[Echo laryngography. A contribution to the method of ultrasonic diagnosis of the larynx].
This article describes a method for sonographic investigation of the larynx, the suggested term for which is "echo laryngography". It is more purposeful if M-mode is employed as well as B-mode for the assessment of laryngeal function and performance. Intra- und extralaryngeal sound windows are described and a discussion concerning their access by means of a systematic transversal section from caudal to cranial and coronary and sagittal sections in the vertical plane will ensue. The varying degrees of ossification of the laryngeal cartilage and the air-filled parts of the larynx make sonography more difficult. The transverse and vertical epiglottis function test which we developed extends the range for sonography of the larynx. The possibilities for clinical application of "echo laryngography" will be published in subsequent presentations.


The last three days of life: a comparison of pain management in the young old and the oldest old hospitalised patients using the Resident Assessment Instrument for Palliative Care.
Pain is a common symptom in older patients at the end of life. Little research has evaluated pain management among the oldest hospitalised dying patients. To compare the pain characteristics documented by healthcare workers for the young old and the oldest old hospitalised patients and the types of analgesics administered in the last three days of life. A retrospective cross-sectional comparative study. The study included 190 patients from a Norwegian general hospital: 101 young old patients (aged 65-84 years) and 89 oldest old patients (aged 85-100 years). Data were extracted from electronic patient records (EPRs) using the Resident Assessment Instrument for Palliative Care. No significant differences were found between the young old and the oldest old patients with regard to pain characteristics. Pain intensity was poorly recorded in the EPRs. Most of the patients received adequate pain control. Morphine was the most frequently administered analgesic for dying patients. Compared to the oldest old patients, a greater proportion of the young old patients received paracetamol combined with codeine (OR = 3.25, 95% CI 1.02-10.40). There appeared to be no differences in healthcare workers' documentation of pain characteristics in young old and oldest old patients, but young old patients were more likely to receive paracetamol in combination with codeine. A limitation of the study is the retrospective design and that data were collected from a single hospital. Therefore, caution should be taken for interpretation of the results. The use of systematic patient-reported assessments in combination with feasible validated tools could contribute to more comprehensive documentation of pain intensity and improved pain control.


High-resolution global profiling of genomic alterations with long oligonucleotide microarray.
Cancer represents the phenotypic end point of multiple genetic lesions that endow cells with a full range of biological properties required for tumorigenesis. Among the hallmark features of the cancer genome are recurrent regional gains and losses that, upon detailed characterization, have provided highly productive discovery paths for new oncogenes and tumor suppressor genes. In this study, we describe the use of an oligonucleotide-based microarray platform and development of requisite assay conditions and bioinformatic mining tools that permits high-resolution genome-wide array-comparative genome hybridization profiling of human and mouse tumors. Using a commercially available 60-mer oligonucleotide microarray, we demonstrate that this platform provides sufficient sensitivity to detect single-copy difference in gene dosage of full complexity genomic DNA while offering high resolution. The commercial availability of the microarrays and associated reagents, along with the technical protocols and analytical tools described in this report, should provide investigators with the immediate capacity to perform DNA analysis of normal and diseased genomes in a global and detailed manner.


[Body mass index and albuminemia in patients under mechanical circulatory assistance before cardiac transplantation].
To evaluate the prognostic influence of peri-implantation nutritional status of patients under mechanical circulatory assist (MCA) prior to cardiac transplantation (CT). Retrospective analysis of patients with cardiogenic shock included from June 1997 to December 2002. Evaluation at MCA's implantation, at day (D) 30 and at CT or patient's death (D) of body mass index (BMI=body weight (kg)/size (m(2)), albuminemia (Alb g/l), expressed as median values (med) and range (min-max). Odds ratio (OR) and CI 95%) were calculated. A multivariate analysis was performed to determine variables related to D or CT success. Thirty-four patients (30 men), median age 40.5 years (10-63), were included. MCA types were cardiac pumps (N=3); pneumatic (N=18) or electric (N=5) ventricular assist devices and artificial heart (N=8). Global mortality was 56% (19 over 34 patients) and at implantation in the global population (N=34) BMI was 19.4 (9.3-28.1) and Alb 24.6 g/l (15-37.5). At MCA's implantation and D30 respectively, 38 and 42% of the patients had a severe hypoAlb (Alb<30 g/l) and a BMI<19 attesting of a seriously deteriorated nutritional status. No significant statistical difference was observed on median BMI of transplanted patients T (N=15) and expired patients D (N=19). Alb was significantly different (p<10(-4)) between T and D patients: median Alb: 30 g/l (20-37.5) in T patients, 20 g/l (15-31) in D patients. HypoAlb<21 g/l was an independent prognostic factor of death (p=0.004; OR: 0.541; IC95% : 0.36-0.82) and Alb>33 g/l an independent prognostic factor of CT success (p=0.003; OR:1.38; IC95% : 1.12-1.71). These results seem to demonstrate that at MCA implantation, a seriously deteriorated albuminemia level (<30 g/l) negatively impacts patients overall survival after CT.


Modulation of vascular tone by atrial natriuretic factor.
Synthetic atrial natriuretic factor (ANF) has been found to be a potent relaxant of isolated vascular preparations. ANF is more effective in relaxing agonist-induced versus depolarized contractile events and the relaxation efficacy appears inversely related to the level of contractile preload. The vasorelaxation to ANF is associated with elevations of cyclic GMP via an activation of the particulate form of guanylate cyclase. Both species and regional-vascular differences exist, in vitro as well as in vivo, in the vasorelaxation response to ANF which may reflect an altered distribution of high affinity receptors and/or different states of active vascular tone of the particular preparation.


Moderate Humidity Delays Electron-Hole Recombination in Hybrid Organic-Inorganic Perovskites: Time-Domain Ab Initio Simulations Rationalize Experiments.
Experiments show both positive and negative changes in performance of hybrid organic-inorganic perovskite solar cells upon exposure to moisture. Ab initio nonadiabatic molecular dynamics reveals the influence of humidity on nonradiative electron-hole recombination. In small amounts, water molecules perturb perovskite surface and localize photoexcited electron close to the surface. Importantly, deep electron traps are avoided. The electron-hole overlap decreases, and the excited state lifetime increases. In large amounts, water forms stable hydrogen-bonded networks, has a higher barrier to enter perovskite, and produces little impact on charge localization. At the same time, by contributing high frequency polar vibrations, water molecules increase nonadiabatic coupling and accelerate recombination. In general, short coherence between electron and hole benefits photovoltaic response of the perovskites. The calculated recombination time scales show excellent agreement with experiment. The time-domain atomistic simulations reveal the microscopic effects of humidity on perovskite excited-state lifetimes and rationalize the conflicting experimental observations.


OMICS and 21st century brain surgery from education to practice: James Rutka of the University of Toronto interviewed by Joseph B. Martin (Boston) and Türker Kılıç (İstanbul).
The Science-in-Backstage interviews aim to share experiences by global medical and life sciences thought leaders on emergent technologies and novel scientific, medical, and educational practices, situating them in both a historical and contemporary science context so as to "look into the biotechnology and innovation futures" reflexively and intelligently. OMICS systems diagnostics and personalized medicine are greatly impacting brain surgery, not to forget the training of the next generation of neurosurgeons. What do the futures hold for the practice of, and education in 21(st) century brain surgery in the age of OMICS systems science, personalized medicine, and the use of simulation in surgeon training? James Rutka is a clinician scientist and a world leader in diagnosis and treatment of brain tumors. He is Professor and Chair of the Department of Surgery at the Faculty of Medicine, University of Toronto, a President Emeritus of the American Association of Neurological Surgeons, and Editor-in-Chief of the Journal of Neurosurgery. Professor Rutka was interviewed for the global medical, biotechnology, and life sciences readership of the OMICS: A Journal of Integrative Biology to speak on these pressing questions in his personal capacity as an independent senior scholar. The issues debated in the present interview are of broad relevance for 21(st) century surgery and postgenomics medicine. The interviewers were Professor Joseph B. Martin, Harvard Medical School Dean Emeritus in Boston and Joint Dean of Medicine at Bahçeşehir University in İstanbul, and the author of "Alfalfa to Ivy: Memoir of a Harvard Medical School Dean," and Professor Türker Kılıç, Dean of Medicine at Bahçeşehir University in İstanbul, and an elected member of the Turkish Academy of Sciences.


Civic Science for Public Use: Mind in the Making and Vroom.
Mind in the Making and Vroom are partner initiatives that exemplify a unique "civic science" approach to "bringing developmental science into the world." Mind in the Making offers families and professionals working with children 0-8 access to developmental research, by engaging them in an active process of professional development and community outreach. Vroom is an outreach and communication initiative that brings "brain building basics" to communities, inviting parents to participate in the science of early learning through partnerships with trusted entities. These initiatives use collaborative, iterative processes in disseminating findings and implications of child development research. Preliminary evidence shows early promise of these initiatives to help promote engaged learning and life skills based on executive function in adults and children.


Unusual rheumatological and cardiological manifestations of acute myelogenous leukemia in a patient with Klinefelter's syndrome.
We report the case of a 40-year-old man with Klinefelter's syndrome who presented with a complex multisystem illness, the predominant manifestations of which were rheumatological and cardiological. This disorder coincided with a diagnosis of acute myelogenous leukemia evolving out of a myelodysplastic syndrome and resolved completely after chemotherapy. It is concluded that the hematological malignancy probably played a causal role in the development of this unusual illness which was likely immunologically mediated.


Sparse Analyzer Tool for Biomedical Signals.
The virtual (software) instrument with a statistical analyzer for testing algorithms for biomedical signals' recovery in compressive sensing (CS) scenario is presented. Various CS reconstruction algorithms are implemented with the aim to be applicable for different types of biomedical signals and different applications with under-sampled data. Incomplete sampling/sensing can be considered as a sort of signal damage, where missing data can occur as a result of noise or the incomplete signal acquisition procedure. Many approaches for recovering the missing signal parts have been developed, depending on the signal nature. Here, several approaches and their applications are presented for medical signals and images. The possibility to analyze results using different statistical parameters is provided, with the aim to choose the most suitable approach for a specific application. The instrument provides manifold possibilities such as fitting different parameters for the considered signal and testing the efficiency under different percentages of missing data. The reconstruction accuracy is measured by the mean square error (MSE) between original and reconstructed signal. Computational time is important from the aspect of power requirements, thus enabling the selection of a suitable algorithm. The instrument contains its own signal database, but there is also the possibility to load any external data for analysis.


Supraglottic airway devices are associated with asphyxial physiology after prolonged CPR in patients with refractory Out-of-Hospital cardiac arrest presenting for extracorporeal cardiopulmonary resuscitation.
Multiple randomized clinical trials have compared specific airway management strategies during ACLS with conflicting results. However, patients with refractory cardiac arrest died in almost all cases without the availability of extracorporeal cardiopulmonary resuscitation (ECPR). Our aim was to determine if endotracheal intubation (ETI) was associated with improved outcomes compared to supraglottic airways (SGA) in patients with refractory cardiac arrest presenting for ECPR. We retrospectively studied 420 consecutive adult patients with refractory out-of-hospital cardiac arrest due to shockable presenting rhythms presenting to the University of Minnesota ECPR program. We compared outcomes between patients receiving ETI (n = 179) and SGA (n = 204). The primary outcome was the pre-cannulation arterial PaO2 upon arrival to the ECMO cannulation center. Secondary outcomes included neurologically favorable survival to hospital discharge and eligibility for VA-ECMO based upon resuscitation continuation criteria applied upon arrival to the ECMO cannulation center. Patients receiving ETI had significantly higher median PaO2 (71 vs. 58 mmHg, p = 0.001), lower median PaCO2 (55 vs. 75 mmHg, p < 0.001), and higher median pH (7.03 vs. 6.93, p < 0.001) compared to those receiving SGA. Patients receiving ETI were also significantly more likely to meet VA-ECMO eligibility criteria (85% vs. 74%, p = 0.008). Of patients eligible for VA-ECMO, patients receiving ETI had significantly higher neurologically favorable survival compared to SGA (42% vs. 29%, p = 0.02). ETI was associated with improved oxygenation and ventilation after prolonged CPR. This resulted in increased rate of candidacy for ECPR and increased neurologically favorable survival to discharge with ETI compared to SGA.


Elderly who refuse to use hearing aids: an analysis of the causes.
The present research sought to describe the elements that interfere with the use of hearing aids in the elderly beneficiaries of a hearing aid delivery from Chile in a Family Health Center. A descriptive, cross-sectional study was conducted with 24 beneficiary users, with application of a closed-question questionnaire prepared by the researchers. A 75% adherence to the use of hearing aids is reported. There was a difference of 3.8 h in the use between adherents and non-adherents and in the frequency of use. The main reasons for not using the hearing aids are discomfort due to mold and noise. It is necessary to provide quality education during the implementation process, as well as to address the technical difficulties related to atrial adjustment and calibration of the hearing aid in order to increase adherence.


Total synthesis of marine natural products separacenes A and B.
A short and convergent route for the stereoselective total synthesis of separacenes A and B has been developed using (+)-methyl d-lactate and d-(-)-tartaric acid as the chiral pools. The characteristic features of this synthesis include the Trost-Rychnovsky alkyne rearrangement to construct the C7-C9 conjugated diene, the Horner-Wadsworth-Emmons olefination to form the C5-C6 and C11-C12 olefins and the Corey-Bakshi-Shibata reaction to install the C-13 hydroxy functionality.


[Indications of conventional chest physiotherapy in acute bronchiolitis].
To evaluate the benefits of conventional chest physiotherapy in acute bronchiolitis, 32 patients were allocated in a randomized controlled trial, 16 were given twice daily chest physiotherapy compared with 16 controls who were not given chest physiotherapy. The treatment group showed a mean clinical score for respiratory disability at admission of 5.56 (+/- 1.96), and 3.25 (+/- 1.27) when discharged. The control group presented a score of 5.75 (+/- 1.61) and 3.12 (+/- 1.30), p=0.77 and p=0.76 respectively. The mean length of illness in hospital in the treatment group was 4.00 (+/- 2.00) vs 3.87 (+/- 1.30) in the control group, p=0.84. Chest physiotherapy does not produce clinically important benefits in the treatment of acute bronchiolitis.


A Proteome Approach Reveals Differences between Fertile Women and Patients with Repeated Implantation Failure on Endometrial Level⁻Does hCG Render the Endometrium of RIF Patients?
The molecular signature of endometrial receptivity still remains barely understood, especially when focused on the possible benefit of therapeutical interventions and implantation-related pathologies. Therefore, the protein composition of tissue and isolated primary cells (endometrial stromal cells, ESCs) from endometrial scratchings of ART (Assisted Reproductive Techniques) patients with repeated implantation failure (RIF) was compared to volunteers with proven fertility during the time of embryo implantation (LH + 7). Furthermore, an analysis of the endometrial tissue of fertile women infused with human chorionic gonadotropin (hCG) was conducted. Endometrial samples (n = 6 RIF, n = 10 fertile controls) were split into 3 pieces: 1/3 each was frozen in liquid nitrogen, 1/3 fixed in PFA and 1/3 cultured. Protein lysates prepared from fresh frozen tissue were processed for mass spectrometric analysis. Three proteins (EPPK1, BCLAF1 and PTMA) showed a statistically altered abundance in the endometrial tissue of RIF patients. Furthermore, pathways like metabolism, immune system, ferroptosis and the endoplasmic reticulum were altered in RIF patients. Remarkably, endometrial tissues of RIF patients showed a significantly higher (p-value = 9 × 10-8) protein intensity correlation (Pearson's correlation coefficient = 0.95) compared to fertile women (Pearson's correlation coefficient = 0.88). The in vivo infusion of hCG stimulated proteins of endocytosis, HIF1 signalling and chemokine production. Notably, patients suffering from RIF had a clinical pregnancy rate of 19% after the intrauterine infusion of hCG before embryo transfer (ET) compared to their failed previous cycles. Our study showed for the first time that the endometrial proteome composition of RIF patients differs from fertile controls during the window of implantation. The intrauterine infusion of hCG prior to an embryo transfer might improve the chemokine triggered embryo-endometrial dialogue and intensify the angiogenesis and immune response. From a clinical point of view, the hCG infusion prior to an embryo transfer might increase the pregnancy rate of RIF patients.


M-mode echocardiographic values in a cohort of young healthy individuals.
To determine normal M-mode values in healthy young adults and to evaluate whether these values differ among those in whom echocardiography was performed routinely and those in whom echocardiography was performed based on clinical grounds. A cross-sectional study evaluating a large cohort of young academy applicants of the Israeli air force in the years 1994-2010. Studies were divided into those performed routinely and those performed because of abnormal ECG or physical examination findings. Echocardiographic variables were compared between the two groups and values are expressed as mean ± SD. Echocardiography was performed routinely in 3525 applicants (age 18.5 ± 1.0 years) and following a clinical referral in 3517 applicants (age 18.2 ± 0.9 years). Those in whom echocardiography was performed routinely had slightly higher left ventricular end-systolic diameter (31.2 ± 3.3 vs. 30.7 ± 3.4 mm; P < 0.0001) and aortic root diameter (28.5 ± 2.1 vs. 27.9 ± 2.2 mm; P < 0.0001), and slightly lower left ventricular mass index (108.8 ± 15.8 vs. 109.9 ± 16.5 g/m; P = 0.005). No differences were noted between the two groups in left atrial diameter, left ventricular end-diastolic volume, posterior wall thickness and interventricular septum thickness. Certain M-mode characteristics may differ (although to a slight degree) in young healthy individuals with electrocardiographic and physical findings compared with those with normal physical examination and electrocardiography.


Urinary guanidinoacetate and creatine levels in patients with HPRT deficiency.
Neurobehavioral manifestations of complete HPRT deficiency include severe action dystonia, choreathetosis, alteration of executive functions, and self-injurious behavior. Dystonic manifestations are also present in patients with partial HPRT deficiency. Pathophysiology of these manifestations is unknown. Guanidinoacetate is a neurotoxin implicated in certain dystonic syndromes. We have examined guanidinoacetate and creatine levels in urine from 11 HPRT deficient patients (9 with Lesch-Nyhan syndrome and 2 with partial deficiency). Urinary guanidinoacetate and creatine levels in HPRT deficient patients were within the normal range. Guanidinoactetate alteration does not seem to be implicated in the pathogenesis of the neurological disease associated with HPRT deficiency.


Intranuclear defect in beta-globin mRNA accumulation due to a premature translation termination codon.
We have analyzed a cloned beta O-thalassemia (beta O-thal) gene from a patient doubly heterozygous for hemoglobin Lepore and beta O-thalassemia. Studies of 3H-uridine incorporation into beta-globin mRNA in this patient's erythroblasts suggested an intranuclear defect in both beta and Lepore (delta beta) mRNA synthesis, as did S1 nuclease analysis of nuclear RNA. However, the nucleotide sequence of the beta O-thal gene revealed only a single base change in codon 39 (CAG----UAG), which created a premature translation termination codon. The 5' flanking sequence, including transcription promotor boxes and the mRNA initiation (CAP) site, were normal. The unexpected effect of this mutation on intranuclear beta-mRNA synthesis in vivo was studied by insertion of the cloned gene into a plasmid expression vector and transfection into tissue culture (COS-1) cells. beta-Globin mRNA produced by the transfected cells was assessed by S1 nuclease analysis. The beta O-39 thalassemia gene generated five- to tenfold less beta-mRNA than a normal beta-gene in both nuclear and cytoplasmic RNA, simulating the results observed in vivo. Moreover, the small amount of beta O-39 mRNA produced was as stable as normal beta-mRNA during an actinomycin D chase, ruling out rapid cytoplasmic turnover as a cause of the reduced accumulation. Cotransfection of the beta O-39 thalassemia gene with a mutant tyrosine suppressor tRNA gene resulted in restoration of the beta O-39 mRNA accumulation to near-normal levels. On the basis of these results, we suggest that the low levels of beta-mRNA known to exist in the common form of beta O-thalassemia, beta O-39 thalassemia, result from a lesion in transcription, or early posttranscriptional processes; the defect appears to be corrected by restoration of proper translational potential to the mutant mRNA, at least in a gene transfer-expression system in tissue-culture cells.


Effects of Antiviral Drugs on Organic Anion Transport in Human Placental BeWo Cells.
Placental drug transfer is important for achieving better pharmacotherapy in pregnant women and in fetuses. In the present study, we examined the effects of anti-hepatitis C virus (HCV) and anti-HIV drugs on organic anion transport in human placental BeWo cells. The cellular uptake of two fluorescence organic anions, 8-(2-[fluoresceinyl]aminoethylthio)adenosine-3',5'-cyclic monophosphate (8-FcAMP) and fluorescein, was temperature and concentration dependent. The Michaelis constant (Km) and the maximum uptake rate (Vmax) for 8-FcAMP transport in BeWo cells were estimated to be 6.45 ± 0.75 μM and 25.55 ± 5.93 pmol/mg protein/10 min, respectively. The Km and Vmax values for fluorescein uptake were estimated to be 31.2 ± 11.8 μM and 510.9 ± 90.6 pmol/mg protein/10 min, respectively. Several known substrates of organic anion transporters in human placenta, including atorvastatin, glibenclamide, estrone-3-sulfate, and rifampin, inhibited cellular uptake of 8-FcAMP and fluorescein in BeWo cells. Transport of 8-FcAMP and fluorescein was inhibited by the antiviral drugs boceprevir, telaprevir, elvitegravir, and maraviroc. These findings suggest that some antiviral drugs are sufficiently potent to influence placental drug transfer and cause drug-drug interactions.


Induced radioactivity of a GSO scintillator by secondary fragments in carbon ion therapy and its effects on in-beam OpenPET imaging.
The accumulation of induced radioactivity within in-beam PET scanner scintillators is of concern for its long-term clinical usage in particle therapy. To estimate the effects on OpenPET which we are developing for in-beam PET based on GSOZ (Zi doped Gd2SiO5), we measured the induced radioactivity of GSO activated by secondary fragments in a water phantom irradiation by a (12)C beam with an energy of 290 MeV u(-1). Radioisotopes of Na, Ce, Eu, Gd, Nd, Pm and Tb including positron emitters were observed in the gamma ray spectra of the activated GSO with a high purity Ge detector and their absolute radioactivities were calculated. We used the Monte Carlo simulation platform, Geant4 in which the observed radioactivity was assigned to the scintillators of a precisely reproduced OpenPET and the single and coincidence rates immediately after one treatment and after one-year usage were estimated for the most severe conditions. Comparing the highest coincidence rate originating from the activated scintillators (background) and the expected coincidence rate from an imaging object (signal), we determined the expected signal-to-noise ratio to be more than 7 within 3 min and more than 10 within 1 min from the scan start time. We concluded the effects of scintillator activation and their accumulation on the OpenPET imaging were small and clinical long-term usage of the OpenPET was feasible.


Investigating the PM2.5 mass concentration growth processes during 2013-2016 in Beijing and Shanghai.
The North China Plain and the Yangtze River Delta are the two of the most heavily polluted regions in China. Observational studies revealed that 'explosive' PM2.5 mass concentration growths frequently occurred in the two regions. This study analyzed all the PM2.5 mass concentration growth processes from clean condition (i.e., <35 μg m-3) to heavy pollution condition (i.e., >150 μg m-3) in Beijing (BJ) and Shanghai (SH), two representative cities of the two regions, using hourly monitored PM2.5 concentrations during 2013-2016. 173 and 76 growth processes were identified in BJ and SH, respectively. PM2.5 rising rates (PMRR) and dynamic growth durations were calculated to illustrate the characteristics of the growth processes. Hourly particulate chemical composition data and meteorological data in BJ and SH were further analyzed. The 4-year averaged PMRR of PM2.5 total mass were similarly of 7.11 ± 9.82 μg m-3 h-1 in BJ and 6.71 ± 6.89 μg m-3 h-1 in SH. A decreasing trend was found for the PM2.5 growth processes in two cities from 2013 to 2016, reflecting the effectiveness of emission controls implemented in the past years. The contributions of particulate components to the PM2.5 total mass growth were different in BJ and SH. Average PMRR value of PM1 organic aerosols (OA), SO42-, NO3-, and NH4+ in BJ was 1.90, 0.95, 0.82, and 0.53 μg m-3 h-1, respectively. Average PMRR of PM2.5 OA, SO42-, NO3-, and NH4+ in SH was 1.70, 1.18, 1.99 and 1.14 μg m-3 h-1, respectively. Based on the contributions of different components, the PM2.5 mass concentration growth processes in BJ and SH were proposed to be classified into 'other components-dominant growth processes', 'all components-contributing growth processes', 'one or more explosive secondary components-dominant growth processes', and 'mixed-factor growth processes'. Potential source contribution function analysis and the meteorological condition analysis showed that source origins and prevailing wind for the two cities during different categories of growth processes had substantial difference. The important source areas included Hebei and Shandong for BJ, and Jiangsu and Anhui for SH. The dominant wind directions during growth processes were northeast, south and southwest in BJ, and were west to north in SH. The results suggested the contributing components, the prevailing wind conditions, and the formation processes were substantially different in the two cities, despite the similar PMRR of PM2.5 total mass during the growth processes between BJ and SH. Future research is needed to study the detailed formation mechanisms of the different PM2.5 mass concentration growth processes in the two cities.


Multichannel CNN Model for Biomedical Entity Reorganization.
Biomedical researchers and biologists often search a large amount of literature to find the relationship between biological entities, such as drug-drug and compound-protein. With the proliferation of medical literature and the development of deep learning, the automatic extraction of biological entity interaction relationships from literature has shown great potential. The fundamental scope of this research is that the approach described in this research uses technologies like dynamic word vectors and multichannel convolution to learn a larger variety of relational expression semantics, allowing it to detect more entity connections. The extraction of biological entity relationships is the foundation for achieving intelligent medical care, which may increase the effectiveness of intelligent medical question answering and enhance the development of precision healthcare. In the past, deep learning methods have achieved specific results, but there are the following problems: the model uses static word vectors, which cannot distinguish polysemy; the weight of words is not considered, and the extraction effect of long sentences is poor; the integration of various models can improve the sample imbalance problem, the model is more complex. The purpose of this work is to create a global approach for eliminating different physical entity links, such that the model can effectively extract the interpretation of the expression relationship without having to develop characteristics manually. To this end, a deep multichannel CNN model (MC-CNN) based on the residual structure is proposed, generating dynamic word vectors through BERT (Bidirectional Encoder Representation from Transformers) to improve the accuracy of lexical semantic representation and uses multihead attention to capture the dependencies of long sentences and by designing the Ranking loss function to replace the multimodel ensemble to reduce the impact of sample imbalance. Tested on multiple datasets, the results show that the proposed method has good performance.


Highly restricted dispersal in habitat-forming seaweed may impede natural recovery of disturbed populations.
Cystoseira sensu lato (Class Phaeophyceae, Order Fucales, Family Sargassaceae) forests play a central role in marine Mediterranean ecosystems. Over the last decades, Cystoseira s.l. suffered from a severe loss as a result of multiple anthropogenic stressors. In particular, Gongolaria barbata has faced multiple human-induced threats, and, despite its ecological importance in structuring rocky communities and hosting a large number of species, the natural recovery of G. barbata depleted populations is uncertain. Here, we used nine microsatellite loci specifically developed for G. barbata to assess the genetic diversity of this species and its genetic connectivity among fifteen sites located in the Ionian, the Adriatic and the Black Seas. In line with strong and significant heterozygosity deficiencies across loci, likely explained by Wahlund effect, high genetic structure was observed among the three seas (ENA corrected FST = 0.355, IC = [0.283, 0.440]), with an estimated dispersal distance per generation smaller than 600 m, both in the Adriatic and Black Sea. This strong genetic structure likely results from restricted gene flow driven by geographic distances and limited dispersal abilities, along with genetic drift within isolated populations. The presence of genetically disconnected populations at small spatial scales (< 10 km) has important implications for the identification of relevant conservation and management measures for G. barbata: each population should be considered as separated evolutionary units with dedicated conservation efforts.


Trajectories of smokeless tobacco use and of cigarette smoking in a cohort of Swedish adolescents: differences and implications.
Developmental trajectories of cigarette smoking have often been described, but there are no such analyses dealing with smokeless tobacco use. A semi-parametric group-based mixture modeling procedure was used to determine the development of smokeless tobacco (snus) use, as well as of cigarette smoking, over time in a cohort of 2,175 Swedish adolescents who were never-users of tobacco at the time of recruitment. An indicator of snus and of cigarette consumption in the previous year was used to model the development of the behavior between 11 and 18 years of age. For snus use three trajectories best described the cohort's experience, while four trajectories provided the best description of cigarette smoking in the cohort. For both tobacco types there were two escalation patterns and one sustained trial trajectory, while an extinction pattern was apparent for cigarette smoking only. Marked sex differences were found, since rapid escalation for snus use was found only among males while high consumption of cigarettes was observed only among females. Dual users (54.9% of all users) showed a trajectory of steeper and more prolonged increase of tobacco consumption than exclusive users of either snus or cigarettes. Several risk factors for tobacco use measured at baseline influenced individual probabilities of belonging to a particular trajectory. The developmental patterns of snus use and cigarette smoking showed high similarity, but they evolved differently in the two sexes. Dual users emerged as a high-risk group for tobacco dependence and tobacco-related harms.


The binding database: overview and user's guide.
The large and growing body of experimental data on molecular binding is of enormous value in biology, pharmacology, and chemistry. Applications include the assignment of function to biomolecules, drug discovery, molecular modeling, and nanotechnology. However, binding data are difficult to find and access because they are available almost exclusively through scientific journals. BindingDB, a public, web-accessible database of measured binding affinities, is designed to address this problem. BindingDB collects data for natural and modified biomolecules and for synthetic compounds, and provides detailed experimental information. Currently, measurements by isothermal titration calorimetry are fully supported; measurements by enzyme inhibition will soon be included as well. The web site allows data to be searched by a range of criteria, including binding thermodynamics, sequence homology, and chemical structure, substructure, and similarity. Experimentalists are encouraged to publicize their data by entering it into BindingDB via the online forms. Such data can be updated or revised by the depositor, if necessary, and will remain publicly accessible. User involvement and feedback are welcomed.


[Study on the safe edible of puffer fish resources].
In order to utilize the puffer fish resources furthest and to develop traditional diet culture, a project on the safe eating of puffer fish resources was conducted. The results showed that the distributing of teterodotoxin(TTX) in puffer body was not in uniformity. Owing that the content of TTX changes in different seasons and bodies, different methods were selected to crank out the delicious globefish food. The number of globefish food consumer has reached the amount to 121239 person-time since 1998. The technological process on teterodotoxin was proved reliable by mice bioassay and feeding trial in human.


[The Nakayama technique of shunt creation for chronic hemodialysis. Experience, complications and possibilities of their removal].
The Brescia-Cimino fistula is carried out as an end-to-end anastomosis for mechanical flow reasons. The Nakayama anastomosis in the upper plexus anesthesia is carried out as a fast and simple apparatus method. Between 1973 and June 1977, 114 Nakayama anastomoses were performed in 80 patients. Till June 1977, 61 were still usable. Time and cause of occlusion were analyzed. Early occlusion (within 30 days) was mainly caused by faulty operation. Late occlusion (within 4 months) was mainly caused by thrombosis at the tantalum ring and improper usage. Shunt occlusion was remedied by a new connection on the same or on the other arm, by vein replantation, or by construction of a vein loop. The arteria femoralis was placed in subcutaneous position when blood vessel conditions were unfavorable. Tests with Spark's prosthesis and autologous vein transplantation produced no usable vessels.


Regulation of smooth muscle alpha-actin expression in vivo is dependent on CArG elements within the 5' and first intron promoter regions.
The aims of the present studies were to define sufficient promoter sequences required to drive endogenous expression of smooth muscle (SM) alpha-actin and to determine whether regulation of SM alpha-actin expression in vivo is dependent on CArG (CC(A/T)6GG) cis elements. Promoter deletions and site directed mutagenesis techniques were used to study gene regulation in transgenic mice as well as in smooth muscle cell (SMC) cultures. Results demonstrated that a Lac Z transgene that contained 547 bp of the 5' rat SM alpha-actin promoter was sufficient to drive embryonic expression of SM alpha-actin in the heart and in skeletal muscle but not in SMCs. Transient transfections into SMC cultures demonstrated that the conserved CArG element in the first intron had significant positive activity, and gel shift analyses demonstrated that the intronic CArG bound serum response factor. A transgene construct from -2600 through the first intron (p2600Int/Lac Z) was expressed in embryos and adults in a pattern that closely mimicked endogenous SM alpha-actin expression. Expression in adult mice was completely restricted to SMCs and was detected in esophagus, stomach, intestine, lung, and nearly all blood vessels, including coronary, mesenteric, and renal vascular beds. Mutation of CArG B completely inhibited expression in all cell types, whereas mutation of the intronic CArG selectively abolished expression in SMCs, which suggests that it may act as an SMC-specific enhancer-like element. Taken together, these results provide the first in vivo evidence for the importance of multiple CArG cis elements in the regulation of SM alpha-actin expression.


Streptococcus pneumoniae: epidemiology and risk factors, evolution of antimicrobial resistance, and impact of vaccines.
Streptococcus pneumoniae (pneumococcus) remains an important cause of pneumonia, meningitis, bacteremias, and acute otitis media worldwide. Antimicrobial resistance among pneumococci has escalated dramatically over the past three decades, and is influenced by patterns of antibiotic use, population density, and spread of a few international clones. Globally, antimicrobial resistance among pneumococci spread rapidly in the 1990s, reflecting dissemination of a few clones. The incidence of resistance varies considerably among different geographic regions and is influenced by patterns of antibiotic use, population density, and local prevalence of resistant strains. The use of specific antibiotic classes not only predisposes to resistance to that class but also may facilitate emergence of resistance to unrelated antibiotic classes. Judicious usage of antibiotics may reduce the incidence of antibiotic-resistant pneumococci. Following usage of the pneumococcal conjugate vaccine in children, the incidence of invasive pneumococcal disease declined in both children and adults (reflecting herd immunity). However, emergence of serotypes not encompassed in the vaccine is worrisome, and may be associated with heightened antimicrobial resistance and virulence. Continued vigilance for emergence of novel serotypes and development of vaccines with expanded coverage and immunogenicity will be critical for optimal prevention of pneumococcal infections.


Correlation of real-time catecholamine release and cytosolic Ca2+ at single bovine chromaffin cells.
Previous investigations of the role of Ca2+ in stimulus-secretion coupling have been undertaken in populations of adrenal chromaffin cells. In the present study, the simultaneous detection of intracellular Ca2+, with the fluorescent probe fura-2, and catecholamine release, using a carbon-fiber microelectrode, are examined at single chromaffin cells in culture. Results from classic depolarizing stimuli, high potassium (30-140 mM) and 1,1-dimethyl-4-phenylpiperazinium (3-50 microM), show a dependence of peak cytosolic Ca2+ concentration and catecholamine release on secretagogue concentration. Catecholamine release induced by transient high K+ stimulation increases logarithmically with K+ concentration. Continuous exposure to veratridine (50 microM) induces oscillations in intracellular Ca2+ and at higher concentrations (100 microM) concomitant fluctuation of cytosolic Ca2+ and catecholamine secretion. Mobilization of both caffeine- and inositol trisphosphate-sensitive intracellular Ca2+ stores is found to elicit secretion with or without extracellular Ca2+. Caffeine-sensitive intracellular Ca2+ stores can be depleted, refilled, and cause exocytosis in medium without Ca2+. Single cell measurement of exocytosis and the increase in cytosolic Ca2+ induced by bradykinin-activated intracellular stores reveal cell to cell variability in exocytotic responses which is masked in populations of cells. Taken together, these results show that exocytosis of catecholamines can be induced by an increase in cytosolic Ca2+ either as a result of transmembrane entry or by release of internal stores.


Biomimetic studies on iodothyronine deiodinase intermediates: modeling the reduction of selenenyl iodide by thiols.
Enzyme mimetic studies on the crucial intermediate (E-SeI) of the iodothyronine deiodinase cycle have been carried out by using an areneselenenyl iodide stabilized by intramolecular Se.N interactions. Treatment of this compound with aromatic thiols and thiobenzoxazole in the presence of NEt(3) affords areneselenenyl sulfides that are stable towards disproportionation reactions. The structures of three of the areneselenenyl sulfides were determined by X-ray crystallography. In one case, in the absence of NEt(3), a diselenide can be formed rather than the selenenyl sulfide. The areneselenenyl iodide also reacts with a related selenol to produce the corresponding diselenide, and this reaction is found to be much faster than that with thiols. The high reactivity of the selenenyl iodide with the selenol suggests that a reduced selenol group (R'-SeH) may react with the E-SeI intermediate to produce a diselenide (E-Se-Se-R') without any thiol cosubstrate. The intermediacy of selenenyl sulfides during the reduction of selenenyl iodide by thiols and its possible relevance to the iodothyronine deiodinase catalytic cycle is also described.


MathIOmica-MSViewer: a dynamic viewer for mass spectrometry files for Mathematica.
MathIOmica-MSViewer is an add-on graphical user interface utility for the Mathematica software system which facilitates the visualization and exploration of spectra from open format mass spectrometry files (mzXML and mzML standard community formats). The viewer was designed for simplicity and handling of large mass spectrometry data files. To facilitate searches, users may use search filters for the spectra based on mass to charge ratios and retention times, and visualize precursor spectra associated to a parent spectrum. The viewer is available as a Mathematica notebook (MathIOmica-MSViewer.nb) at https://doi.org/10.5281/zenodo.321385. The software is provided under an MIT License. © 2017 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons, Ltd.


Self-Supervised Motion Perception for Spatiotemporal Representation Learning.
In this study, we propose a novel pretext task and a self-supervised motion perception (SMP) method for spatiotemporal representation learning. The pretext task is defined as video playback rate perception, which utilizes temporal dilated sampling to augment video clips to multiple duplicates of different temporal resolutions. The SMP method is built upon discriminative and generative motion perception models, which capture representations related to motion dynamics and appearance from video clips of multiple temporal resolutions in a collaborative fashion. To enhance the collaboration, we further propose difference and convolution motion attention (MA), which drives the generative model focusing on motion-related appearance, and leverage multiple granularity perception (MG) to extract accurate motion dynamics. Extensive experiments demonstrate SMP's effectiveness for video motion perception and state-of-the-art performance of self-supervised representation models upon target tasks, including action recognition and video retrieval. Code for SMP is available at github.com/yuanyao366/SMP.


The changing face of acoustic neuroma management in the USA: analysis of the 1998 and 2008 patient surveys from the acoustic neuroma association.
A recent review of the national cancer center registry Surveillance Epidemiology and End Results (SEER) database revealed that in the United States, 25% of Acoustic Neuromas (AN) are managed with observation. Several articles have questioned the aggressive treatment of these slow growing tumors. Concern has been raised that data from the SEER database might be biased towards treatment as patients who chose observation are less likely to be seen at a cancer center. To try and adjust for this potential bias, we decided to investigate management trends of AN in the United States using patient surveys conducted by the Acoustic Neuroma Association (ANA). Study design. Database review. Data from the 1998 and 2008 ANA patient's surveys were analyzed to detect trends between tumor size and treatment modality. Management trends including observation, microsurgical resection and radiation were examined as well based on tumor size criteria. During this study period, tumor size at diagnosis decreased significantly (1966-1998: 23.8% ≤ 1.5 cm; 1999-2008: 45.3% ≤ 1.5 cm). The use of microsurgery decreased from 92.7% to 53.4%, while the use of radiosurgery/radiotherapy increased from 5% to 24.2% and observation increased to 22.4%. Review of data from the ANA confirmed that radiosurgery, and watch and wait are gaining popularity as treatment options. Regardless of this shift in tumor management, microsurgery continues to be the primary method of treatment across tumor sizes in the United States of America and observation remains the least common management modality.


Incorporating genome-wide DNA sequence information into a dynamic whole-cell model of Escherichia coli: application to DNA replication.
The advent of thousands of annotated genomes, detailed metabolic reconstructions and databases within the flourishing field of systems biology necessitates the development of functionally complete computer models of whole cells and cellular systems. Such models would realistically describe fundamental properties of living systems such as growth, division and chromosome replication. This will inevitably bridge bioinformatic technologies with ongoing mathematical modelling efforts and would allow for in silico prediction of important dynamic physiological events. To demonstrate a potential for the anticipated merger of bioinformatic genome-wide data with a whole-cell computer model, the authors present here an updated version of a dynamic model of Escherichia coli, including a module that correctly describes the initiation and control of DNA replication by nucleoprotein DnaA-ATP molecules. Specifically, a rigorous mathematical approach used to explicitly include the genome-wide distribution of DnaA-binding sites on the replicating chromosome into a computer model of a bacterial cell is discussed. A new simple deterministic approximation of the complex stochastic process of DNA replication initiation is also provided. It is shown for the first time that reasonable assumptions about the mechanism of DNA replication initiation can be implemented in a deterministic whole-cell model to make predictions about the timing of chromosome replication. Furthermore, it is proposed that a large increase in the concentration of DnaA-binding boxes will result in a decreased steady-state growth rate in E. coli.


Monocytes as a site of production of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the septic host.
The role of blood monocytes in the secretion of soluble triggering receptor expressed on myeloiod cells (sTREM-1) was studied in 90 patients with septic syndrome due to ventilator-associated pneumonia. Blood monocytes were isolated on 7 consecutive d after initiation of symptoms. Monocytes were incubated in the absence or presence of LPS and concentrations of sTREM-1 and TNFalpha in cell supernatants and serum were estimated by an enzyme-immunoassay. sTREM-1 and TNFalpha were consistently present at detectable levels in the cell supernatants. LPS induced increased levels of TNFalpha but not of sTREM-1. Supernatants recovered from monocytes on d 1 showed levels of sTREM-1 higher than those recovered on any of the following 6 d (p<0.05); these levels were higher in non-survivors than in survivors. Supernatants recovered from monocytes on d 1 of patients with severe sepsis had elevated concentrations of sTREM-1 compared to patients with septic shock and similar to patients with sepsis. A negative correlation was found between levels of sTREM-1 in the cell supernatants and the percentage of apoptotic monocytes. In essence, the above results suggest that monocytes contribute to the production of sTREM-1 in the event of septic syndrome.


CT diagnosis of 52 patients with lymphoma in abdominal lymph nodes.
To assess CT manifestations and its diagnostic value for lymphoma in the abdominal lymph nodes (LALN). CT findings in 52 cases of LALN proved by surgery or biopsy, including Hodgkin's disease (HD) in 16 cases and non-Hodgkin's lymphoma (NHL) in 36 cases, were retrospectively analyzed. (1) CT manifestations based on distribution of the lesions of LALN: Solitary mass type was found in 10 cases, including solitary, round, uniform-density, enlarged lymph nodes in 3 cases; and multiple, enlarged lymph nodes fusing into singular lobular mass in 7 cases. Thirty-four cases of multiple-nodular type showed multiple, round, enlarged lymph nodes with uniform density and clear margins. Vessels-embedded signs, including mesenteric vessels, renal vessels, abdominal aorta or inferior vena cava, were seen in 6 cases, and duodenum-embedded signs were seen in 2 cases. Eight cases of diffuse type showed characteristic "cobblestone signs". (2) CT manifestations correlated with pathological type: CT manifestations of 12 cases of HD were different from those of 40 cases of NHL in distribution, size, quantity and fused lesion of enlarged lymph nodes. (3) Twenty-eight cases of 52 patients were accompanied with extra-nodal lymphoma in the abdomen, especially gastrointestinal lymphoma, which had characteristic CT findings. (4) In follow-up examinations, CT images showed uniform, heterogeneous or rim enhancement in 15 cases, and occasional calcifications accompanied with reduction of the lesion size and quantity in 12 cases, whereas the lesions disappeared in 3 cases after treatment. CT images show many characteristic manifestations valuable for qualitative diagnosis of LALN, and it is also helpful for pathological classification of LALN and therapeutic evaluation in follow-up of patients.


Aging yeast gain a competitive advantage on non-optimal carbon sources.
Animals, plants and fungi undergo an aging process with remarkable physiological and molecular similarities, suggesting that aging has long been a fact of life for eukaryotes and one to which our unicellular ancestors were subject. Key biochemical pathways that impact longevity evolved prior to multicellularity, and the interactions between these pathways and the aging process therefore emerged in ancient single-celled eukaryotes. Nevertheless, we do not fully understand how aging impacts the fitness of unicellular organisms, and whether such cells gain a benefit from modulating rather than simply suppressing the aging process. We hypothesized that age-related loss of fitness in single-celled eukaryotes may be counterbalanced, partly or wholly, by a transition from a specialist to a generalist life-history strategy that enhances adaptability to other environments. We tested this hypothesis in budding yeast using competition assays and found that while young cells are more successful in glucose, highly aged cells outcompete young cells on other carbon sources such as galactose. This occurs because aged yeast divide faster than young cells in galactose, reversing the normal association between age and fitness. The impact of aging on single-celled organisms is therefore complex and may be regulated in ways that anticipate changing nutrient availability. We propose that pathways connecting nutrient availability with aging arose in unicellular eukaryotes to capitalize on age-linked diversity in growth strategy and that individual cells in higher eukaryotes may similarly diversify during aging to the detriment of the organism as a whole.


Structural Basis of Karrikin and Non-natural Strigolactone Perception in Physcomitrella patens.
In plants, strigolactones are perceived by the dual receptor-hydrolase DWARF14 (D14). D14 belongs to the superfamily of α/β hydrolases and is structurally similar to the karrikin receptor KARRIKIN INSENSITIVE 2 (KAI2). The moss Physcomitrella patens is an ideal model system for studying this receptor family, because it includes 11 highly related family members with unknown ligand specificity. We present the crystal structures of three Physcomitrella D14/KAI2-like proteins and describe a loop-based mechanism that leads to a permanent widening of the hydrophobic substrate gorge. We have identified protein clades that specifically perceive the karrikin KAR1 and the non-natural strigolactone isomer (-)-5-deoxystrigol in a highly stereoselective manner.


A generalized bead-rod model for Brownian dynamics simulations of wormlike chains under strong confinement.
This paper is aimed to develop a Brownian dynamics simulation method for strongly confined semiflexible polymers where numerical simulation plays an indispensable role in complementing theory and experiments. A wormlike chain under strong confinement is modeled as a string of virtual spherical beads connected by inextensible rods with length varying according to the confinement intensity of the chain measured by the Odijk deflection length. The model takes hydrodynamic interactions into account. The geometrical constraints associated with the inextensible rods are realized by the so-called linear constraint solver. The model parameters are studied by quantitatively comparing the simulated properties of a double-stranded DNA chain with available experimental data and theoretical predictions.


Application of Fourier transform infrared spectroscopy and chemometrics for differentiation of Salmonella enterica serovar Enteritidis phage types.
Fourier transform infrared (FT-IR) spectroscopy and chemometric techniques were used to discriminate five closely related Salmonella enterica serotype Enteritidis phage types, phage type 1 (PT1), PT1b, PT4b, PT6, and PT6a. Intact cells and outer membrane protein (OMP) extracts from bacterial cell membranes were subjected to FT-IR analysis in transmittance mode. Spectra were collected over a wavenumber range from 4,000 to 600 cm(-1). Partial least-squares discriminant analysis (PLS-DA) was used to develop calibration models based on preprocessed FT-IR spectra. The analysis based on OMP extracts provided greater separation between the Salmonella Enteritidis PT1-PT1b, PT4b, and PT6-PT6a groups than the intact cell analysis. When these three phage type groups were considered, the method based on OMP extract FT-IR spectra was 100% accurate. Moreover, complementary local models that considered only the PT1-PT1b and PT6-PT6a groups were developed, and the level of discrimination increased. PT1 and PT1b isolates were differentiated successfully with the local model using the entire OMP extract spectrum (98.3% correct predictions), whereas the accuracy of discrimination between PT6 and PT6a isolates was 86.0%. Isolates belonging to different phage types (PT19, PT20, and PT21) were used with the model to test its robustness. For the first time it was demonstrated that FT-IR analysis of OMP extracts can be used for construction of robust models that allow fast and accurate discrimination of different Salmonella Enteritidis phage types.


Association of novel lipid indicators with the risk of stroke among participants in Central China: a population-based prospective study.
Several easily and inexpensively measured indicators of visceral adiposity dysfunction are currently available, but it remains unclear whether they are correlated with stroke risk in the community-dwelling population. We aimed to examine the longitudinal association of the triglyceridemic-waist phenotypes, the triglyceride glucose (TyG) index, as well as TyG-related indicators with stroke risk. In this study, we conducted a prospective cohort study in Hunan, a region located in Central China, where the prevalence of stroke is relatively high. We included a total of 20185 subjects aged ≥40 years between November 2017 and December 2018. Triglyceride glucose-body mass index (TyG-BMI) and triglyceride glucose-waist circumference (TyG-WC) were calculated as multiplying TyG index by BMI and WC, respectively. Triglyceride waist phenotypes were categorized into four phenotypes: HTGW (elevated triglyceride and enlarged WC), NTNW (normal triglyceride and normal WC); HTNW (high triglyceride and normal WC), and NTGW (normal triglyceride and enlarged WC). We constructed a multivariable Cox regression model to assess the association between these novel lipid indicators and the risk of stroke. Subgroup analysis was conducted to test the robustness of our research findings. ROC curve was used for assessing the predictive ability of different stroke risk indices. After 2 years of follow- up, 135 participants experienced new stroke events. After adjusting for potential confounders, we found that participants with HTGW had higher likelihood of stroke (HR: 1.96, 95% CI: 1.21 to 3.16). However, we did not find significant associations for HTNW (HR: 1.42, 95% CI: 0.91 to 2.21) and NTGW (HR: 1.09, 95% CI 0.67 to 1.78). when compared to participants in the first TyG quartile, those in the fourth TyG quartile were associated with a 2.06-fold (95% CI: 1.22, 3.50) risk of stroke. Each 1-SD increase in TyG, TyG-BMI, and TyG-WC was associated with a higher risk of stroke, with adjusted HRs of 1.34 (95% CI: 1.11 to 1.61), 1.35 (95% CI: 1.14 to 1.59), and 1.23 (95% CI: 1.04 to 1.46), respectively. In subgroup analyses, those positive relationships appeared to be stronger among male participants with lower levels of physical activity and smoking. HTGW, along with higher levels of TyG and TyG-related indicators, were found to be associated with an elevated risk of stroke. HTGW and these novel lipid indicators might be reliable indicators to identify populations at elevated risk of stroke.


Isolation and culture of hepatic stellate cells from mouse liver.
Hepatic stellate cells (HSCs) are the primary extracellular matrix-producing cells within the liver and have numerous vital functions. A robust protocol for the isolation and culture of HSCs is important for further investigations of cell functions and related mechanisms in liver disease. The volume of the mouse liver is much smaller than that of the rat liver, which makes it much more difficult to isolate mouse HSCs (mHSCs) than rat HSCs. At present, isolating mHSCs is still a challenge because there is no efficient, robust method to isolate and culture these cells. In the present study, C57BL/6J mice were intravenously injected with liposome-encapsulated dichloromethylene diphosphate (CL2MDP) to selectively eliminate Kupffer cells from the liver. The mouse livers were then perfused in situ, and the mHSCs were isolated with an optimized density gradient centrifugation technique. In the phosphate buffer solution (PBS)-liposome group, the yield of mHSCs was (1.37 ± 0.23) × 10(6)/g liver, the cell purity was (90.18 ± 1.61)%, and the cell survival rate was (94.51 ± 1.61)%. While in the CL2MDP-liposome group, the yield of mHSCs was (1.62 ± 0.34) × 10(6)/g liver, the cell purity was (94.44 ± 1.89)%, and the cell survival rate was (94.41 ± 1.50)%. Based on the yield and purity of mHSCs, the CL2MDP-liposome treatment was superior to the PBS-liposome treatment (P < 0.05, P < 0.01). This study established successfully a robust and efficient protocol for the separation and purification of mHSCs, and both a high purity and an adequate yield of mHSCs were obtained.


Participation of the chaperone Hsc70 in the trafficking and functional expression of ASIC2 in glioma cells.
High-grade glioma cells express subunits of the ENaC/Deg superfamily, including members of ASIC subfamily. Our previous work has shown that glioma cells exhibit a basally active cation current, which is not present in low-grade tumor cells or normal astrocytes, and that can be blocked by amiloride. When ASIC2 is present within the channel complex in the plasma membrane, the channel is rendered non-functional because of inherent negative effectors that require ASIC2. We have previously shown that high-grade glioma cells functionally express this current because of the lack of ASIC2 in the plasma membrane. We now hypothesize that ASIC2 trafficking in glioma cells is regulated by a specific chaperone protein, namely Hsc70. Our results demonstrated that Hsc70 co-immunoprecipitates with ASIC2 and that it is overexpressed in glioma cells as compared with normal astrocytes. In contrast, there was no difference in the expression of calnexin, which also co-immunoprecipitates with ASIC2. In addition, glycerol and sodium 4-phenylbutyrate reduced the amount of Hsc70 expressed in glioma cells to levels found in normal astrocytes. Transfection of Hsc70 siRNA inhibited the constitutively activated amiloride-sensitive current, decreased migration, and increased ASIC2 surface expression in glioma cells. These results support an association between Hsc70 and ASIC2 that may underlie the increased retention of ASIC2 in the endoplasmic reticulum of glioma cells. The data also suggest that decreasing Hsc70 expression promotes reversion of a high-grade glioma cell to a more normal astrocytic phenotype.


Trace levels of bacterial lipopolysaccharide prevent interferon-gamma or tumor necrosis factor-alpha from enhancing mouse peritoneal macrophage respiratory burst capacity.
Preexposure of resident mouse peritoneal macrophages for 1 hr to traces of bacterial lipopolysaccharide (LPS) (less than or equal to 1 ng/ml) rendered the cells refractory to activation by recombinant interferon-gamma (rIFN gamma) or recombinant tumor necrosis factor-alpha (rTNF alpha), as evaluated by release of H2O2 upon stimulation with phorbol myristate acetate. Inhibition persisted for at least 4 days. Fifty percent inhibition of activation mediated by rIFN gamma followed 1 hr exposure to 10 pg/ml LPS. Fifty percent inhibition of activation mediated by rTNF alpha was achieved with 1 hr exposure to 1 pg/ml LPS. Such low levels LPS exposures (concentration X time) are far below those reported for many other actions of LPS on host cells. Inhibition was partially prevented by the cyclooxygenase inhibitors indomethacin, ibuprofen, and acetylsalicylic acid. Exogenous prostaglandins PGE1 and PGE2, and the 3',5'-cyclic adenosine monophosphate analog dibutyryl cyclic adenosine monophosphate (cAMP), mimicked the inhibitory effect of LPS in a dose-dependent manner, consistent with the hypothesis that formation of endogenous cyclooxygenase products in response to LPS may elevate intracellular cAMP and that the latter may mediate the observed inhibition. In addition, neutralizing antibody against IFN alpha and IFN beta selectively prevented LPS inhibition of activation mediated by rIFN gamma, but not by rTNF alpha. This suggests that IFN alpha and/or IFN beta induced by LPS also contributed to inhibition of activation by rIFN gamma. Thus, release of LPS may afford microorganisms a means by which to interfere with immunologically mediated enhancement of the respiratory burst-dependent antimicrobial capacity of macrophages.


Clinical burden of terminal phase in cancer patients.
Symptoms, palliative applications and terminal phase (TP) duration mainly constitute clinical burden of TP in cancer. The aim of this study was to describe palliative issues and determine factors that might influence the clinical burden during TP. We retrospectively studied 125 terminally ill cancer patients, of median age 70 years and ECOG performance status (PS) 4, at their TP entry, who died over a 3-year period, 90 (72%) in hospital (group 1) and 35 at home (group 2). During TP, the 10 most prevalent symptoms were anorexia, pain, dyspnoea, cachexia, fever (infectious or not), constipation, ascites, agitation and vomiting. The 10 most frequent palliative applications were administration of i.v. fluids/drugs, oxygen and enemas administration, bladder catheter and central venous (CV) line care, transfusions, gastric, pleural and peritoneal fluid drainage, endoscopic or percutaneous biliary tract decompression, and radiotherapy. In total, TP represented 8% of the whole disease duration, causing 17% of admissions and 28% of hospital stay. Tumor complications and treatment toxicities caused death and shortened TP in 70% of the cases, more frequently in group 1 (p=0.027). Long disease active phase (AP) duration (from initial diagnosis of cancer to TP entry) predicted PS<4 at TP entry (p=0.008). Predictors of TP duration were AP duration (p=0.010), PS <4 (p=0.000) and number of clinical features (p=0.012). TP represents a small percentage of patients' total disease duration, but it constitutes a considerable part of the entire hospital patients' in-stay and professional practice. PS at TP entry predicted TP duration. AP influenced PS at TP entry and predicted TP duration. AP is an easily measurable clinical parameter and may be considered as an additional prognostic factor of TP duration.


[Molecular-cytogenetic characteristics of B-chromosomes in chironomid (Diptera, Chironomidae)].
Morphological and molecular study of B-chromosomes of three Chironomus species (siblings Ch. borokensis and Ch. phumosus from plumosus group, and Ch. heterodentatus from obtusidens group) was carried out. Morphological similarity of B-chromosome banding pattern and telomer-centromeric region banding pattern of chromosome IV in Ch. borokensis was shown. Polytene B-chromosomes of Ch. borokensis and Ch. heterodentatus were microdissected, and their DNA was amplified using degenerate oligonucleotide primer polymerase chain reaction. Comparative analysis of the localization of homologous B-chromosome DNA sequences of A- and B-polytene chromosomes was made using in situ fluorescence hybridization. It has been shown that B-chromosomes in the studied species are composed mainly of repetitive DNA sequences homologous to sequences of centromeric and telomeric DNA of A-chromosomes, and also these of the mobile element NLRCthl. The B-chromosome DNA, homologous to sequences of DNA mobile element, was scattered on A-chromosomes (more than 100 sites). No ribosomal DNA repeats were identified in B-chromosome. Heterologous FISH of B-chromosome DNA to polytene A-chromosomes of Ch. thummi, a species lacking B-chromosomes, enabled us to reveal the presence of numerous sites homologous to DNA of B-chromosomes. These are mainly mobile element sites. An origin of B-chromosomes and peculiarities of their organization in chironomids are discussed.


Novel integrated and portable endotoxin detection system based on an electrochemical biosensor.
This paper describes the design, implementation and validation of a sensitive and integral technology solution for endotoxin detection. The unified and portable platform is based on the electrochemical detection of endotoxins using a synthetic peptide immobilized on a thin-film biosensor. The work covers the fabrication of an optimized sensor, the biofunctionalization protocol and the design and implementation of the measuring and signalling elements (a microfluidic chamber and a portable potentiostat-galvanostat), framed ad hoc for this specific application. The use of thin-film technologies to fabricate the biosensing device and the application of simple immobilization and detection methods enable a rapid, easy and sensitive technique for in situ and real time LPS detection.


Oscillating Chiral-Nematic Fingerprints Wipe Away Dust.
This work presents an approach to create mechanical undulations at a solid organic coating surface under the influence of an electric field. The coating is fabricated through polymerization of chiral reactive mesogens aligned in their fingerprint mode on top of interdigitated electrodes. The fingerprint mode gives a corrugation of the surface perpendicular to the helix axes. When a lateral alternating electric field is applied, the order parameter of the helicoidally packed mesogens is reduced. This simultaneously leads to an inversion of the fingerprint heights, an overall thickness increase, and a chaotic and fast surface oscillation. These three effects work in concert stimulating wavy deformation figures at the coating surface. The process is fast and reversible; the dynamics of the topographic textures stop immediately when the electric field is switched off. The continuous generation of surface undulations sustains transport of species at the coating surface. It removes dust and debris providing an active dust control.


Measuring and Interpreting Oxygen Consumption Rates in Whole Fly Head Segments.
Regulated metabolic activity is essential for the normal functioning of living cells. Indeed, altered metabolic activity is causally linked with the progression of cancer, diabetes, neurodegeneration, and aging to name a few. For instance, changes in mitochondrial activity, the cell's metabolic powerhouse, have been characterized in many such diseases. Generally, the oxygen consumption rates of mitochondria were considered a reliable readout of mitochondrial activity and measurements in some of these studies were based on isolated mitochondria or cells. However, such conditions may not represent the complexity of a whole tissue. Recently, we have developed a novel method that enables the dynamic measurement of oxygen consumption rates from whole isolated fly heads. By utilizing this method, we have recorded lower oxygen consumption rates of the whole head segment in young versus aged flies. Secondly, we have discovered that lysine deacetylase inhibitors rapidly alter the oxygen consumption in the whole head. Our novel technique may therefore aid in uncovering new properties of various drugs, which may impact metabolic rates. Furthermore, our method may give a better understanding of metabolic behavior in an experimental setup that more closely resembles physiological states.


Mechanism for rapid passive-dynamic prey capture in a pitcher plant.
Plants use rapid movements to disperse seed, spores, or pollen and catch animal prey. Most rapid-release mechanisms only work once and, if repeatable, regaining the prerelease state is a slow and costly process. We present an encompassing mechanism for a rapid, repeatable, passive-dynamic motion used by a carnivorous pitcher plant to catch prey. Nepenthes gracilis uses the impact of rain drops to catapult insects from the underside of the canopy-like pitcher lid into the fluid-filled trap below. High-speed video and laser vibrometry revealed that the lid acts as a torsional spring system, driven by rain drops. During the initial downstroke, the tip of the lid reached peak velocities similar to fast animal motions and an order of magnitude faster than the snap traps of Venus flytraps and catapulting tentacles of the sundew Drosera glanduligera. In contrast to these active movements, the N. gracilis lid oscillation requires neither mechanical preloading nor metabolic energy, and its repeatability is only limited by the intensity and duration of rainfall. The underside of the lid is coated with friction-reducing wax crystals, making insects more vulnerable to perturbations. We show that the trapping success of N. gracilis relies on the combination of material stiffness adapted for momentum transfer and the antiadhesive properties of the wax crystal surface. The impact-driven oscillation of the N. gracilis lid represents a new kind of rapid plant movement with adaptive function. Our findings establish the existence of a continuum between active and passive trapping mechanisms in carnivorous plants.


Cryoablation Combined with Left Atrial Appendage Closure: A Safe and Effective Procedure for Paroxysmal Atrial Fibrillation Patients.
Catheter ablation combined with left atrial appendage closure (LAAC) was reported as a feasible strategy for atrial fibrillation (AF) patients with high risk of stroke or contraindications of oral anticoagulants. We aimed to observe the short-term safety and efficacy of combining cryoballoon ablation (CBA) with LAAC in paroxysmal (PAF) patients. Method and Results. From Jan 2016 to Dec 2017, 304 patients diagnosed with nonvalvular, drug-refractory PAF were included, who underwent either CBA alone (n = 262) or combined procedure (n = 42). Instant pulmonary vein isolation (PVI) with CBA was achieved in all patients, while successful LAAC achieved in 41 (97.6%) of combined procedure patients. 1-year freedom of AF rate was lower in combined procedure group (84.7% vs 70.7%, p = 0.04), with unadjusted hazard ratio (HR = 1.97) and 95% confidence interval (CI) 1.03-3.77. However, the multivariate COX model revealed left atrial diameter (p = 0.002, HR = 1.10, and 95% CI 1.04, 1.17), rather than procedure type (p = 0.51, HR = 1.34, and 95% CI 0.57, 3.17), was the predictor for freedom of AF. Only 2 patients in the CBA group had stroke, contributing to the nonsignificant higher stroke incidence (p = 1.00). Transoesophageal echochardiography (TEE) achieved in 35 patients (83.3%) showed complete occlusion with no obvious residual flow (>3 mm), Device-related thrombosis, or pericardial perfusion. All-cause mortality, rehospitalization, and complication rates were similar. Combining CBA with LAAC in a single procedure is a feasible strategy for PAF patients, with comparable short-term safety and efficacy to CBA alone.


Cytoprotective effects of myristicin against hypoxia‑induced apoptosis and endoplasmic reticulum stress in rat dorsal root ganglion neurons.
The aim of the present study was to investigate the role of myristicin (Myr; 1‑allyl‑5‑methoxy‑3,4‑methylenedioxybenzene), an active aromatic compound isolated from nutmeg, carrot, basil, cinnamon and parsley, in hypoxia‑induced apoptosis in rat dorsal root ganglion (DRG) neurons. It was observed that Myr significantly enhanced cell viability in hypoxia‑induced DRG neurons in a dose‑dependent manner; the optimal concentration of Myr was 50 µM. Furthermore, Myr reduced the percentage of deoxynucleotidyl transferase‑mediated dUTP nick end‑labeling‑positive neuronal cells and influenced the expression of the pro‑apoptotic gene B‑cell lymphoma 2 (Bcl‑2) associated X protein, the apoptosis protease cleaved caspase‑3 and the anti‑apoptotic gene Bcl‑2, in the hypoxia‑induced group. In addition, Myr protected against hypoxic injury in DRG neurons by inhibiting malondialdehyde and lactate dehydrogenase, however upregulating superoxide dismutase and glutathione peroxidase. Myr reduced the expression of endoplasmic reticulum stress (ERS) markers, including CCAAT/enhancer‑binding protein‑homologous protein, glucose‑related protein 78 and cleaved caspase‑12 in the hypoxia‑induced group. To the best of our knowledge, this is the first demonstration of the activity of Myr against hypoxia‑induced apoptosis in rat DRG neurons via inhibition of the ERS pathway.


A Brønsted base-promoted diastereoselective dimerization of azlactones.
A novel Brønsted base system for the diastereoselective dimerization of azlactones using trichloroacetate salts and acetonitrile has been developed. Desired products were obtained in good yields (60-93%) and with up to >19:1 dr after one hour of reaction. Additionally, the relative stereochemistry of the major dimer was assigned as being trans, by X-ray crystallographic analysis. The kinetic reaction profile was determined by using 1H NMR reaction monitoring and revealed a second order overall kinetic profile. Furthermore, by employing this methodology, a diastereoselective total synthesis of a functionalized analogue of streptopyrrolidine was accomplished in 65% overall yield.


Flaxseed diet caused inflammation by altering the gut microbiota of Peking ducks.
To study why flaxseed supplementation causes adverse effects on the performance of poultry, we investigated the gut microbiota of Peking ducks after consumption of a flaxseed diet. A total of 792, 12-day-old white Peking ducks were divided into four groups. In the control group, birds were provided with a basal diet. In the three experimental groups, the birds were fed flaxseed containing diet (10% flaxseed and 90% basal diet) for 30, 20 and 10 d, respectively. On day 42, ceca were collected to evaluate the bacterial diversity of the gut microbiota using microbial 16S rDNA gene profiling; serums were obtained to determine the levels of inflammatory mediators. The flaxseed diet decreased the alpha diversity and shifted the predominant genera of the gut microbiota. Flaxseed-fed groups had higher abundances of Escherichia/Shigella (p < 0.1) and Campylobacter (p < 0.05) than the control group. The abundance of pro-inflammatory bacteria such as Veillonellaceae increased (p < 0.05) at first and then decreased (p < 0.05) with prolonged flaxseed supplementation. The levels of prostaglandin E2 and Leukotriene B4 in serum showed the same pattern as that of the pro-inflammatory bacteria. In conclusion, flaxseed diets are associated with inflammation by altering the cecal microbiota dynamics.


Immunoprecipitation of radiolabeled human thyroid cell proteins by serum from patients with autoimmune thyroid disease.
Characterization of the antigen to thyroid-stimulating immunoglobulin (TSI), presumably the TSH receptor, remains elusive. We, therefore, attempted immunoprecipitation of the TSI antigen using cultured human thyroid cells radiolabeled to high specific activity by [35S]methionine (all proteins labeled) or by 125I and lactoperoxidase (primarily cell surface proteins labeled). Both techniques produced similar results. Crude membrane preparations from the labeled cells were solubilized in buffer containing 1% Triton and then incubated with TSI-containing or control serum. Immunoglobulin was precipitated with goat antihuman immunoglobulin and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. About 30 proteins were immunoprecipitated by both normal and control sera. However, only 1 protein (mol wt, approximately 320,000) was preferentially selected by TSI-containing serum (6 of 6 tested). This protein was also immunoprecipitated by the majority of sera from patients with Hashimoto's thyroiditis. The 320,000 mol wt protein constituted only a minute amount of total radiolabeled membrane protein, because it was not apparent on electrophoresis of the membrane extract before immunoprecipitation. It corresponded (in migration) to a human thyroglobulin (Tg) standard. Tg also inhibited immunoprecipitation of the 320,000 mol wt band. The anti-Tg antibody titer correlated significantly with the degree of immunoprecipitation of the 320,000 mol wt band. No specific immunoprecipitation of any protein was observed when radiolabeled guinea pig membrane proteins were used. These data provide insight into the difficulties involved in the identification of the TSH receptor with serum containing TSI.


Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness.
The short- and long-term effects of gene therapy using AAV-mediated RPE65 transfer to canine retinal pigment epithelium were investigated in dogs affected with disease caused by RPE65 deficiency. Results with AAV 2/2, 2/1, and 2/5 vector pseudotypes, human or canine RPE65 cDNA, and constitutive or tissue-specific promoters were similar. Subretinally administered vectors restored retinal function in 23 of 26 eyes, but intravitreal injections consistently did not. Photoreceptoral and postreceptoral function in both rod and cone systems improved with therapy. In dogs followed electroretinographically for 3 years, responses remained stable. Biochemical analysis of retinal retinoids indicates that mutant dogs have no detectable 11-cis-retinal, but markedly elevated retinyl esters. Subretinal AAV-RPE65 treatment resulted in detectable 11-cis-retinal expression, limited to treated areas. RPE65 protein expression was limited to retinal pigment epithelium of treated areas. Subretinal AAV-RPE65 vector is well tolerated and does not elicit high antibody levels to the vector or the protein in ocular fluids or serum. In long-term studies, wild-type cDNA is expressed only in target cells. Successful, stable restoration of rod and cone photoreceptor function in these dogs has important implications for treatment of human patients affected with Leber congenital amaurosis caused by RPE65 mutations.


Understanding the Nature and Properties of Hydrogen-Hydrogen Bonds: The Stability of a Bulky Phosphatetrahedrane as a Case Study.
Recently, the first mixed C/P phosphatetrahedranes (tBuC)3P and (tBuCP)2 were reported. Unlike (tBuCP)2, (tBuC)3P exhibits remarkable thermal stability, which can be partially attributed to a network of nine hydrogen-hydrogen bonds (HHBs) localized between the tert-butyl substituents. The stabilizing contribution arising from this network of HHBs was obtained from local energy decomposition (LED) analysis calculated at the domain-based local pair natural orbital CCSD(T) (DLPNO-CCSD(T)) level of theory. These calculations suggest that each HHB contributes approximately -0.7 kcal/mol of stabilization; however, the net stabilization energy likely lies between -0.25 and -0.5 kcal/mol because of steric repulsion. Spatial analysis of the London dispersion energy via a dispersion interaction density (DID) plot reveals that the DID surface is localized at key C-H groups involved in HHBs, consistent with London dispersion interactions predominantly arising from HHBs. In addition, we present a computed mechanism that supports a phosphinidenoid species as a key reaction intermediate in the synthesis of (tBuC)3P.


Estrogen activates the high-density lipoprotein receptor gene via binding to estrogen response elements and interaction with sterol regulatory element binding protein-1A.
The effects of E2 on the high-density lipoprotein receptor (HDL-R) scavenger receptor class B type I (SR-BI) gene were examined. Four putative estrogen response element half-site motifs (ERE(1/2)) (-2176, -1726, -1622, and -1211, designated ERE(1/2)-1, 2, 3, and 4, respectively) were identified in the HDL-R SR-BI promoter. Transfection studies and mutation analysis demonstrated that E2 significantly increased HDL-R SR-BI promoter activity and that mutating ERE(1/2)-1, 2, and 4 resulted in a loss of E2 responsiveness. Both ER alpha and ER beta formed specific complexes with ERE(1/2)-1, 2, and 4 but did not bind ERE(1/2)-3 in vitro. Interestingly, ERE(1/2)-3 was the motif shown not to be important for E2-activation of the HDL-R SR-BI promoter in the mutational analysis studies. The influence of SREBP-1a (sterol regulatory element binding protein-1a) on E2 regulation of the HDL-R SR-BI gene was also examined. SREBP-1a was able to bind directly to the ERE(1/2) motifs and enhanced ER binding when both ER subtypes were present. ER alpha and beta also bound to a sterol response element motif, but they did not enhance SREBP-1a binding. Cotransfection studies demonstrated that the presence of the three factors, ER alpha, ER beta, and SREBP-1a, enhanced the overall luciferase activity produced from the HDL-R SR-BI promoter construct in the presence of only one of the factors. Interaction of SREBP-1a with both ERs was demonstrated using a mammalian two-hybrid assay. The data confirmed that E2 through the ERs can positively regulate the HDL-R SR-BI through binding and activation of three ERE(1/2) motifs and identified SREBP-1a as a potential coactivator of the E2-ER-dependent effects on the HDL-R SR-BI gene.


Decanuclear Ln10 Wheels and Vertex-Shared Spirocyclic Ln5 Cores: Synthesis, Structure, SMM Behavior, and MCE Properties.
The reaction of a Schiff base ligand (LH3) with lanthanide salts, pivalic acid and triethylamine in 1:1:1:3 and 4:5:8:20 stoichiometric ratios results in the formation of decanuclear Ln10 (Ln = Dy (1), Tb (2), and Gd (3)) and pentanuclear Ln5 complexes (Ln = Gd (4), Tb (5), and Dy (6)), respectively. The formation of Ln10 and Ln5 complexes are fully governed by the stoichiometry of the reagents used. Detailed magnetic studies on these complexes (1-6) have been carried out. Complex 1 shows a SMM behavior with an effective energy barrier for the reversal of the magnetization (Ueff) = 16.12(8) K and relaxation time (τo) = 3.3×10(-5) s under 4000 Oe direct current (dc) field. Complex 6 shows the frequency dependent maxima in the out-of-phase signal under zero dc field, without achieving maxima above 2 K. Complexes 3 and 4 show a large magnetocaloric effect with the following characteristic values: -ΔSm = 26.6 J kg(-1) K(-1) at T = 2.2 K for 3 and -ΔSm = 27.1 J kg(-1) K(-1) at T = 2.4 K for 4, both for an applied field change of 7 T.


Assessing psychiatric impairment in primary care with the Sheehan Disability Scale.
Several recent studies have documented that substantial functional impairment is associated with many of the mental disorders seen in primary care. However, brief measures of mental health-related functional impairment are not commonly applied in primary care settings. The Sheehan Disability Scale (SDS), a three-item instrument for assessing such impairment, is evaluated in this study. A psychometric analysis of the SDS was conducted with a sample of 1001 primary care patients at Kaiser Permanente In Oakland, California. The SDS and the Symptom Driven Diagnostic System for Primary Care assessments were completed. The internal consistency reliability of the SDS is high, with coefficient alpha of 0.89. The construct validity was substantiated in two ways. A one-factor model fit the data quite well. Furthermore, patients with each of six psychiatric disorders had significantly higher impairment scores than those who did not. Finally, over 80 percent of the patients with mental disorder diagnoses had an elevated SDS score and nearly 50 percent of those with elevated SDS scores had at least one disorder. The psychometric properties of the SDS were evaluated in primary care. The internal consistency reliability was high. The analyses also lend empirical support for the construct validity. The scale is a sensitive tool for identifying primary care patients with mental health-related functional impairment, who would warrant a diagnostically-oriented mental health assessment.


Cystic carcinoma ex pleomorphic adenoma of the lacrimal gland.
In a 48-year-old male patient, a well-circumscribed, round tumor in the lacrimal fossa was detected by CT. During total excision of the tumor, a wall of the tumor ruptured, resulting in leakage of the fluid contents. The wall of the tumor formed a cyst that contained residual yellowish fluid. Histologically, the cyst wall included an adenocarcinomatous component and a focus of pleomorphic adenoma. The tumor was diagnosed as a carcinoma ex pleomorphic adenoma of the lacrimal gland. The carcinoma cells showed positive immunoreactivity for androgen receptor and BRST-2, indicating that the tumor was equivalent to a salivary duct carcinoma. Postoperatively, the patient underwent involved field irradiation. This case demonstrates that a carcinoma ex pleomorphic adenoma of the lacrimal gland may develop in a cyst.


Reliable co-segregation analysis for prenatal diagnosis and heterozygote detection in Gaucher disease.
Mutations in the gene encoding beta-glucocerebrosidase are the main cause of Gaucher disease. The identification of some of these mutations in prenatal tests is a good complement to enzymatic assay and allows diagnosis and, in some cases, prognosis of the disease to be made. DNA analysis is particularly useful for carrier detection since the results of biochemical analyses are often ambiguous. The main drawback of mutation analysis for prenatal diagnosis and carrier detection in Gaucher disease is that rare mutations account for more than 30 per cent of the mutant alleles in most populations. The individual detection of these mutations is too expensive and time-consuming for routine use. Here we present a diagnostic protocol based on co-segregation analysis, using highly polymorphic markers, to be applied when at least one disease allele does not correspond to the most common mutations. Because of the frequency of the N370S mutation and its relevance for prognosis, an improved PCR detection method is included.


Quantification of cosmesis for patients affected by adolescent idiopathic scoliosis.
The aim of this study was to quantify cosmesis for patients affected by adolescent idiopathic scoliosis. Eight nonmedical judges were asked to examine photographs of 40 patients with adolescent idiopathic scoliosis, and to score the cosmesis of their backs without any information. Various parameters were measured from radiographs, Moiré topographies, and physical measurements of patients, and these were compared with the cosmetic scores of the judges. The judges' scoring proved to be reliable. The cosmetic scores showed a significant correlation with the Cobb angle, hump severity, asymmetry of the waist line, circumference of the chest, and obesity. Multivariate analysis produced equations to calculate the cosmetic score for the back. This equation is thought to have a useful clinical application.


Primate displacement activities as an ethopharmacological model of anxiety.
Using a within-subject cross-over, vehicle-controlled design, we investigated the acute effects of benzodiazepine receptor ligands with different mechanisms of action on the displacement activities (scratching, self-grooming, and body shake) of seven male macaques living in social groups. Our aim was to test the discriminative validity of displacement activities as an ethopharmacological model of anxiety. Subjects were given i.m. lorazepam (0.10, 0.20, 0.25 mg/ kg) and FG 7142 (0.1, 0.3, 1.0 mg/kg). The frequency of displacement activities was decreased by the anxiolytic lorazepam and increased by the anxiogenic FG 7142 in a dose-dependent manner. Displacement activities were apparently more sensitive to anxiolytic treatment than other behavior patterns indicative of an anxiety state (i.e., visual scanning of the social environment and fear responses directed to dominant males). These results suggest that primate displacement activities are a valid ethopharmacological model of anxiety.


Secondary oesophageal or gastric cancer in patients treated for head and neck squamous cell carcinoma.
Patients with head and neck squamous cell carcinoma (HNSCC) are at an elevated risk of developing second primary malignancies (SPM). Our objectives were to estimate the excess risk of oesophageal and gastric SPMs in patients with malignancies of the pharynx or larynx and, additionally, to examine possible risk factors of developing SPMs. Data on all patients treated for HNSCC with curative intent in the Region of Southern Denmark in the period between 1 January 2000 and 31 December 2010 were reviewed. A total of 1,172 patients were identified. The combined data from the DAHANCA database, the Danish National Pathology Registry and the patient charts were analysed. A total of 27 patients developed an SPM in the oesophagus or stomach corresponding to a standardised incidence ratio of 9.5 (95% confidence interval (CI): 6.5-13.9). Supraglottic (odds ratio (OR) = 6.9; p < 0.004) and hypopharyngeal (OR = 3.9; p < 0.049) index tumour sites were significant risk factors for developing SPM. The median survival of patients with SPM was 3.6 years (95% CI: 1.6-5.1; range: 0.7-12.4) from diagnosis of the index cancer compared with 3.4 years (95% CI: 3.1-4.3; range: 0.04-13.7) for patients without SPM. In this study, we confirm that there is an elevated risk of developing oesophageal and gastric cancer in the Danish population of patients with a cancer in the supraglottic or hypopharyngeal region. Therefore, we recommend close follow-up of these patients and a low threshold for examination of the oesophagus and stomach. not relevant. not relevant.


Effects of parental supportiveness on toddlers' emotion regulation over the first three years of life in a low-income African American sample.
The purpose of this study was to examine how parental supportiveness and child gender are related to toddlers' emotion regulation over time among low-income African American mothers and their children (n = 803). Data for the current study were collected as part of the Early Head Start Research and Evaluation Project. Using latent growth curve modeling, results indicated that parental supportiveness predicted toddlers' emotion regulation skills, on average (intercepts), and rates of growth of parental supportiveness predicted the rates of growth in emotion regulation over time (slope), beyond the effects of initial parental risk status, child gender, Early Head Start treatment effects, and infant emotionality. However, parental supportiveness over time did not differentially predict toddler emotion regulation over time for boys as compared to girls. Results suggest that parental supportiveness may represent a subtle form of emotion socialization by providing a context in which toddlers may be better able to utilize their mothers as effective resources in managing emotions. Practitioners should emphasize with the parents the role of parent-child interactions as a context for development. The lack of gender differences suggests that differential parenting towards boys and girls, evident in research with older children, may not yet be present in toddlerhood. Recognizing similarities in parenting across racial groups early on as well as being sensitive to differences that may emerge later will position practitioners to provide support within a culturally sensitive framework.


NMR crystallography to probe the breathing effect of the MIL-53(Al) metal-organic framework using solid-state NMR measurements of 13C-27Al distances.
The metal-organic framework MIL-53(Al) (aluminium terephthalate) exhibits a structural transition between two porous structures with large pore (lp) or narrow pore (np) configurations. This transition, called the breathing effect, is observed upon changes in temperature or external pressure, as well as with the adsorption of guest molecules, such as H2O, within the pores. We show here how these different pore openings can be detected by observing the dephasing of 13C magnetization under 13C-27Al dipolar couplings using Rotational-Echo Saturation-Pulse Double-Resonance (RESPDOR) solid-state NMR experiments with Simultaneous Frequency and Amplitude Modulation (SFAM) recoupling. These double-resonance NMR experiments between 13C and 27Al nuclei, which have close Larmor frequencies, are feasible thanks to the use of a frequency splitter. The experimental SFAM-RESPDOR signal fractions agree well with those simulated from the MIL-53(Al)-lp and -np crystal structures obtained from powder X-ray diffraction analysis. Hence, these 13C-27Al solid-state NMR experiments validate these structures and confirm their rigidity. A similar agreement is reported for the framework ligands in the as-synthesized (as) MIL-53(Al), in which the pores contain free ligands. Furthermore, in this case, 13C-{27Al} SFAM-RESPDOR experiments allow an estimation of the average distance between the free ligands and the 27Al nuclei of the framework.