Observing polymerization in 2D dynamic covalent polymers.
The quality of crystalline two-dimensional (2D) polymers1-6 is intimately related to the elusive polymerization and crystallization processes. Understanding the mechanism of such processes at the (sub)molecular level is crucial to improve predictive synthesis and to tailor material properties for applications in catalysis7-10 and (opto)electronics11,12, among others13-18. We characterize a model boroxine 2D dynamic covalent polymer, by using in situ scanning tunnelling microscopy, to unveil both qualitative and quantitative details of the nucleation-elongation processes in real time and under ambient conditions. Sequential data analysis enables observation of the amorphous-to-crystalline transition, the time-dependent evolution of nuclei, the existence of 'non-classical' crystallization pathways and, importantly, the experimental determination of essential crystallization parameters with excellent accuracy, including critical nucleus size, nucleation rate and growth rate. The experimental data have been further rationalized by atomistic computer models, which, taken together, provide a detailed picture of the dynamic on-surface polymerization process. Furthermore, we show how 2D crystal growth can be affected by abnormal grain growth. This finding provides support for the use of abnormal grain growth (a typical phenomenon in metallic and ceramic systems) to convert a polycrystalline structure into a single crystal in organic and 2D material systems.


The matchstick grasshopper genus Warramaba (Morabidae: Morabinae): a description of four new species and a photographic guide to the group.
Matchstick grasshoppers are a unique and diverse element of Australia's insect fauna with great potential as a model system for ecological, evolutionary and biogeographical studies. The genus Warramaba comprises four bisexual species. It is of special interest from an evolutionary point of view because two parthenogenetic lineages (the Standard and Boulder-Zanthus phylads of W. virgo) have evolved through hybridization events between two of the sexual species. Despite the extensive genetic and systematic work that has been done on this genus, three of the bisexual species are yet to be formally named (P196, P169 and P125) and no key exists for their identification. Here I formally describe these species, respectively, as W. whitei sp. nov., W. flavolineata sp. nov. and W. grandis sp. nov. and split the parthenogenetic species W. virgo into two distinct species (the addition of W. ngadju sp. nov.). I also provide a photographic guide and key to the identification of all species in the genus.


Cognitive and motor reaction times in obstructive sleep apnea syndrome: A study based on computerized measures.
Obstructive Sleep Apnea Syndrome (OSAS) is mainly associated with executive dysfunction. Although delayed reaction times (RTs) in patients with OSAS have been reported, sensitivity of processing speed has not been adequately assessed. This study suggests sensitive and reliable measures to clarify whether different components of information processing speed, i.e. cognitive and motor responses, are equally impaired in OSAS. Thirty-three patients with OSAS were compared with thirty healthy controls. The MoCA test was administered to assess participants' global neuropsychological profile. Cognitive and motor reaction times were measured using a detector panel which allows to distinguish between stimulus encoding, decision processing, and selection of the appropriate motor response. Logistic regression models highlighted both MoCA test and motor RTs as the best predictors differentiating patients from healthy participants. Results support the hypothesis of a slight decline in the cognitive profile of patients with OSAS and identify significant slowing down in the motor component of responses. It could be hypothesized that slower motor responsiveness is the cause of the global cognitive profile of these patients. With aging, motor movements and RTs usually become impaired and hypoxia might accelerate the aging process by compromising first of all the motor component of RTs.


Customized Locator abutment fabrication on inclined implants: A clinical report.
Implant parallelism is rarely achieved, particularly when anatomic limitations are present. The problem of nonparallel implants has been addressed by using angled or bar abutments to compensate for the implant angulation. However, an angled abutment or bar attachment has disadvantages in terms of cost, laboratory process, and the maintenance of oral hygiene. In this clinical report, a solution for the management of an inclined implant is presented by using customized Locator abutment fabricated by computer-aided design and computer-aided manufacturing (CAD-CAM).


Focal plane internal energy flows of singular beams in astigmatically aberrated low numerical aperture systems.
Singular beams have circulating energy components. When such beams are focused by low numerical aperture systems suffering from astigmatic aberration, these circulating energy components get modified. The phase gradient introduced by this type of aberration splits the higher charge vortices. The dependence of the charge, the aberration coefficient, and the size of the aperture on the nature of the splitting process are reported in this paper. The transverse components of the Poynting vector fields that can be derived from the phase gradient vector field distributions are further decomposed into solenoidal and irrotational components using the Helmholtz-Hodge decomposition method. The solenoidal components relate to the orbital angular momentum of the beams, and the irrotational components are useful in the transport of intensity equations for phase retrieval.


Transnasal esogastroduodenoscopy (EGD): comparison with conventional EGD and new applications.
Technical improvements have allowed to significantly reduce the diameter of endoscopes used to examine the upper gastrointestinal tract. Hence, transnasal introduction of endoscopes used to perform a standard esogastroduodenoscopy (EGD) has become possible. Transnasal EGD (T-EGD) is better tolerated by patients than conventional EGD (C-EGD), and it presents the advantage of requiring no sedation in most patients (and, consequently, to reduce associated costs). However, the reduction in endoscope diameter has been obtained at the expense of a somewhat inferior image quality and a smaller biopsy channel diameter. Specific diagnostic and therapeutic applications taking advantage of the transnasal approach have also recently emerged (e.g., cholangioscopy placement of feeding tubes or of nasobiliary drains). The technique, feasibility, patient tolerance to unsedated procedure, diagnostic accuracy, costs, and novel therapeutic applications of T-EGD are reviewed.


The influence path of community green exposure index on activity behavior under multi-dimensional spatial perception.
The purpose of this research is to reveal the internal relationship among community green space, space perception, and activity behavior response to supplement the lack of research results on the binary relationship between green space and behavior. Nine residential community green spaces and 398 residents were selected as the research objects. Thematic clustering and factor identification were used to determine the spatial dimensions of community green space that residents were concerned about. The analysis of the green exposure index, spatial perception evaluation, and activity behavior survey were combined to determine the influence of the green exposure index on spatial perception and activity behavior and its internal correlation path. According to research data, the community green view index (GVI) and normalized difference vegetation index (NDVI) negatively affected the perception factor, while the perception factor positively affected the activity frequency. The SEM model shows that the green exposure index stimulated activity behavior through the intermediate effect of the internal perception path of perceived landscape quality, perceived workability, and perceived accessibility. Spatial perception as the basis of the instantaneous emotional reaction process may affect people's choices for activities but be unable to extend the duration of the activities. The internal association among community green space, spatial perception, and physical activity behavior develops on the basis of spatial patterns at certain scales. This study provides a theoretical basis for understanding the spatial experience and residents' behavioral needs, evaluating the quality of urban green space scientifically, and promoting the optimization of community green space structure.


Correlation between work experiences and physical assessment in Japan.
The purpose of this study was to obtain baseline data of Japanese nurses' knowledge, skills and attitudes concerning physical assessment. The design of the study was survey research, using a self-administered questionnaire. Nurses with more experience were more knowledgeable about almost all physical assessment skills. Fourteen of the physical assessment skills were used more often by respondents with more experience in nursing practise. Ten of the physical assessment skills were cited as more difficult to carry out by respondents with less experience in nursing. The group with more clinical practise experience had more knowledge of physical assessment skills, used the skills more frequently and had less difficulty in using them. The results of this study indicated that Japanese nurses learn physical assessment skills 'on the job'.


How should clinicians discuss hospice for patients with dementia? Anticipating caregivers' preconceptions and meeting their information needs.
This study was designed to determine whether Alzheimer disease (AD) caregivers view the benefits of hospice as more relevant to themselves or to patients, to identify the features of hospice care that are most important to caregivers, and to determine how often these features are described in hospice promotional materials. Telephone interviews were conducted with AD caregivers from a Memory Disorders Clinic of an urban academic medical center (N = 45). A nationwide mail survey of randomly selected hospices was also conducted (N = 66). Caregivers were twice as likely to say that hospice would benefit them than they were to say it would benefit the patient (26 vs. 13; p = 0.002). The features of hospice that were most important to caregivers were continued follow-up evaluation by the patient's primary care provider and hospice's emphasis on helping patients to avoid hospital admission. The least important was the availability of a chaplain. There was moderate agreement between the importance of various hospice features to caregivers, and the representation of that feature in hospice promotional materials. AD caregivers have generally positive opinions about hospice's benefits for themselves. In discussing hospice with AD caregivers, clinicians may want to emphasize selected features of hospice that are particularly important to caregivers.


Tensor methods for hyperspectral data analysis: a space object material identification study.
An important and well-studied problem in hyperspectral image data applications is to identify materials present in the object or scene being imaged and to quantify their abundance in the mixture. Due to the increasing quantity of data usually encountered in hyperspectral datasets, effective data compression is also an important consideration. In this paper, we develop novel methods based on tensor analysis that focus on all three of these goals: material identification, material abundance estimation, and data compression. Test results are reported in all three perspectives.


[New formula for the determination od fetal age].
The methods utilised in anthropology for foetal age assessment are generally rather old, based on small samples and have never been tested on other samples than the one they were established on. In this study, we establish a formula on 344 foetuses of known age, and compare it with other age determination methods found in the scientific literature. Except our formula, the tested other methods do not give the limits of the prediction's confidence interval, and therefore do not take into account the total variability. Therefore, we demonstrate the necessity to establish formulas based on large samples and on a validated methodology.


Accelerated solvent extraction and confirmatory analysis of sulfonamide residues in raw meat and infant foods by liquid chromatography electrospray tandem mass spectrometry.
This paper describes a new method for the rapid extraction and unequivocal confirmation of 13 sulfonamides (SAs) in raw meat and infant foods. The highly automated extraction procedure is based on accelerated solvent extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a confirmatory analysis. After 1 g of food matrix was blended with 2 g of C18 as a solid support material, the mixture was packed into the extraction cell and the SAs were extracted with 10 mL of hot water at 160 degrees C and 100 atm; 100 microL of the extract was directly injected into the LC-MS system. The analytes were ionized in an electrospray interface operating in the positive ion mode and were identified by selecting two multireaction monitoring transitions, which guaranteed method specificity. Typical recoveries from crude meat and baby food samples ranged from 70 to 101% at a fortification level of 100 ppb, corresponding to the maximum residue limits established by the European Union and the U.S. Food and Drug Administration. The interday method precision was less than 8.5%, and the limits of detection were below 2.6 ppb. This study has taken matrix-induced suppression of ionization into account, by comparing standard and matrix-matched calibration curves. Four of the 13 monitored SAs have been detected in some baby foods and raw meat samples, bought from Roman supermarkets and butchers' shops, using the described methodology.


MR imaging in male infertility.
In patients with male infertility, endorectal magnetic resonance (MR) imaging provides high-resolution images of the prostate gland and ejaculatory apparatus. The multiplanar capability of MR imaging allows production of a detailed map of the reproductive tract for guiding treatment. Causes of male infertility can be classified as congenital, acquired, infectious, or hormonal. Wolffian duct abnormalities include agenesis of the kidney, vas deferens, or seminal vesicle and cysts of the vas deferens, seminal vesicle, or urogenital sinus-ejaculatory duct. Müllerian duct abnormalities are less common and consist of müllerian duct cysts and utricle cysts. Cowper duct cysts and peripheral-zone prostatic cysts are acquired causes of male infertility. Prostatitis, an infectious cause of male infertility, may mimic carcinoma on long repetition time/echo time images. A low testosterone levels is one of the hormonal causes of male infertility. Pitfalls in the interpretation of MR images can be avoided by familiarity with normal and abnormal findings in patients with male infertility.


Can volunteering in later life reduce the risk of dementia? A 5-year longitudinal study among volunteering and non-volunteering retired seniors.
We propose that voluntary work, characterized by social, physical and cognitive activity in later life is associated with fewer cognitive problems and lower dementia rates. We test these assumptions using 3-wave, self-reported, and registry data from the 2010, 2012, and 2014 Swedish National Prescribed Drug Register. We had three groups of seniors in our data: 1) no volunteering (N = 531), 2) discontinuous volunteering (N = 220), and 3) continuous volunteering (N = 250). We conducted a path analysis in Mplus to investigate the effect of voluntary work (discontinuously and continuously) on self-reported cognitive complaints and the likelihood of being prescribed an anti-dementia treatment after controlling for baseline and relevant background variables. Our results indicated that seniors, who continuously volunteered, reported a decrease in their cognitive complaints over time, whereas no such associations were found for the other groups. In addition, they were 2.44 (95%CI [1.86; 3.21]) and 2.46 (95%CI [1,89; 3.24]) times less likely to be prescribed an anti-dementia treatment in 2012 and 2014, respectively. Our results largely support the assumptions that voluntary work in later life is associated with lower self-reported cognitive complaints and a lower risk for dementia, relative to those who do not engage, or only engage episodically in voluntary work.


PspG, a new member of the Yersinia enterocolitica phage shock protein regulon.
The Yersinia enterocolitica phage shock protein (Psp) system is induced when the Ysc type III secretion system is produced or when only the YscC secretin component is synthesized. Some psp null mutants have a growth defect when YscC is produced and a severe virulence defect in animals. The Y. enterocolitica psp locus is made up of two divergently transcribed cistrons, pspF and pspABCDycjXF. pspA operon expression is dependent on RpoN (sigma(54)) and the enhancer-binding protein PspF. Previous data indicated that PspF also controls at least one gene that is not part of the psp locus. In this study we describe the identification of pspG, a new member of the PspF regulon. Predicted RpoN-binding sites upstream of the pspA genes from different bacteria have a common divergence from the consensus sequence, which may be a signature of PspF-dependent promoters. The Y. enterocolitica pspG gene was identified because its promoter also has this signature. Like the pspA operon, pspG is positively regulated by PspF, negatively regulated by PspA, and induced in response to the production of secretins. Purified His(6)-PspF protein specifically interacts with the pspA and pspG control regions. A pspA operon deletion mutant has a growth defect when the YscC secretin is produced and a virulence defect in a mouse model of infection. These phenotypes were exacerbated by a pspG null mutation. Therefore, PspG is the missing component of the Y. enterocolitica Psp regulon that was previously predicted to exist.


Uroflow nomogram for male adolescents.
Uroflowmetry is well established for investigating lower urinary tract symptoms. Current nomograms are based on sample sizes limited to 8 men of the same age. We generated percentile curves for the maximum urinary flow rate (Qmax) in relation to voided volume in male adolescents in a large homogenous healthy group. A total of 348 males who were 18 years old were investigated, excluding probands with a urological history. Only samples with a voided volume of 150 cc or more were included. One micturition was obtained per proband to determine Qmax, the average urinary flow rate, time to Qmax and volume. Resulting curves were compared with nomograms for children and adults. Average voided volume +/- SD was 262 +/- 91.9 cc (range 151 to 664). Qmax was 28.4 +/- 9.7 cc per second (range 11.4 to 76) with an average urinary flow rate of 18.6 +/- 5.5 cc per second (range 4 to 44), a micturition time of 16.9 +/- 6.8 seconds (range 7 to 48) and a mean time to Qmax of 7.8 +/- 4.1 seconds (range 1 to 25). A total of 341 probands had a Qmax of more than 15 cc per second, while only 7 showed a Qmax of less than 15 cc per second. At up to 350 cc Qmax increased with volume, followed by a plateau phase at 350 to 550 cc and a Qmax decrease at higher volumes. Voiding volumes in a large homogenous adolescent group demonstrated optimal Qmax at voiding volumes between 350 and 550 cc with a decrease at higher volumes. Therefore, uroflow studies in adolescent males should be interpreted with caution at volumes less than 350 and more than 550 cc.


Propionic acidemia and anorectal anomalies in three siblings.
Three siblings suffering from recurrent vomiting, hypotonia, hyperpnea, dehydration, and ketoacidosis were diagnosed as having ketotic hyperglycinemia secondary to propionic acidemia. They also had leukopenia and thrombocytopenia, and two of them had anorectal malformations, one an imperforate anus with rectoperineal fistula, and the other an ectopic anus. The occurrence of propionic acidemia and anorectal anomalies in three siblings out of eight children in a consanguineous marriage suggests an autosomal recessive genetic inheritance.


Cardioprotection of cortistatin against isoproterenol-induced myocardial injury in rats.
The present study was designed to examine whether cortistatin (CORT) could protect rats from myocardial injury induced by subcutaneously injecting isoproterenol (ISO) and to clarify the possible mechanisms. Male Sprague-Dawley (SD) rats were placed at random into four groups: the control group, the ISO group, the ISO + CORT 25 µg/(kg·d) group, and the ISO + CORT 50 µg/(kg·d) group. Rat models of myocardial injury were established with the subcutaneous (s.c.) injections of 85 mg/kg ISO for 2 days. In the ISO+ CORT 25 µg/(kg·d) group and ISO+ CORT 50 µg/(kg·d) group, rats were given s.c. injections of CORT 25 µg/(kg·d) and CORT 50 µg/(kg·d) on the day before ISO, 3 days, respectively. Serum malondialdehyde (MDA) content, lactate dehydrogenase (LDH) activity, and creatine kinase isoenzyme (CK-MB) activity were measured by corresponding test kits. Western blot was applied to evaluate the expression of endoplasmic reticulum stress-related protein glucose regulatory protein 78 (GRP78), enhancer-binding protein homologous protein (CHOP), cysteinyl aspartate specific proteinase-12 (caspase-12), LC3-II, Beclin-1, and p62 in the rat myocardium. CORT alleviated the increased enzyme activities of serum LDH and CK-MB, and content of MDA (a typical marker of lipid peroxidation) in rats induced by ISO. CORT also prevented pathological myocardial injury in rats induced by ISO. Moreover, CORT attenuated the increased protein levels of GRP78, CHOP, and caspase-12, and reduced the increase of LC3-II, LC3-II/I, Beclin-1, and p62 in rats induced by ISO. These data demonstrate that CORT can attenuate ISO-induced acute myocardial injury in rats likely by reducing lipid peroxidation, and inhibiting endoplasmic reticulum stress and autophagy. This supports CORT as a potentially being a new target for preventing and treating myocardial injury and its related disease.


Metabolic Fingerprints of Effective Fluoxetine Treatment in the Prefrontal Cortex of Chronically Socially Isolated Rats: Marker Candidates and Predictive Metabolites.
The increasing prevalence of depression requires more effective therapy and the understanding of antidepressants' mode of action. We carried out untargeted metabolomics of the prefrontal cortex of rats exposed to chronic social isolation (CSIS), a rat model of depression, and/or fluoxetine treatment using liquid chromatography-high resolution mass spectrometry. The behavioral phenotype was assessed by the forced swim test. To analyze the metabolomics data, we employed univariate and multivariate analysis and biomarker capacity assessment using the receiver operating characteristic (ROC) curve. We also identified the most predictive biomarkers using a support vector machine with linear kernel (SVM-LK). Upregulated myo-inositol following CSIS may represent a potential marker of depressive phenotype. Effective fluoxetine treatment reversed depressive-like behavior and increased sedoheptulose 7-phosphate, hypotaurine, and acetyl-L-carnitine contents, which were identified as marker candidates for fluoxetine efficacy. ROC analysis revealed 4 significant marker candidates for CSIS group discrimination, and 10 for fluoxetine efficacy. SVM-LK with accuracies of 61.50% or 93.30% identified a panel of 7 or 25 predictive metabolites for depressive-like behavior or fluoxetine effectiveness, respectively. Overall, metabolic fingerprints combined with the ROC curve and SVM-LK may represent a new approach to identifying marker candidates or predictive metabolites for ongoing disease or disease risk and treatment outcome.


Genes required for osmoregulation and apical secretion in Caenorhabditis elegans.
Few studies have investigated whether or not there is an interdependence between osmoregulation and vesicular trafficking. We previously showed that in Caenorhabditis elegans che-14 mutations affect osmoregulation, cuticle secretion, and sensory organ development. We report the identification of seven lethal mutations displaying che-14-like phenotypes, which define four new genes, rdy-1-rdy-4 (rod-like larval lethality and dye-filling defective). rdy-1, rdy-2, and rdy-4 mutations affect excretory canal function and cuticle formation. Moreover, rdy-1 and rdy-2 mutations reduce the amount of matrix material normally secreted by sheath cells in the amphid channel. In contrast, rdy-3 mutants have short cystic excretory canals, suggesting that it acts in a different process. rdy-1 encodes the vacuolar H+-ATPase a-subunit VHA-5, whereas rdy-2 encodes a new tetraspan protein. We suggest that RDY-1/VHA-5 acts upstream of RDY-2 and CHE-14 in some tissues, since it is required for their delivery to the epidermal, but not the amphid sheath, apical plasma membrane. Hence, the RDY-1/VHA-5 trafficking function appears essential in some cells and its proton pump function essential in others. Finally, we show that RDY-1/VHA-5 distribution changes prior to molting in parallel with that of actin microfilaments and propose a model for molting whereby actin provides a spatial cue for secretion.


[Association between collateral circulation and myocardial viability evaluated by cardiac magnetic resonance imaging in patients with coronary artery chronic total occlusion].
Objective: Late gadolinium enhancement(LGE) cardiac magnetic resonance imaging(CMR) was used to evaluate the myocardial viability of chronic total occlusion(CTO) in patients with coronary heart disease and to observe the relationship between collateral circulation and myocardium viability in these patients. Methods: This retrospective study included 40 patients with CTO diagnosed by invasive coronary angiography (CAG) from September 2015 to June 2016 in our department, all patients performed CMR examination within one week after CAG.The collateral circulation of CTO was graded with Rentrop classification as follows: poor or no collateral circulation group, moderate collateral circulation group and good collateral circulation group.According to CMR images, the delayed enhancement transmural extent of myocardial segments were scored, the ventricular wall motion of the myocardial segment were graded, and the wall motion score index (WMSI) was calculated.Spearman correlation analysis was used to analyze the relationship between the delayed enhancement transmural extent of myocardial segments and WMSI. Results: In the no or poor collateral group of 6 myocardial regions, 1 myocardial region had viable myocardium and 3 myocardial regions had no viable myocardium; in the moderate collateral group of 16 myocardial regions, 11 myocardial regions had viable myocardium and 5 myocardial regions had no viable myocardium; in the good collateral group of 24 myocardial regions, 21 myocardial regions had viable myocardium and 3 myocardial regions had no viable myocardium, there was significant difference between the groups (P=0.002). The WMSI of poor or no collateral circulation group, moderate collateral circulation group and good collateral circulation group were 1.54±0.50, 1.21±0.34 and 1.26±0.40, respectively, there was no significant difference between the groups (P=0.063). Spearman correlation analysis showed that the extent of delayed enhancement transmural extent of myocardial segment was significantly associated with WMSI (r=0.638, P<0.01). Conclusion: Collateral circulation in patients with chronic total occlusion can predict myocardial viability.Increase of Rentrop grade is linked with higher possibility of the presence of viable myocardium.


Utilization of exogenous thymidine by Chlamydia psittaci growing in the thymidine kinase-containing and thymidine kinase-deficient L cells.
The incorporation of [3H]thymidine into the deoxyribonucleic acid (DNA) of Chlamydia psittaci (strain 6BC) growing in thymidine kinase (adenosine 5'-triphosphate-thymidine 5'-phosphotransferase, EC 22.214.171.124)-containing L cells, L(TK+), and thymidine kinase-deficient L cells, LM(TK-), was examined by autoradiography. Label was detected over C. psittaci inclusions in L(TK+) but not LM(TK-) cells. No evidence for a chlamydia-specific thymidine kinase activity in either L(TK+) or LM(TK-) cells was obtained. Entry of [3H]thymidine into the DNA of C. psittaci growing in L(TK+) cells was quantitated by measuring label in purified C. psittaci. It was 265 times less efficient than entry into infected host cell DNA. It is concluded that low levels of exogenous thymidine are incorporated into the DNA of C. psittaci and that this incorporation is dependent on a fully competent host thymidine kinase activity. Evidence also is presented that L cells possess at least two thymidine kinase activities, both of which are capable of supplying thymidylate precursors for nuclear DNA synthesis.


Insulin induced reversibility of altered responsiveness in femoral arterial bed of diabetic dogs.
The altered reactivities of femoral arterial bed to noradrenaline, phenylephrine, adenosine and prostacyclin were compared in 18, clinically manifest but aketotic, alloxan diabetic mongrel dogs. Alloxan treatment markedly increased the vasoconstrictor responses to noradrenaline and phenylephrine, as well as the adenosine-induced vasodilation in the femoral vasculature. These changes were prevented or normalized, respectively, in the early or late insulin-treated alloxan diabetic animals. In the case of noradrenaline not only a normalization but also an explicit overcompensation could be observed by insulin treatment. The altered reactivity to prostacyclin could not be influenced by insulin therapy. These results indicate a significant difference in the effect of insulin treatment on the altered diabetic vascular responsiveness to catecholamines and adenosine or to prostacyclin.


Mutations in DNA repair genes are associated with the Haarlem lineage of Mycobacterium tuberculosis independently of their antibiotic resistance.
The analysis of the DNA repair genes ogt and ung was carried out in 117 Mycobacterium tuberculosis clinical isolates from Argentina and Colombia in order to explore correlation between mutations in these genes and multi-drug resistance. With the exception of two Beijing family isolates, the rest of the strains harbored either two wild-type or two mutant alleles with identical single nucleotide polymorphisms (SNPs) in each gene (ogt44 and ung501). These ogt44 and ung501 mutations were not associated with multi-drug resistance and occurred simultaneously in circulating Haarlem genotype M. tuberculosis strains. We therefore propose the use of these markers as tools in phylogenetic and epidemiologic studies.


Tyrosyl and phosphatidylinositol kinases of human erythrocyte membranes.
The tyrosyl kinase and phosphatidylinositol (PI) kinase activities of human red cells have been partially purified and characterized. Although the PI kinase required detergent for solubilization, the major tyrosyl kinase of the red cell could be extracted by high salt. A very small residual activity remained associated with the membranes, however, that was solubilized with the PI kinase and copurified through an ammonium sulfate precipitation and diethylaminoethyl (DEAE) ion-exchange step gradient elution. However, the two activities were found to differ with respect to their apparent KmS for ATP and Mg2+; they showed different half-lives for temperature inactivation, possessed different relative activities in the presence of Mn2+ and Ca2+, and were separable by elution from a DEAE-Trisacryl ion exchange column using a linear NaCl gradient. The kinetic parameters of the membrane-associated tyrosyl kinase differed from those of the salt-extracted enzyme. PI kinase was not activated by pretreatment with the tyrosyl kinase p68v-ros or by addition of the phosphotyrosyl phosphatase inhibitor, vanadate, to intact membranes, and was not competitively inhibited by the tyrosyl kinase substrate poly(Glu4, Tyr). We conclude that the human red cell phosphatidylinositol and tyrosyl kinases are distinct and separate activities, and that at least two separable tyrosyl kinases are present in human erythrocytes.


[Chinese expert consensus for non-antiinfective effects and clinical use of macrolides].
Important/potential value of macrolides has been proved in the management of chronic respiratory diseases by increasing basic and clinical trials.Through three face-to-face discussions, 10 experts examined important data and drafted this consensus related to macrolides: (1) mechanism of non-antiinfective effects; (2) clinical use in chronic respiratory diseases; (3) cautions of long-term use.The mechanism out of non-antiinfective effects includes anti-inflammatory effect, modifying airway secretion, immune-regulation related to antibacterial effect, corticoid saving effect and anti-viral effect.The efficacy of long-term use of low-dose macrolides is definitely confirmed in diffuse panbronchiolitis, chronic rhinosinusitis. It is considerably used in bronchiectasia, cystic fibrosis, severe asthma and chronic obstructive pulmonary disease. Further studies should be conducted in cryptogenic organizing pneumonia and respiratory viral infection. It should be paid attention to its possible adverse effects (including drug interactions, cardiac toxicity, ototoxicity and disturbance of intestinal flora) and drug resistance in long-term use.A Chinese consensus for non-antiinfective effects and clinical use of macrolides is developed for the first time, which aims to expand their rational use and the further research.


An endoplasmic reticulum-targetable fluorescent probe for highly selective detection of hydrogen sulfide.
Hydrogen sulfide (H2S), a critical endogenous signaling molecule, is widely involved in many physiological processes. Endoplasmic reticulum, an important organelle with a sac-like structure, plays crucial roles in maintaining the normal function of cells. Accordingly, monitoring the H2S levels in endoplasmic reticulum is of great importance. Herein, we have developed an endoplasmic reticulum-targetable fluorescent probe, ER-CN, for H2S detection. ER-CN features excellent sensing properties, such as high sensitivity and selectivity. In addition, ER-CN exhibits low cytotoxicity and a fine endoplasmic reticulum targeting property (with a Pearson's colocalization coefficient of 0.95). Significantly, visualization of H2S in the endoplasmic reticulum of living HeLa cells by using ER-CN was successfully realized.


Advances in Radiotherapy for Glioblastoma.
External beam radiotherapy (RT) has long played a crucial role in the treatment of glioblastoma. Over the past several decades, significant advances in RT treatment and image-guidance technology have led to enormous improvements in the ability to optimize definitive and salvage treatments. This review highlights several of the latest developments and controversies related to RT, including the treatment of elderly patients, who continue to be a fragile and vulnerable population; potential salvage options for recurrent disease including reirradiation with chemotherapy; the latest imaging techniques allowing for more accurate and precise delineation of treatment volumes to maximize the therapeutic ratio of conformal RT; the ongoing preclinical and clinical data regarding the combination of immunotherapy with RT; and the increasing evidence of cancer stem-cell niches in the subventricular zone which may provide a potential target for local therapies. Finally, continued development on many fronts have allowed for modestly improved outcomes while at the same time limiting toxicity.


Fast Isomerization Before Isomerization-Hydroformylation: Probing the Neglected Period with A Novel Microfluidic Device.
By combining the concept of flash chemistry and radial synthesis, a novel microreactor (Flashstop reactor) was designed to study isomerization process of hydroformylation by a Rh/tetraphosphite catalyst in a time scale of seconds. It was found that in the initial 313 seconds, 60-99 % of 1-octene was isomerized to 2- and 3-octenes before the formation of aldehydes. Within this period, two different types of isomerization reactions were observed. It was proposed that a monohydride complex without CO ligand accounts for the ultrafast isomerization in the initial 30 seconds. The isomerization rate with such monohydride species was calculated much faster than that with the well-known H(CO)Rh(P-P) species. Both experimental and DFT computational studies were carried out to support this assumption. Fast transformations early on in catalytic cycles have been rarely studied due to the lack of proper tools. We believe that the Flashstop reactor is a powerful tool for analysis of kinetics in gas-liquid biphasic reactions within a time scale of seconds to minutes.


[Comparison of robotic surgery with laparoscopy for surgical staging of endometrial cancer: a meta-analysis].
Objective: To evaluate the safety and effectiveness of robotic surgery in surgical staging of endometrial cancer. Methods: Searched English and Chinese databases, including Cochrane library, PubMed, Embase, Web of Science, China National Knowledge Internet, data base of Wanfang, China Science and Technology Journal (CSTJ) , and relevant journals and magazines by hand from Jan. 2000 to Oct. 2016. (1) In accordance with the inclusion criteria, two independent investigators screened databases and extracted the relevant data respectively, then evaluated the quality of including studies in Newcastle-Ottawa Scale (NOS) . (2) Meta-analysis was performed with RevMan 5.3 software. Heterogeneity inspection was done for each study and different effect model included the random effect model and fixed effect model was chose according to the results: of the inspection. At last, the related parameters of the robotic surgery and laparoscopic surgery was analysed. Results (1) Thirteen articles were ultimately included. All of them were written in English and included a total of 1 554 patients, included 739 cases of robotic surgery and 815 cases of laparoscopic surgery. Thirteen articles were all cohort study, four of them were prospective cohort study, while others were retrospective cohort study. After quality assessment, all studies had more than 5 stars and illustrated the higher quality. (2) Meta-analysis results showed: compared with laparoscopic surgery in surgical staging of endometrial cancer, robotic surgery had less estimated blood loss [standard deviation (SD)=-72.31 ml, 95%CI:-107.29 to-37.33, P<0.01], less time for hospital stay (SD=-0.29 days, 95%CI:-0.46 to-0.13, P=0.001), less need for blood transfusion [risk ratio (RR)=0.57, 95%CI: 0.33 to 0.97, P=0.040], and conversion to open surgery (RR=0.41, 95%CI: 0.26 to 0.65, P=0.000), less intraoperative complications (RR=0.43, 95%CI: 0.24 to 0.76, P=0.004) in surgical staging of endometrial cancer. There was no statistically significant difference in aspects of operative time (SD=10.26 minutes, 95% CI:-13.62 to 34.13, P=0.400), postoperative complications (RR=0.87, 95% CI: 0.67 to 1.12, P=0.280), the total number of lymph nodes removed (SD=-0.04, 95% CI:-3.99 to 3.91, P=0.980), the number of pelvic lymph node dissection (SD=0.48, 95%CI:-1.76 to 2.71, P=0.680) and the number of para-aortic lymph node dissection (SD=0.46, 95%CI:-1.42 to 2.34, P=0.630). Conclusions: Compared the robotic surgery with laparoscopic surgery in surgical staging of endometrial cancer, robotic surgery has less estimated blood loss, less need for blood transfusion and conversion to open surgery, less intraoperative complications and other advantages. While its cost is so expensive that restrict clinical application.


CRIF1-CDK2 Interface Inhibitors: An Unprecedented Strategy for Modulation of Cell Radiosensitivity.
Cyclin-dependent kinases (CDKs) are historic therapeutic targets implicated in tumorigenic events due to their critical involvement in the cell cycle phase. However, selectivity has proven to be a bottleneck, causing repeated failures. Previously, we reported CR6-interacting factor 1 (CRIF1), acting as a cell cycle negative regulator through interaction with CDK2. In the current report, we identified the CRIF1-CDK2 interaction interface by in silico studies and shortlisted interface inhibitors through virtual screening on CRIF1 using 40 678 drug-like compounds. These compounds were tested by cell proliferation assay, and four of these molecules were found to selectively inhibit the proliferation of osteosarcoma (OS) cell lines, but do not affect normal bone mesenchymal stem cells (BMSC). A binding study reveals significant affinities of the inhibitors on CRIF1. More importantly, treatment of the OS cells with a combination of ionizing radiation (IR) and the best-performing inhibitors remarkably increased IR inhibition potential from 19.9% to 59.6%. This occurred by selectively promoting G2/M arrest and apoptosis related to CDK2 overactivation in OS cells but not in BMSC and was supported by significant CDK2 phosphorylation modifications. Knocking down of CRIF1 by siRNA treatment showed similar effects to the interface inhibitors. Together we substantiate the identification of novel lead molecules, which may provide a new treatment to overcome selectivity issues and enhance the radiosensitivity of tumor cells, opening a conceptually novel strategy of CDK-targeting for different cancer types.


Praeruptorin C alleviates cognitive impairment in type 2 diabetic mice through restoring PI3K/AKT/GSK3β pathway.
Diabetic encephalopathy is a common consequence of diabetes mellitus that causes cognitive dysfunction and neuropsychiatric disorders. Praeruptorin C (Pra-C) from the traditional Chinese medicinal herb Peucedanum praeruptorum Dunn. is a potential antioxidant and neuroprotective agent. This study was conducted to investigate the molecular mechanisms underlying the effect of Pra-C on diabetic cognitive impairment. A novel object recognition test and the Morris water maze test were performed to assess the behavioral performance of mice. Electrophysiological recordings were made to monitor synaptic plasticity in the hippocampus. A protein-protein interaction network of putative Pra-C targets was constructed, and molecular docking simulations were performed to predict the potential mechanisms of the action of Pra-C. Protein expression levels were detected by western blotting. Pra-C administration significantly lowered body weight and fasting blood glucose levels and alleviated learning and memory deficits in type 2 diabetic mice. Network pharmacology and molecular docking results suggested that Pra-C affects the PI3K/AKT/GSK3β signaling pathway. Western blot analysis confirmed significant increases in phosphorylated PI3K, AKT, and GSK3β levels in vivo and in vitro upon Pra-C administration. Pra-C alleviated cognitive impairment in type 2 diabetic mice by activating PI3K/AKT/GSK3β pathway.


The Fate of the World's Plants.
A recent report assessing the world's plant species finds continuing progress in completing the taxonomic catalog. However, many undescribed species remain. The report concludes that, presently, 21% of known species risk extinction. We show this statement applies to the short-term and ignores the as-yet undescribed species, which are also likely at risk of extinction. Human actions will extirpate many more by the end of this century.


APUD cells and neuroepithelial bodies in hamster lung: methods, quantitation, and response to injury.
A comparative study of the Falck-Hillarp Technique, a modification of Eaton-Fedde procedure and silver staining of aldehyde-fixed tissue was carried out to determine the most efficient procedure to demonstrate neuroendocrine cells of the hamster and rat lung. The modified Eaton-Fedde procedure is the most efficient method of observing these cells, and is also the easiest to perform. With this method, the normal hamster lung contains a total of 2.00 x 10(-1) to 3.00 x 10(-1) neuroendocrine cells/mm in the small and large bronchioles. In the larger airways approximately 3.51 x 10(-1) neuroepithelial bodies (NEB)/mm are observed. Immediately after 24-hour exposure to NO2 the number of APUD cells dropped to approximately 25% of the control levels. These cells were decreased to 50% of the control levels throughout the 28 days of exposure. The number of NEB decreased transiently after 24 hours of NO2 but returned to normal numbers by day 14. We recommend the application of fluorescence techniques coupled with standardised sections and quantitative methods of study for analysis of APUD cells and NEB.


Delayed initiation of anti-osteoporosis medications increases subsequent hip and vertebral fractures in patients on long-term glucocorticoid therapy: A nationwide health insurance claims database study in Japan.
Early initiation of anti-osteoporosis medications (AOMs) is recommended for patients on long-term glucocorticoid (GC) therapy. This study aimed to examine whether physicians prescribe AOMs as soon as GC therapy is initiated, and whether a delay in AOM initiation affects hip and vertebral fracture incidence, using the nationwide health insurance claims database of Japan (NDBJ). Patients aged ≥50 years who were prescribed GC (≥5 mg/day prednisolone or equivalent) for ≥90 days and who were followed for AOM use and hip and vertebral fracture events for the subsequent 1080 days in 2012-2018 were selected from NDBJ. Delay in AOM initiation was defined as the number of days without AOMs following GC therapy initiation. Associations between delay in AOM initiation and hip and vertebral fracture risk were evaluated by Cox proportional hazards regression. In total, 92,143 women and 94,772 men were included in the analysis, of which only 39.3% of women and 28.5% of men received AOMs within 90 days from GC therapy initiation. Approximately, 15% of hip fractures and 30% of vertebral fractures occurred before AOM initiation in patients with delayed AOM initiation. HRs of both fractures were significantly greater in patients with a longer delay in AOM initiation (p value for trend<0.001). After excluding patients who had fractures before AOM initiation, the magnitude of HRs significantly decreased, and HR trends for hip fracture became insignificant. Delayed initiation of AOMs may result in increased fracture events, which may be reduced by early initiation of AOMs.


The development of a complementary pathway for the synthesis of aliskiren.
The synthesis of aliskiren (1), a recently marketed drug for the treatment of hypertension, is presented. The focus of our synthetic effort is to develop an efficient pathway for the synthesis of (2S,7R,E)-2-isopropyl-7-(4-methoxy-3-(3-methoxypropoxy) benzyl)-N,N,8-trimethylnon-4-enamide (2a), which has been used as the advanced intermediate toward aliskiren. After an extensive investigation of three different strategies designed to construct the E-olefin functionality in 2a by employing the olefin cross-metathesis, Horner-Wadsworth-Emmons (HWE), and Julia-type olefinations, we have established a new protocol for the synthesis of 2a with a substantially improved overall efficiency in terms of the yield (ca. 33%), and diastereo- and E/Z-selectivity. The key transformations were the Evans chiral auxiliary-aided asymmetric allylation for the synthesis of the appropriate chiral intermediates in excellent enantiomeric purity of higher than 97% ee and a modified Julia-Kocienski olefination for the highly selective construction of E-2a with up to 13.6:1 E/Z ratio from the chiral intermediates. Consequently, the results provide an appealing option for the synthesis of aliskiren.


Phospholipase A2-mediated hydrolysis of cardiac phospholipids: the use of molecular and transgenic techniques.
Under pathophysiological conditions, like myocardial ischemia and reperfusion, cardiac phospholipid homeostasis is severely disturbed, resulting in a net degradation of phospholipids and the accumulation of degradation products, such as lysophospholipids and (non-esterified) fatty acids. The derangements in phospholipid metabolism are thought to be involved in the sequence of events leading to irreversible myocardial injury. The net degradation of phospholipids as observed during myocardial ischemia may result from increased hydrolysis and/or reduced resynthesis, while during reperfusion hydrolysis is likely to prevail in this net degradation. Several studies indicate that the activation of phospholipases A2 plays an important role in the hydrolysis of phospholipids. In this review current knowledge regarding the potential role of the different types of phospholipases A2 in ischemia and reperfusion-induced damage is being evaluated. Furthermore, it is indicated how recent advances in molecular biological techniques could be helpful in determining whether disturbances in phospholipid metabolism indeed play a crucial role in the transition from reversible to irreversible myocardial ischemia and reperfusion-induced injury, the knowledge of which could be of great therapeutic relevance.


Further analysis of the risk of adverse birth outcome after maternal use of fluoroquinolones.
In a database cohort study, the risk of adverse birth outcome in Danish women who redeemed a fluoroquinolone prescription during pregnancy was examined. Among 87 women who redeemed a fluoroquinolone prescription at any time during the pregnancy, the prevalence ratio of preterm birth was 1.4 (95% confidence interval (CI), 0.6-3.2), one woman had a stillbirth, and no children died during the perinatal period. Among 130 women who redeemed a prescription during the first trimester or 30 days before conception, the prevalence ratio of congenital malformation was 0.7 (95% CI, 0.3-2.0) and the prevalence ratio of bone malformations was 2.2 (95% CI, 0.7-6.7). Our study raises the concern that prenatal fluoroquinolone exposure may be associated with an increased risk of bone malformations.


Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in signal transducers and activators of transcription (STAT)6-deficient mice.
Signal transducers and activators of transcription 6 (STAT6) is essential for interleukin 4-mediated responses, including class switching to IgE and induction of type 2 T helper cells. To investigate the role of STAT6 in allergic asthma in vivo, we developed a murine model of allergen-induced airway inflammation. Repeated exposure of actively immunized C57BL/6 mice to ovalbumin (OVA) aerosol increased the level of serum IgE, the number of eosinophils in bronchoalveolar lavage (BAL) fluid, and airway reactivity. Histological analysis revealed peribronchial inflammation with pulmonary eosinophilia in OVA-treated mice. In STAT6-deficient (STAT6-/-) C57BL/6 mice treated in the same fashion, there were no eosinophilia in BAL and significantly less peribronchial inflammation than in wild-type mice. Moreover STAT6-/- mice had much less airway reactivity than wild-type mice. These findings suggest that STAT6 plays a crucial role in the pathogenesis of allergen-induced airway inflammation.


Yolk androgens and embryo sex: maternal effects or confounding factors?
Maternal effects occur when offspring phenotype is affected by environmental factors experienced by the mother and, in egg-laying species, are often mediated via egg resources. There is currently great interest among behavioural ecologists in maternally allocated yolk androgens, especially their relationship with offspring sex and development. Such studies need embryonic tissue for sexing, however, requiring eggs to be incubated (usually for 3 days). Therefore, there are concerns about whether the androgen concentrations assayed reflect those allocated by the mother. In addition, studies showing sex biases in maternal allocation of androgens could be confounded if male and female embryos uptake or metabolise androgens at different rates. We ran a series of experiments using zebra finch (Taeniopygia guttata) eggs to address these potential confounding factors. First we showed, using eggs naturally incubated for up to 5 days, that eggs containing embryos had lower yolk androgen concentrations than eggs that had failed to form embryos. We then tested various hypotheses for this difference using controlled incubation treatments. Our results suggested that (a) embryo development causes the yolk to become progressively more diluted with albumin; and (b) between 3 and 5 days of incubation embryos start uptaking or metabolising androgens. Crucially, we found no decline in yolk androgen concentration at 3 days incubation, and no evidence for sex-specific rates of uptake or metabolism of androgens. This strongly suggests that yolk androgen levels up to 3 days incubation do reflect those allocated by the mother, and that studies of sex biased maternal allocation of yolk androgens are not confounded by sex differences in embryo development.


Optimization of metabolite extraction of human vein tissue for ultra performance liquid chromatography-mass spectrometry and nuclear magnetic resonance-based untargeted metabolic profiling.
Human vein tissue is an important matrix to examine when investigating vascular diseases with respect to understanding underlying disease mechanisms. Here, we report the development of an extraction protocol for multi-platform metabolic profiling of human vein tissue. For the first stage of the optimization, two different ratios of methanol/water and 5 organic solvents--namely dichloromethane, chloroform, isopropanol, hexane and methyl tert-butyl ether (MTBE) solutions with methanol--were tested for polar and organic compound extraction, respectively. The extraction output was assessed using (1)H Nuclear Magnetic Resonance (NMR) spectroscopy and a panel of Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) methodologies. On the basis of the reproducibility of extraction replicates and metabolic coverage, the optimal aqueous (methanol/water) and organic (MTBE/methanol) solvents identified from the first stage were used in a sequential approach for metabolite extraction, altering the order of solvent-mixture addition. The combination of organic metabolite extraction with MTBE/methanol (3 : 1) followed by extraction of polar compounds with methanol/water (1 : 1) was shown to be the best method for extracting metabolites from human vein tissue in terms of reproducibility and number of signals detected and could be used as a single extraction procedure to serve both NMR and UPLC-MS analyses. Molecular classes such as triacylglycerols, phosphatidylcholines, phosphatidylethanolamines, sphingolipids, purines, and pyrimidines were reproducibly extracted. This study enabled an optimal extraction protocol for robust and more comprehensive metabolome coverage for human vein tissue. Many of the physiological and pathological processes affecting the composition of human vein tissue are common to other tissues and hence the extraction method developed in this study can be generically applied.


Metabonomics Analysis of Brain Stem Tissue in Rats with Primary Brain Stem Injury Caused Death.
To explore the potential biomarkers for the diagnosis of primary brain stem injury (PBSI) by using metabonomics method to observe the changes of metabolites in rats with PBSI caused death. PBSI, non-brain stem brain injury and decapitation rat models were established, and metabolic maps of brain stem were obtained by LC-MS metabonomics method and annotated to the HMDB database. Partial least square-discriminant analysis (PLS-DA) and random forest methods were used to screen potential biomarkers associated with PBSI diagnosis. Eighty-six potential metabolic markers associated with PBSI were screened by PLS-DA. They were modeled and predicted by random forest algorithm with an accuracy rate of 83.3%. The 818 metabolic markers annotated to HMDB database were used for random forest modeling and prediction, and the accuracy rate was 88.9%. According to the importance in the identification of cause of death, the most important metabolic markers that were significantly up-regulated in PBSI group were HMDB0038126 (genipinic acid, GA), HMDB0013272 (N-lauroylglycine), HMDB0005199 [(R)-salsolinol] and HMDB0013645 (N,N-dimethylsphingosine). GA, N-lauroylglycine, (R)-salsolinol and N,N-dimethylsphingosine are expected to be important metabolite indicators in the diagnosis of PBSI caused death, thus providing clues for forensic medicine practice.


Change in IQ in schizophrenia patients and their siblings: a controlled longitudinal study.
Lower intelligence quotient (IQ) has frequently been reported in patients with schizophrenia. However, it is unclear whether IQ declines (further) after illness onset and what the familial contribution is to this change. Therefore, we investigate IQ changes during the course of illness in patients with non-affective psychosis, their siblings and controls. Data are part of the longitudinal Genetic Risk and Outcome of Psychosis (GROUP) study in the Netherlands and Belgium. Participants underwent three measurements, each approximately 3 years apart. A total of 1022 patients with non-affective psychosis [illness duration: 4.34 (s.d. = 4.50) years], 977 of their siblings, and 565 controls had at least one measure of IQ (estimated from four subtests of the WAIS-III). At baseline, IQ was significantly lower in patients (IQ = 97.8) and siblings (IQ = 108.2; p < 0.0001) than in controls (IQ = 113.0; p < 0.0001), and in patients as compared with siblings (p < 0.0001). Over time, IQ increased in all groups. In siblings, improvement in IQ was significantly more pronounced (+0.7 points/year) than in patients (+0.5 points/year; p < 0.0001) and controls (+0.3 points/year; p < 0.0001). IQ increase was not significantly correlated with improvement in (sub)clinical outcome in any of the groups. During the first 10 years of the illness, IQ increases to a similar (and subtle) extent in a relatively high-functioning group of schizophrenia patients and controls, despite the lower IQ in patients at baseline. In addition, the siblings' IQ was intermediate at baseline, but over time the increase in IQ was more pronounced.


New cholinesterase inhibiting bisbenzylisoquinoline alkaloids from Cocculus pendulus.
Phytochemical investigation on Cocculus pendulus (J. R. & G. FORST.) resulted in the isolation of two new and three known bisbenzylisoquinoline alkaloids. The structures of the new alkaloids, kurramine-2'-beta-N-oxide (1) and kurramine-2'-alpha-N-oxide (2), were elucidated with the help of spectroscopic techniques. The cholinesterase inhibitory activities of these bisbenzylisoquinoline alkaloids are reported here for the first time.


Increased mid-abdominal circumference is a predictor for surgical wound complications in kidney transplant recipients: A prospective cohort study.
Kidney transplant recipients are at an increased risk of developing surgical site wound complications due to their immunosuppressed status. We aimed to determine whether increased mid-abdominal circumference (MAC) is predictive for wound complications in transplant recipients. A prospective study was performed on all kidney transplant recipients from October 2014 to October 2015. "Controls" consisted of kidney transplant recipients without a surgical site wound complication and "cases" consisted of recipients that developed a wound complication. In total, 144 patients underwent kidney transplantation and 107 patients met inclusion criteria. Postoperative wound complications were documented in 28 (26%) patients. Patients that developed a wound complication had a significantly greater MAC, body mass index (BMI), and body weight upon renal transplantation (P<.001, P=.011, and P=.011, respectively). On single and multiple logistic regression analyses, MAC was a significant predictor for developing a surgical wound complication (P=.02). Delayed graft function and a history of preformed anti-HLA antibodies were also predictive for surgical wound complications (P=.003 and P=.014, respectively). Increased MAC is a significant predictor for surgical wound complications in kidney transplant recipients. Integrating clinical methods for measuring visceral adiposity may be useful for stratifying kidney transplant recipients with an increased risk of a surgical wound complication.


Genomic analyses of germline and somatic variation in high-grade serous ovarian cancer.
High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association with relapse-free and overall survival. Using a targeted capture of 557 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations (SCNA). Approximately one-third of tumors had loss-of-function (LOF) germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM, and PALB2. LOF germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP, and NF1. In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of LOF variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536, and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival. From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 557 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.


COVID-19-Associated Bifacial Weakness with Paresthesia Subtype of Guillain-Barré Syndrome.
We report a case of bifacial weakness with paresthesia, a recognized Guillain-Barré syndrome subtype characterized by rapidly progressive facial weakness and paresthesia without ataxia or other cranial neuropathies, which was temporally associated with antecedent coronavirus 2019 (COVID-19). This case highlights a potentially novel but critically important neurologic association of the COVID-19 disease process. Herein, we detail the clinicoradiologic work-up and diagnosis, clinical course, and multidisciplinary medical management of this patient with COVID-19. This case is illustrative of the increasingly recognized but potentially underreported neurologic manifestations of COVID-19, which must be considered and further investigated in this pandemic disease.


Epidemiology of gastroenteropancreatic neuroendocrine neoplasms in Krakow and Krakow district in 2007-2011.
Gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) are rare and heterogeneous tumours with variable biology. The aim of this study was to evaluate the epidemiology of GEPNEN in the population of Krakow and Krakow district in 2007-2011. The Database of the Chair and Department of Endocrinology, Jagiellonian University Medical College, comprising the data on NEN cases collected from the Endocrinology Department, University Hospital in Krakow and from independent sources: surgery, pathology, and endocrinology departments located in the Krakow area, was searched for cases of GEPNEN patients living in Krakow and Krakow district, diagnosed between 2007 and 2011. Eighty-eight such patients (39 males, 49 females, median age at diagnosis 59 ± 17 years) were identified and characterised. The mean follow-up time was 2.67 ± 1.6 years. The most frequent primary location of GEPNEN was small intestine (20%), followed by the appendix (18%), stomach (16%), pancreas (16%), rectum (15%), and colon (15%). NENG1 predominated (64%) in the analysed group. Most well-differentiated GEPNEN (63%) were diagnosed at stage I; however, 18% of them were diagnosed at stage IV. Metastases at diagnosis were found in 31% of patients. The GEPNEN incidence rate in 2007-2011 was 2.1/100000 inhabitants/year, without significant increase during the studied period. GEPNEN incidence and epidemiology in the population of Krakow and Krakow district is similar to the incidence observed in most European countries. Registers are important tools to evaluate GEPNEN epidemiology. (Endokrynol Pol 2017; 68 (1): 42-46).


Analysis of disease activity and response to treatment in a large Spanish cohort of patients with systemic lupus erythematosus.
The objectives of this paper are to study the impact of disease activity in a large cohort of patients with systemic lupus erythematosus (SLE) and estimate the rate of response to therapies. We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients. Data on demographics, disease characteristics: activity (SELENA-SLEDAI), damage, severity, hospitalizations and therapies were collected. Factors associated with refractory disease were identified by logistic regression. A total of 3658 patients (90% female; median SLE duration (interquartile range): 10.4 years (5.3-17.1)) were included. At the time of their last evaluation, 14.7% of the patients had moderate-severe SLE (SELENA-SLEDAI score ≥6). There were 1954 (53.4%) patients who were hospitalized for activity at least once over the course of the disease. At some stage, 84.6% and 78.8% of the patients received glucocorticoids and antimalarials, respectively, and 51.3% of the patients received at least one immunosuppressant. Owing to either toxicity or ineffectiveness, cyclophosphamide was withdrawn in 21.5% of the cases, mycophenolate mofetil in 24.9%, azathioprine in 40.2% and methotrexate in 46.8%. At some stage, 7.3% of the patients received at least one biologic. A total of 898 (24.5%) patients had refractory SLE at some stage. Renal, neuropsychiatric, vasculitic, hematological and musculoskeletal involvement, a younger age at diagnosis and male gender were associated with refractory disease. A significant percentage of patients have moderately-to-severely active SLE at some stage. Disease activity has a big impact in terms of need for treatment and cause of hospitalization. The effectiveness of the standard therapies for reducing disease activity is clearly insufficient. Some clinical features are associated with refractory SLE.


Passive avoidance training induces enhanced levels of immunoreactivity for muscarinic acetylcholine receptor and coexpressed PKC gamma and MAP-2 in rat cortical neurons.
Changes in neocortical immunoreactivity (ir) for muscarinic acetylcholine receptors (mAChRs), protein kinase C gamma (PKC gamma), microtubule-associated protein 2 (MAP-2), and the calcium-binding protein parvalbumin (PARV) induced by the performance of a one-trial passive shock avoidance (PSA) task were studied in young adult male Wistar rats. In experiment I, four groups of animals were formed: three control groups (N, naive; H, habituated but nonshocked; and S, habituated and shocked), and a fully trained group (T, habituated and shocked, followed by a retention trial 24 hr after the footshock). Compared to naive animals, the H, S, and T animals all revealed enhanced cortical ir for mAChRs, PKC gamma, and MAP-2 in discrete subsets of cortical neurons in layers 2, 3, and 5, while no changes were found for PARV. The neurons displaying enhanced levels of ir are of the pyramidal and nonpyramidal cell type and are arranged in a columnar manner. Immunofluorescent double-labeling experiments for mAChR, PKC gamma, and MAP-2 revealed that individual cortical neurons localized within the columns display enhanced ir for all three functionally related proteins. Compared to naive animals, all experimental groups revealed significant increases in the total size of cortical areas showing enhanced ir (H, S, and T over N). A further significant increase is found in animals receiving a footshock over nonshocked animals (S over H, respectively). The retention trial, however, did not induce a further increase (T over S). In some of the animals the patterns appeared to be lateralized, in either the left or right hemisphere. In order to test the role of cholinergic innervation in the induction of enhanced mAChR-ir, unilateral lesions of the nucleus basalis magnocellularis (nbm) were performed in experiment II. Apparently, an intact cholinergic innervation from the nbm is not required for the occurrence of the aforementioned columnar patterns. However, when the enhanced columnar patterns in the sensory areas of the cortex are cholinergically deprived, clear deficits in PSA performance are observed. These results indicate that although ACh is not a prerequisite for the induction of enhanced ir for mAChRs in cortical cells, such neurons demand cholinergic neurotransmission for optimal retention of the shock experience. The alterations in ir for coexpressed mAChR, PKC gamma, and MAP-2 in a discrete subset of cholinoceptive cortical neurons arranged in characteristic patterns most likely represent part of the neuronal substrate involved in functional cortical plasticity related to PSA training.


Metabolomics diagnostic approach to mustard airway diseases: a preliminary study.
This study aims to evaluate combined proton nuclear magnetic resonance (1H NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) metabolic profiling approaches, for discriminating between mustard airway diseases (MADs) and healthy controls and for providing biochemical information on this disease. In the present study, analysis of serum samples collected from 17 MAD subjects and 12 healthy controls was performed using NMR. Of these subjects, 14 (8 patients and 6 controls) were analyzed by GC-MS. Then, their spectral profiles were subjected to principal component analysis (PCA) and orthogonal partial least squares regression discriminant analysis (OPLS-DA). A panel of twenty eight metabolite biomarkers was generated for MADs, sixteen NMR-derived metabolites (3-methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, lactic acid, lysine, glutamic acid, proline, hydroxyproline, dimethylamine, creatine, citrulline, choline, acetic acid, acetoacetate, cholesterol, alanine, and lipid (mainly VLDL)) and twelve GC-MS-derived metabolites (threonine, phenylalanine, citric acid, myristic acid, pentadecanoic acid, tyrosine, arachidonic acid, lactic acid, propionic acid, 3-hydroxybutyric acid, linoleic acid, and oleic acid). This composite biomarker panel could effectively discriminate MAD subjects from healthy controls, achieving an area under receiver operating characteristic curve (AUC) values of 1 and 0.79 for NMR and GC-MS, respectively. In the present study, a robust panel of twenty-eight biomarkers for detecting MADs was established. This panel is involved in three metabolic pathways including aminoacyl-tRNA biosynthesis, arginine, and proline metabolism, and synthesis and degradation of ketone bodies, and could differentiate MAD subjects from healthy controls with a higher accuracy.


Comparative evaluation of shock absorption ability of custom-fit mouthguards with new-generation polyolefin self-adapting mouthguards in three different maxillary anterior teeth alignments using Fiber Bragg Grating (FBG) sensors.
Prevention of orofacial injuries is one of the biggest pre-occupations in sports dentistry. The custom-fitted mouthguard is considered the best choice for fit and protection when compared to over-the-counter commercial mouthguards. However, cost and time prohibit their mass production. It is therefore imperative to have an over-the-counter true mouth-formed mouthguard with comparable properties. The present in vitro experimental study was carried out to compare the shock absorption ability of EVA laminate mouthguards with self-adapting polyolefin material mouthguards in three different anterior teeth alignments. Finite element analysis (FEA) was performed to simulate the stress distribution due to impact on the respective mouthguards. Customized pendulum device with three interchangeable standard size impact objects was used. Response of grating was monitored using a FBG interrogation system. Shift in wavelength for each impact was measured. Three standardized jaw models were subjected to a total of 72 impact strikes with three different balls on two specified sites by releasing the objects from two different heights H1 24 cm and H2 48 cm. Two-way ANOVA was applied and comparative values computed. It was found that the percentage shock absorption ability of self-adapted polyolefin mouthguard was highly significant at <0.001 level in both regions. The influence of height on the shock absorption ability of both mouthguards was highly significant at P < 0.001. It was concluded that self-adapting polyolefin mouthguards fulfill similar protection requirement as custom-fit mouthguards and can be used for millions of athletes if properly fitted chairside by a dentist without requiring laboratory fabrication.


Management by commitment: theoretical personnel management.
The commitment to quality patient care is an untapped motivational resource. A theory, Management by Commitment, can assist in the development of this resource to its fullest potential. The end result is a renewed dedication to quality patient care, as well as an improved working relationship between the manager and his subordinates.


[Effect of 17beta-estradiol on myocardial inducible NOS and endothelial NOS activities after ischemia-reperfusion in rat heart model].
To study the effect of 17beta-estradiol (E(2)) on myocardial inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) activities of ischemia-reperfusion myocardium in rat model. 40 Langendorff perfused hearts isolated from bilateral ovariectomy (OVX) rat were randomly divided into four groups: control group (Group C), in which hearts were reperfused ex vivo for 15 minutes before ischemia in rat; ischemia-reperfusion control (Group I-R), in which modified St. Thomas II cardioplegic solution was perfused to perform the ischemia-reperfusion; dissolved control group (Group D), in which 0.1% dimethyl sulfoxide (DMSO) was dissolved in cardioplegic solution; E(2) group (Group E), in which 0.1% DMSO and 5 micromol of E(2) were dissolved in cardioplegic solution. Myocardial iNOS and eNOS activities were detected before and after reperfusion. Creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and nitric oxide (NO) of coronary flow were measured, and heart function was evaluated to observe the effect of E(2) on myocardial ischemia-reperfusion injury (MIRI). Myocardial eNOS activity declined (P < 0.01) and iNOS activity increased after ischemia-reperfusion (8.87 +/- 3.74 nmol/min/g in Group C, 15.83 +/- 2.42 nmol/min/g in Group I-R, 17.60 +/- 5.21 nmol/min/g in Group E; P < 0.01), moreover, iNOS activity was much higher in Group E (25.85 +/- 5.21 nmol/min/g, P < 0.01). NO production was lower in Group I-R and Group D (P < 0.05), and higher in Group E (30.96 +/- 4.91 micromol/L in Group C, 33.16 +/- 5.57 micromol/L in Group E; P < 0.01). CPK and LDH were lower in Group E (P < 0.05). Recovery of heart function was better in Group E (P < 0.05). E(2) can relieve the injury of MIRI and promote heart function recovery by increasing iNOS activity and NO production.


New molecular beacon for p53 gene point mutation and significant potential in serving as the polymerization primer.
Molecular beacon (MB) is usually explored as a convenient probe for various bioassays. In an enzymatic polymerization-based biosensing system, primer, and MB, sometimes involving other oligonucleotides, are often required to collaboratively generate an amplified fluorescent signal to detect target molecules with high sensitivity and specificity. In the current study, a multifunctional primer-integrated MB (MP-MB) was developed to detect the p53 tumor suppressor gene. Compared with the traditional MB, our MP-MB can not only selectively identify the target of interest and signal sensitively its hybridization event, but also act as the primer during enzymatic polymerization. Specifically, hybridization of MP-MB to target p53 gene restored the fluorescence intensity and activated the pre-locked primer designed by changing the molecular configuration of MP-MB. Moreover, the p53 gene could be detected down to 1nM with a linear response range of 1×10(-9)-3×10(-7)M, and p53 gene point mutation was readily distinguished from the wild-type one. Its potential application as a primer of replication in enzymatic polymerization-based assay systems was validated by running parallel gel electrophoreses in comparison with the native counterpart of MP-MB without any chemical modification. Owning to its excellent assay characteristics, less species requirement, broad sequence diversity and preserved intrinsic bioactivity, the proof-of-concept of MP-MB exhibits a great potential in various biomedical applications.


[Structural elucidation of the anticoagulation and anticancer constituents from Allium chinense].
Six compounds were isolated from the anticoagulation and anticancer fractions of the bulbs of Allium chinense G. Don. On the basis of chemical evidence and spectral analysis (IR, EI-MS, 1HNMR, 13CNMR, 1H-1H COSY, HMBC, HMQC and NOESY), their structures were established as (25R, S)-5 alpha-spirostane-3 beta-ol 3-O-(beta-D-glucopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->3)]-beta-D- glucopyranosyl-(1-->4)-beta-D-galactopyranoside) (1), (25R, S)-5 alpha-spirostane-3 beta-ol 3-O-(beta-D-glucopyranosyl (1-->2)-[beta-D-glucopyranosyl-(1-->3)](6-acetyl-beta-D-glucopyranosyl)- (1-->4)-beta-D-galactopyranoside) (2), (25R, S)-5 alpha-spirostane-2 alpha, 3 beta-diol 3-O-(beta-D-glucopyranosyl-(1-->2)-O-beta-D-glucopyranosyl-(1-->4)-beta-D- galactopyranoside) (3), (25S)-24-O-beta-D-glucopyranosyl-3 beta, 24 beta-dihydroxy-5 alpha-spirost-3-O-alpha-arabinopyranosyl-(1-->6)-beta-D-glucopyranoside (4), chinenoside II (5) and 2,3,4,9-tetrahydro-1-methyl-1H-pyrido [3,4-b] indole-3-carboxylic acid (6). 4 is a new steroidal saponin, named chinenoside VI. Compounds 1 to 3 are three pairs of steroidal saponin epimers. Among them, the 25S epimer of 2 is first reported, the 25R epimer of 2 and compound 6 were isolated from this title plant for the first time. The relative configuration of compound 6 was firstly determined by NOESY spectrum, and signals of C, H were assigned definitely.


[Antimicrobial and hemolytic activities of gradex].
Gradex is a polymer preparation resulting from formation of covalent bonds between the molecules of gramicidin S, a polypeptide antibiotic, and dextran, a polymeric carrier. Antimicrobial and hemolytic activities of gradex were studied. It was shown that the antimicrobial activity of gradex was due to the presence of gramicidin S in its composition. The activity level was lower than that of gramicidin S. It was also found that the gradex reduced form in concentrations up to 300 micrograms/ml had practically no hemolytic effect against human erythrocytes. The reduced form of gradex is promising for development of an artificial ++anti-brucellosis vaccine.


Strengthening new graduate nurse residency programs in critical care: recommendations from nurse residents and organizational stakeholders.
Thirty-four new graduate nurses participated in a critical care nurse residency program in preparation for opening a new intensive care unit. At the end of the program, multi-constituent focus groups were held to assess program effectiveness. Participants included 34 new graduate nurses, 18 preceptors and staff nurse partners, five clinical nurse specialists, and five nurse directors. Twelve focus groups were held; groups included four to eight nurses from the same role group. Two independent reviewers analyzed recordings and transcripts of focus group content to identify themes. Five themes were identified: program design, developing nursing expertise, program impact on the unit, future expectations, and communication. Comments were used to guide program improvements and offer new insights for residency programs in acute and critical care. Obtaining structured input from multiple program stakeholders is beneficial in evaluating a program's impact and identifying areas for improvement.


Multilocus sequence typing of Bordetella pertussis based on surface protein genes.
Despite more than 50 years of vaccination, Bordetella pertussis has remained endemic in The Netherlands, causing epidemic outbreaks every 3 to 5 years. Strain variation may play a role in the persistence of B. pertussis and was studied by sequencing 15 genes coding for surface proteins, including genes for all five components of acellular pertussis vaccines: pertussis toxin (Ptx), pertactin (Prn), filamentous hemagglutinin, and fimbriae (Fim2 and Fim3). A low level of allelic variation was observed, confirming a recent evolutionary origin of B. pertussis. In modern isolates, polymorphism was observed only in prn, ptxS1, ptxS3, and tcfA. Polymorphism in ptxS1, ptxS3, and tcfA was used to categorize isolates in multilocus sequence types (MLSTs). Analysis of Dutch isolates from 1949 to 1999 revealed five MLSTs, which showed a highly dynamic temporal behavior. We observed significant changes in the MLSTs after the introduction of pertussis vaccination in The Netherlands. Epidemic years were found to be associated with the expansion of MLST-4 or MLST-5. MLST-5 showed a remarkable expansion from 10% in 1997 to 80% in 1999. The MLST analysis was extended to a number of widely separated geographic regions: Finland, Italy, Japan, and the United States. MLST-4 and MLST-5 were found to dominate in Italy and the United States. In Finland and Japan, MLST-3 and MLST-2, respectively, were predominant. Thus, although each region showed distinctive MLST frequencies, in three of the five regions MLST-4 and MLST-5 were predominant. These types may represent newly emerged, successful clones. The identification of highly successful clones may shed light on the question of how B. pertussis is able to maintain itself in vaccinated populations.


Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens.
To determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed. Ten CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system. An average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR q < 0.05, fold change >2) were identified. Expression of selected DEGs (n = 32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90 % of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value <0.05, minimum inclusion level difference >0.1). The RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis.


Mid-peripheral hemorrhages secondary to Waldenström's macroglobulinemia.
Waldenström's macroglobulinemia is a progressive neoplastic syndrome of the reticuloendothelial system and is characterized by the presence of monoclonal IgM paraproteins. The ocular manifestations of macroglobulinemia can include mid-peripheral hemorrhages, sludging of blood in the conjunctival vessels, blurred disc margins, exudates in the fundus and serous retinal detachment. Waldenström's macroglobulinemia and its ocular complications are herein presented.


Latent heat calculation of the three-dimensional q=3, 4, and 5 Potts models by the tensor product variational approach.
Three-dimensional (3D) q-state Potts models (q=3, 4, and 5) are studied by the tensor product variational approach, which is a recently developed variational method for 3D classical lattice models. The variational state is given by a 2D product of local factors, and is improved by way of self-consistent calculations assisted by the corner transfer matrix renormalization group. It should be noted that no a priori condition is imposed for the local factor. Transition temperatures and latent heats are calculated from the observations of thermodynamic functions in both ordered and disordered phases.


A Bayesian bird's eye view of 'Replications of important results in social psychology'.
We applied three Bayesian methods to reanalyse the preregistered contributions to the Social Psychology special issue 'Replications of Important Results in Social Psychology' (Nosek & Lakens. 2014 Registered reports: a method to increase the credibility of published results. Soc. Psychol.45, 137-141. (doi:10.1027/1864-9335/a000192)). First, individual-experiment Bayesian parameter estimation revealed that for directed effect size measures, only three out of 44 central 95% credible intervals did not overlap with zero and fell in the expected direction. For undirected effect size measures, only four out of 59 credible intervals contained values greater than [Formula: see text] (10% of variance explained) and only 19 intervals contained values larger than [Formula: see text]. Second, a Bayesian random-effects meta-analysis for all 38 t-tests showed that only one out of the 38 hierarchically estimated credible intervals did not overlap with zero and fell in the expected direction. Third, a Bayes factor hypothesis test was used to quantify the evidence for the null hypothesis against a default one-sided alternative. Only seven out of 60 Bayes factors indicated non-anecdotal support in favour of the alternative hypothesis ([Formula: see text]), whereas 51 Bayes factors indicated at least some support for the null hypothesis. We hope that future analyses of replication success will embrace a more inclusive statistical approach by adopting a wider range of complementary techniques.


A multiplex PCR for the simultaneous detection of Tenacibaculum maritimum and Edwardsiella tarda in aquaculture.
A specific and sensitive multiplex PCR (mPCR) method was developed as a useful tool for the simultaneous detection of two important flatfish pathogens in marine aquaculture, Tenacibaculum maritimum and Edwardsiella tarda. In fish tissues, the average detection limit for these mPCR-amplified organisms was 2 × 10 ⁵ ± 0.2 CFU/g and 4 × 10 ⁵ ± 0.3 CFU/g, respectively. These values are similar or even lower than those previously obtained using the corresponding single PCR. Moreover, mPCR did not produce any nonspecific amplification products when tested against 36 taxonomically related and unrelated strains belonging to 33 different bacterial species. Large amounts of DNA from one of the target bacterial species in the presence of low amounts from the other did not have a significant effect on the amplification sensitivity of the latter.


Ipilimumab-Induced Autoimmune Hypophysitis: Diagnostic and Management Challenges Illustrated by a Clinical Case.
Autoimmune hypophysitis has been described in patients on ipilimumab, a humanised monoclonal antibody increasingly used in the treatment of metastatic melanoma. A 67-year-old woman presented with severe fatigue, nausea and headaches following the third dose of ipilimumab, which was being given as treatment for metastatic melanoma (four administrations at three-weekly intervals). Hormonal evaluation confirmed hypocortisolism, with low gonadotrophins and a low thyroid-stimulating hormone with normal free T4 (she was on long-standing levothyroxine because of past surgery for a multinodular goitre). Magnetic resonance imaging scanning revealed pituitary enlargement compatible with autoimmune hypophysitis. She was commenced on replacement with hydrocortisone with significant improvement of her symptoms. The enlarged pituitary was reduced in size 4 months later. The patient is currently asymptomatic on glucocorticoid and levothyroxine replacement. This case highlights relevant clinical, diagnostic and management aspects of ipilimumab-induced autoimmune hypophysitis, and emphasises the need for increasing awareness for potential side-effects of these new immunomodulatory therapies, including autoimmune hypophysitis.


Structure-Property Study on Two New D-A Type Materials Comprising Pyridazine Moiety and the OLED Application as Host.
In this paper, two new pyridazine based donor-acceptor type materials, i.e., 3CzPyaPy: 9,9'-(3-(6-(9H-carbazol-9-yl)pyridazin-3-yl)pyridine-2,6-diyl)bis(9H-carbazole) and 4CzPyPyaPy: 3,6-bis(2,6-di(9H-carbazol-9-yl)pyridin-3-yl)pyridazine, were synthesized with high yields. These two materials exhibited strong absorption/emission with high molar extinction coefficients and moderate photoluminescence quantum yield. The glass transition temperature of 3CzPyaPy was detected to be as high as 131 °C, showing its high thermal stability. Although the absorption energies and oxidation/reduction behaviors of the two materials were similar, the emission from 4CzPyPyaPy with longer effective-conjugation length presented hypsochromic shift both in films and in dilute solutions, contradicting to the common sense. The single crystal structure study disclosed their different space stretching and packing: 3CzPyaPy was twisted in larger angles and adopted dimerlike packing, while 4CzPyPyaPy showed smaller torsion angles and exhibited slipped herringbone packing. The dimerlike packing in 3CzPyaPy is responsible for its bathochromic shift of emission in solid state, while its unsymmetrical molecular structure accounts for that in solution. We believe that the unsymmetrical molecular structure of 3CzPyaPy is partially responsible for its high thermal-stability and also responsible for its HOMO dispersion which renders it slightly more difficult to oxidize. 3CzPyaPy was proved to be a bipolar-transport material and when served as a phosphor host, a green phosphorescent device achieved maximum efficiencies of 54.0 cd A-1, 42.4 lm W-1, and 17.7%, which are among the best with nonoptimized device structure, demonstrating its great potential for optoelectronic application. Furthermore, the new synthesized pyridazine derivatives and the corresponding structural and molecular-packing influences on material properties give a new insight into molecule tailoring.


Applications of TiO2, ZnO and Ag Nanomaterials to Denim Fabric.
In previous studies much research has reported the determination of applications of TiO2 (rutile and anatase), ZnO and Ag nanomaterials onto various textile surfaces, but in this study for the first time application to denim fabric and testing of the finished fabric for antimicrobial activities of these nanomaterials was investigated. The presence of nanoparticles on dyed denim fabric surfaces was confirmed by Scanning Electron Microscope (SEM). The nanomaterial-impregnated denim fabric (100% cotton) showed significant antibacterial activity against Staphylococcus aureus, Escherichia coli and Escherichia coli isolated from pasta. Additionally, the UV tests indicated excellent improvement in the UV absorbing activity of the TiO2 (rutile and anatase), ZnO and Ag nanomaterial-treated fabrics.


Bioelectric perturbations of bone. Research directions and clinical applications.
Bioelectric perturbation of living hard tissue produces clinically useful effects. It is being used effectively in the treatment of intractable orthopedic problems such as nonunion and avascular necrosis. Dental applications of this phenomenon are still in the early stages of research and development. Barring untoward circumstances, this form of local growth control may be used as an adjunct to localized bone induction therapy such as in the treatment of periodontal diseases, bone grafting or implantation of biocompatible products. It also appears to show promise in enhancing the rate of tooth movement or the stability of anchor teeth. The mechanism for these perturbation-induced changes in cells has not been explained. This is an active area of research with many implications for helping the clinician understand the molecular biology of hard-tissue cell proliferation, migration and differentiation.


Families filling the gap: comparing family involvement for assisted living and nursing home residents with dementia.
The purpose of this study was to compare the sociodemographics, self-rated health, and involvement levels of family caregivers of residents with dementia in residential care/assisted living (RC/AL) versus nursing home settings. We conducted telephone interviews with the family caregivers most involved with 353 residents of 34 residential care and 10 nursing home facilities. We measured involvement by caregiver self-report of monthly out-of-pocket spending, involvement and burden ratings, and the frequency of engaging in eight specific care activities. Open-ended questions elicited areas in which caregivers preferred different involvement and ways the facility could facilitate involvement. Nursing home caregivers rated their health poorer than RC/AL caregivers, but there were no sociodemographic differences between the two. RC/AL caregivers rated both their perception of involvement and burden higher and engaged more frequently in monitoring the resident's health, well-being, and finances than did nursing home caregivers, although the reported time spent per week on care did not differ. RC/AL and nursing home caregivers to residents with dementia may tailor their care to fit the needs of the resident and setting. Results are discussed in relation to the Congruence Model of Person-Environment Fit.


[The phagocytic activity (ingestion and bactericidal activity) of neutrophil leukocytes in chronic myelosis].
The paper deals with the results obtained by investigating the function of phagocytes (ingestion and bactericidity) in germs of a stem of staphylococcus aureus 209 and escherichia coli 0-III of mature neutrophilic granulocytes in 30 patients with chronic, not-lymphocytic leukaemia. The ingestion corresponded to the norm. Bactericidity towards the germs of staphylococcus aureus was statistically significant decreased, viz. it was retarded as well as diminished. In certain patients this deviation from the norm found a particularly strong expression, which became evident in clinical appearances. As it was to be expected, no interconnection could be detected between the activity of alkaline granulocytic phosphatase and the function of phagocytosis.


Mucosal expression of aquaporin-4 in the stomach of histamine type 2 receptor knockout mice and Helicobacter pylori-infected mice.
Basolateral water channel, aquaporin-4 (AQP4), is known to be expressed in gastric parietal cells, especially in the basal side of gastric mucosa. However, the role of AQP4 in the stomach is still unknown. Histamine type 2 receptor (H2R) knockout mice, which are characterized by suppressed gastric acid secretion, are known as formation of mucosal hyperplasia with cystic dilatation and spasmolytic polypeptide-expressing metaplasia (SPEM) in the stomach. The aim of the present study is to investigate whether the expression of AQP4 is changed by the condition of acid suppression and Helicobacter pylori infection. Male H2 R knockout mice and their controls (C57BL/6) were used. H. pylori was orally infected at the age of 5 weeks. The distributions of AQP4 and H+/K+-ATPase in the gastric mucosa were investigated by fluorescent immunohistochemistry. The mRNA expressions of AQP4, H+/K+-ATPase, sonic hedgehog (Shh), and trefoil factor-2 (TFF2) were investigated by quantitative reverse transcription polymerase chain reaction (RT-PCR). In the H2 R knockout mice, the distribution of AQP4-positive parietal cells was extended toward the surface of the fundic glands. Although the mRNA expression levels of AQP4 and H+/K+ATPase were elevated in H2 R knockout mice at the age of 20 weeks, the elevations were not maintained by aging or H. pylori infection. In H2 R knockout mice with H. pylori infection, the expression level of TFF2 mRNA was elevated while the ratio between AQP4 and H+/K+ ATPase mRNA expression was decreased compared with the H2 R knockout mice without H. pylori infection. In the H2 R knockout mice, massive SPEM was induced by H. pylori colonization and the ratio between AQP4 and H+/K+ATPase mRNA expression was decreased.