of the present study was to investigate the role of the 6-min walk test (6MWT) in severe asthma. Consecutive patients with severe eosinophilic asthma were enrolled. A 6MWT was performed before and after 12 months. Inhaled therapy dose, oral corticosteroids dose, pulmonary function tests, eosinophil blood count, fractional exhaled nitric oxide (FeNO), Asthma Control Test (ACT) score and responses to the Asthma Quality of Life Questionnaire (AQLQ) were also recorded. Of the 22 patients enrolled, 13 were treated with mepolizumab 100 mg every 4 weeks in addition to conventional therapy and nine with conventional therapy only. The majority of the patients were treated with high-dose inhaled corticosteroids/long-acting β-agonists/long-acting muscarinic receptor antagonists, while approximately half were on continuous oral corticosteroids. After 12 months, the mepolizumab group only showed a significant improvement in pulmonary function tests (percentage forced expiratory volume in 1 s and percentage forced expiratory flow at 25-75% forced vital capacity (FEF25-75%), both p<0.001; percentage forced vital capacity, p<0.01) and clinical laboratory parameters (eosinophil count, FeNO measured at a flow rate of 50 mL·s-1, ACT and AQLQ, p<0.001). No significant changes in the proportion of patients using continuous oral corticosteroids and high-dose inhaled corticosteroids/long-acting β-agonists/long-acting muscarinic receptor antagonists were observed in either group (p>0.05). By paired comparisons, statistically significant improvements of the mean 6-min walk distance (6MWD) were observed in the mepolizumab (p<0.001) and conventional therapy (p<0.01) groups, while no improvement was seen in dyspnoea Borg scale, heart rate, percentage oxygen saturation or systolic and diastolic blood pressure. 6MWD showed significant direct correlations with ACT (r=0.5998, p<0.001), AQLQ (r=0.3978, p=0.009) and FEF25-75% (r=0.3589, p=0.017). The 6MWT could complement severe asthma assessment and be relevant in evaluating the objective response to treatment, including biological therapies like mepolizumab.


Universal relations for nonsolvable statistical models.
We present the first rigorous derivation of a number of universal relations for a class of models with continuously varying indices (among which are interacting planar Ising models, quantum spin chains and 1D Fermi systems), for which an exact solution is not known, except in a few special cases. Most of these formulas were conjectured by Luther and Peschel, Kadanoff, and Haldane, but only checked in the special solvable models; one of them, related to the anisotropic Ashkin-Teller model, is novel.


[Diagnostic significance of electrocortical responses to rhythmic and solitary photic stimuli in patients with hepato-portal encephalopathy].
In order to clarify some diagnostical criteria of latent hepato-portal encephalopathy in 57 patients with intrahepatic forms of portal hypertension the authors studied the character of driving response in photorhythmical stimulation. In 9 patients the development of evoked potentials depending upon the significance of the stimula was studied as well. The studies confirmed the prognostical significance of a slowing down the mean frequency of rhythms in the EEG in relation to the development of acute encephalopathy and a certain tendency to the shift in the spectrum of driving responses to low frequency and a worsening of driving responses in slowing down the medium rhythm frequency of EEG. In patients with changed resting activity in the Background EEG there was a drop in the amplitude of late components of evoked potentials.


Some preliminary data on the nature/structure of the PC-glycan of the major excretory-secretory product of Acanthocheilonema viteae (ES-62).
The structure of the PC-glycan of the major excretory-secretory product (ES-62) of Acanthocheilonema viteae has been investigated using endoglycosidases and lectins. Results obtained raise the possibility that it may be of the high mannose type. This, and the insensitivity of the PC-glycan to treatments which remove PC or choline from bacterial PC-glycans, suggests that it may be more analogous to fungal, than to bacterial PC-containing glycans.


Cardiac pathology in status epilepticus.
Massive catecholamine release resulting in the formation of cardiac contraction bands may represent the cause of death in status epilepticus (SE). We reviewed the cardiac pathology of patients who died during SE to asses for contraction bands. Eight of 11 patients who died during SE had identifiable myocardial contraction bands compared with 5 of 22 control patients (p < 0.05, Fisher's exact t test). These findings delineate a pathological substrate and provide compelling evidence that excessive catecholamine release is the mechanism responsible for death in SE.


[New antigenic variants of influenza A(H1N1) virus detected in the USSR in 1979].
Studies of influenza A (H1N1) viruses isolated in the spring of 1979 in the USSR showed all the 73 strains to belong to influenza A (H1N1) virus but to be heterogeneous. Apart from the strains identical with the reference A/USSR/90/77 and A/Brazil/11/78 as well as intermediate ones, 14 strains were identified and found to be new drift variants. A composite analysis of representative strains of this group (A/USSR/50/79 and A/USSR/61/79) by HI test with diagnostic rat and ferret sera as well as monoclonal antibody and by immunoadsorption method confirmed their individual natures and showed them not to be identical completely to any one of the previously known drift variants of the A (H1N1) subtype. The neuraminidase of the new strains also acquired some changes in the antigenic composition and resistance to detergents destroying disulfide bonds indicating certain alterations in this subunit as well. Besides, a comparison of the drift variants of influenza A (H1N1) virus variants isolated in 1947-1957 and in 1977-1979 showed the drift of the new A (H1N1) strain to occur in a different way than in those isolated in 1947-1957.


Transient osteoporosis of the hip during pregnancy: a case report.
Transient osteoporosis associated with pregnancy is a rare, self-limiting skeletal disorder, the origin of which remains unclear. We report the case of a 36-year-old Japanese woman who developed pain in the left hip, groin, and knee in the seventh month of pregnancy. The pain gradually worsened and prevented weight-bearing. The hip and knee pain progressed to bilateral involvement and persisted after an emergent cesarean section at 35 weeks. Radiographs after delivery revealed gross osteopenia of both the femoral heads, left distal femur, and proximal tibia, consistent with transient osteoporosis associated with pregnancy. The patient remained mostly wheelchair-dependent because of severe hip and knee pain. Several weeks later, the patient was started on alendronate, a biphosphonate, which provided dramatic relief of hip and knee pain. The patient's ambulatory function subsequently improved dramatically as a result of pain relief and assistance with gait training. This case is unique for several reasons. First, it is rare for transient osteoporosis associated with pregnancy to involve both hip joints, and it rarely involves the knee. Second, this is the first reported case of pain management of transient osteoporosis associated with pregnancy being successfully treated with an antiresorptive agent. Finally, the use of alendronate in transient osteoporosis associated with pregnancy may help shorten disability by providing pain relief and decreasing the fracture risk associated with this disease.