Characterization of Pseudomonas aeruginosa-induced MDCK cell injury: glycosylation-defective host cells are resistant to bacterial killing.
As a model for bacterium-induced epithelial cell injury, we have studied the interaction of Pseudomonas aeruginosa with polarized Madin-Darby canine kidney (MDCK) cells grown on filters. Following an initial period of bacterial adhesion, foci of injured host cells, which consisted of a central region of cell debris, surrounded by cells that were permeable and apparently necrotic, were formed. Host cell death was quantified by measuring the increased permeability of the monolayer to the macromolecular tracer [14C]inulin. Using this MDCK model system, we have identified bacterial and host cell factors necessary for the host cell damage. The ability of P. aeruginosa to cause MDCK cell damage was independent of elastase or exotoxin A production. In contrast, bacteria with a mutation in the regulatory locus exsA (which are deficient in exoenzyme S production) neither bound to nor caused host cell injury. MDCK cells with defects in cell surface glycosylation were resistant to cell injury, indicating that bacteria may require host cell glycolipids and/or glycoproteins as points of adhesion to cause subsequent host cell injury.


Cartesian message passing neural networks for directional properties: Fast and transferable atomic multipoles.
The message passing neural network (MPNN) framework is a promising tool for modeling atomic properties but is, until recently, incompatible with directional properties, such as Cartesian tensors. We propose a modified Cartesian MPNN (CMPNN) suitable for predicting atom-centered multipoles, an essential component of ab initio force fields. The efficacy of this model is demonstrated on a newly developed dataset consisting of 46 623 chemical structures and corresponding high-quality atomic multipoles, which was deposited into the publicly available Molecular Sciences Software Institute QCArchive server. We show that the CMPNN accurately predicts atom-centered charges, dipoles, and quadrupoles and that errors in the predicted atomic multipoles have a negligible effect on multipole-multipole electrostatic energies. The CMPNN is accurate enough to model conformational dependencies of a molecule's electronic structure. This opens up the possibility of recomputing atomic multipoles on the fly throughout a simulation in which they might exhibit strong conformational dependence.


A giant jejunal gastrointestinal stromal tumor misconceived as pancreatic cystic neoplasm: A case report.
Gastrointestinal stromal tumors (GISTs), although not common in gastrointestinal (GI) tumors, constitute the most frequent mesenchymal tumors of the GI tract. This report describes a patient with a large sporadic GIST at proximal jejunum that mimicked the pancreatic cystic neoplasm. We report a 59-year-old female patient with unexplained weight loss and palpable left upper quadrant abdominal mass for 6 months. Computed tomography (CT) scan demonstrated a heterogeneously mass measuring 10 cm in a maximal diameter at pancreatic body and tail. Laparotomy was done, and the tumor was found at proximal jejunum closed to the ligament of Treitz, so en bloc resection of the tumor was done. The pathological and immunohistochemical study confirmed GISTs. Although most GISTs are originated from the intestine, they frequently arise from the stomach, the duodenum and rarely from the jejunum. And jejunal GISTs are usually asymptomatic. The misdiagnosis as mucinous cystadenoma of this case might be due to the proximity of the tumor to the body and tail of pancreas, and compressing the adjacent organ due to its large size. GISTs are most frequently small and arising from the stomach. GISTs are rarely present as a large tumor of the jejunum, and particularly mimicked a pancreatic tumor.


An Illustration of FY-3E GNOS-R for Global Soil Moisture Monitoring.
An effective soil moisture retrieval method for FY-3E (Fengyun-3E) GNOS-R (GNSS occultation sounder II-reflectometry) is developed in this paper. Here, the LAGRS model, which is totally oriented for GNOS-R, is employed to estimate vegetation and surface roughness effects on surface reflectivity. Since the LAGRS (land surface GNSS reflection simulator) model is a space-borne GNSS-R (GNSS reflectometry) simulator based on the microwave radiative transfer equation model, the method presented in this paper takes more consideration on the physical scattering properties for retrieval. Ancillary information from SMAP (soil moisture active passive) such as the vegetation water content and the roughness coefficient are investigated for the final algorithm's development. At first, the SR (surface reflectivity) data calculated from GNOS-R is calculated and then calibrated, and then the vegetation roughness factor is achieved and used to eliminate the effects on both factors. After receiving the Fresnel reflectivity, the corresponding soil moisture estimated from this method is retrieved. The results demonstrate good consistency between soil moisture derived from GNOS-R data and SMAP soil moisture, with a correlation coefficient of 0.9599 and a root mean square error of 0.0483 cm3/cm3. This method succeeds in providing soil moisture on a global scale and is based on the previously developed physical LAGRS model. In this way, the great potential of GNOS-R for soil moisture estimation is presented.


Cardioprotective Effects of Sodium Glucose Cotransporter 2 Inhibition in Angiotensin II-Dependent Hypertension Are Mediated by the Local Reduction of Sympathetic Activity and Inflammation.
The cardioprotective effects of sodium glucose cotrasponter 2 (SGLT2) inhibitors seem to be independent from the effects on glycemic control, through little-known mechanisms. In this study, we investigate whether the cardioprotective effects of empagliflozin, a SGLT2 inhibitor, may be associated with myocardial sympathetic activity and inflammatory cell infiltration in an experimental model of angiotensin II-dependent hypertension. Angiotensin II (Ang II), Ang II plus Empagliflozin, physiological saline, or physiological saline plus empagliflozin were administered to Sprague Dawley rats for two weeks. Blood pressure was measured by plethysmographic method. Myocardial hypertrophy and fibrosis were analysed by histomorphometry, and inflammatory cell infiltration and tyrosine hydroxylase expression, implemented as a marker of sympathetic activity, were evaluated by immunohistochemistry. Ang II increased blood pressure, myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase expression, as compared to the control group. Empagliflozin administration prevented the development of myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase overexpression in Ang II-treated rats, without affecting blood glucose and the Ang II-dependent increase in blood pressure. These data demonstrate that the cardioprotective effects of SGLT2 inhibition in Ang II-dependent hypertension may result from the myocardial reduction of sympathetic activity and inflammation and are independent of the modulation of blood pressure and blood glucose levels.


The right hemisphere as an anomaly detector: evidence from visual perception.
V. S. Ramachandran (1998) has suggested that the right hemisphere, which tends to be specialized for the analysis of global-level information, serves as an anomaly detector. Its role is to judge whether a given percept is possible and whether there are elements of that percept that seem incongruent with the other elements. In contrast, the left hemisphere tends to create a "story" to make sense of the incongruities. In the current study, pictures of possible or impossible objects were displayed for brief exposure durations to either the left visual field/right hemisphere or to the right visual field/left hemisphere). The results provide tentative support for the work of Ramachandran. In male participants, the right hemisphere was superior to the left in detecting impossible objects.


ABL1 amplification in T-cell acute lymphoblastic leukemia.
ABL1 amplification, due to a cryptic episomal translocation NUP214/ABL1, is a novel finding in T-cell acute lymphoblastic leukemia (ALL). Here we report on the incidence and clinical features of this genetic defect in a series of 30 consecutive adult T-cell ALL patients. Multiple copies of the ABL1 gene were detected in two patients (6.6%), one with the karyotype 46,XY,t(1;3)(p36;p21),del(6)(q23)/46,XY and the other without analyzable metaphases. Metaphase/interphase fluorescence in situ hybridization (FISH) detected multiple uncountable signals corresponding to ABL1 in mitotic cells and nuclei from both patients. In one patient, no signals corresponded with the 9p21 chromosomal region, which contains the p16INK4a gene, and in the other one signal was observed. Quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) demonstrated that in these patients ABL1 gene expression was 14- and 18-fold greater than in normal controls, and returned to normal levels only when complete remission was achieved. We reached the following conclusions: (1) FISH is the only technique that promptly identifies T-cell ALL patients with ABL1 amplification, (2) quick identification with FISH is fundamental in the clinic because this T-cell ALL subset is imatinib sensitive but may become resistant due to development of additional mutations, and (3) ABL1 quantitative RT-PCR may be easily applied to monitor minimal residual disease.


Correlates of recent HIV infection among men who have sex with men recruited through the internet in Huzhou City, Eastern China.
To identify factors associated with recent HIV infection among men who have sex with men (MSM) in Huzhou City, Eastern China, who seek sexual partners via the internet. Adult members of Tencent QQ instant messaging software, who completed a face-to-face interview questionnaire and serological HIV testing at baseline, were enrolled into this prospective cohort study. Questionnaires and serological testing were also completed at 6 and 12 months. Cox proportional hazards was used for initial bivariate analyses of differences between participants with or without recent HIV infection, and for subsequent forward stepwise multiple regression of statistically significant variables. Out of 415 baseline participants, 283 completed the 12-month follow-up (25 with recent HIV infection and 258 without; recent HIV infection rate, 8.20 per 100 person-years). Recent HIV infection was shown to be significantly associated with ≤ high school education (versus college/university), registered residence outside Huzhou City (versus within Huzhou City), having ≥ two male sexual partners, and syphilis infection. Improving education levels, treating syphilis promptly, and reducing the number of male sexual partners may reduce HIV transmission among MSM in Eastern China.


Tripartite-GAN: Synthesizing liver contrast-enhanced MRI to improve tumor detection.
Contrast-enhanced magnetic resonance imaging (CEMRI) is crucial for the diagnosis of patients with liver tumors, especially for the detection of benign tumors and malignant tumors. However, it suffers from high-risk, time-consuming, and expensive in current clinical diagnosis due to the use of the gadolinium-based contrast agent (CA) injection. If the CEMRI can be synthesized without CA injection, there is no doubt that it will greatly optimize the diagnosis. In this study, we propose a Tripartite Generative Adversarial Network (Tripartite-GAN) as a non-invasive, time-saving, and inexpensive clinical tool by synthesizing CEMRI to detect tumors without CA injection. Specifically, our innovative Tripartite-GAN combines three associated-networks (an attention-aware generator, a convolutional neural network-based discriminator, and a region-based convolutional neural network-based detector) for the first time, which achieves CEMRI synthesis and tumor detection promoting each other in an end-to-end framework. The generator facilitates detector for accurate tumor detection via synthesizing tumor-specific CEMRI. The detector promotes the generator for accurate CEMRI synthesis via the back-propagation. In order to synthesize CEMRI of equivalent clinical value to real CEMRI, the attention-aware generator expands the receptive field via hybrid convolution, and enhances feature representation and context learning of multi-class liver MRI via dual attention mechanism, and improves the performance of convergence of loss via residual learning. Moreover, the attention maps obtained from the generator newly added into the detector improve the performance of tumor detection. The discriminator promotes the generator to synthesize high-quality CEMRI via the adversarial learning strategy. This framework is tested on a large corpus of axial T1 FS Pre-Contrast MRI and axial T1 FS Delay MRI of 265 subjects. Experimental results and quantitative evaluation demonstrate that the Tripartite-GAN achieves high-quality CEMRI synthesis that peak signal-to-noise rate of 28.8 and accurate tumor detection that accuracy of 89.4%, which reveals that Tripartite-GAN can aid in the clinical diagnosis of liver tumors.


Investigating mammalian target of rapamycin inhibitors for their anticancer properties.
The mammalian target of rapamycin (mTOR) is a key element of the PI3KAkt (protein kinase B) signalling pathway, responsible for the regulation of cell growth and proliferation. There are two main downstream messengers of the mTOR kinase, eukaryotic initiation factor 4E-binding protein-1 and the 40S ribosomal protein S6 kinase 1, that control translation and cell-cycle progression. Abnormal activation of the mTOR pathway occurs frequently in numerous human malignancies; therefore, mTOR represents an attractive target for anticancer drug development. Rapamycin and its analogues CCI-779, RAD-001 and AP-23573 are known specific inhibitors of the mTOR kinase. Several clinical Phase I/II trials showed their activity in solid tumours and haematological malignancies. Moreover, inhibitors of mTOR were found to synergise with some cytostatics or other biological agents, which seems to be a promising direction for future strategies of antitumour treatment.


Apoptosis of epitope-specific antiretroviral cytotoxic T lymphocytes via Fas ligand-Fas interactions.
C57BL/6 (B6; H-2b) mice are capable of mounting a vigorous AKR/Gross Murine Leukemia Virus (MuLV)-specific cytotoxic T lymphocyte (CTL) response to AKR/Gross MuLVs whereas AKR.H- 2b congenic mice, although carrying the responder H-2b major histocompatibility haplotype, are specifically nonresponsive. Furthermore, when viable AKR.H-2b spleen cells are cocultured with primed responder B6 antiviral precursor CTLs, the AKR.H-2b cells function as "veto" cells that actively mediate the inhibition by apoptosis of B6 antiviral CTL generation in a contact-dependent, MHC-restricted, and veto cell Fas ligand (FasL)/responder T cell Fas-dependent manner. In the present study we show that antigen-specific, antiviral CTLs that survive apoptotic inhibition by AKR.H-2b veto cells display a less activated cell surface phenotype, and are less able to bind specific MHC-peptide tetramers, including on a per-T cell receptor (TcR) basis. In addition, surviving antiviral CTLs also appeared to be functionally deficient, based on both their reduced ability to lyse specific target cells and to produce interferon (IFN)-gamma. Carboxyfluorescein diacetate succinimidyl ester staining confirmed that AKR/Gross MuLV-specific CTLs proliferated less extensively when AKR.H-2b veto cells were included in cocultures. AKR/Gross MuLV-specific effector CTLs as well as memory CTLs were each efficiently targeted for inhibition by AKR.H-2b veto cells. Attempts to enhance the quality of the priming by multiple in vivo immunizations did not alter the capacity of the AKR.H-2b cells to inhibit the antiviral CTL response. These results further characterize the nature of the interaction between veto cells and antiviral CTLs, and underscore the efficiency of veto cell-mediated inhibition of the CTL response.


Recording of one-dimensionally dispersed holograms in white light.
A conventional lens system is incorporated into a three-grating interferometer, producing a system for making 1-D dispersed holograms in white light. A hologram of a 2-D transparency was made so that in 1-D the object was imaged onto the hologram, whereas in the orthogonal dimension, the image formed some distance from the hologram plane.


Co-recycling of acrylonitrile-butadiene-styrene waste plastic and nonmetal particles from waste printed circuit boards to manufacture reproduction composites.
This study investigated the feasibility of using acrylonitrile-butadiene-styrene (ABS) waste plastic and nonmetal particles from waste printed circuit boards (WPCB) to manufacture reproduction composites (RC), with the aim of co-recycling these two waste resources. The composites were prepared in a twin-crew extruder and investigated by means of mechanical testing, in situ flexural observation, thermogravimatric analysis, and dimensional stability evaluation. The results showed that the presence of nonmetal particles significantly improved the mechanical properties and the physical performance of the RC. A loading of 30 wt% nonmetal particles could achieve a flexural strength of 72.6 MPa, a flexural modulus of 3.57 GPa, and an impact strength of 15.5 kJ/m2. Moreover, it was found that the application of maleic anhydride-grafted ABS as compatilizer could effectively promote the interfacial adhesion between the ABS plastic and the nonmetal particles. This research provides a novel method to reuse waste ABS and WPCB nonmetals for manufacturing high value-added product, which represents a promising way for waste recycling and resolving the environmental problem.


The Loss of GSTM1 Associates with Kidney Failure and Heart Failure.
Glutathione S-transferase mu 1 (GSTM1) encodes an enzyme that catalyzes the conjugation of electrophilic compounds with glutathione to facilitate their degradation or excretion. The loss of one or both copies of GSTM1 is common in many populations and has been associated with CKD progression. With the hypothesis that the loss of GSTM1 is also associated with incident kidney failure and heart failure, we estimated GSTM1 copy number using exome sequencing reads in the Atherosclerosis Risk in Communities (ARIC) Study, a community-based prospective cohort of white and black participants. Overall, 51.2% and 39.8% of white participants and 25.6% and 48.5% of black participants had zero or one copy of GSTM1, respectively. Over a median follow-up of 24.6 years, 256 kidney failure events occurred in 5715 participants without prevalent kidney failure, and 1028 heart failure events occurred in 5368 participants without prevalent heart failure. In analysis adjusted for demographics, diabetes, and hypertension, having zero or one copy of GSTM1 associated with higher risk of kidney failure and heart failure (adjusted hazard ratio [95% confidence interval] for zero or one versus two copies of GSTM1: kidney failure, 1.66 [1.27 to 2.17]; heart failure, 1.16 [1.04 to 1.29]). Risk did not differ significantly between participants with zero and one copy of GSTM1 (P>0.10). In summary, the loss of GSTM1 was significantly associated with incident kidney and heart failure, independent of traditional risk factors. These results suggest GSTM1 function is a potential treatment target for the prevention of kidney and heart failure.


[Treatment of scaphoid nonunion with bone flap pedicled on the recurrent branch of radial artery to the styloid process].
To report the clinical outcome of the transposition of the radial styloid bone flap pedicled on the recurrent branch of the radial artery in the treatment of scaphoid nonunion. From March 2000 to June 2005, the procedure was done in 18 patients with scaphoid nonunion, a small bone flap (1.5 cm x 3.5 cm x 0.5 cm) pedicled on the recurrent branch of radial artery to the styloid process was raised from the radial styloid process and grafted into the corresponding slot chiseled along the vertical axis of scaphoid crossing the fracture line. Of 18 patients, 15 were males and 3 were females, aging 18-39 years. The locations were lumbar scaphoid in 11 patients and proximal scaphoid in 7 patients, among whom 5 had presented avascular necrosis in the proximal fragments of the scaphoid. Pain occurred in the act of wrist motion, and became obvious in the case of dorsiextension and radial deviation. Compression pain was observed in the stuff nest. The wrist joint activity is subjected to limit. The X-ray showed hardening and cystic degeneration at fracture end and obviously widening fracture line. The scaphoid fracture healed in all 18 cases, the 5 proximal scaphoid fracture fragments which had previously been necrosed survived, a mean healing time of scaphoid was 4 months. A follow-up of 1 to 5 years revealed normal wrist motion without pain in all cases. The life and job was good every day. Transposition of the bone flap pedicled on the recurrent branch of the radial artery to the scaphoid is relatively simple and can effectively treat scaphoid nonunion and avascular necrosis with a great value in clinical application.


Exposure of Dunaliella tertiolecta to lead and aluminum: toxicity and effects on ultrastructure.
The growth response of the marine alga Dunaliella tertiolecta to different concentrations of lead and aluminum was investigated. Both metals had a stimulatory effect at low concentration and an inhibitory effect at high concentration (hormesis). The IC25 values of lead are 8.43, 7.29, and 6.74 mg L-1 for 24, 48, and 72 h, respectively. The corresponding values for aluminum are 30.54, 22.42, and 18.16 mg L-1. Although it seems that the two metals are not directly toxic to the alga at the concentrations found in the environment, as implied by the IC25 values and the environmental concentrations of the metals, low concentrations of both metals, alone and in combination, affected the ultrastructure. The growth of batch-grown cells exposed to 0.5 mg L-1 lead and aluminum, alone and combined, during the 24-h exponential phase was investigated. The same cells were also examined under an electron microscope to determine the biological effects of the two metals on the ultrastructure. The most obvious effects of lead were disrupted thylakoidal membranes, accumulated polyphosphate bodies and vacuoles, and lead precipitates on the cell surface. These ultrastructural alterations were partially present in aluminum-treated and lead-aluminum-treated cells. In joint exposure, the most important change was the lysis of the cell membrane. Aluminum and lead seem to act synergistically on the cell membrane leading to cell membrane lysis.


COVID-19 vaccination and menstrual disorders among women: Findings from a meta-analysis study.
COVID - 19 vaccine can lead to various local and systemic side effects, including menstrual irregularities in women. There is no robust quantitative evidence of the association between the COVID - 19 vaccine and menstrual irregularities. A meta-analysis was performed to estimate the pooled prevalence of a range of menstrual disorders that may occur in women following COVID - 19 vaccination. After searching for epidemiological studies, we systematically performed a meta-analysis on PubMed/Medline, EMBASE, and Science Direct. Sixteen studies were finally included in the study. We estimated the pooled prevalence and corresponding 95 % confidence intervals (CIs) for a group of menstrual disorders, including menorrhagia, polymenorrhea, abnormal cycle length, and oligomenorrhea. Heterogeneity was assessed using the I2 statistic and the Q test. Overall, the pooled prevalence of menorrhagia was 24.24 % (pooled prevalence 24.24 %; 95 % CI: 12.8-35.6 %). The pooled prevalence of polymenorrhea was 16.2 % (pooled prevalence: 16.2 %; 95 % CI: 10.7-21.6 %). The pooled prevalence of abnormal cycle length was relatively lower than that of the other disorders (pooled prevalence: 6.6 %; 95 % CI: 5.0-8.2 %). The pooled prevalence of oligomenorrhea was 22.7 % (95 % CI: 13.5-32.0 %). The findings indicate that menorrhagia, oligomenorrhea, and polymenorrhea were the most common menstrual irregularities after vaccination. The findings also suggest that a relatively high proportion of women suffer from menstrual irregularities. Further longitudinal studies are needed to confirm the causal relationship between COVID-19 vaccination and menstrual irregularities.


Research education: findings of a study of teaching-learning research using multiple analytical perspectives.
This multimethod, qualitative study provides results for educators of nursing doctoral students to consider. Combining the expertise of an empirical analytical researcher (who uses statistical methods) and an interpretive phenomenological researcher (who uses hermeneutic methods), a course was designed that would place doctoral students in the midst of multiparadigmatic discussions while learning fundamental research methods. Field notes and iterative analytical discussions led to patterns and themes that highlight the value of this innovative pedagogical application. Using content analysis and interpretive phenomenological approaches, together with one of the students, data were analyzed from field notes recorded in real time over the period the course was offered. This article describes the course and the study analysis, and offers the pedagogical experience as transformative. A link to a sample syllabus is included in the article. The results encourage nurse educators of doctoral nursing students to focus educational practice on multiple methodological perspectives.


Summer dormancy in edible dormice (Glis glis) without energetic constraints.
Average longevity in free-living edible dormice (Glis glis) can reach 9 years, which is extremely high for a small rodent. This remarkable life span has been related to a peculiar life history strategy and the rarity of reproductive bouts in these seed eaters. Most females (96%) reproduce only once or twice in their lifetime, predominantly during years of mast seeding of, e.g., beech, but entire populations can skip reproduction in years of low seed availability. Surprisingly, in non-reproductive years, large fractions of populations apparently vanished and were never captured above ground. Therefore, we determined the duration of above-ground activity, and body temperature profiles in a subset of animals, of dormice under semi-natural conditions in outdoor enclosures. We found that non-reproductive dormice returned to dormancy in underground burrows throughout summer after active seasons as short as <2 weeks. Thus, animals spent up to >10 months per year in dormancy. This exceeds dormancy duration of any other mammal under natural conditions. Summer dormancy was not caused by energy constraints, as it occurred in animals in good condition, fed ad libitum and without climatic stress. We suggest that almost year-round torpor has evolved as a strategy to escape birds of prey, the major predators of this arboreal mammal. This unique predator-avoidance strategy clearly helps in explaining the unusually high longevity of dormice.


Reference ranges for fetal brain structures using magnetic resonance imaging: systematic review.
To evaluate the methodology of studies reporting reference ranges for fetal brain structures on magnetic resonance imaging (MRI). MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to 31 December 2020 to identify studies investigating biometry and growth of the fetal brain and reporting reference ranges for brain structures using MRI. The primary aim was to evaluate the methodology of these studies. A list of 26 quality criteria divided into three domains, including 'study design', 'statistical and reporting methods' and 'specific aspects relevant to MRI', was developed and applied to evaluate the methodological appropriateness of each of the included studies. The overall quality score of a study, ranging between 0 and 26, was defined as the sum of scores awarded for each quality criterion and expressed as a percentage (the lower the percentage, the higher the risk of bias). Fifteen studies were included in this systematic review. The overall mean quality score of the studies evaluated was 48.7%. When focusing on each domain, the mean quality score was 42.0% for 'study design', 59.4% for 'statistical and reporting methods' and 33.3% for 'specific aspects relevant to MRI'. For the 'study design' domain, sample size calculation and consecutive enrolment of women were the items found to be at the highest risk of bias. For the 'statistical and reporting methods' domain, the presence of regression equations for mean and SD for each measurement, the number of measurements taken for each variable and the presence of postnatal assessment information were the items found to be at the highest risk of bias. For the 'specific aspects relevant to MRI' domain, whole fetal brain assessment was not performed in any of the included studies and was therefore considered to be the item at the highest risk of bias. Most of the previously published studies reporting fetal brain reference ranges on MRI are highly heterogeneous and have low-to-moderate quality in terms of methodology, which is similar to the findings reported for ultrasound studies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.


Overexpression of c-src enhances beta-adrenergic-induced cAMP accumulation.
During our investigations into the physiological role of c-src tyrosine kinase in normal cells, we found that clonal transfectants of C3H10T1/2 murine fibroblasts overexpressing chicken c-src exhibited strikingly elevated levels of cAMP accumulation in response to adrenergic stimulation as compared to control cells. Enhanced cAMP accumulations were detected when cells were treated with the beta-agonists, epinephrine, isoproterenol, or terbutaline and were blocked by treatment with the beta-specific antagonist propranolol, indicating action through beta-adrenergic receptors. The hyperresponsiveness was not observed in cells overexpressing kinase-defective c-src. No differences in basal levels of cAMP, agonist concentration dependence, or kinetics of cAMP accumulation were detected between cells containing elevated levels of wild-type or kinase-defective c-src protein and control cells. To determine if the degree of c-src overexpression could influence the response, multiple clones, transfected with DNA encoding genes for wild-type or kinase-defective c-src plus neomycin resistance or neomycin resistance alone, were derived in parallel and assayed for the amounts of c-src protein produced and the levels of cAMP accumulated in response to epinephrine. Only clones with abundant wild-type c-src protein (greater than 10-fold above endogenous) exhibited enhanced cAMP accumulation, averaging 3.3-fold above control cells. We conclude, therefore, that the enhanced degree of cAMP accumulation in cells overexpressing c-src is dependent upon activation of beta-adrenergic receptors and upon a threshold level of pp60c-src that retains full tyrosine kinase activity.


Impaired activity of volume-sensitive Cl- channel is involved in cisplatin resistance of cancer cells.
The platinum-based drug cisplatin is a widely used anticancer drug which acts by causing the induction of apoptosis. However, resistance to the drug is a major problem. In this study we show that the KCP-4 human epidermoid cancer cell line, which serves as a model of acquired resistance to cisplatin, has virtually no volume-sensitive, outwardly rectifying (VSOR) chloride channel activity. The VSOR chloride channel's molecular identity has not yet been determined, and semi-quantitative RT-PCR experiments in this study suggested that the channel corresponds to none of three candidate genes. However, because it is known that the channel current plays an essential role in apoptosis, we hypothesized that lack of the current contributes to cisplatin resistance in these cells and that its restoration would reduce resistance. To test this hypothesis, we attempted to restore VSOR chloride current in KCP-4 cells. It was found that treatment with trichostatin A (TSA), a histone deacetylase inhibitor, caused VSOR chloride channel function to be partially restored. Treatment of the cells with both TSA and cisplatin resulted in an increase in caspase-3 activity at 24 h and a decrease in cell viability at 48 h. These effects were blocked by simultaneous treatment of the cells with a VSOR chloride channel blocker. These results indicate that restoration of the channel's functional expression by TSA treatment leads to a decrease in the cisplatin resistance of KCP-4 cells. We thus conclude that impaired activity of the VSOR chloride channel is involved in the cisplatin resistance of KCP-4 cancer cells.


[Seasonal and national differences in the selenium supply of horses across Europe].
Evaluation of the differences in the selenium supply to horses across Europe. Serum samples from 137,152 horses all over Europe, which had been sent by veterinarians to IDEXX Vet Med Labor between January 1st 2006 and December 31st 2011, were routinely analyzed for the selenium concentration by means of ICP-analytic. The selenium content of the soil appears to play a key role in the selenium supply to horses. Countries closer to the ocean provided a better selenium supply than countries in central Europe. The best selenium supply can be seen in Denmark and in the Netherlands. The lowest values are obtained from Austria and Luxembourg. Furthermore, very large differences exist in the selenium supply in different regional areas within a country. This is particularly obvious across the German federal states, with a very good supply in the western areas and a very poor supply in the eastern states. The north-south divide is less obvious, similar to the selenium content of the soil. A very poor situation exists for central Austria, where more than 50% of the equine samples revealed an undersupply. Individual horse-keeping and feeding represent key points in the selenium supply. Because of the differences in the selenium concentrations in pasture, silage and hay, and due to the lack of routinely performed analysis of the mineral content of food, it is extremely difficult from a management point of view to precisely adapt the intake of minerals. Hence, serum analyses of selenium in horses are very important and should be performed annually. In the case of an undersupply, selenium has to be supplemented with mineral food.


Shrimp and cockroach co-sensitization in Southern China: Association with moth sensitization.
Background: Moth is a common allergen in southern China. Shrimp sensitization might be related to the moth allergen. Objective: This study investigated sensitization to moth allergen in patients in southern China sensitized to shrimp and explored the effect of moth sensitization on different allergic diseases. Methods: Serum samples from 212 patients sensitized to shrimp were tested for specific immunoglobulin E (sIgE) to Dermatophagoides pteronyssinus, crab, cockroach, and moth. Results: The patients sensitized to shrimp were co-sensitized to D. pteronyssinus (88.7%), crab (85.4%), cockroach (89.2%), and moth (92.0%). Overall, 75% of the patients sensitized to shrimp tested positive to the above allergens; only four patients were sensitized to shrimp alone. The median (interquartile range [IQR]) concentrations of sIgE to shrimp (2.66 kU/L [1.02-6.11 kU/L] versus 1.61 kU/L [0.70-3.67 kU/L]), crab (2.35 kU/L [0.83-4.18 kU/L] versus 1.30 kU/L [0.59-3.14 kU/L]), cockroach (3.78 kU/L [0.98-6.91 kU/L] versus 1.56 kU/L [0.85-3.17 kU/L]), and moth (4.70 kU/L [2.98-9.62 kU/L] versus 2.85 kU/L [1.16-7.01 kU/L]) in patients with skin allergic diseases was significantly higher than in patients with respiratory allergic diseases (all p < 0.05). The median (IQR) concentration of sIgE to cockroach in the young adults (2.33 kU/L [0.86-5.56 kU/L]) was the highest among all age groups as well as to moth (young adults: 4.14 kU/L [1.93-8.24 kU/L]). With the increasing positive class of shrimp allergen, the sIgE concentration of moth, cockroach, and crab also increased, and the optimal scaling analysis showed that the sIgE of crab, cockroach, and moth had a strong correlation with sIgE to shrimp (Cronbach α = 93.8%). Conclusion: This study found a high rate of co-sensitization between moth, D. pteronyssinus, cockroach, and crab among patients sensitized to shrimp and a strong correlation between shrimp, moth, and cockroach. Shrimp and cockroach co-sensitization might be related to moth allergens.


Mental health - cultural competence.
Depression, and its associated anxiety, is very common in the community and frequently managed in general practice. Yet it remains a problematic concept. Differing views of depression influence both clinical practice and research. This article discusses the way each patient's culture interacts with other important contexts of clinical practice to shape how depression is understood and managed. Cultural and linguistic diversity interacts with socioeconomic factors in determining the known prevalence of depression and anxiety. Detection of depression may be shaped by expectations and assumptions of both the general practitioner and patient. Language and communication barriers mean interpreters are critical to mental health care. Culturally sensitive care for depression requires a reflective approach based on a negotiated understanding of the patient's experiences and symptoms.


A micro-CT study of microstructure change of alveolar bone during orthodontic tooth movement under different force magnitudes in rats.
The dynamic changes of the microstructure of alveolar bone during orthodontic tooth movement in rats was explored by employing micro-computed tomography (micro-CT) system and to provide theoretical reference for clinical orthodontic treatment. Ten rats were selected randomly as control among 70 adult female Wistar rats, and the other 60 rats were divided into 25-g and 75-g groups of equal number. Orthodontic appliance with force of 25 g and 75 g was installed to perform the molar mesial movement. Microstructural parameters for trabecular bone mesial to the distobuccal root were evaluated at different time points using micro-CT system. Moreover, distance for mesial movement of the molar were measured. Microstructural parameters for trabecular bone of two groups showed no significant changes from day 0 to day 3 (P>0.05); from day 3 to day 7, bone mineral density (BMD), bone volume/total volume (BV/TV) and trabecular thickness (Tb.Th) decreased significantly (P<0.05), whereas trabecular separation (Tb.Sp) and structure model index (SMI) increased significantly (P<0.05); from day 7 to day 14, in 25-g group, BMD, BV/TV and Tb.Th increased significantly (P<0.05), while Tb.Sp and SMI decreased significantly (P<0.05). Correspondingly, in 75-g group, changes of parameters did not carry any statistical significance (P>0.05). Furthermore, the 75-g group showed larger distance than 25-g group only at day 14 (P<0.05). In conclusion, in order to maintain the health of periodontal tissues, adequate time for repair and recovery is needed to ensure reasonable remolding of alveolar bone and healthy movement of the orthodontic tooth.


Biodegradation of genetically modified seeds and plant tissues during composting.
The increasing global market of genetically modified (GM) crops amplifies the potential for unintentional contamination of food and feed with GM plants. Methods proposed for disposal of crop residues should be assessed to prevent unintended distribution of GM materials. Composting of organic material is inexpensive and location-independent. The objective of this study was to determine the effectiveness of composting for disposal of GM plants in terms of reducing seed viability and promoting the degradation of endogenous as well as transgenic DNA. Duplicate samples of corn kernels, alfalfa leaves, and GM canola seeds, meal and pellets were sealed in porous nylon bags and implanted in duplicate 85,000 kg (initial weight) feedlot manure compost piles. Samples were collected at intervals over 230 days of composing. Canola seeds and corn kernels were not viable after 14 days of composting with temperatures in the piles exceeding 50 degrees C. In all samples, PCR analyses revealed that plant endogenous and transgenic fragments were substantially degraded after 230 days of composting. Southern blotting of genomic DNA isolated from canola seeds identified differences in the persistence of endogenous, transgenic, and bacterial DNA. Composting GM and non-GM plant materials with manure rendered seeds non-viable, and resulted in substantial, although not complete, degradation of endogenous and transgenic plant DNA. This study demonstrates that composting could be effective for disposing of GM crops in the event of their inadvertent entry into the food or feed chain.


Analytical methods for immunogenetic population data.
In this chapter, we describe analyses commonly applied to immunogenetic population data, along with software tools that are currently available to perform those analyses. Where possible, we focus on tools that have been developed specifically for the analysis of highly polymorphic immunogenetic data. These analytical methods serve both as a means to examine the appropriateness of a dataset for testing a specific hypothesis, as well as a means of testing hypotheses. Rather than treat this chapter as a protocol for analyzing any population dataset, each researcher and analyst should first consider their data, the possible analyses, and any available tools in light of the hypothesis being tested. The extent to which the data and analyses are appropriate to each other should be determined before any analyses are performed.


Inside the fragile world of eating disorders.
'Take yourself back to the age of 15. What thoughts swirled around your head? Did you worry about how you looked or what your friends and teachers thought of you?' Wendy Clarke, specialist lead for eating disorders at Aneurin Bevan University Health Board in South Wales, believes nurses should be asking themselves these questions if they are to fully empathise, engage with and help young people with eating disorders.


Flavonoids and strigolactones in root exudates as signals in symbiotic and pathogenic plant-fungus interactions.
Secondary plant compounds are important signals in several symbiotic and pathogenic plant-microbe interactions. The present review is limited to two groups of secondary plant compounds, flavonoids and strigolactones, which have been reported in root exudates. Data on flavonoids as signaling compounds are available from several symbiotic and pathogenic plant-microbe interactions, whereas only recently initial data on the role of strigolactones as plant signals in the arbuscular mycorrhizal symbiosis have been reported. Data from other plant-microbe interactions and strigolactones are not available yet. In the present article we are focusing on flavonoids in plant-fungal interactions such as the arbuscular mycorrhizal (AM) association and the signaling between different Fusarium species and plants. Moreover the role of strigolactones in the AM association is discussed and new data on the effect of strigolactones on fungi, apart from arbuscular mycorrhizal fungi (AMF), are provided.


Synthesis of medium-sized (6-7-6) ring compounds by iron-catalyzed C-H activation/annulation [corrected].
In this report, we have described a FeCl3-catalyzed process involving intramolecular annulation of o-phenoxy diarylacetylenes via hydroarylation to afford a series of biologically potent fused seven-membered (6-7-6) ring compounds under mild reaction conditions. This reaction was believed to proceed through Friedel-Crafts type sequential carbometallation followed by protonation to produce phenyldibenz[b,f]oxepines. This method was also extended to synthesize seven-membered rings that are fused with coumarins.


Comparison of Bioactive Secondary Metabolites and Cytotoxicity of Extracts from Inonotus obliquus Isolates from Different Host Species.
Inonotus obliquus, a wood-decaying mushroom, has been used as a health-promoting supplement and nutraceutical for centuries. It is a source of bioactive compounds accumulated in both the conks (pseudosclerotia/sclerotia) and the biomass obtained in vitro. This study aimed to qualitatively and quantitatively analyze the bioelements and selected metabolites produced in mycelial cultures obtained from different host species. The mycochemical potential of mycelial cultures isolated from pseudosclerotia grown in Betula pendula, Alnus glutinosa, and Carpinus betulus was compared. Parent cultures were obtained in two types of medium (malt extract agar substrates without and with birch wood). Experimental cultures were developed in 2 L bioreactors for 10 days. The content of bioelements was determined using FAAS and FAES methods. Organic compounds were estimated using the RP-HPLC-DAD method. The cytotoxicity of the extracts was evaluated in human keratinocytes HaCaT, human skin fibroblasts BJ, human liver cancer HepG2, human melanoma A375, and mouse melanoma B16-F10. The extracts showed the presence of bioelements: sodium, potassium, magnesium, calcium, zinc, manganese, iron, and copper; phenolic acids: p-hydroxybenzoic, caffeic, p-coumaric, and protocatechuic; sterols: lanosterol, ergosterol, ergosterol peroxide; triterpene compounds: betulin, betulinic acid, inotodiol; indole compounds: L-tryptophan, tryptamine, 5-methyltryptamine, melatonin. The content of bioactive substances in the biomass was dependent on both the origin of the host species of the fungus isolate and the type of culture medium. Based on the results of this study, mycelial cultures can be proposed as a potential source of bioactive compounds and are promising naturally derived cytotoxic agents.


[Therapy of herpes simplex].
The efficiency of nucleoside analogs for the management of herpes-simplex-infections has been established. It has been pointed out by many studies, that aciclovir is well tolerated and shortens both symptoms and lesions of herpes-simplex-infections. A continuous oral aciclovir management up to six month suppresses recurrences of genital herpes under therapy significantly.


[Multiple molecular forms of glutamine synthetase in carp muscles].
Cytoplasmic and mitochondrial molecular forms of glutamine synthetase (CE 220.127.116.11) have been isolated from the carp muscle with purification degree of 100 and 165 times and output 9.0%. It is established that the temperature optimum of the cytoplasmic form activity is 30 degrees C and that of mitochondrial one--20 degrees C; the pH optimum for the both molecular forms is 6.0 and 8.2. The optimal ratio [Me2+] : [ATP] for the isolated form is 2:1; Km (seeming) of the cytoplasmic form in the presence of Mg2+ is 6.0 mM for glutamate, 0.035 for ammonium, for ATP 0.5 and 0.7 for magnesium ions; these values for the mitochondrial form are: 14.3, 0.048, 1.0 and 0.8 mM, respectively. Activity of the both glutamine synthetases with Mg2+ ions is almost by 50% higher than that of glutamine synthetases with Mn2+ ions. Seasonal regularities of the synthesis of molecular glutamine synthetase forms have been established in vivo. Cytoplasmic form is present in the muscles all year round, while mitochondrial one only in winter at low temperature of the environment and fish starvation. Differences in properties and seasonal character of synthesis of molecular glutamine synthetase forms in carp muscles are a result of diversity of their functional role.


Neuroleptic management of schizophrenia: a survey and commentary on Australian psychiatric practice.
We seek to assess Australian psychiatrists' views and practices concerning provision of neuroleptic medication to patients with schizophrenia, and to determine whether such management strategies are likely to have changed over time and the extent to which they correspond to published treatment guidelines. A sample of 139 psychiatrists based in three Australian capital cities was derived, with respondents completing a brief questionnaire by choosing from a limited-option answer set. Co-authors of this paper comment on the extent to which responses are in line with contemporary recommendations driven by experts or empirical studies. Overall, survey findings indicate that there has been considerable change in clinical practice over the last decade and provide some estimate of the extent to which Australian management practices are congruent with contemporary recommendations. We identify a number of issues of concern (more in relation to dose levels of neuroleptic medication rather than treatment duration) revealed by survey data and make recommendations for addressing a number of practical clinical issues. As this report focuses on central issues involved in managing schizophrenia, and integrates a number of treatment guidelines, we suggest that it should be of assistance for practice review by clinicians.


Specific mitochondrial DNA mutation in mice regulates diabetes and lymphoma development.
It has been hypothesized that respiration defects caused by accumulation of pathogenic mitochondrial DNA (mtDNA) mutations and the resultant overproduction of reactive oxygen species (ROS) or lactates are responsible for aging and age-associated disorders, including diabetes and tumor development. However, there is no direct evidence to prove the involvement of mtDNA mutations in these processes, because it is difficult to exclude the possible involvement of nuclear DNA mutations. Our previous studies resolved this issue by using an mtDNA exchange technology and showed that a G13997A mtDNA mutation found in mouse tumor cells induces metastasis via ROS overproduction. Here, using transmitochondrial mice (mito-mice), which we had generated previously by introducing G13997A mtDNA from mouse tumor cells into mouse embryonic stem cells, we provide convincing evidence supporting part of the abovementioned hypothesis by showing that G13997A mtDNA regulates diabetes development, lymphoma formation, and metastasis--but not aging--in this model.


Impact of Extracapsular Lymph Node Involvement After Neoadjuvant Chemoradiation Therapy Followed by Surgery in Carcinoma of the Esophagus: A Multicenter Study.
The current study aims to examine the impact of extracapsular lymph node involvement (EC-LNI) on survival for both esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) treated with neoadjuvant chemoradiation therapy (nCRT) followed by surgery. Studies have demonstrated the negative prognostic value of EC-LNI in primary surgery, but its impact after nCRT remains unclear. From the databases of 6 European high-volume centers 1505 patients with R0 resections were withheld. Oncologic variables, including ypT, ypN, number of positive lymph nodes, and lymph node capsular status: EC-LNI and intracapsular lymph node involvement (IC-LNI), were examined. Statistical analysis was performed by Cox proportional hazards modeling. In SCC 182 patients (31.6%) had positive lymph nodes, of whom 60 (33.0%) showed EC-LNI. In AC 391 patients (42.1%) had positive lymph nodes, of whom 147 (37.6%) showed EC-LNI. Overall 5-year survival (O5YS) in SCC was 42.0%. Presence of EC-LNI meant a significantly worse O5YS than IC-LNI or pN0 (10.6%, 39.5%, and 47.4%, respectively; P < 0.05). O5YS in AC was 41.2%. No significant difference was observed between EC-LNI and IC-LNI (P = 0.322). In the multivariate analysis, among the examined possible prognosticators, presence of EC-LNI showed the highest hazard ratio (2.29, confidence interval: 1.52-3.47) as an independent prognosticator for overall survival in SCC, but it was not in AC. Based on this international multicenter study, the presence of EC-LNI after nCRT is at least as important as N-stage for survival and EC-LNI is the strongest prognosticator for overall survival in SCC but not in AC.


Evaluation of combined effects of brief electrical stimulation and Schwann-like cells on sciatic nerve injury model.
Severe nerve injuries can be treated with electrical stimulation and stem cell therapies, but little is known about the potential benefits of combining these two treatments. In an effort to investigate this combination, we conducted a study to evaluate the effectiveness of electrical stimulation and Schwann-like cell transplantation in female Wistar albino rats. Our study consisted of five groups of rats: a sham group, an injury group, an electrical stimulation group, a Schwann-like cell group, and a combination group. The experimental groups received electrical stimulation, Schwann-like cell transplantation, or both. The animals sciatic function index was evaluated during a 6-week recovery period, and nerve conduction velocity, wet muscle mass, and nerve tissues were also analyzed. The results of the study showed that all experimental groups had a faster functional recovery compared to the injury group, although the difference between groups was not statistically significant. Both the combination group and the Schwann-like cell transplantation group had a higher nerve conduction velocity compared to the other experimental groups. However, there was no significant difference between the combination and Schwann-like cell transplantation groups. Nonetheless, histological analysis showed a better axonal reorganization in the combination group. The study provides preliminary evidence of the potential benefits of combining electrical stimulation and Schwann-like cell transplantation in treating severe nerve injuries. However, further studies with larger sample sizes are needed to confirm these findings and optimize the treatment parameters.


Network Structure Explains the Impact of Attitudes on Voting Decisions.
Attitudes can have a profound impact on socially relevant behaviours, such as voting. However, this effect is not uniform across situations or individuals, and it is at present difficult to predict whether attitudes will predict behaviour in any given circumstance. Using a network model, we demonstrate that (a) more strongly connected attitude networks have a stronger impact on behaviour, and (b) within any given attitude network, the most central attitude elements have the strongest impact. We test these hypotheses using data on voting and attitudes toward presidential candidates in the US presidential elections from 1980 to 2012. These analyses confirm that the predictive value of attitude networks depends almost entirely on their level of connectivity, with more central attitude elements having stronger impact. The impact of attitudes on voting behaviour can thus be reliably determined before elections take place by using network analyses.


Efficacy of platelet-rich fibrin on bone formation, part 2: Guided bone regeneration, sinus elevation and implant therapy.
To investigate the effect of platelet-rich fibrin on bone formation by investigating its use in guided bone regeneration, sinus elevation and implant therapy. This systematic review and meta-analysis were conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The eligibility criteria comprised human controlled clinical trials comparing the clinical outcomes of platelet-rich fibrin with those of other treatment modalities. The outcomes measured included percentage of new bone formation, percentage of residual bone graft, implant survival rate, change in bone dimension (horizontal and vertical), and implant stability quotient values. From 320 articles identified, 18 studies were included. Owing to the heterogeneity of the investigated parameters, a meta-analysis was only possible for sinus elevation. There is a general lack of data from comparative randomised clinical trials evaluating platelet-rich fibrin for guided bone regeneration procedures (only two studies), with no quantifiable advantages in terms of new bone formation or dimensional bone gain found in the platelet-rich fibrin group. For sinus elevation, the meta-analysis demonstrated no advantage in terms of histological new bone formation in the control group (bone graft alone) compared with the test group (bone graft and platelet-rich fibrin). Two studies demonstrated that platelet-rich fibrin may shorten healing periods prior to implant placement. Platelet-rich fibrin was also shown to slightly enhance primary implant stability (implant stability quotient value < 5) as assessed using implant stability quotients and resonance frequency analysis parameters, with no histological data evaluating bone-implant contact yet available on this topic. In one study, platelet-rich fibrin was shown to improve the clinical parameters when utilised as an adjunct for the treatment of peri-implantitis. In the majority of studies, platelet-rich fibrin offered little or no clear advantage in terms of new bone formation as evaluated in various studies on guided bone regeneration and sinus elevation, nor in implant stability and treatment of peri-implantitis. Various authors and systematic reviews on the topic have now expressed criticism of the various study designs and protocols, and the lack of appropriate controls and available information regarding patient selection. Well-controlled human studies on these specific topics are required.


A validated HPLC assay for simultaneous analysis of salmon calcitonin and duck ovomucoid.
A highly sensitive and selective analytical HPLC method is reported for the simultaneous measurement of salmon calcitonin (sCT) and its enzyme inhibitor, duck ovomucoid (dOVM). The method used a reversed phase C-18 column (4.6 x 250 mm, 5 microm) at room temperature. The elution was achieved using a gradient technique (20-35% B for 10 min, 35-37% B from 10th to 20th min and 37-20% B from 20th to 25th min). The mobile phase used was 0.05% v/v trifluoroacetic acid (TFA) in water and 0.05% v/v TFA in acetonitrile with a flow rate of 1 ml/min. Detection was carried out by UV spectrophotometry at 210 nm. sCT and dOVM were eluted at 7.8 and 15.4 min respectively, free from any interfering endogenous peaks during a run time of 25 min. Linear relationships were observed between the detector response and the concentrations of the analytes (10-100 microg/ml for CT (r2 = 0.996) and 10-100 microg/ml for the dOVM (r2 = 0.999)). The assay was found to be highly selective and sensitive due to the absence of any interfering peaks. The lower C.V. and % error values of the assay indicates that the assay could accurately and precisely quantitate both sCT and dOVM in the examined concentration range. This method can be usedfor the simultaneous quantitative analysis of sCT and dOVM.


Regioselective Metal-Free Decarboxylative Multicomponent Coupling of α-Amino Acids, Aldehydes and Isonitriles Leading to N-Substituted Azacyclic-2-carboxamides with Antithrombotic Activity.
An atom-economical regioselective synthesis of N-substituted prolinamides or N-substituted piperidine-2-carboxamides via a metal-free decarboxylative multicomponent coupling between l-proline or pipecolic acid, aldehydes, and isonitriles is described. The cascade event involves sequential imine formation, decarboxylation, isonitrile insertion, and hydrolysis to afford the product in one-pot. Two of the prolinamides were found to display appreciable antithrombotic activity via inhibition of platelet aggregation.


Perceived utility of an integrated psychological intervention for gynaecological cancer patients admitted for surgery: preliminary data.
To investigate patients' satisfaction and perceived utility for psychological consultations delivered by clinical psychologists in a sample of gynaecological cancer patients hospitalised for surgery. A total of 51 gynaecological cancer patients who scored higher than four on the distress thermometer (DT) were proposed and received a psychological consultation during hospitalisation for surgery. After six months from discharge, patients were asked, during a telephone interview, to rate their level of distress post-treatment, their perceived satisfaction, and usefulness of the psychological intervention received. At the time of the telephone interview, the distress levels stated by patients tended to be lower than those at hospital admission, and around 61% of the patients expressed maximum satisfaction with psychological intervention. Among these, 60.8% rated the psychological consultation useful for dealing with the hospitalisation itself, 45.1% useful for dealing with personal issues and 58.8% for dealing with issues related to returning home. People who were at their first diagnosis and those who had no other reason to be distressed beyond their cancer found psychological support significantly more useful for facing up to personal issues. Patients are highly satisfied with integrative psychological interventions delivered by clinical psychologists in a medical setting such as that of gynaecological cancer surgery and from the six-month follow-up, it emerged that such interventions help in promoting patients' adjustment to the phase of hospitalisation and post-hospital discharge.


Frequency and long-term impact of myonecrosis after coronary stenting.
To study the frequency of creatine kinase MB elevation in stent recipients and to correlate the magnitude of myonecrosis with long-term ischaemic events. We evaluated the frequency and impact (major adverse ischaemic events) of creatine kinase MB elevation in 3478 patients undergoing planned coronary stenting and divided them in five strata according to peak creatine kinase MB: normal, 1-3 x, 3-5 x, 5-10 x and >10 x above upper limit of normal. Graft intervention was done in 15% and 61% received platelet glycoprotein IIb/IIIa receptor inhibitors. The average follow-up period was 15+/-15 (range 1-72) months. Creatine kinase MB elevation above upper limit of normal occurred in 24% and in 5.3% it was greater than 5 x upper limit of normal. The unadjusted rates of actuarial mortality in the five strata were: 7.5% (198/2637), 8.0% (40/502), 11.0% (17/155), 10.8% (11/102) and 29.3% (24/82), respectively, P<0.001. Logistic regression analysis including 18 demographic and procedural variables revealed that, in addition to age, extent of coronary disease, ventricular function and coronary risk profile, creatine kinase MB elevation was associated with a significant increase in major ischaemic events at follow-up. The excess risk was concentrated mainly in the highest stratum of creatine kinase MB elevation. Thus, in the era of stenting and aggressive adjunctive pharmacology, peri-procedural myonecrosis still remains frequent and has an important impact on long-term event-free survival. Intensive efforts to reduce creatine kinase MB elevation after revascularization are warranted and should lead to important benefits.


Effects of intermaxillary elastic traction on orthodontic tooth movement.
Intermaxillary elastics are commonly used in orthodontic treatment, yet the exact mechanism by which they effect tooth movement has been unclear. A photoelastic model was produced to stimulate this type of therapy in examples of Class II and III malocclusions. In the open situation, inter-arch activity precipitated occlusal plane rotation; counter clockwise in Class II malocclusion and clockwise in Class III. Comment is made on the force vectors involved when using intermaxillary elastics.


Long-term study on the effects of electroejaculation on seminal characteristics of the domestic cat.
Semen was collected by electroejaculation from 9 random-source cats. There were 22 seminal collections over 32 weeks. An electroejaculate was defined as the seminal fluid and spermatozoa collected during the application of 60 electrical stimuli--the 1st 40 stimuli at 2.0 V, and immediately afterward, 20 stimuli at 3.0 V. Four sequential electroejaculates were obtained from each cat at each seminal collection. The volume and number of spermatozoa for each electroejaculate were determined. There was a significant (P less than 0.005) effect of cat and sequence of electroejaculate for both the volume and number of spermatozoa in the electroejaculate . There was no effect of week of collection; however, there was a trend (P less than 0.1) for the volume of electroejaculate to increase with time. The interactions of cat X week of collection and electroejaculate sequence X week of collection for the volume and for the number of spermatozoa per electroejaculate were not significant (P greater than 0.05). The volume of the 1st electroejaculate of the sequence was lower (P less than 0.01) and the number of spermatozoa in the 2nd of the sequential electroejaculates was higher (P less than 0.05). There was considerable variation within and between cats in the volume and number of spermatozoa. Repeated anesthesia and electrical stimulation did not appear to alter the ejaculatory capacity of the cat.


Impact of Preoperative Risk Factors on Inpatient Stay and Facility Discharge After Free Flap Reconstruction.
To determine the preoperative risk factors most predictive of prolonged length of stay (LOS) or admission to a skilled nursing facility (SNF) or inpatient rehabilitation center (IPR) after free flap reconstruction of the head and neck. Retrospective cohort study. Tertiary academic medical center. Retrospective review of 1008 patients who underwent tumor resection and free flap reconstruction of the head and neck at a tertiary referral center from 2002 to 2019. Of 1008 patients (65.7% male; mean age of 61.4 years, SD 14.0 years), 161 (15.6%) were discharged to SNF/IPR, and the median LOS was 7 days. In multiple linear regression analysis, Charlson Comorbidity Index (CCI; P < .001), American Society of Anesthesiologists (ASA) classification (P = .021), female gender (P = .023), and inability to tolerate oral diet preoperatively (P = .006) were statistically significantly related to increased LOS, whereas age, body mass index (BMI), modified frailty index (MFI), a history of prior radiation or chemotherapy, and home oxygen use were not. Multiple logistic regression analysis demonstrated that CCI (odds ratio [OR] = 1.119, confidence interval [CI] 1.023-1.223), age (OR = 1.082, CI 1.056-1.108), and BMI <19.0 (OR = 2.141, CI 1.159-3.807) were the only variables statistically significantly related to posthospital placement in an SNF or IPR. Common tools for assessing frailty and need for additional care may be inadequate in a head and neck reconstructive population. CCI appears to be the best of the aggregate metrics assessed, with significant relationships to both LOS and placement in SNF/IPR.


Neuropsychological Effects of Placebo Stimulants in College Students.
Many college students underestimate or ignore the side-effects associated with nonmedical use of prescription stimulants (NMUPS) and are motivated by hopes of academic enhancement. The present study measured the effect a placebo stimulant and personal expectancies have on subjective physiological changes and cognitive enhancement. Undergraduate college students participated in a two-phase study. Phase 1 (n = 305) involved completing an online survey to gather distal study variables and individual stimulant expectancy data. Phase 2 (n = 166) required students to attend an in-person session where they completed physiological and neuropsychological measures (e.g., Physical Symptom Checklist, Digit Span, Passage Comprehension). Students were randomized to receive a placebo stimulant medication (experimental) or no medication (control). Following a 30-minute absorption period, participants completed another set of physiological and neuropsychological measures. Experimental participants reported significant increases in positive symptoms resulting from the placebo stimulant. Expectancies moderated the impact of the placebo stimulant on Passage Comprehension performance; no other neuropsychological task performance was impacted. Despite subjective reports of feeling the effects of stimulants, task performance was unaffected. Moreover, expectancies may play a small role in perceptions of the effects of stimulants.


[Qualitative characterization of flavonoids in Scutellariae Radix by using PREC-IDA-EPI].
Flavonoids are the most abundant constituents and induce these the rapeutic effects against inflammation, gastrointestinal infections, cardiovascular diseases, and respiratory. Most of these flavonoids have low content in Scutellarie Radix. It was difficult to detect some minor compounds by using LC-MS method with full scan. Based on the review of flavonoids that had been extracted from Scutellariae Radix, a method with PREC-IDA-EPI technique was developed and applied to Scutellariae Radix by using UPLC-MS/MS. A total of 97 flavonoids were identified, including 29 aglycones and 68 O-glycosides. This study laid the foundation for pharmacodynamicss of Scutellariae Radix.It is believed that an individual detection scheme based on the PREC-IDA-EPI technique could be used to identify unknown compounds.


Proximity Amplification-Enabled Electrochemical Analysis of Tumor-Associated Glycoprotein Biomarkers.
Glycoproteins produced and secreted from specific cells and tissues are associated with several diseases and emerge as typical biomarkers to provide useful information in cancer diagnosis considering their abnormal expression levels. In this work, we design a universal method to achieve the accurate and sensitive analysis of tumor-associated glycoprotein biomarkers based on both carbohydrate recognition and protein recognition at the same protein surface. The byproduct of dual recognition-induced proximity amplification, pyrophosphate, triggers the disassembly of methylene blue-encapsulated metal-organic frameworks, MB@ZIF-90. As a result, methylene blue molecules are released to arouse amplified electrochemical responses for glycoprotein analysis. Experimental results demonstrate the high-accuracy analysis of carcinoembryonic antigen, a typical glycoprotein biomarker in cancer diagnosis, in a linear range of 0.001-100 ng mL-1 with a low limit of detection of 0.419 pg mL-1. The method also displays satisfactory specificity and recoveries in complex serum samples and proves good versatility by adopting two other tumor-associated glycoprotein biomarkers, α-fetoprotein and mucin-1, as the targets. Therefore, this work provides a valuable tool for the analysis of glycoprotein biomarkers, which may be of great potential in early warning of malignant tumors in clinical applications.


The effect of Ramadan fasting and maternal hypoalbuminaemia on neonatal anthropometric parameters and placental weight.
In Islamic religion, daytime fasting during the month called Ramadan is an annual practice. In this study, we aimed to investigate the effect of Ramadan fasting and maternal hypoalbuminaemia on neonatal growth parameters. A prospective case-control study was conducted in Diyarbakir and Istanbul, Turkey. The sample size of fasting group was 168 and that of non-fasting group was 170. Demographic characteristics, obstetrics ultrasonographic findings and laboratory parameters of the participants were recorded. Neonatal anthropometric parameters and placental weight were noted. The mean placental weight was significantly higher in the fasting group (p = 0.037). Also, in the fasting group, pregnant women with hypoalbuminaemia had significantly higher placental weight (p = 0.009). In conclusion, the mean placental weight in the fasting group was significantly higher. Also a significant correlation between placental weight and maternal serum albumin level was observed in the fasting group.


3T phased array MRI improves the presurgical evaluation in focal epilepsies: a prospective study.
Although detection of concordant lesions on MRI significantly improves postsurgical outcomes in focal epilepsy (FE), many conventional MR studies remain negative. The authors evaluated the role of phased array surface coil studies performed at 3 Tesla (3T PA MRI). Forty patients with medically intractable focal epilepsies were prospectively imaged with 3T PA-MRI including high matrix TSE T2, fluid attenuated inversion recovery, and magnetization prepared rapid gradient echo. All patients were considered candidates for epilepsy surgery. 3T PA-MRIs were reviewed by a neuroradiologist experienced in epilepsy imaging with access to clinical information. Findings were compared to reports of prior standard 1.5T MRI epilepsy studies performed at tertiary care centers. Experienced, unblinded review of 3T PA-MRI studies yielded additional diagnostic information in 48% (19/40) compared to routine clinical reads at 1.5T. In 37.5% (15/40), this additional information motivated a change in clinical management. In the subgroup of patients with prior 1.5T MRIs interpreted as normal, 3T PA-MRI resulted in the detection of a new lesion in 65% (15/23). In the subgroup of 15 patients with known lesions, 3T PA-MRI better defined the lesion in 33% (5/15). Phased array surface coil studies performed at 3 Tesla read by an experienced unblinded neuroradiologist can improve the presurgical evaluation of patients with focal epilepsy when compared to routine clinical 1.5T studies read at tertiary care centers.


Nonverifiable research publications among applicants to an academic trauma and surgical critical care fellowship program.
The purpose of this study was to determine the incidence and predictors of nonverifiable research publications among applicants to a trauma and surgical critical care fellowship program. All complete applications submitted to our trauma and surgical critical care fellowship program were prospectively collected for 4 application cycles (2009 to 2012). All publications listed by applicants were tabulated and underwent verification using MEDLINE and direct journal search with verification by a team of professional health sciences librarians. Demographics and academic criteria were compared between applicants with nonverifiable and verifiable publications. A total of 100 applicants reported 301 publications. Of those, 20 applicants (20%) listed 32 papers (11%) that could not be verified. These applicants comprised 30% of those with 1 or more peer-reviewed publications. There were no significant differences in sex (male, 55% nonverifiable vs 60% verifiable, p = 0.684) or age (34.3 ± 6.6 years vs 34.2 ± 5.0 years, p = 0.963). There were no differences with regard to citizenship status (foreign medical graduates, 20% nonverifiable vs 28% verifiable, p = 0.495). Applicants with nonverified publications were less likely to be in the military (0% vs 14%, p = 0.079), more likely to have presented their work at surgical meetings (80% vs 58%, p = 0.064), and to be individuals with 3 or more peer-reviewed publications (55% vs 25%, p = 0.009). In this analysis of academic integrity, one-fifth of all applicants applying to a trauma and surgical critical care fellowship program and 30% of those with 1 or more peer-reviewed publications had nonverifiable publications listed in their curricula vitae. These applicants were less likely to be in the military, more likely to have presented their work at surgical meetings and to have 3 or more peer-reviewed publications.


Preoperative thrombocytosis predicts prognosis in stage II colorectal cancer patients.
Thrombocytosis is known to be a poor prognostic factor in several types of solid tumors. The prognostic role of preoperative thrombocytosis in colorectal cancer remains limited. The aim of this study is to investigate the prognostic role of preoperative thrombocytosis in stage II colorectal cancer. Two hundred eighty-four patients with stage II colorectal cancer who underwent surgical resection between December 2003 and December 2009 were retrospectively reviewed. Thrombocytosis was defined as platelet > 450 × 10(9)/L. We compared patients with thrombocytosis and those without thrombocytosis in terms of survival. The 5-year disease-free survival (DFS) rates were lower in patients with thrombocytosis compared to those without thrombocytosis in stage II colorectal cancer (73.3% vs. 89.6%, P = 0.021). Cox multivariate analysis demonstrated that thrombocytosis (hazard ratio, 2.945; 95% confidence interval, 1.127-7.697; P = 0.028) was independently associated with DFS in patients with stage II colorectal cancer. This study showed that thrombocytosis is a prognostic factor predicting DFS in stage II colorectal cancer patients.


Immunocytochemical localization of relaxin in the ovaries of pregnant rats.
Relaxin was localized in the ovaries of pregnant rats by employing for the first time a highly specific rabbit anti-rat relaxin serum and the peroxidase-antiperoxidase complexing technique. The corpora lutea of pregnancy contained essentially all of the immunostaining in ovarian sections obtained on Days 12 and 20 of pregnancy. Very few cells in the corpora lutea of the previous cycle stained for relaxin. There appeared to be variation in the intensity of staining for relaxin among luteal cells on both Days 12 and 20 of pregnancy. Ovaries from nonpregnant lactating rats contained very little, if any, relaxin immunostaining. It is concluded that the corpus luteum is the principal, and, in all likelihood, the sole source of relaxin in the pregnant rat.


Native American medicine and cardiovascular disease.
Native American medicine provides an approach to the treatment of cardiovascular disease that is unique and that can complement modern medicine treatments. Although specific practices among the various Native American tribes (Nations) can vary, there is a strong emphasis on the power of shamanism that can be supplemented by the use of herbal remedies, sweat lodges, and special ceremonies. Most of the practices are passed down by oral tradition, and there is specific training regarding the Native American healer. Native American medicine has strong testimonial experiences to suggest benefit in cardiac patients; however, critical scientific scrutiny is necessary to confirm the validity of the benefits shown to date.


A new benzofuran from the heartwood of Dalbergia latifolia.
A new benzofuran compound, named 2-[5-hydroxy-4-methoxy-2-(3-p-henyl-trans-allyloxy)benzyl]-5-hydroxy-6-methoxy-3-phenylbenzofuran (1), together with (+)-obtusafuran (2) and isoparvifuran (3), was isolated from the heartwood of Dalbergia latifolia. Their structures were elucidated by a combination of spectroscopic methods and comparison with the literature. Compounds 2 and 3 were obtained from this plant for the first time. Compound 1 exhibited moderated antioxidant effect for scavenging 1,1-diphenyl-2-picryhydrazyl (DPPH) free radical (IC50 = 96.7 ± 8.9 μM).


Switchable C-H Functionalization of N-Tosyl Acrylamides with Acryloylsilanes.
A controllable Rh-catalyzed protocol to access alkylation and alkenylation-annulation of N-tosyl acrylamide with acryloyl silane is reported. In contrast to the directing group or catalyst-dependent divergent sp2 C-H alkylation/alkenylation, the intrinsic property of acryloylsilane allows the switchable reaction manifold, thereby affording either alkylation or annulation products with slight modification of the reaction conditions.


Adipose Tissue Stem Cells for Therapy: An Update on the Progress of Isolation, Culture, Storage, and Clinical Application.
Adipose tissue stem cells (ASCs), known as multipotent stem cells, are most commonly used in the clinical applications in recent years. Adipose tissues (AT) have the advantage in the harvesting, isolation, and expansion of ASCs, especially an abundant amount of stem cells compared to bone marrow. ASCs can be found in stromal vascular fractions (SVF) which are easily obtained from the dissociation of adipose tissue. Both SVFs and culture-expanded ASCs exhibit the stem cell characteristics such as differentiation into multiple cell types, regeneration, and immune regulators. Therefore, SVFs and ASCs have been researched to evaluate the safety and benefits for human use. In fact, the number of clinical trials on ASCs is going to increase by years; however, most trials are in phase I and II, and lack phase III and IV. This systemic review highlights and updates the process of the harvesting, characteristics, isolation, culture, storage, and application of ASCs, as well as provides further directions on the therapeutic use of ASCs.


Application of the refinements of ICF linking rules to the Visual Analogue Scale, Roland Morris questionnaire and SF-36.
The Visual Analogue Scale (VAS), Roland Morris Disability Questionnaire (RMDQ), Short Form Health Survey (SF-36) are broadly used and had their content linked to ICF by the linking rules of 2002 and 2005. In 2016 were refined and were not applied yet. To apply the refinements of ICF linking rules to VAS, RMDQ, and SF-36. Two health professionals identified the meaningful concepts and linked to the most precise ICF categories and a third triggered in divergences. The degree of agreement was calculated by kappa statistic. There was almost perfect agreement (Kappa=0.93 p<0,001). The main concept of VAS was linked to ICF category b280, the 24 main concepts of RMDQ linked to b28013, and 27 additional linked to other categories. The SF-36 had 36 main concepts and 30 additional concepts identified which 27 were definable by the ICF and 17 do not. From the total of ICF linked concepts, 39 refer to Body Functions, 57 to Activities and Participation and 4 to Environmental Factors. The refinements of linking rules propitiated more clarity in the process to identify, to link instruments content with ICF and to expose the results. Thus, increased the number of identified and linked concepts as well as the categories in the instruments.


Biological effects of Auger processes of bromine on yeast cells induced by monochromatic synchrotron X-rays.
The biological effects of inner-shell ionization in bromine atoms incorporated into DNA in the form of bromodeoxyuridine monophosphate (BrdUMP), induced by monochromatized synchrotron X-rays, were studied using a deoxythymidine monophosphate (dTMP)-permeable mutant of yeast, Saccharomyces cerevisiae. The BrdUMP-incorporated yeast cells were irradiated with monochromatic X-rays of 13.51 or 13.45 keV, between which the bromine K-absorption edge (13.47 keV) is located. The cells were 1.07 times more sensitive to irradiation by 13.51 keV X-rays than at 13.45 keV, while dTMP-incorporated cells did not show any difference in sensitivity. In the presence of a radioprotector during irradiation, BrdUMP-incorporated cells showed a larger enhancement (1.20). These enhancements observed in the bromine-incorporated cells cannot be explained only by an increase of the absorbed dose due to a substitution of CH3 group of thymine by bromine. It may be concluded that a major part of the enhancement was caused by inner-shell photoionization, followed by an Auger cascade of the bromine in the DNA. The quantum yield of lethality caused by the photoabsorption of bromine K-shell is not affected by the presence of cysteamine, suggesting the biological enhancement by the Auger processes may not be influenced by chemical protection.


[Bone involvement in endocrinopathies].
Progress in bone densitometry, particularly biphotonic absoptiometry, has made it possible to better identify the effects of endocrinopathies on bone. Both cortical and trabecular bone structures can be evaluated quantitatively and topographically revealing important information on the pathophysiology of bone loss. Sex hormones play a major role in the regulation of bone mineralization and hypogonadism, whatever the origin, can lead to deleterious effects. Bone loss is known to be significative in high performance female athletes with amenorrhoea; long-term consequences are not yet determined, but stress fractures have been reported in up to 50%. Other hypogonadisms leading to bone demineralization include anorexia nervosa, chronic intake of gonadotrophin releasing hormone analogues and anti-oestrogens, and hyperprolactinism. Hyperthyroidism leads to a negative calcium balance and demineralization with remodelling, predominantly in cortical bone. In hypothyroid states a 10% bone loss is observed in vertebrae. In both cases, bone densitometry should be performed in order to evaluate the effect of treatment. The deleterious effect of spontaneous or iatrogenic hypercortisism is well known, leading to spontaneous wedge fractures of the vertebrae due to predominating trabecular bone loss. The mechanism of action of corticosteroids on bone metabolism is complex, but the major effect is an inhibition of osteoblast maturation. Recovery may be possible, but no large long-term series have yet been reported. Hyperparathyroidism and acromegaly also affect bone mineralization. The information provided by bone densitometry is essential to properly manage patients with endocrinopathies affecting bone mineralization.


Welfare brokers and European Union migrants' access to social protection.
In spite of the existence of an extensive national and supranational legal framework, European Union (EU) citizens who exercise their right to freedom of movement to work in another Member State face numerous hurdles in accessing social protection. While recent scholarship on street-level bureaucracy and on migration and welfare has shed light on the role of discretion and stereotypes in access to rights, little is known about the processes through which such hurdles are overcome. In this article, we focus on a specific strategy which is the recourse to what we call "welfare brokers". These actors offer assistance to EU migrants to overcome specific cross-border administrative challenges in the area of social protection that derive from their use of the right to freedom of movement. Relying on qualitative data collected with brokers and Romanian migrants working in Germany, the article also demonstrates that welfare brokers attempt to transform the norms, bureaucratic practices and representations that condition access to these entitlements. The article concludes by underlining how the existence of a brokerage industry is a sign of existing inequalities in the exercise of freedom of movement within the EU.


[Treatment of various malignancies with recombinant IFN-gamma (S-6810). The IFN-gamma Study Group].
Recombinant interferon-gamma (rIFN-gamma) was given to patients with malignancies by continuous daily administration or by intermittent high doses. Local administration was performed for patients with skin malignancy, and bladder and hepatic carcinoma. Among 239 cases eligible for evaluation (144 cases treated by systemic administration and 95 cases by local injection), complete response was observed in one case each of renal cell carcinoma, malignant lymphoma and mycosis fungoides, all treated by systemic administration. Intermittent high doses of rIFN-gamma induced a response rate of 21.4% in renal cell carcinoma. This rate was higher than the 8.6% obtained following continuous administration. Average response rate to local injection of rIFN-gamma in skin malignancies was 55.3%. This value was comparable with that obtained by IFN-alpha treatment. Fever was observed in 89% of the cases treated by systemic administration. Chills, malaise and anorexia were the main side effects. Local injection also induced similar side effects, although the incidence was lower in comparison with systemic administration. Incidence of side effects was higher in the intermittent high-dose group than in the continuous administration group for all items except fever. However, patients showed good tolerance to high doses of rIFN-gamma reaching 40 X 10(6) U/m2/day.


Trends in spoligotype patterns of Mycobacterium tuberculosis strains in central India.
This study aims to understand trends in spoligotype patterns of Mycobacterium tuberculosis (MTB) in Central India. Elucidation of these trends may provide baseline information to understand the transmission dynamics of strains of MTB in the region. Spoligotyping was carried out on 340 MTB strains isolated from clinical samples received from 2007 to 2011. The prevalence of ST26/CAS1_Del, ST11/EAI3_IND, ST288/CAS2, ST25/CAS1_Del and Beijing lineages showed waxing and waning trends. ST26/CAS1_Del and ST11/EAI3_IND lineages were consistently present and were predominant. Well-established lineages showed a consistent presence in the community. New orphan lineages appeared to be less capable of establishing themselves.


SHORT-TERM EFFICACY OF CONBERCEPT AND RANIBIZUMAB FOR POLYPOIDAL CHOROIDAL VASCULOPATHY.
To compare the 6-month efficacy of the intravitreal injection of conbercept or ranibizumab for patients with polypoidal choroidal vasculopathy (PCV). This is a retrospective case-control study involved 79 PCV eyes of 77 patients. The PCV eyes were treated with an intravitreal injection of either ranibizumab (n = 44) or conbercept (n = 35). Three monthly loading doses were injected and followed by retreatment as needed. The best-corrected visual acuity and angiographic characteristics were evaluated after 6 months. The mean logarithm of the minimum angle of resolution best-corrected visual acuity had improved from 0.86 (Snellen equivalent, 20/145) at baseline to 0.70 (Snellen equivalent, 20/100) at 6 months in the conbercept group (P < 0.001), and from 0.74 (Snellen equivalent, 20/110) at baseline to 0.63 (Snellen equivalent, 20/85) at 6 months in the ranibizumab group (P = 0.032), respectively. The central foveal thickness was decreased from 407 ± 146 μm to 230 ± 71 μm in the conbercept group (P < 0.001), and from 394 ± 93 μm to 208 ± 56 μm in the ranibizumab group (P < 0.001). Polyps were completely regressed and in 21 (47.7%) eyes in the conbercept group at 6 months, significant higher than in 10 (28.6%) eyes in the ranibizumab group (P = 0.029). Both conbercept and ranibizumab effectively increased the visual acuity and regressed the polyps of PCV eyes. No significant difference was found in the visual acuity improvement of the patients with PCV between the conbercept group and ranibizumab group at 6 months. However, conbercept was superior to ranibizumab monotherapy in the regression of polyps.


Calcitonin gene-related peptide elevates calcium and polarizes membrane potential in MG-63 cells by both cAMP-independent and -dependent mechanisms.
Published data suggest that the neuropeptide calcitonin gene-related peptide (CGRP) can stimulate osteoblastic bone formation; however, interest has focused on activation of cAMP-dependent signaling pathways in osteogenic cells without full consideration of the importance of cAMP-independent signaling. We have now examined the effects of CGRP on intracellular Ca(2+) concentration ([Ca(2+)](int)) and membrane potential (E(m)) in preosteoblastic human MG-63 cells by single-cell fluorescent confocal analysis using fluo 4-AM-fura red-AM and bis(1,3-dibarbituric acid)-trimethine oxanol [DiBAC(4)(3)] bis-oxonol assays. CGRP produced a two-stage change in [Ca(2+)](int): a rapid transient peak and a secondary sustained increase. Both responses were dose dependent with an EC(50) of approximately 0.30 nM, and the maximal effect (initially approximately 3-fold over basal levels) was observed at 20 nM. The initial phase was sensitive to inhibition of Ca(2+) mobilization with thapsigargin, whereas the secondary phase was eliminated only by blocking transmembrane Ca(2+) influx with verapamil or inhibiting cAMP-dependent signaling with the Rp isomer of adenosine 3',5'-cyclic monophosphorothioate (Rp-cAMPS). These data suggest that CGRP initially stimulates Ca(2+) discharge from intracellular stores by a cAMP-independent mechanism and subsequently stimulates Ca(2+) influx through L-type voltage-dependent Ca(2+) channels by a cAMP-dependent mechanism. In addition, CGRP dose-dependently polarized cellular E(m), with maximal effect at 20 nM and an EC(50) of 0.30 nM. This effect was attenuated with charybdotoxin (-20%) or glyburide (glibenclamide; -80%), suggesting that E(m) hyperpolarization is induced by both Ca(2+)-activated and ATP-sensitive K(+) channels. Thus CGRP signals strongly by both cAMP-dependent and cAMP-independent signaling pathways in preosteoblastic human MG-63 cells.


The lateral radiograph is useful in predicting shortening in 31A2 pertrochanteric hip fractures.
We sought to determine if angulation or translation measured on the lateral preoperative injury radiographs of patients with 31A2 pertrochanteric fractures is related to excessive postoperative shortening when treated with a sliding hip screw. We retrospectively reviewed the radiographs of consecutive patients with hip fractures treated at a level I university trauma centre between 2003 and 2008. Patients with 31A2 pertrochanteric fractures treated with a sliding hip screw were identified through a search of medical records. The study variables were angulation and translation on the preoperative injury lateral radiograph. The outcome measure was radiographic evidence of fracture shortening, measured as the change in length of sliding hip screw visible outside the barrel between the time of fixation and final follow up. Of the 131 patients treated, 23 met our inclusion criteria and had sufficient follow-up (mean 6.4 mo). The average shortening for 31A2 fractures with angulation on the injury lateral radiograph was 1.83 (95% confidence interval [CI] 1.18-2.47) cm, compared with 0.93 (95% CI 0.49-1.36) cm for fractures with no angulation (p = 0.019). There was no statistical difference in quality of reduction, tip-apex distance, Orthopedic Trauma Association (AO/OTA) classification or incidence of lateral wall fracture across groups based on the presence of angulation. Angulation on the lateral preoperative injury radiograph may be useful in predicting excessive shortening in 31A2 pertrochanteric fractures. Further investigation is warranted to confirm this result and to identify the role of other predictors, such as fracture comminution.


Isolation and identification of a new bifidogenic growth stimulator produced by Propionibacterium freudenreichii ET-3.
We have found a new growth stimulator for bifidobacteria in the culture broth of Propionibacterium freudenreichii ET-3. The bifidogenic growth stimulator (BGS) was purified by Diaion HP-20 column chromatography and preparative HPLC. Spectroscopic methods including 1H-NMR, UV, and LC-ESI-MS experiments indicated that the chemical structure of the bifidogenic growth stimulator was 1,4-dihydroxy-2-naphthoic acid (DHNA). Approximately 10 mg/L of DHNA was found to be produced in the culture broth of P. freudenreichii ET-3.


Confidence Estimation for Medical Image Registration Based On Stereo Confidences.
In this paper, we propose a novel method to estimate the confidence of a registration that does not require any ground truth, is independent from the registration algorithm and the resulting confidence is correlated with the amount of registration error. We first apply a local search to match patterns between the registered image pairs. Local search induces a cost space per voxel which we explore further to estimate the confidence of the registration similar to confidence estimation algorithms for stereo matching. We test our method on both synthetically generated registration errors and on real registrations with ground truth. The experimental results show that our confidence measure can estimate registration errors and it is correlated with local errors.


A Comparison of Inhaled Nitric Oxide Versus Inhaled Epoprostenol for Acute Pulmonary Hypertension Following Cardiac Surgery.
Direct comparisons of inhaled nitric oxide (iNO) to inhaled epoprostenol (iEPO) in patients with acute pulmonary hypertension (PHT) following cardiac surgery are lacking. To compare the relative efficacy, safety, and cost of iNO versus iEPO in patients with acute PHT following cardiac surgery. This is a single-center, retrospective, observational, cohort study comparing iNO to iEPO for acute postoperative PHT following cardiac surgery. The primary outcome was reduction of mean pulmonary artery pressure (mPAP) to < 30 mm Hg, 6 hours after ICU admission from the operating room. Secondary outcomes, included ICU and hospital length of stay, duration of mechanical ventilation, bleeding complications, hypotension, in-hospital mortality, and cost. A total of 98 patients met inclusion criteria (iNO, n = 49; iEPO, n = 49). There was no difference in the primary outcome of reduction of mPAP to < 30 mm Hg 6 hours after ICU admission (iNO, 33 [67%] vs iEPO, 35 [71%]; P = 0.83) or in the incidence of adverse events collected (iNO, 10 [20%] vs iEPO, 11 [22%]; P = 1.00). Based on cost estimates, the median cost of iEPO per patient was $363.53 ($226-$864.60) versus $2562.50 ($1875-$8625) for iNO (P < 0.01). The relative efficacy of iEPO appeared to be similar to that of iNO in reducing mPAP following cardiac surgery, in this retrospective review. Significant cost savings were associated with the use of iEPO.