Familial transmission of urogenital prolapse and incontinence.
To summarize recent evidence suggesting a genetic basis for the development of urogenital prolapse and stress urinary incontinence. Epidemiological evidence suggests that some women have a genetic predisposition to the development of urogenital prolapse and stress incontinence. Abnormal expression of various structural proteins is thought to be the molecular genetic mechanism for the development of these conditions. A group of families with an autosomal dominant pattern of transmission of urogenital prolapse with high penetrance has been identified. No similar cohort of families with familial stress incontinence currently exists, although candidate genes have been identified that appear to predispose women to urogenital prolapse and stress incontinence. Additionally, animal models of urogenital prolapse have been developed that closely parallel the development of prolapse in humans. A growing body of evidence suggests a genetic basis for the development of urogenital prolapse and stress incontinence. Candidate genes have been identified that may result in alteration of the normal metabolism of various structural proteins which may ultimately predispose some women to both urogenital prolapse and stress incontinence. Further research into the genetic basis of these conditions may provide a comprehensive understanding of the biological basis of these disorders.


Primary heterologous carcinosarcoma (metaplastic carcinoma) of the urinary bladder: a clinicopathologic, immunohistochemical, and ultrastructural analysis of eight cases and a review of the literature.
Heterologous carcinosarcomas of the urinary bladder are rare neoplasms, the histogenesis of which is still disputed. The clinicopathologic, immunohistochemical, and ultrastructural features of eight cases were analyzed. The patients, 5 males and 3 females, had a median age of 70 years. Gross hematuria, dysuria, and urinary tract infections were the main presenting symptoms. Tumors were solitary in all cases and located in the right wall in six cases. Tumor size ranged from 2 to 12 cm (median, 5 cm). Four patients died of disease 2, 6, 17, and 42 months postoperatively, respectively. Microscopically, the tumors consisted mostly of a varied mixture of high grade transitional cell carcinoma with chondrosarcoma, osteosarcoma, rhabdomyosarcoma, and undifferentiated spindle cell (leiomyosarcoma-like) components with occasional transitional features between one component and another. All tumors but one invaded the muscularis propria or the perivesical fatty tissue. Immunohistochemically, keratin expression was observed focally in the sarcoma component as well as the carcinoma component. Reactivity for vimentin, desmin, muscle specific actin, and S-100 protein was observed in poorly differentiated areas in addition to the expected positivity of each histologic subtype of sarcoma. Ultrastructurally, one tumor showed evidence of both epithelial and chondrosarcomatous differentiation, whereas three contained rhabdomyosarcomatous elements. On the basis of the current series and a review of 55 reports from the literature, primary heterologous carcinosarcoma of the urinary bladder proved to be a highly malignant type of neoplasm occurring predominantly in elderly males that was most often in an advanced stage at presentation and rapidly became lethal. Histogenetically, some heterologous carcinosarcomas should be regarded as a variant of sarcomatoid carcinoma (metaplastic carcinoma) that shows prominent heterologous differentiation.


Novel fragmentation reaction of correolide.
[reaction: see text] Pentacyclic triterpenoid natural product correolide (1) was converted to ketone 2 via ozonolysis. An unusual fragmentation reaction of ketone 2 with LiCl was discovered. This reaction is general among several similar substrates examined and appears to be specific for the correolide-type E-ring structure (ketone). A mechanism involving a retroaldol reaction, a nucleophilic opening of the epoxide, and a subsequent acetoxy elimination reaction was proposed.


Severe Fatigue Is Common Among Pediatric Patients with Primary Immunodeficiency and Is Not Related to Disease Activity.
Fatigue is a distressing symptom commonly reported among pediatric patients with primary immunodeficiency (PID). However, the relationship between fatigue and disease activity is currently unknown. In this cross-sectional study, we examined the prevalence of severe fatigue, the effect of fatigue on health-related quality of life (HRQoL), and the effects of disease activity and comorbidity on fatigue severity among pediatric patients 2-18 years of age with PID. Fatigue and HRQoL were assessed using the pediatric quality of life inventory multidimensional fatigue scale (PedsQL MFS) and generic core scales (PedsQL GCS), respectively. Linear regression analyses and an analysis of covariance were used to compare the fatigue scores with the scores obtained from a healthy control group. Data were adjusted for age and sex. Of the 91 eligible patients, 79 were assessed (87% participation rate), with a mean age of 10.4 ± 4.4 years. Pediatric patients with PID reported significantly higher fatigue levels compared to healthy peers, with an 18.9% prevalence of severe fatigue. Moreover, higher fatigue levels were inversely associated with HRQoL in all domains and directly associated with school absences. We found that severe fatigue was comparable between common variable immunodeficiency (CVID), combined immunodeficiency (CID), and selective immunoglobulin A deficiency (SIgAD) patients, but was not reported in the X-linked agammaglobulinemia (XLA) patients studied. Finally, fatigue severity was not significantly associated with disease activity or comorbidity. Nearly 20% of pediatric patients with PID reported experiencing severe fatigue, and fatigue was reported among a wide range of PID subcategories. In addition, severe fatigue negatively affected the patient's quality of life and daily functioning, but was not associated with disease activity or comorbidity. Thus, targeting severe fatigue might be a promising strategy for improving the overall well-being and quality of life of pediatric patients with PID.


Amino acid residue Ala-62 in the FimH fimbrial adhesin is critical for the adhesiveness of meningitis-associated Escherichia coli to collagens.
Adhesion of meningitis-associated Escherichia coli O18acK1H7 to collagens was characterized. The E. coli strain IHE 3034 adhered to type IV and type I collagens but not to type III collagen immobilized on glass. Collagens lack terminal mannosyl units, yet the bacterial adhesion was completely abolished in the presence of alpha-methyl-D-mannoside. A cat cassette was introduced into the filmA gene of IHE 3034, and the resulting mutant strain IHE 3034-2 failed to adhere to collagens. In contrast, insertion of a Gm cassette into the sfaA gene of IHE 3034, encoding the S-fimbrillin, had no significant effect on the adhesiveness. The fim cluster from IHE 3034 was cloned and expressed in trans in the fimA::cat mutant strain IHE 3034-2. The complemented strain IHE 3034-2(pRPO-1) exhibited adhesiveness to type IV and type I collagens, confirming the function of the type 1 fimbria in the adhesion. We have previously shown that the type 1 fimbria from E. coli K-12 strain PC31 does not confer bacterial adhesiveness to collagens. The fimH genes from E. coli IHE 3034 as well as from PC31 were expressed in the fimH-null strain MS4. The FimH from IHE 3034 potentiated collagen adherence, whereas the FimH from PC31 was inactive. Sequence comparison of fimH from IHE 3034 and PC31 revealed five amino-acid differences in the predicted mature FimH proteins: at residues 27, 62, 70, 78 and 201. Each of these residues in the IHE 3034-FimH were individually substituted to the corresponding amino acid in the PC31-FimH. The substitution S62-->A completely abolished collagen adhesiveness. The reverse substitution A62-->S in the PC31-FimH as well as in the FimH from another E. coli strain induced collagen adhesiveness to the level seen with IHE 3034-FimH. Out of nine fimH genes analysed from isolates of E. coli, collagen adhesiveness as well as alanine at position 62 in FimH were found only in two O18acK1H7 isolates with the isoenzyme profile ET type 1. Our results demonstrate that the amino-acid residue Ala-62 in the FimH lectin is critical for the adhesion to collagens by a highly virulent clonal group of E. coli.


[Stereo display of MR angiograms].
To provide methods for stereoscopic visual demonstration from 3D reconstructed MR angiographic images. Stereoscopic viewing can be obtained with pairs of images that are displayed at angles of 15 degrees. Optical devices as stereoscopic binoculars or minor stereoscopes facilitate stereoscopic viewing. The possibility of stereoscopic projections for a larger auditorium is mentioned. Using three clinical examples the advantages of stereoscopic display of MR angiograms are demonstrated. MR angiography allows stereoscopic viewing with simple methods, like CT- and conventional rotation angiography. This principle, which has been known for 100 years, may thus acquire a new significance.


Correlations between spectral-domain OCT measurements and visual acuity in cystoid macular edema associated with retinitis pigmentosa.
To evaluate the characteristics of spectral-domain optical coherence tomography (SD-OCT) findings associated with visual outcome and compare OCT measurements according to presence of cystoid macular edema (CME) in retinitis pigmentosa (RP) patients. Patients with typical RP who underwent SD-OCT were included. We compared OCT measurements such as central retinal thickness (CRT), photoreceptor thickness, and photoreceptor inner segment/outer segment (IS/OS) junctional status at the fovea between the CME and non-CME groups. Also, correlations between best-corrected visual acuity (BCVA) and each parameter were determined. Among a total of 220 eyes in 128 RP patients, 46 eyes of 30 patients (20.9%) had CME. CRT was 303.1 ± 81.8 μm and 209.2 ± 46.8 μm in the CME and non-CME groups, respectively (P < 0.001). BCVA did not differ between the two groups (P = 0.690). However, among a subgroup with unilateral CME, BCVA was significantly worse in CME eyes than in the fellow eyes (P = 0.046). In the CME group, eyes with increased CRT showed worse BCVA (P = 0.010). Among 12 eyes with severe CME, defined as 350 μm or more CRT, 10 (83.3%) showed an absent IS/OS junction. In the non-CME group, in contrast, eyes with decreased CRT showed worse BCVA (P < 0.001). In both groups, severe IS/OS disruption was correlated with worse BCVA (P < 0.001). The risk of IS/OS disruption was higher in the CME group (P = 0.016). The presence of CME in RP patients was not necessarily correlated with loss of visual acuity. In eyes with CME, however, severe CME was strongly correlated with IS/OS disruption and visual impairment. Thus, severe CME seemed to be a predictor of poor visual outcome in RP patients.


A metal matrix composite prepared from electrospun TiO2 nanofibers and an Al 1100 alloy via friction stir processing.
Electrospun TiO2 nanofibers, consisting of anatase phase TiO2 single-crystalline crystallites with sizes of approximately 10 nm, were impregnated into an Al 1100 alloy by the technique of friction stir processing (FSP). The studies of the resulting TiO2-Al composite revealed that the electrospun TiO2 nanofibers with diameters of approximately 200 nm were broken into nanoparticles during FSP; the in situ generated pristine surfaces led to the interfacial reaction between TiO2 and Al and resulted in the formation of strong interfaces between the electrospun TiO2 nanoparticles and the Al 1100 matrix. This was evidenced by the fact that the filler-matrix fracture always occurred on the Al matrix side in the interfacial region. Consequently, the TiO2-Al composite made from the electrospun TiO2 nanofibers possessed a significantly higher Vickers hardness than that made from a commercially available anatase phase TiO2 nanopowder, of which the organic and/or carbonaceous contaminants on the surface impeded the interfacial reaction between TiO2 and Al during FSP.


High resolution infrared spectra of a carbon dioxide molecule solvated with helium atoms.
Infrared spectra of He(N)-CO(2) clusters with N up to about 20 have been studied in the region of the CO(2) nu(3) fundamental band ( approximately 2350 cm(-1)) using a tunable diode laser spectrometer and pulsed supersonic jet source with cooled (>-150 degrees C) pinhole or slit nozzles and high backing pressures (<40 atm). Compared to previous studies of He(N)-OCS and -N(2)O clusters, the higher symmetry of CO(2) results in simpler spectra but less information content. Discrete rotation-vibration transitions have been assigned for N=3-17, and their analysis yields the variation of the vibrational band origin and B rotational constant over this size range. The band origin variation is similar to He(N)-OCS, with an initial blueshift up to N=5, followed by a monotonic redshift, consistent with a model where the first five He atoms fill a ring around the equator of the molecule, forcing subsequent He atom density to locate closer to the ends. The B value initially drops as expected for a normal molecule, reaching a minimum for N=5. Its subsequent rise for N=6 to 11 can be interpreted as the transition from a normal (though floppy) molecule to a quantum solvation regime, where the CO(2) molecule starts to rotate separately from the He atoms. For N>13, the B value becomes approximately constant with a value about 17% larger than that measured in much larger helium nanodroplets.


Do Hounsfield Units have any significance in predicting intra- and postoperative outcomes in retrograde intrarenal surgery using Holmium and Thulium fiber laser? Results from the FLEXible ureteroscopy Outcomes Registry (FLEXOR).
To evaluate outcomes of flexible ureteroscopy for renal stones by comparing hard versus soft stones based on their attenuation on computed tomography (Hounsfield Units-HU). Patients were divided into two groups according to the type of laser employed [Holmium:YAG (HL) or Thulium fiber laser (TFL)]. Residual fragments (RF) were defined as > 2 mm. Multivariable logistic regression analysis was performed to evaluate factors associated with RF and RF needing further intervention. 4208 patients from 20 centers were included. In whole series, age, recurrent stones, stone size, lower pole stones (LPS), and multiple stones were predictors of RF at multivariable analysis and LPS and stone size with RF requiring further treatment. HU and TFL were associated with lesser RF and RF requiring an additional treatment. In HU < 1000 stones, recurrent stones, stone size, and LPS were predictors of RF at multivariable analysis, whereas TFL was less likely associated with RF. Recurrent stones, stone size, and multiple stones were predictors of RF requiring further treatment, while LPS and TFL were associated with lesser RF requiring further treatment. In HU ≥ 1000 stones, age, stone size, multiple stones, and LPS were predictors of RF at multivariable analysis, while TFL was less likely associated with RF. Stone size and LPS were predictors of RF requiring further treatment, whereas TFL was associated with RF requiring further treatment. Stone size, LPS, and use of HL are predictors of RF after RIRS for intrarenal stones regardless of stone density. HU should be considered an important parameter in predicting SFR.


[Humoral immunity in smokers].
B-lymphocyte counts, immunoglobulin levels, blood serum antiA and antiB isoagglutinin concentrations and lysozyme activity, and hemolytic activity of the complement were measured in 85 healthy men aged 18 to 42 (mean age 34) smoking 15-25 cigarettes daily for 2-25 years and in a reference group of 49 nonsmokers aged 17 to 50 (mean age 31). Tobacco smoking was found to have no effect on the peripheral blood B lymphocyte count, nor on the blood serum concentrations of group isoagglutinins. In men smoking for 6.5 years on an average the absolute count of lymphocytes was elevated vs. the reference value. In those smoking for 18.5 years on an average IgA, IgG, and lysozyme concentrations were lowered. These results evidence that the mechanism of humoral immunity weakening in tobacco smokers is intricate and related to a deficit of many proteins responsible for immunobiological processes in human body.


Molecular mechanism of Afadin substrate recruitment to the receptor phosphatase PTPRK via its pseudophosphatase domain.
Protein tyrosine phosphatase receptor-type kappa (PTPRK) is a transmembrane receptor that links extracellular homophilic interactions to intracellular catalytic activity. Previously we showed that PTPRK promotes cell-cell adhesion by selectively dephosphorylating several cell junction regulators including the protein Afadin (Fearnley et al, 2019). Here, we demonstrate that Afadin is recruited for dephosphorylation by directly binding to the PTPRK D2 pseudophosphatase domain. We mapped this interaction to a putative coiled coil (CC) domain in Afadin that is separated by more than 100 amino acids from the substrate pTyr residue. We identify the residues that define PTP specificity, explaining how Afadin is selectively dephosphorylated by PTPRK yet not by the closely related receptor tyrosine phosphatase PTPRM. Our work demonstrates that PTP substrate specificity can be determined by protein-protein interactions distal to the active site. This explains how PTPRK and other PTPs achieve substrate specificity despite a lack of specific sequence context at the substrate pTyr. Furthermore, by demonstrating that these interactions are phosphorylation-independent and mediated via binding to a non-catalytic domain, we highlight how receptor PTPs could function as intracellular scaffolds in addition to catalyzing protein dephosphorylation.


Metabolic futile cycles and their functions: a systems analysis of energy and control.
It has long been hypothesised that futile cycles in cellular metabolism are involved in the regulation of biochemical pathways. Following the work of Newsholme and Crabtree, a quantitative theory was developed for this idea based on open-system thermodynamics and metabolic control analysis. It is shown that the stoichiometric sensitivity of an intermediary metabolite concentration with respect to changes in steady-state flux is governed by the effective equilibrium constant of the intermediate formation, and the equilibrium can be regulated by a futile cycle. The direction of the shift in the effective equilibrium constant depends on the direction of operation of the futile cycle. High stoichiometric sensitivity corresponds to ultrasensitivity of an intermediate concentration to net flow through a pathway; low stoichiometric sensitivity corresponds to super-robustness of concentration with respect to changes in flux. Both cases potentially play important roles in metabolic regulation. Futile cycles actively shift the effective equilibrium by expending energy; the magnitude of changes in effective equilibria and sensitivities is a function of the amount of energy used by a futile cycle. This proposed mechanism for control by futile cycles works remarkably similar to kinetic proofreading in biosynthesis. The sensitivity of the system is also intimately related to the rate of concentration fluctuations of intermediate metabolites. The possibility of different roles for the two major mechanisms within cellular biochemical regulation, namely reversible chemical modifications via futile cycles and shifting equilibrium by macromolecular binding, are discussed.


Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors.
Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD. Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis RESULTS: No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II-IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis. These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.


Control of embryonic lung branching morphogenesis by the Rho activator, cytotoxic necrotizing factor 1.
Lung development is sensitive to physiological stresses, and its development may be impaired by physical distortion, as in patients with congenital diaphragmatic hernia. Yet, little is known about how mechanical forces can influence lung morphogenesis. Studies with cultured cells suggest that cytoskeletal tension may play a key role in growth control. Since the small GTPase Rho plays an important role in the control of cell tension generation, we carried out studies to test the hypothesis that changes in Rho-mediated cell tension may influence branching morphogenesis. Embryonic lung buds from timed pregnant Swiss Webster mice were microdissected on Embryonic Day 12 (E12), and whole organs were cultured in serum-free medium in the presence of the Rho activator cytotoxic necrotizing factor 1 (CNF-1) for 48 h. Serial measurements of the degree of epithelial branch formation and tissue maturation were performed using light microscopy and computerized image analysis. At 48 h, embryonic lungs treated with 2 ng/ml CNF-1 increased their terminal bud count by 236 +/- 18% (P = 0.01) compared with 132 +/- 2% for untreated controls. However, dose-response experiments revealed biphasic behavior: at a higher dose of CNF-1 (200 ng/ml), bud number was actually decreased relative to controls (43 +/- 1%, P < 0.001). Histological analysis revealed that individual glands appeared to be more highly developed at low-dose CNF-1, whereas the high dose produced gland contraction. These data support a potential role for Rho and cytoskeletal tension in control of epithelial pattern formation during lung development.


Physcion 8-O-β-Glucopyranoside Exerts Anti-Tumor Activity Against Non-Small Cell Lung Cancer by Targeting PPARγ.
Lung cancer is one of the most common causes of cancer related mortality. The present study is designed to investigate whether a naturally occurring anthraquinone compound, physcion 8-O-β-glucopyranoside (PG) could exert anti-cancer activity against non-small cell lung cancer (NSCLC). Cell viability was determined by Cell Counting Kit-8 (CCK-8) assay. Cell cycle distribution and cell apoptosis were determined by flow cytometry. Expressions of marker proteins were assessed by western blot analysis. To examine the role of PPARγ (peroxisome proliferator-activated receptor γ) in PG-induced apoptosis and cell cycle arrest, PPARγ was knockdown using siRNA. In addition, a xenograft model was established to investigate the effect of PG in vivo. The results showed that PG markedly induced cell cycle arrest and apoptosis in human NSCLC cell lines A549 and H358. The anti-tumor effect of PG in NSCLC cells was mediated by upregulation of PPARγ. Besides, in NSCLC cell lines, the anti-cancer activity of PG was also examined in the xenograft mice model, which showed that PG could significantly reduce tumor burden and activate apoptotic signaling. Our results demonstrated that PG can be regarded as a candidate chemotherapeutic agent for lung cancer. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 302:785-793, 2019. © 2018 Wiley Periodicals, Inc.


Cabozantinib in Advanced Hepatocellular Carcinoma: Efficacy and Safety Data from an International Multicenter Real-Life Cohort.
The multikinase inhibitor cabozantinib has been approved for hepatocellular carcinoma (HCC) previously treated with sorafenib. We report safety and efficacy data of an international, multicenter, real-life cohort of patients with advanced HCC treated with cabozantinib. Patients with HCC who were treated with cabozantinib were retrospectively identified across 11 centers in Austria, Switzerland, and Germany. Patients' characteristics, adverse events, duration of treatment and overall survival (OS) data were analyzed until April 1, 2020. Eighty-eight patients from 11 centers were included. The predominant underlying liver diseases were NAFLD/NASH in 26 (30%) and hepatitis C infection in 21 (24%) patients. Seventy-eight patients (89%) were classified as Barcelona clinic liver cancer (BCLC) stage C. Sixty patients (68%) were Child-Pugh A, whereas 22 (25%) were Child-Pugh B, respectively. Cabozantinib was used as systemic second- and third-line or later treatment in 41 (47%) and 46 (52%) patients, respectively. The following best responses under cabozantinib were documented: partial response in 6 (7%), stable disease in 28 (32%), and progressive disease in 28 (32%) patients, respectively. Fifty-two patients (59%) died during follow-up. The median OS from start of cabozantinib treatment was 7.0 months in the entire cohort and 9.7 months in Child-Pugh A patients, while Child-Pugh B patients had a median OS of 3.4 months, respectively. Thirty-seven (42%) patients fulfilled the CELESTIAL inclusion and exclusion criteria, showing a median OS of 11.1 months. Most common adverse events were fatigue (15.6%) and diarrhea (15.6%). Cabozantinib treatment was effective, safe, and feasible in patients with advanced HCC in patients with compensated cirrhosis. Patients in the real-life setting had more advanced liver disease - in which 25% of patients were Child-Pugh B. However, OS in patients with Child-Pugh A cirrhosis was similar to that reported in the phase 3 trial (CELESTIAL).


[Scombroid poisoning at an Icelandic restaurant].
We report four cases of scombroid poisoning. During a lunch meeting three males had the same dish: a club sandwich with raw tuna. All developed erythema over the face and neck within two hours of eating the tuna. The severity of symptoms varied. Other symptoms were profuse sweating, a feeling of intense thirst and palpitations. The symptoms disappeared after few hours. Samples obtained from the tuna revealed histamine levels above the recommended FDA levels. We also report a case with similar symptoms after eating canned tuna in a mixed salad. Scombroid poisoning has been associated with the consumption of dark-flesh fish with high levels of histidine, which can be converted to histamine by decarboxylase from Gram-negative bacteria in the fish. The fish most often implicated is tuna. It is of great importance to increase the awareness of this type of poisoning for correct diagnosis and to prevent other cases by improving storage.


Clinical and translational values of spatial transcriptomics.
The combination of spatial transcriptomics (ST) and single cell RNA sequencing (scRNA-seq) acts as a pivotal component to bridge the pathological phenomes of human tissues with molecular alterations, defining in situ intercellular molecular communications and knowledge on spatiotemporal molecular medicine. The present article overviews the development of ST and aims to evaluate clinical and translational values for understanding molecular pathogenesis and uncovering disease-specific biomarkers. We compare the advantages and disadvantages of sequencing- and imaging-based technologies and highlight opportunities and challenges of ST. We also describe the bioinformatics tools necessary on dissecting spatial patterns of gene expression and cellular interactions and the potential applications of ST in human diseases for clinical practice as one of important issues in clinical and translational medicine, including neurology, embryo development, oncology, and inflammation. Thus, clear clinical objectives, designs, optimizations of sampling procedure and protocol, repeatability of ST, as well as simplifications of analysis and interpretation are the key to translate ST from bench to clinic.


Fingertip force planning during grasp is disrupted by impaired sensorimotor integration in children with hemiplegic cerebral palsy.
In the present study we examine the ability of children with hemiplegic cerebral palsy (CP) to use anticipatory control of fingertip forces during grasping, and whether anticipatory control is facilitated by lifts with the contralateral hand. Eight children with CP (age 4-13) were asked to perform several lifts of either a 250-g or 500-g object instrumented with force transducers with one hand, followed immediately by several lifts with the contralateral hand. This was repeated for each combination of weight and starting (involved or non-involved) hand. Similar to previous studies, the rate of load force development showed impaired anticipatory control during lifts with the involved hand, intact anticipatory control in the non-involved hand, and transfer of anticipatory control from the non-involved to the involved hand. Surprisingly, however, we also found a transfer from the involved hand to the non-involved hand. The results suggest that the impaired anticipatory control in the involved hand is not purely a sensory or motor problem, and instead is due to an inability to appropriately integrate sensory information with subsequent motor output of the same hand. These results provide important information about the mechanisms underlying impaired anticipatory control, and may have important clinical implications.


Comparative proteomics using 2-D gel electrophoresis and mass spectrometry as tools to dissect stimulons and regulons in bacteria with sequenced or partially sequenced genomes.
We propose two-dimensional gel electrophoresis (2-DE) and mass spectrometry to define the protein components of regulons and stimulons in bacteria, including those organisms where genome sequencing is still in progress. The basic 2-DE protocol allows high resolution and reproducibility and enables the direct comparison of hundreds or even thousands of proteins simultaneously. To identify proteins that comprise stimulons and regulons, peptide mass fingerprint (PMF) with matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF-MS) analysis is the first option and, if results from this tool are insufficient, complementary data obtained with electrospray ionization tandem-MS (ESI-MS/MS) may permit successful protein identification. ESI-MS/MS and MALDI-TOF-MS provide complementary data sets, and so a more comprehensive coverage of a proteome can be obtained using both techniques with the same sample, especially when few sequenced proteins of a particular organism exist or genome sequencing is still in progress.


Blood collection, shipment, processing, and storage.
As part of the AACR Annual Meeting Methods Workshop "Sample Collection, Processing, and Storage for Large-Scale Studies: Biorepositories to Support Cancer Research," blood specimen collection, processing, storage, and dissemination issues were discussed. Whole blood and blood fractions comprise a major portion of biospecimen collections for population-based studies. Although procedures for collecting, processing, storing, and shipping blood components are generally standardized and well documented, several important factors need to be considered before a new study involving blood collection is initiated. Blood is collected from study participants for a variety of purposes, including as a source of DNA, and for a variety of laboratory analyses that may be done on whole blood or blood fractions, including serum, plasma, and lymphocytes. Blood or blood fractions may be shipped to laboratories and biorepositories either at ambient temperature, cooled or frozen, depending on the intended analyses. Blood processing may include fractionation, cryopreservation to preserve the viability of lymphocytes, or purification of nucleic acids. The proper storage conditions depend on a variety of factors, including the intended analyses and whether the specimens will be used within a short period or need to be stored for longer periods. As for all laboratory and biorepository procedures, blood collection, shipment, processing, and storage should be conducted under a strict quality assurance program, including standard operating procedures and regular quality control reviews.


Asymmetries in reactive and anticipatory balance control are of similar magnitude in Parkinson's disease patients.
Many Parkinson's disease (PD) patients show asymmetries in balance control during quiet stance and in response to perturbations (i.e., reactive balance control) in the sagittal plane. In addition, PD patients show a reduced ability to anticipate to self-induced disturbances, but it is not clear whether these anticipatory responses can be asymmetric too. Furthermore, it is not known how reactive balance control and anticipatory balance control are related in PD patients. Therefore, we investigated whether reactive and anticipatory balance control are asymmetric to the same extent in PD patients. 14 PD patients and 10 controls participated. Reactive balance control (RBC) was investigated by applying external platform and force perturbations and relating the response of the left and right ankle torque to the body sway angle at the excited frequencies. Anticipatory postural adjustments (APAs) were investigated by determining the increase in the left and right ankle torque just before the subjects released a force exerted with the hands against a force sensor. The symmetry ratio between the contribution of the left and right ankle was used to express the asymmetry in reactive and anticipatory balance control; the correlation between the two ratio's was investigated with Spearman's rank correlation coefficients. PD patients were more asymmetric in anticipatory (p=0.026) and reactive balance control (p=0.004) compared to controls and the symmetry ratios were significantly related (ρ=0.74; p=0.003) in PD patients. These findings suggest that asymmetric reactive balance control during bipedal stance may share a common pathophysiology with asymmetries in the anticipation of voluntary perturbations during, for instance, gait initiation.


Deletion analysis of Duchenne muscular dystrophy using cDNA probes and multiplex PCR.
The authors studied Duchenne muscular dystrophy (DMD) in 14 Yugoslav families with 16 diseased men. All the sixteen patients showed typical phenotypic features of DMD. The linkage analysis was done with five probes 754, C7, PERT87.15, pERT87.30, and pERTBir. A deletion with pERT87.15 (DX 164) in one family was found. Deletion analysis was mainly performed using cDNA probes and multiplex PCR analysis. Preferential deletions were in the hot spot deletion region covered by cDNA probe 8. Among 14 examined patients with cDNA hybridization deletions were found in 5 cases (5/14). For quick and prenatal analysis the authors used multiplex PCR. With this methods deletions were found in 4 cases (4/15). The percentage of the observed deletions cases was 50% (8/16) in Yugoslav population, which shows good correlation with other European and American populations studied. Prenatal diagnosis was done for two consultants with highly ambiguous carrier risk, and no deletions were found.


Presumed ocular histoplasmosis syndrome. A clinicopathologic correlation of a treated case.
A patient with bilateral presumed ocular histoplasmosis had been successfully treated in his symptomatic right eye with laser photocoagulation for subretinal neovascularization in two areas of the macula. The left eye also showed neovascularization clinically and histopathologically but was not treated because there was no detectable leakage and the vision was not affected. There was no change in the left eye over a two-year period. Clinicopathologic correlation of the treated and untreated macular lesions and the peripapillary and peripheral lesions is presented.


Immunomodulation of the inflammatory response in atherosclerosis.
Cardiovascular disease, as manifested in the formation of atherosclerotic lesions, can be described as a chronic inflammatory autoimmune-like disease that proceeds in the context of enhanced plasma lipid levels. Modulation of the immune response may therefore form a valuable therapy in addition to standardized cholesterol and blood pressure-lowering therapies. The purpose of this review is to describe a number of recent approaches to immunomodulate atherosclerosis: immunization against mediators involved in atherosclerosis, such as cytokines and modified low-density lipoprotein; intervention in cytokine pathways; intervention in co-stimulatory pathways; activation of regulatory T cells; and modulation of natural killer T cells. The most recent findings point to an important role for regulatory T cells in atherosclerotic lesion formation. The function of the regulatory T cells is modulated by chemokines and by co-stimulatory pathways, whereas the function of these cells can be strongly upregulated by anti-CD3 treatment and tolerance induction. In the near future the first exponents of this approach, such as immunization and enhancement of the function of regulatory T cells, may enter the first phase of clinical trials, and may ultimately add to the current therapies in atherosclerosis.


Chloroplast Cpn20 forms a tetrameric structure in Arabidopsis thaliana.
Chloroplast chaperonin 20 (Cpn20) in higher plants is a functional homologue of the Escherichia coli GroES, which is a critical regulator of chaperonin-mediated protein folding. The cDNA for a Cpn20 homologue of Arabidopsis thaliana was isolated. It was 958 bp long, encoding a protein of 253 amino acids. The protein was composed of an N-terminal chloroplast transit peptide, and the predicted mature region comprised two distinct GroES domains that showed 42% amino acid identity to each other. The isolated cDNA was constitutively expressed in transgenic tobacco. Immunogold labelling showed that Cpn20 is accumulated in chloroplasts of transgenic tobacco. A Northern blot analysis revealed that mRNA for the chloroplast Cpn20 is abundant in leaves and is increased by heat treatment. To examine the oligomeric structure of Cpn20, a histidine-tagged construct lacking the transit peptide was expressed in E. coli and purified by affinity chromatography. Gel-filtration and cross-linking analyses showed that the expressed products formed a tetramer. The expressed products could substitute for GroES to assist the refolding of citrate synthase under non-permissive conditions. The analysis on the subunit stoichiometry of the GroEL-Cpn20 complex also revealed that the functional complex is composed of a GroEL tetradecamer and a Cpn20 tetramer.


Correcting arterial blood gases for temperature: (when) is it clinically significant?
Interpreting arterial blood gases (ABGs) is a common practice in intensive care units. The use of the temperature correction facility, however, is not standardized, and the effects of temperature correction on the ABG result may affect the overall management of the patient. The aim of this study was to discuss the significance of temperature correction. Current practice in the UK and Australia is discussed along with a review of physiological principles of oxygenation and acid-base balance. The alpha-stat and pH-stat methods of blood gas analysis are presented, with arguments for and against using the temperature correction facility for blood gas analysis. The study concludes with recommendations for practice.


Chemoproteomic Profiling of Bile Acid Interacting Proteins.
Bile acids (BAs) are a family of endogenous metabolites synthesized from cholesterol in liver and modified by microbiota in gut. Being amphipathic molecules, the major function of BAs is to help with dietary lipid digestion. In addition, they also act as signaling molecules to regulate lipid and glucose metabolism as well as gut microbiota composition in the host. Remarkably, recent discoveries of the dedicated receptors for BAs such as FXR and TGR5 have uncovered a number of novel actions of BAs as signaling hormones which play significant roles in both physiological and pathological conditions. Disorders in BAs' metabolism are closely related to metabolic syndrome and intestinal and neurodegenerative diseases. Though BA-based therapies have been clinically implemented for decades, the regulatory mechanism of BA is still poorly understood and a comprehensive characterization of BA-interacting proteins in proteome remains elusive. We herein describe a chemoproteomic strategy that uses a number of structurally diverse, clickable, and photoreactive BA-based probes in combination with quantitative mass spectrometry to globally profile BA-interacting proteins in mammalian cells. Over 600 BA-interacting protein targets were identified, including known endogenous receptors and transporters of BA. Analysis of these novel BA-interacting proteins revealed that they are mainly enriched in functional pathways such as endoplasmic reticulum (ER) stress response and lipid metabolism, and are predicted with strong implications with Alzheimer's disease, non-alcoholic fatty liver disease, and diarrhea. Our findings will significantly improve the current understanding of BAs' regulatory roles in human physiology and diseases.


The family Pasteurellaceae: modern approaches to taxonomy.
Historically, members of the family Pasteurellaceae were classified on the basis of a limited number of phenotypic characteristics. In particular, organisms were assigned to the family on the basis of their requirements for the growth factors hemin and/or nicotinamide adenine dinucleotide and on the basis of their ability to cause disease in vertebrates. More recent genotypic studies have shown that many members of the family Pasteurellaceae have been misclassified. In this paper we review some of the current taxonomic methods which can be used to emend the classification of Haemophilus, Actinobacillus and Pasteurella spp. and suggest some approaches and criteria for restructuring the family Pasteurellaceae.


The Association of Education, Employment and Living with a Partner with the Treatment among Patients with Head and Neck Cancer.
The aim of this study was to explore possible associations between social and socioeconomic status and ongoing treatment among patients with head and neck cancer. Data from 159 examined patients treated with head and neck cancer during the period from 2011 to 2012 were explored. A logistic regression analysis was used to assess association of social status (living with somebody vs. living alone), socioeconomic status (employed vs. unemployed) and education (primary/secondary/university) with treatment. The results from logistic regression showed significant association of employment status and education with both interruption in radiochemotherapy and searching for additional help after surgery. Interruption of radiochemotherapy was almost 3 times more likely in a group of unemployed compared to the employed patients. Lack of searching for help after surgery was almost 4 times more likely in a group of unemployed compared to the employed and 5 times more likely in the group with the lowest education compared with the group with the highest education. The study suggests that special attention needs to be paid, not only during but also after treatment, to the patients from low socioeconomic groups.


Bilateral sciatic nerve palsy following a bariatic operation.
Iatrogenic nerve injuries have been rarely reported following laparoscopic abdominal surgeries. These can be serious complications with the potential for long-term disability. We present a rare case of bilateral sciatic nerve palsy following laparoscopic sleeve gastrectomy on a super-super-obese male with BMI 78.04 kg/m2. The procedure was completed laparoscopically in 7 hours duration, and in spite of adequate precautions, he developed bilateral sciatic nerve palsy. Nerve conduction studies showed denervation of L5/S1 confirming the diagnosis. The patient showed gradual recovery with physiotherapy, and at 18 months follow-up he was mobilizing without any walking aids, with BMI 47.34 kg/m2. Compressive nerve injuries following prolonged laparoscopic operations should be included in the list of procedural complications, especially in morbidly obese patients where the risk is significantly higher.


Tranexamic acid increases early perioperative functional outcomes after total knee arthroplasty.
The purpose of this study was to investigate the influence of tranexamic acid (TXA) on functional outcomes in the immediate postoperative period after total knee arthroplasty (TKA). We hypothesized that the known benefits of TXA would confer measurable clinical improvements in physical therapy (PT) performance, decrease pain, and decrease hospital length of stay (LOS). We retrospectively analyzed 560 TKA patients, including 280 consecutive patients whose surgery was performed before the initiation of a standardized TXA protocol and the first 280 patients who received TXA after protocol initiation. Outcome measurements included postoperative changes in hemoglobin and hematocrit, LOS, pain scores, destination of discharge, and steps ambulated with PT over 5 sessions. TXA administration resulted in less overall drops in hemoglobin (P < .001) and hematocrit levels (P < .001). Moreover, patients administered TXA ambulated more than their counterparts during every PT session, which was statistically significant during the second (P = .010), third (P = .011), and fourth (P = .024) sessions. On average, the TXA cohort ambulated 20% more per PT session than patients who did not receive TXA (P < .001). TXA administration did not influence pain levels during PT, hospital LOS, or discharge destination in this investigation. It is well known that TXA reduces postoperative anemia, but this study also demonstrates that it confers early perioperative functional benefits for TKA patients. Potential mechanisms for this benefit include reduced rates of postoperative anemia and reduced rates of hemarthroses.


[Study of unresectable pancreatic cancer - successful resections after gemcitabine-based chemotherapy].
Pancreatic ductal adenocarcinoma( PDAC) is an extremely malignant tumor and carries a poor prognosis. Therefore, PDAC should be treated with multiple modalities. Chemotherapy has proven effective in some cases of unresectable (UR) PDAC, and there are published reports of cases in which curative surgery could be performed after chemotherapy. We examined the cases from January 2010 through November 2012 in which initially UR PDAC could be treated surgically after chemotherapy. Whether or not each cancer was resectable was evaluated according to the National Comprehensive Cancer Network (NCCN) guidelines. We performed surgery in 7 of the 25 patients initially diagnosed as UR during this period. The cancer proved inoperable in 2 of these 7 patients: 1 patient with peritoneal dissemination and 1 with locally advanced tumor. Some reports have suggested that resection after chemotherapy for UR pancreatic cancer improved the prognosis in patients relative to those in whom surgery was not attempted. From our experience, we believe that it very important for patients undergoing chemotherapy for UR pancreatic cancer to consider surgical treatment.


An in vitro comparison of root canal measurement in primary teeth.
To compare the accuracy of root canal lengths in primary teeth determined by tactile sense, electronic apex locator, conventional radiography, and digital radiography in primary teeth. The study sample consisted of twenty 20 extracted, single-rooted primary teeth. A comparison was made between the working length measurements obtained by tactile sensation, electronic apex locator, conventional film, and digital radiography, using stereomicroscopic measurements to obtain real canal length. The mean readings obtained were 15.91+/-2.06 by tactile measurement, 15.94 94+/-1.42 by apex locator, 16.06+/-1.73 by conventional radiography, and 15.91+/-1.60 by digital radiography. No statistically significant differences were seen between the techniques.


Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles.
Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons.


Striatum on the anxiety map: Small detours into adolescence.
Adolescence is the most sensitive period for the development of pathological anxiety. Moreover, specific neural changes associated with the striatum might be related to adolescent vulnerability to anxiety. Up to now, the study of anxiety has primarily focused on the amygdala, bed nucleus of the stria terminalis (BNST), hippocampus and ventromedial prefrontal cortex (vmPFC), while the striatum has typically not been considered as part of the anxiety system. This review proposes the addition of the striatum, a complex, multi-component structure, to the anxiety network by underscoring two lines of research. First, the co-occurrence of the adolescent striatal development with the peak vulnerability of adolescents to anxiety disorders might potentially reflect a causal relationship. Second, the recognition of the role of the striatum in fundamental behavioral processes that do affect anxiety supports the putative importance of the striatum in anxiety. These behavioral processes include (1) attention, (2) conditioning/prediction error, and (3) motivation. This review proposes a simplistic schematic representation of the anxiety circuitry that includes the striatum, and aims to promote further work in this direction, as the role of the striatum in shaping an anxiety phenotype during adolescence could have critical implications for understanding and preventing the peak onset of anxiety disorders during this period. This article is part of a Special Issue entitled SI: Adolescent plasticity.


Effects of CO₂ Euthanasia of C57BL/6 Mice on Sperm Motility, In Vitro Fertilization, and Embryonic Developmental Competence.
Cryopreservation of epididymal sperm collected after euthanasia is a common method to preserve and distribute valuable mouse models worldwide. However, the euthanasia method used prior to sperm collection must not adversely affect sperm quality. The most common method of euthanasia in mice is CO₂ asphyxiation, but its effect on the quality of sperm collected postmortem is largely unknown. The objective of this study was to determine the effects of CO₂ euthanasia of C57BL/6 mice on both freshly recovered sperm and sperm subjected to freezing and thawing. First, sperm concentration, progressive motility, curvilineal velocity (VCL), average path velocity (VAP), and progressive velocity (VSL) were analyzed for mice euthanized by cervical dislocation (CD), high flow CO₂ (100%), or low flow CO₂ (30%) displacement/minute, respectively. Then, in-vitro fertilization and embryonic development rates were determined using frozen-thawed sperm from each euthanasia method. Neither fresh nor frozen-thawed sperm showed significant differences in sperm concentration, progressive motility, VAP, or VCL when compared to CD and CO₂ groups. However, frozen-thawed sperm collected from CD mice had higher VCL values than did those collected from the low flow mice (P = 0.039). VCL was not different in fresh or frozen-thawed sperm collected after mouse euthanasia by CD as compared with high flow CO₂ or by high flow as compared with low flow CO₂. Frozen-thawed sperm showed no differences among the 3 euthanasia groups for fertilization (P = 0.452) or blastocyst development rates (P = 0.298). The results indicate that CO₂ euthanasia can be used as an alternative to CD to obtain optimal quality mouse sperm for cryopreservation while remaining compliant with welfare requirements.


Proliferation and differentiation of cultured human keratinocytes is modulated by 1,25(OH)2D3 and synthetic vitamin D3 analogues in a cell density-, calcium- and serum-dependent manner.
The natural form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) decreases proliferation and promotes terminal differentiation of cultured human epidermal keratinocytes. The purpose of this study was to find out to what extent the culture conditions determine the sensitivity of keratinocytes to 1,25(OH)2D3 and synthetic vitamin D analogues. Human keratinocytes were grown in microplates. Cell proliferation (MTT-assay) and differentiation (quantity of transglutaminase type I) were measured consecutively in the same monolayer. When vitamin D3 analogues were added to 50-60% confluent keratinocytes grown in serum-free keratinocyte growth medium with 0.09 mM Ca2+, stimulation of the proliferation was either minimal or non-existent, while differentiation was unaffected or slightly inhibited. There was no difference in the sensitivity to 1,25(OH)2D3 and the vitamin D3 analogues. When 1,25(OH)2D3 was added to less confluent keratinocytes (30%) a marked antiproliferative effect was observed. Addition of 3% charcoal stripped foetal calf serum further enhanced the antiproliferative effect of 1,25(OH)2D3, and a difference in the sensitivity of the vitamin D3 analogues was noted. If, finally, the Ca2+ concentration was raised to 0.3 mM, 1,25(OH)2D3 and the vitamin D3 analogues stimulated differentiation. Also, a biphasic effect on proliferation occurred: stimulation at low vitamin D concentrations and inhibition at higher concentrations. Furthermore, keratinocytes became more sensitive to the synthetic vitamin D3 analogues than to 1,25(OH)2D3: KH1060 > EB1089 > GS1500 > or = EB1213 > calcipotriol > 1,25(OH)2D3. For all compounds tested differentiation occurred at concentrations 10 to 30 times lower than for proliferation. These results indicate that the sensitivity to vitamin D3 analogues as well as the direction of the response to vitamin D3 analogues is dependent on the keratinocyte density, the availability of serum and Ca2+ concentrations.


Surgical repair of renal artery aneurysms.
The pathogenesis of renal artery aneurysms (RAAs) is degenerative, which eventually leads to weakening of the vessel wall and, in extreme cases, rupture. RAAs are a rare occurrence. Patients generally are asymptomatic, with a small number presenting with uncontrollable hypertension or hematuria. Most RAAs are discovered incidentally on imaging and do not pose an immediate health threat. However, the risk of rupture is an indication for prophylactic repair in certain patients. Interest in interventional radiologic procedures in the management of RAAs has recently increased; however, open repair should still be considered in select instances. In this case series, we present three patients for whom an open approach was indicated and performed.


[Recent advances in the research of Creutzfeldt-Jakob disease (CJD) and Gerstmann-Strüssler syndrome (GSS)].
The abnormal isoform of prion protein (PrP) was detected by Western blotting and immunohistochemistry in all brains of 53 CJD and 20 GSS patients. Formic acid pretreatment on formalin fixed, paraffin-embedded thin sections enhanced immunostaining of PrP in both congophilic and non-congophilic kuru plaques which were absent in sporadic CJD patients with short clinical courses. Newly developed pretreatment on tissue sections, called hydrolytic autoclaving, could detect fine granular deposits of PrP in the synaptic structures. The fine PrP grains were detected in almost all CJD patients, regardless of the length of clinical courses, but never in control brains. This method can be applied to long preserved paraffin blocks. We analysed the PrP gene and found following variations. Proline-to-leucine change at codon 102 was found in 10 Japanese families with GSS and 7 sporadic CJD patients with kuru plaques. Alanine-to-valine change at codon 117 was found in a big Alsatian family with cerebral neurologic signs and dementia. In one Japanese family, 4 members died from typical CJD and showed glutamate-to-lysine change at codon 200. A 168 bp insertion which codes for 56 amino acids corresponding to 7 extra uninterrupted repeats of proline-glycine rich octapeptide (PHGGGWGQ) was detected in the N terminal region of PrP gene. This new insertion was found in a Japanese woman who showed slowly progressive dementia for 7 years but lacked particular pathological changes, except for a few kuru-like plaques in the cerebellum.


PERSPECTIVE METAZOAN COMPLEXITY AND EVOLUTION: IS THERE A TREND?
The notion that complexity increases in evolution is widely accepted, but the best-known evidence is highly impressionistic. Here I propose a scheme for understanding complexity that provides a conceptual basis for objective measurement. The scheme also shows complexity to be a broad term covering four independent types. For each type, I describe some of the measures that have been devised and review the evidence for trends in the maximum and mean. In metazoans as a whole, there is good evidence only for an early-Phanerozoic trend, and only in one type of complexity. For each of the other types, some trends have been documented, but only in a small number of metazoan subgroups.


Metal-Free Oxidative 1,2-Arylmethylation Cascades of N-(Arylsulfonyl)acrylamides Using Peroxides as the Methyl Resource.
A new, metal-free oxidative 1,2-arylmethylation cascades of N-(arylsulfonyl)acrylamides for the assembly of 2,2-disubstituted-N-arylbutanamides containing an all-carbon quaternary center is presented. This reaction enables the one-step formation of two new C-C bonds through a sequence of methylation/1,4-aryl migration/desulfonylation using an organic peroxide as the methyl resource with a broad substrate scope and excellent functional group tolerance.


Establishment of a prognostic risk prediction modelfor non-small cell lung cancer patients with brainmetastases: a retrospective study.
Patients with non-small cell lung cancer (NSCLC) who develop brain metastases (BM) have a poor prognosis. This study aimed to construct a clinical prediction model to determine the overall survival (OS) of NSCLC patients with BM. A total of 300 NSCLC patients with BM at the Yunnan Cancer Centre were retrospectively analysed. The prediction model was constructed using the least absolute shrinkage and selection operator-Cox regression. The bootstrap sampling method was employed for internal validation. The performance of our prediction model was compared using recursive partitioning analysis (RPA), graded prognostic assessment (GPA), the update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA), the basic score for BM (BSBM), and tumour-lymph node-metastasis (TNM) staging. The prediction models comprising 15 predictors were constructed. The area under the curve (AUC) values for the 1-year, 3-year, and 5-year time-dependent receiver operating characteristic (curves) were 0.746 (0.678-0.814), 0.819 (0.761-0.877), and 0.865 (0.774-0.957), respectively. The bootstrap-corrected AUC values and Brier scores for the prediction model were 0.811 (0.638-0.950) and 0.123 (0.066-0.188), respectively. The time-dependent C-index indicated that our model exhibited significantly greater discrimination compared with RPA, GPA, Lung-molGPA, BSBM, and TNM staging. Similarly, the decision curve analysis demonstrated that our model displayed the widest range of thresholds and yielded the highest net benefit. Furthermore, the net reclassification improvement and integrated discrimination improvement analyses confirmed the enhanced predictive power of our prediction model. Finally, the risk subgroups identified by our prognostic model exhibited superior differentiation of patients' OS. The clinical prediction model constructed by us shows promise in predicting OS for NSCLC patients with BM. Its predictability is superior compared with RPA, GPA, Lung-molGPA, BSBM, and TNM staging.


Ribbon scanning confocal for high-speed high-resolution volume imaging of brain.
Whole-brain imaging is becoming a fundamental means of experimental insight; however, achieving subcellular resolution imagery in a reasonable time window has not been possible. We describe the first application of multicolor ribbon scanning confocal methods to collect high-resolution volume images of chemically cleared brains. We demonstrate that ribbon scanning collects images over ten times faster than conventional high speed confocal systems but with equivalent spectral and spatial resolution. Further, using this technology, we reconstruct large volumes of mouse brain infected with encephalitic alphaviruses and demonstrate that regions of the brain with abundant viral replication were inaccessible to vascular perfusion. This reveals that the destruction or collapse of large regions of brain micro vasculature may contribute to the severe disease caused by Venezuelan equine encephalitis virus. Visualization of this fundamental impact of infection would not be possible without sampling at subcellular resolution within large brain volumes.


[Development of binding antibodies to interferon-beta during treatment of multiple sclerosis with different types of interferon-beta].
Interferon beta (IFN-beta) is generally considered an effective treatment for multiple sclerosis (MS). Importance of binding antibodies (BAb), which are created during the treatment of MS by the use of IFN-beta, hasn't been completely explained, however it is generally reckoned that they might be one of the factors diminishing treatment efficacy. The aim of the study was the appreciation of BAb occurrence during the treatment of MS by the use of different types of interferon beta and their impact on clinical efficacy. The study included 47 patients with relapsing-remitting MS. Within 24 months 37 patients were given two different preparations of IFN-beta 1-a and 10 patients were given IFN-beta 1-b. Every 6 months clinical parameters and BAb level in serum by EIA method were estimated. All preparations of IFN-beta induced appearance of BAb, but frequency of developing BAb to IFN-beta varied according to the IFN beta given. The high levels of BAb appeared significant frequently in patients treated with IFN-beta 1-b than in patients treated with both preparations of IFN-beta 1-a. After 2 years of treatment greater disability, measured by EDSS scale was encountered in patients with high levels of BAb but differences weren't statistically significant. As well, it wasn't stated significant correlation between exacerbation numbers during the treatment.


Long-Term Dietary Supplementation with Selenium-Enriched Yeast Improves Cognitive Impairment, Reverses Synaptic Deficits, and Mitigates Tau Pathology in a Triple Transgenic Mouse Model of Alzheimer's Disease.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by multiple histopathological changes in the brain and by impairments in memory and cognitive function. Currently, there is no effective treatment that can halt or reverse the progression of this disease. Here, we explored the effects of 3 months of treatment with selenium-enriched yeast (Se-yeast), which is commonly used as a source of organic selenium (Se) for nutrition, on cognitive dysfunction and neuropathology in the triple transgenic mouse model of AD (3×Tg-AD mice). As the results revealed that Se-yeast significantly improved the spatial learning and memory retention of 3×Tg-AD mice, promoted neuronal activity, attenuated the activation of astrocytes and microglia, mitigated synaptic deficits, and reduced the levels of total tau and phosphorylated tau though inhibiting the activity of GSK-3β, dietary supplementation with Se-yeast exerted multiple beneficial effects on the prevention or treatment of AD. These findings provide evidence of a potentially viable compound for AD treatment.


Effects of irrigation water qualities on biomass and sugar contents of sugar beet and sweet sorghum cultivars.
An experiment involving four qualities of irrigation water two sugar beet and three sweet sorghum cultivars was conducted in a split plot design with four replications at Rudasht Drainage and Reclamation Experiment Station in 1999. The results showed salinity of water has an adverse effect on sugar beet and sweet sorghum biomass. Sweet sorghum cultivar SSV108 had the lowest biomass under all qualities of irrigation water Sweet sorghum cultivar Rio had the maximum biomass with water qualities of 2, 5, and 8 dS m(-1). Sugar beet cultivar 7233 had the maximum biomass with 11 dS m(-1). The effect of irrigation water quality was not significant for sugar characteristics such as brix, pol and purity. However, responses of cultivars on the above parameters were significant and sugar beet cultivars had higher brix, pol and purity and lower invert sugar and starch than sweet sorghum cultivars. In conclusion, sweet sorghum cultivars are not recommended to be irrigated with saline water of more than 8 dS m(-1) for sugar production. Under such condition, they may be suitable to be grown for forage purposes.


Intracellular signalings underlying bradykinin-induced matrix metalloproteinase-9 expression in rat brain astrocyte-1.
Bradykinin (BK), an inflammatory mediator, has been shown to increase the expression of proteins such as matrix metalloproteinases (MMPs) on brain cells and contributes to the pathophysiology of inflammatory responses. However, the mechanisms regulating MMP-9 expression by BK in rat brain astrocytes-1 (RBA-1) remain unclear. Here we report that the mitogen-activated protein kinase (MAPK) and NF-kappaB pathways participate in the induction of MMP-9 expression induced by BK in RBA cells. Zymographic, Western blotting, and RT-PCR analyses showed that BK increased expression of MMP-9 mRNA and protein in a time- and concentration-dependent manner. BK-induced MMP-9 mRNA and protein expression was inhibited by MEK1/2 inhibitor PD98059, PI3-K inhibitor LY294002, and NF-kappaB inhibitor helenalin. In accordance with these findings, BK-induced phosphorylation of p42/p44 MAPK and Akt and activation of NF-kappaB was attenuated by prior treatment with PD98059, LY294002, and helenalin, respectively. The effects of BK on MMP-9 expression and p42/p44 MAPK and Akt phosphorylation were inhibited by B(2) receptor antagonist Hoe 140, indicating the involvement of B(2) receptors revealed by [(3)H]-BK binding assay. Furthermore, BK-stimulated translocation of NF-kappaB into the nucleus was revealed by Western blotting and immnofluorescence staining and blocked by Hoe140, PD98059, LY294002, and helenalin. Taken together, these results suggest that in RBA cells, activation of p42/p44 MAPK and Akt cascades mediated through NF-kappaB pathway are essential for BK-induced MMP-9 gene expression. This study may provide insights into the regulation of MMP-9 production in CNS, which may occur in vivo in pathological situations such as CNS inflammation and brain astrocytoma.


Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats.
CS-045 is a new oral antidiabetic agent that was effective in insulin-resistant diabetic animal models, including the KK mouse, the ob/ob mouse, and the Zucker fatty rat. CS-045 was not effective in the streptozocin-treated mouse, an insulin-deficient diabetic animal model. In fed KK mice, CS-045 lowered the plasma glucose levels in a dose-dependent manner after a single oral administration, and the hypoglycemic effect lasted for at least 18 h. In normal rats, however, plasma glucose levels were not changed after administration of CS-045. CS-045 when given chronically (2 wk) to diabetic KK and ob/ob mice as a 0.2% food admixture dramatically improved hyperglycemia, hyperinsulinemia, and hypertriglyceridemia to near-normal values and decreased plasma lactate, free fatty acid, and ketone body levels without reducing food intake or body weight. In the obese Zucker fatty rat, oral administration of CS-045 had a similar effect in lowering plasma glucose, insulin, triglyceride, free fatty acid, lactate, and ketone body levels. The CS-045-treated Zucker fatty rats showed increased glucose tolerance and decreased insulin secretion in response to oral glucose. After 9 days of treatment, insulin binding to adipocyte plasma membranes from both CS-045-treated Zucker fatty rats and KK mice was increased. Furthermore, 2-deoxyglucose uptake in CS-045-treated adipocytes was increased and the insulin dose-response curve was shifted to the left. These findings suggest that CS-045 increases not only insulin sensitivity but also insulin responsiveness. Based on its pharmacological profile, CS-045 is a new orally effective antidiabetic agent that may reduce abnormalities of glucose and lipid metabolism in obese and non-insulin-dependent diabetes mellitus patients with insulin resistance.


Study of risk factors for atopic sensitization, asthma, and bronchial hyperresponsiveness in animal laboratory workers.
The aim of this estudy was to investigate the influence of allergen exposure levels and other risk factors for allergic sensitization, asthma, and bronchial hyperresponsiveness (BHR) in workers exposed to laboratory animals. This was a cross-sectional study performed at two universities, 123 workplaces with 737 subjects. Dust samples were collected from laboratories and animal facilities housing rats, mice, guinea pigs, rabbits, or hamsters and analyzed by enzyme-linked immunosorbent assay (ELISA) to measure allergen concentrations. We also sampled workplaces without animals. Asthma was defined by both symptoms and BHR to mannitol. The concentrations of allergens were tested for association with a skin prick test, respiratory symptoms, spirometry data, and BHR. This multivariate analysis was performed by using Poisson regression to estimate the relative risk (RR) for the exposed group. Our sample comprised students and workers, with 336 subjects in the nonexposed group and 401 subjects in the exposed group. Sixty-nine subjects (17%) had positive results in the skin prick test for animal allergens in the exposed group; in the nonexposed group, 10 subjects had positive results (3%) (p<0.001). Exposure to laboratory animals over 2.8 years was associated with atopic sensitization (RR=1.85; 95% confidence interval: 1.09-3.15; p=0.02). Allergen concentration was not associated with sensitization, asthma, or BHR. Exposure to laboratory animals was associated with atopic sensitization. However, we did not find a cutoff allergen concentration that increased the risk for sensitization. Duration of exposure seems to be more relevant to sensitization than concentration of allergens in dust.


[Quantification of Neisseria gonorrhoeae from the cervicovaginal area in nonpregnant women infected with gonorrhoea].
The authors studied quantification of Neisseria gonorrhoeae from the cervicovaginal area of 53 nonpregnant women with gonorrhoea. The variability of the amount of gonococci in cervicovaginal secretion was rather high from 1.0.10(1) to 1.1.10(8) cfu N. gonorrhoeae in 1 ml. Maximum values of N. gonorrhoeae have been found intra menses (from 1.0.10(2) to 3.0.10(8) cfu N. gonorrhoeae in 1 ml). These findings allow the authors to make some, already more or less known, conclusions usable in clinical practice.


Zinc transporters ZnT3 and ZnT6 are downregulated in the spinal cords of patients with sporadic amyotrophic lateral sclerosis.
The loss of homeostasis of essential metals is associated with various diseases, including neurodegenerative diseases. Previous studies have shown that the levels of zinc (Zn) are significantly higher in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS). Zn transporters and metallothioneins tightly control intracellular and extracellular Zn levels. This study investigated the protein levels of ZnT, a Zn transporter family, in ALS patients and model mice. The mRNA expression of ZnT1, -3, -4, -5, -6, -7, and -10 was assessed in the spinal cords of human control subjects. ZnT3 and ZnT6 protein levels were significantly diminished in the spinal cords of sporadic ALS patients compared with controls. Furthermore, immunohistochemical staining demonstrated decreased ZnT3 and ZnT6 immunoreactivity in the ventral horn of the spinal cords in ALS patients. Moreover, immunohistochemical analysis revealed that all ZnTs expressed in the spinal cords were localized in a distinct subset of motor neurons. In addition, ZnT3 and ZnT6 protein levels were not altered in SOD1 (G93A) mutant transgenic mice before or after the onset of ALS symptoms compared with controls. These results suggest that ZnT3 and ZnT6 protein levels are decreased in the spinal cords of sporadic ALS patients; however, this did not occur merely via loss of motor neurons.


New Zealand's first general anaesthetic.
The administration of New Zealand's first general anaesthetic took place at the Colonial Gaol, Wellington, on the morning of Monday, September 27th, 1847. The agent used was sulphuric ether which was administered by Mr. Marriot, the manufacturer of the Herapath-type inhaler used on this occasion. The operation, a dental extraction, was performed by the Colonial Surgeon, Dr. J. P. Fitzgerald.


Self-Compassion, Work Engagement and Job Performance among Intensive Care Nurses during COVID-19 Pandemic: The Mediation Role of Mental Health and the Moderating Role of Gender.
(1) Background: The COVID-19 pandemic has highlighted attention on the importance of certain variables in predicting job performance. Among these, mental health is one of the main variables affected by this pandemic. It can have an important mediating role in predicting job performance by individual, occupational, and organizational variables, especially in the nursing community. However, there is little information about its mediation role among the predictors of job performance. This cross-sectional study aimed to examine the role of mental health as a mediating factor in the influence of self-compassion and work engagement on ICU nurses' job performance during the COVID-19 pandemic, as well as the moderating effect of gender on all model relations. A survey of 424 ICU nurses (men 193 and women 231) was undertaken in three Coronavirus hospitals in Isfahan, Iran. (2) Method: Questionnaires were distributed and collected among the statistical sample, and the data from the questionnaires were analyzed using AMOS24 software (version 24). The research model was evaluated in two stages (the main model and the two sub-models in two gender groups). (3) Result: The analysis revealed that work engagement (β = 0.42, p < 0.001), mental health (β = 0.54, p < 0.001) and job performance (β = 0.51, p < 0.001) were discovered to be positively related to self-compassion. Work engagement is positively associated with mental health (β = 0.16, p < 0.01) and job performance (β = 0.21, p < 0.001), and mental health is linked positively to job performance (β = 0.23, p < 0.001). Furthermore, the effects of self-compassion and work engagement on job performance are mediated by mental health. According to the findings, gender moderates the link between self-compassion and work engagement, work engagement and job performance, and self-compassion and job performance. (4) Conclusion: Mental health has a mediating role in the effect of self-compassion and work engagement on ICU nurses' job performance. Gender also acted as a moderator in some relationships. Males are dominant in all of these relationships as compared to females.


Transducing pathways involved in the control of NaCl reabsorption in the thick ascending limb of Henle's loop.
The thick ascending limb of Henle's loop (TAL) is involved in the urinary dilution/concentration process by actively reabsorbing NaCl through a complex mechanism. Some years ago, compelling evidence was provided that cAMP stimulates NaCl reabsorption through the activation of adenylyl cyclase by several hormones other than antidiuretic hormone (ADH). Synthesis of cyclic AMP is inhibited by prostaglandin E2 (PGE2) and arachidonic acid per se, via the pertussis toxin-sensitive protein Gi activation. Cyclic GMP cascade down-regulates NaCl reabsorption, through activation of both guanylyl cyclase receptors (by ANF and urodilatin), and soluble guanylyl cyclase (by nitric oxide, NO). In TAL, NO is produced by the cytokine-inducible form of NO synthase, but not by the constitutive one. Agonists known to activate protein kinase C (PKC) in TAL elicit opposite effects on NaCl reabsorption. Five PKC isoforms belonging to the conventional, novel, and atypical enzyme subclasses have been recently defined in TAL and might differently regulate NaCl flux. Increments in intracellular calcium ([Ca2+]i) inhibit NaCl reabsorption via three pathways: (i) a possible direct effect on ion channels, (ii) a PLA2-mediated production of arachidonic acid derivatives (20-HETE), and (iii) inhibition of the ADH-induced cAMP accumulation. This last effect results from activation of phosphodiesterase (common to the agents that increase [Ca2+]i), and inhibition of adenylyl cyclase (only elicited by Ca2+c). Finally, the apical localization of some agonists effects is documented.


[Clinical study and diagnostic criteria of periarteritis nodosa. Apropos of 27 cases].
Periarteritis nodosa is a necrotizing vasculitis diagnosed on clinical, angiographic and histological criteria. We conducted a retrospective study of the various clinical and paraclinical manifestations of the disease in a series of 27 patients hospitalized in an Internal Medicine department. Visceral angiography showed microaneurysms in only 12.5% of the cases, and we consider that the indications of this method are limited. Segmental necrotizing vasculitis of the medium- and small-caliber arteries was found in only 33% of muscle biopsies. This criterion has low sensitivity and must be improved by systematic electromyography which showed abnormal results in 87% of the patients. Due to the insufficient sensitivity of paraclinical criteria, the clinical criteria proposed by Godeau and Guillevin are of great practical value. However, we suggest that their definition should be modified on three points: multineuritis should be replaced by peripheral neuropathies; livedo should be included in the cutaneous criterion, and positive serology for hepatitis B or C virus should be added to the positivity criteria.


Relationships between metabolic syndrome and left ventricular mass in hypertensive patients: does sex matter?
Several studies documented an association between metabolic syndrome (MetS) and left ventricular (LV) hypertrophy. However, only in a few of these studies the impact of MetS on left ventricular mass (LVM) was separately analysed by gender, with conflicting results. The aim of our study was to verify, in a wide sample of essential hypertensive patients, the influence of gender, if any, on the relationship between MetS and LVM. We enrolled 475 non-diabetic subjects (mean age: 46 +/- 11 years), with mild-to-moderate essential hypertension, of whom 40% had MetS, defined on the basis of Adult Treatment Panel III (ATPIII) criteria. All the patients underwent a 24-h ambulatory blood pressure monitoring and an echocardiogram. LVM indexed for height (2.7) (LVMH (2.7)) was significantly (P < 0.001) higher in women with MetS (n=83) than in those without it (n=97; 54+/-17 vs 42+/-11 g m(-2.7)). An equally significant difference in LVMH (2.7) was documented also in male gender between the two groups with (n=105) and without MetS (n=190; 51+/-14 vs 43+/-11 g m(-2.7); P < 0.001). The relationship between MetS and LVMH (2.7) remained statistically significant (P < 0.001) in both sexes, in multiple regression analyses, even after adjustment for potential confounding factors. Our results seem to suggest that the relationship between MetS and LVM is not significantly affected by gender, being LVM increased in both hypertensive women and men with MetS.


[Association of the polymorphic marker Glu23Lys in the KCNJ11 gene with hypertension in Kyrgyz patients].
To study the association of the polymorphic marker Glu23Lys in the KCNJ11 with the development of hypertension in Kyrgyz patients. This case-control study enrolled 214 unrelated ethnic Kyrgyzes, in which a study group included 152 hypertensive patients (82 men and 70 women) and a control group consisted of 109 apparently healthy individuals (61 men and 48 women). The examinees' mean age was 55.2±10.1 years. Hypertension was verified when blood pressure (BP) was above 140/90 mm Hg. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to identify the polymorphic marker Glu23Lys in the KCNJ11 gene. In the hypertension and control groups, the prevalence of 3 genotypes (Glu23Glu, Glu23Lys, and Lys23Lys) of the Glu23Lys polymorphism in the KCNJ11 gene differed significantly (χ2=8.04; p=0.018). The Lys23Lys and Glu23Lys genotypes were statistically more frequently recorded in the hypertension group and the homozygous Glu23Glu genotype was, on the contrary, more common in the control group than in the study one. In the hypertension group, the 23Lys allele frequency was statistically significantly higher than that in the control one (χ2=7.36; p=0.0067). The carriage of the 23Lys allele increased the risk of hypertension by 1.68 times (odds ratio (OR), 1.68; 95% confidence interval (CI), 1.17-2.41), that of the Glu23 allele had, on the contrary, a protective effect (OR, 0.60; 95% CI, 0.41-0.86). The polymorphic marker Glu23Lys in the KCNJ11 gene is associated with hypertension in the Kyrgyzes. The 23Lys allele is a marker for the higher risk of hypertension.


Repeated dosing of botulinum toxin type A for upper limb spasticity following stroke.
The authors evaluated the long-term efficacy and safety of botulinum toxin type A (BTX-A) in poststroke spasticity patients who completed a 12-week placebo-controlled study and received multiple open-label treatments with 200 to 240 U BTX-A for 42 weeks. Significant and sustained improvements were observed for Disability Assessment and Ashworth scores. Adverse events were generally mild. This extension of a double-blind study demonstrates that repeated treatments of BTX-A significantly improve function and tone in spasticity.


Liquid biopsy in breast cancer: A comprehensive review.
Breast cancer is the most common cancer among women worldwide. Due to its complexity in nature, effective breast cancer treatment can encounter many challenges. Traditional methods of cancer detection such as tissue biopsy are not comprehensive enough to capture the entire genomic landscape of breast tumors. However, with the introduction of novel techniques, the application of liquid biopsy has been enhanced, enabling the improvement of various aspects of breast cancer management including early diagnosis and screening, prediction of prognosis, early detection of relapse, serial sampling and efficient longitudinal monitoring of disease progress and response to treatment. Various components of tumor cells released into the blood circulation can be analyzed in liquid biopsy sampling, some of which include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell-free RNA, tumor-educated platelets and exosomes. These components can be utilized for different purposes. As an example, ctDNA can be sequenced for genetic profiling of the tumors to enhance individualized treatment and longitudinal screening. CTC plasma count analysis or ctDNA detection after curative tumor resection surgery could facilitate early detection of minimal residual disease, aiding in the initiation of adjuvant therapy to prevent recurrence. Furthermore, CTC plasma count can be assessed to determine the stage and prognosis of breast cancer. In this review, we discuss the advantages and limitations of the various components of liquid biopsy used in breast cancer diagnosis and will expand on aspects that require further focus in future research.


[The effect of group size on salience of member desirability].
This study tested the hypothesis that undesirable members are salient in a small group, while desirable members become salient in a larger group. One hundred and forty-five students were randomly assigned to twelve conditions, and read sentences desirably, undesirably, or neutrally describing each member of a college student club. The twelve clubs had one of three group sizes: 13, 39, or 52, and the proportion of the desirable or undesirable to the neutral was either 11:2 or 2:11, forming a three-way (3 x 2 x 2) factorial. Twelve subjects each were asked to make proportion judgments and impression ratings. Results indicated that proportion of the undesirable members was over estimated when the group size was 13, showing negativity bias, whereas proportion of the desirable was overestimated when the size was 52, displaying positivity bias. The size 39 showed neither positivity nor negativity bias. These results along with those from impression ratings suggested that salience of member desirability interacted with group size. It is argued that illusory correlation and group cognition studies may well take these effects into consideration.


Chemically exfoliated MoS₂ nanosheets as an efficient catalyst for reduction reactions in the aqueous phase.
Chemically exfoliated MoS2 (ce-MoS2) nanosheets that incorporate a large fraction of metallic 1T phase have been recently shown to possess a high electrocatalytic activity in the hydrogen evolution reaction, but the potential of this two-dimensional material as a catalyst has otherwise remained mostly uncharted. Here, we demonstrate that ce-MoS2 nanosheets are efficient catalysts for a number of model reduction reactions (namely, those of 4-nitrophenol, 4-nitroaniline, methyl orange, and [Fe(CN)6](3-)) carried out in aqueous medium using NaBH4 as a reductant. The performance of the nanosheets in these reactions is found to be comparable to that of many noble metal-based catalysts. The possible reaction pathways involving ce-MoS2 as a catalyst are also discussed and investigated. Overall, the present results expand the scope of this two-dimensional material as a competitive, inexpensive, and earth-abundant catalyst.


Rab11 is required for membrane trafficking and actomyosin ring constriction in meiotic cytokinesis of Drosophila males.
Rab11 is a small GTPase that regulates several aspects of vesicular trafficking. Here, we show that Rab11 accumulates at the cleavage furrow of Drosophila spermatocytes and that it is essential for cytokinesis. Mutant spermatocytes form regular actomyosin rings, but these rings fail to constrict to completion, leading to cytokinesis failures. rab11 spermatocytes also exhibit an abnormal accumulation of Golgi-derived vesicles at the telophase equator, suggesting a defect in membrane-vesicle fusion. These cytokinesis phenotypes are identical to those elicited by mutations in giotto (gio) and four wheel drive (fwd) that encode a phosphatidylinositol transfer protein and a phosphatidylinositol 4-kinase, respectively. Double mutant analysis and immunostaining for Gio and Rab11 indicated that gio, fwd, and rab11 function in the same cytokinetic pathway, with Gio and Fwd acting upstream of Rab11. We propose that Gio and Fwd mediate Rab11 recruitment at the cleavage furrow and that Rab11 facilitates targeted membrane delivery to the advancing furrow.


[Alpha-2 macroglobulin from cerebrospinal fluid in neurosurgical diseases].
Content of alpha 2-macroglobulin (alpha 2-MG) was estimated in cerebrospinal fluid (CSF) of patients with neurosurgical impairments. Minimal content of the globulin was found in patients with brain concussion (0.011 +/- 0.001 g/L, control group), maximal concentration--in severe craniocerebral trauma with brain contraction (0.056 +/- 0.007 g/L) and moderately increased content of alpha 2-MG was detected in intracranial tumors and drug-resistant epilepsy, 0.028 +/- 0.004 g/L and 0.025 +/- 0.004 g/L, respectively. Alteration in content of alpha 2-MG during postoperational period corresponded to clinical state of patients. Estimation of alpha 2-MG in CSF might be used as a criterion of brain impairment severity as well as for monitoring the treatment course.


What is the nature, extent and impact of bullying in surgical settings? Insights of surgeons in Australia and Aotearoa New Zealand.
A significant body of literature has examined the impact of verbal and non-verbal bullying in surgical settings, where a central focus has been on the experiences of trainee and junior members of the surgical team, women in surgery and other health professionals, such as nurses. Research on how surgeons' perceive or experience bullying is more limited. Therefore, this study aims to investigate the views of surgeons on negative and disrespectful verbal and non-verbal behaviour and bullying in surgical settings, including its impact on surgeons themselves and the surgical staff they oversee. Semi-structured interviews were undertaken with surgeons between February and November 2019. Questions explored surgeons' perceptions of interpersonal communication and behaviour in their surgical workplaces in the preceding 6-months. A narrative analysis approach was used to code, interpret, and report the interview data. Thirty-one interviews were conducted with surgeons (19 male and 12 female), from Australia (26) and Aotearoa New Zealand (5) from 10 surgical specialties. Three themes were identified with associated subthemes: bullying (five subthemes), non-verbal bullying (seven subthemes), and impact and outcomes of bullying (six subthemes). This study revealed a notable shift in the reported verbal and non-verbal bullying behaviour among surgeons, demonstrating a decrease in intensity, physicality and violence for the 6-months prior to interviews conducted in 2019, when compared with surgeons' historic experiences. Despite reported behaviour being more subtle and indirect, it nonetheless continues to have a marked impact on many surgeons as well as the staff they oversee.


An Adaptive Feature Learning Model for Sequential Radar High Resolution Range Profile Recognition.
This paper proposes a new feature learning method for the recognition of radar high resolution range profile (HRRP) sequences. HRRPs from a period of continuous changing aspect angles are jointly modeled and discriminated by a single model named the discriminative infinite restricted Boltzmann machine (Dis-iRBM). Compared with the commonly used hidden Markov model (HMM)-based recognition method for HRRP sequences, which requires efficient preprocessing of the HRRP signal, the proposed method is an end-to-end method of which the input is the raw HRRP sequence, and the output is the label of the target. The proposed model can efficiently capture the global pattern in a sequence, while the HMM can only model local dynamics, which suffers from information loss. Last but not least, the proposed model learns the features of HRRP sequences adaptively according to the complexity of a single HRRP and the length of a HRRP sequence. Experimental results on the Moving and Stationary Target Acquisition and Recognition (MSTAR) database indicate that the proposed method is efficient and robust under various conditions.


[Personality features in multiple sclerosis patients with a relapsing-remitting course of the disease].
The aim of this article was to find the differences between level of anxiety, level of depression and certain features of self-image during relapse and remission in multiple sclerosis patients. Subjects were 42 patients of the Neurology Department at the Military Hospital in Lublin with relapsing--remitting multiple sclerosis (RR-MS); 26 patients in relapse and 16 in remission of the disease. All patients included into the study had a diagnosis of multiple sclerosis according to the McDonald criteria. Mean age of the studied patients was 36 years, mean disease duration--8 years. Patients were investigated with the use of Beck Depression Inventory, State-Trait Anxiety Inventory (STAI), Gough and Heilbrunn Adjective Check List (ACL)--a questionnaire designed for the study. . Using the T-Student test, we compared results from MS patients in the period of relapse and in remission. Our results revealed statistically significant differences in the level of anxiety in State Trait Anxiety Inventory (STAI) and in Free Child (FC) scale of Adjective Check List (ACL). Our results show that patients in relapse have a higher level of anxiety, more negative attitude towards themselves, lack of self-confidence and they isolate more from the society as compared to multiple sclerosis patients in remission.


Immunogenicity and safety of a trivalent inactivated influenza vaccine produced in Shenzhen, China.
A split-virion trivalent inactivated influenza vaccine produced according to the Chinese pharmacopeia (Shz-IIV3) has been commercially available in China since 2014. Here, we describe the results of a phase IV open-label trial to describe the immunogenicity and safety of the 2014-2015 Northern Hemisphere formulation of Shz-IIV3 in individuals ≥ 6 months of age. Subjects 6-35 months of age received 2 half-doses of Shz-IIV3 (0.25 ml) 28 d apart, and subjects ≥ 3 y of age received a single full dose (0.5 ml). The study included 602 subjects. Except for the A (H3N2) strain in subjects 3-17 years, geometric mean hemagglutination inhibition titer ratios were ≥ 10 and rates of seroconversion/significant increase in titer were ≥ 78% in all age groups. For the H3N2 strain in subjects 3-17 years, the geometric mean titer ratio was 3.8 and the rate of seroconversion/significant increase was 56%. Post-vaccination seroprotection rates were ≥ 88% for all strains in all age groups. The most common solicited reactions were injection-site pain/tenderness and fever, most of which were grade 1 and resolved within 3 d. Vaccine-related unsolicited adverse events were reported only by subjects 6-23 months, most of which were mild abnormal crying and irritability. No vaccine-related serious adverse events and no deaths were reported. No new safety signals or unexpected safety events occurred, although an immediate anaphylactic skin reaction occurred in one subject. This study confirmed that the 2014-2015 Northern Hemisphere formulation of Shz-IIV3 was well tolerated and highly immunogenic in subjects ≥ 6 months of age.


Cationic technetium-99m complexes of N-substituted pyridoxal derivatives as renal function agents.
New cationic technetium-chelating agents containing a pyridinium group have been synthesized and evaluated as potential renal radiopharmaceuticals. The pyridinium compounds used in the study are N-methyl pyridoxal chloride, N-ethyl pyridoxal chloride, N-propyl pyridoxal chloride, 1-methyl-3-hydroxy-4-formylpyridinium chloride, 1-methyl-2-formyl-3-hydroxypyridinium chloride and the Schiff's bases of N-methyl pyridoxal chloride with amino acid, amino acid ester and amino acid amide. Complexes of these chelating agents with 99mTc were prepared using a Na2S2O4 or a SnCl2 solution as a reducing agent. The purity of the 99mTc complexes was determined by paper electrophoresis in 0.1 M tris buffer. Electrophoresis indicates slightly positive-charged species. The log P values of these complexes showed a hydrophilic nature. Urinary excretion of the 99mTc N-alkylated pyridoxal derivatives, 99mTc-diethylenetriaminepentaacetic acid, 99mTc-mercaptoacetylglycylglycylglycine (MAG3) and 131I-O-iodohippurate were determined in mice and rats at different time intervals. In a rat model, the pyridoxal-derived 99mTc complexes are rapidly excreted in urine and provide clear renal scintigrams. Hepatobiliary excretion was negligible, reducing scan interference from the intestines. Total clearances were lower than that of 131I-hippurate and 99mTc-MAG3. The rate of urinary clearance of the new tracers was not significantly faster than 99mTc diethylenetriaminepentaacetic acid and the inhibitor N1-methylnicotinamide had only a minimal effect on the renal behavior. Though the new tracers have cationic properties, the pyridinium group did not contribute largely to the excretion of active transport.