Kimura's Disease Presenting As Scrotal Mass: A Difficult Diagnosis.
Herein we report a case of Kimura's disease with unusual manifestations. A 46-year- old Chinese man presented with mass in scrotum which gradually increased in size for approximately 7 years. A computerized tomographic scan of abdomen revealed a soft-tissue density shadow in scrotum and enlargement of lymph nodes in groin and retroperitoneum. The scrotal mass was excised and the biopsy specimen revealed angiolymphoid hyperplasia with infiltration of eosinophils. In conclusion, clinical doctors should pay attention that the patient with eosinophilia and scrotal mass could be indicative for Kimura's disease.


Advancing Urinary Protein Biomarker Discovery by Data-Independent Acquisition on a Quadrupole-Orbitrap Mass Spectrometer.
The promises of data-independent acquisition (DIA) strategies are a comprehensive and reproducible digital qualitative and quantitative record of the proteins present in a sample. We developed a fast and robust DIA method for comprehensive mapping of the urinary proteome that enables large scale urine proteomics studies. Compared to a data-dependent acquisition (DDA) experiments, our DIA assay doubled the number of identified peptides and proteins per sample at half the coefficients of variation observed for DDA data (DIA = ∼8%; DDA = ∼16%). We also tested different spectral libraries and their effects on overall protein and peptide identifications and their reproducibilities, which provided clear evidence that sample type-specific spectral libraries are preferred for reliable data analysis. To show applicability for biomarker discovery experiments, we analyzed a sample set of 87 urine samples from children seen in the emergency department with abdominal pain. The whole set was analyzed with high proteome coverage (∼1300 proteins/sample) in less than 4 days. The data set revealed excellent biomarker candidates for ovarian cyst and urinary tract infection. The improved throughput and quantitative performance of our optimized DIA workflow allow for the efficient simultaneous discovery and verification of biomarker candidates without the requirement for an early bias toward selected proteins.


Effect of Gum Arabic (Acacia Senegal) supplementation on visceral adiposity index (VAI) and blood pressure in patients with type 2 diabetes mellitus as indicators of cardiovascular disease (CVD): a randomized and placebo-controlled clinical trial.
There is a strong association between cardiometabolic risk and adipose tissue dysfunction with great consequences on type 2 diabetic patients. Visceral Adiposity Index (VAI) is an indirect clinical marker of adipose tissue dysfunction. Gum Arabic (GA) is a safe dietary fiber, an exudate of Acacia Senegal. Gum Arabic had shown lipid lowering effect in both humans and animals. The aim of this trial was to determine the effect of GA supplementation on anthropometric obesity marker, Visceral Adiposity Index (VAI) and blood pressure in patients with type 2 diabetes mellitus. This randomized, double blinded, placebo controlled trial recruited a total of 91 type 2 diabetic patients (73 females, 18 males), age (mean ± SD) 50.09 ± 9.3 years on hypoglycemic agents and were randomly assigned into two groups, either to consume 30 g of GA or 5 g of placebo daily for 3 months. Anthropometric obesity markers were measured and indices were calculated. Blood pressure was measured and high density lipoprotein (HDL) and triglycerides (TG) were determined in fasting blood samples at the start and end of the study period. After intervention, Gum Arabic decreased BMI and VAI significantly (P < 0.05) in GA group by 2 and 23.7% respectively. Body adiposity index significantly decreased by 3.9% in GA group while there were no significant changes in waist circumference or waist-to-hip ratio (WHR). Systolic blood pressure significantly decreased by 7.6% in GA group and by 2.7% in placebo group from baseline with no significant changes in diastolic blood pressure in the two groups. Gum Arabic consumption at a dose of 30 g/d for 3 months may play an effective role in preventing weight gain and modulating adipose tissue dysfunction in type 2 diabetic patients, although no effect has been shown in waist-to-hip ratio. The trial had been registered as prospective interventional clinical trials in the Pan African Clinical Trial Registry (PACTR) PACTR201403000785219 , on 7th March 2014.


[Interferon treatment for chronic hepatitis C].
To determine the factors influencing the response to interferon (IFN) therapy, we studied 156 patients with chronic hepatitis C who underwent IFN alpha treatment Either 9MU of recombinant IFN alpha 2a or 3MU of natural IFN alpha was administered daily for 2 weeks and then three times a week for 22 weeks. IFN responses were divided into three types on the basis of the results of the polymerase chain reaction (PCR) assay detecting the 5 noncoding regions of HCV in sera. A complete response (CR) was defined as sustained elimination of HCV for at least 6 months after treatment, partial response (PR) as HCV elimination for a limited period, no response (NR) as continuously HCV-RNA positive. HCV genotyping was done by PCR with genotype-specific primers, by analyzing the variations in nucleotide sequence within the core region of HCV, namely HCV-I, -II, -III and -IV. Quantitation of serum HCV-RNA was performed by competitive PCR assay using synthetic mutant RNA. CR was obtained in 43 patients, PR in 64, and NR in 49. The IFN responses, CR/PR/NR, were 7/10/3 in 20 patients with chronic persistent hepatitis histologically, 34/38/24 in 96 patients with chronic active hepatitis (CAH)2A, and 2/16/22 in 40 with CAH2B. Median values of pretreatment serum HCV-RNA amount (copies/ml) in CR, PR, and NR groups were 10(3.55), 10(4.56) and 10(5.97), respectively. On HCV genotyping of sera from 114 patients, HCV-I, -II, -III, -IV and mixed (II+of) were seen in 1, 94, 11, 6 and 2 patients, respectively. CR/PR/NR in patients infected with HCV-I, -II, -III, -IV and -II + IV were 0/0/1, 28/26/40, 3/5/3, 1/3/2 and 0/1/1, respectively. Patients who had low viremia levels were likely to show good IFN responses, and those who had progressed liver histologies were resistant to IFN therapy.


Automated Cell Culture Systems and Their Applications to Human Pluripotent Stem Cell Studies.
Pluripotent stem cells are an extremely powerful tool in modeling human diseases and hold much promise for personalized regenerative or cell replacement therapies. There is an increasing need for reproducible large-scale stem cell and differentiated progeny production, with minimal variation, rendering manual approaches impracticable. Here, we provide an overview of systems currently available for automated stem cell culture, and undertake a review of their capacities, capabilities, and relative limitations. With the merging of modern technology and stem cell biology, an increased demand and implementation of automated platforms for stem cell studies is anticipated.


Aminocaproic acid and tranexamic acid increase the rate of acute corneal reepithelialization in Sprague Dawley rats.
Antifibrinolytic agents, epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA), have been reported to be efficacious in the treatment of chronic persistent epithelial defects. Within the regulatory mechanism of corneal reepithelialization, fibronectin serves as a primary adhesive component in the healing process and anchors regenerating epithelial cells to underlying stroma. EACA and TXA inhibit the activation of plasmin thereby decreasing plasmin-induced catabolism of fibronectin. In this study, acute reepithelialization following treatment with EACA and TXA was evaluated in the cultured rat cornea model. Sprague Dawley rat corneal explants with 3 mm corneal defects, induced with 1 N NaOH, were cultured with either EACA or TXA. After 12 or 24 hr incubation periods, corneal explants were stained with bromodeoxyuridine stain for measuring cellular division and migration or Trypan Blue for measuring the extent of dead cells. Both EACA and TXA increased the rate of reepithelialization in comparison to an untreated control. EACA was up to 35% more efficacious than TXA. Thus, this study demonstrated an acute effect for EACA and TXA versus the previously reported efficacy of chronic therapy required for persistent epithelial defects. Broad applications may prove beneficial in the clinical treatment of corneal abrasions, persistent corneal epithelial defects, or alkali burns.


Tailored Chemical Properties of 4-Arm Star Shaped Poly(d,l-lactide) as Cell Adhesive Three-Dimensional Scaffolds.
Biodegradable poly(lactic acid) (PLA) is widely used to fabricate 3D scaffolds for tissue regeneration. However, PLA lacks cell adhering functional moieties, which limit its successful application in tissue engineering. Herein, we have tailored the cell adhesive properties of star shaped poly(d,l-lactide) (ss-PDLLA) by grafting gelatin to their 4 arms. Grafting of gelatin on PDLLA backbone was confirmed by 1H NMR and FTIR. The synthesized star shaped poly(d,l-lactide)-b-gelatin (ss-pLG) exhibited enhanced wettability and protein adsorption. The modification also facilitated better cell adhesion and proliferation on their respective polymer coated 2D substrates, compared to their respective unmodified ss-PDLLA. Further, 3D scaffolds were fabricated from gelatin grafted and unmodified polymers. The fabricated scaffolds were shown to be cytocompatible to 3T3-L1 cells and hemocompatible to red blood cells (RBCs). Cell proliferation was increased up to 2.5-fold in ss-pLG scaffolds compared to ss-PDLLA scaffolds. Furthermore, a significant increase in cell number reveals a high degree of infiltration of cells into the scaffolds, forming a viable and healthy 3D interconnected cell community. In addition to that, burst release of docetaxal (DTX) was observed from ss-pLG scaffolds. Hence, this new system of grafting polymers followed by fabricating 3D scaffolds could be utilized as a successful approach in a variety of applications where cell-containing depots are used.


CARLoquium 2022.
The Chiropractic Academy for Research Leadership (CARL) is an innovative program that provides mentorship, training, and leadership opportunities to the next generation of chiropractic researchers through an open application process. The first CARLoquium was launched by in 2021 by the CARL Fellows as a means to meet and disseminate research findings from the chiropractic community during the COVID-19 pandemic with the second CARLoquium held virtually in March 2022. To date, the conference has featured numerous keynote speakers, hundreds of abstracts and continues to provide a cost-effective avenue for our researcher community to gather.


Clinical Characteristics and Histopathology of Coronavirus Disease 2019-Related Deaths in African Children.
Globally, very few childhood deaths have been attributed to coronavirus disease 2019 (COVID-19). We evaluated clinical, microbiologic and postmortem histopathologic findings in childhood deaths in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified antemortem or postmortem. Surveillance of childhood deaths was ongoing during the initial COVID-19 outbreak in South Africa from April 14, 2020, to August 31, 2020. All children hospitalized during this time had a SARS-CoV-2 test done as part of standard of care. Postmortem sampling included minimally invasive tissue sampling (MITS) of lung, liver and heart tissue; blood and lung samples for bacterial culture and molecular detection of viruses (including SARS-CoV-2) and bacteria. The cause of death attribution was undertaken by a multidisciplinary team and reported using World Health Organization framework for cause of death attribution. SARS-CoV-2 was identified on antemortem and/or postmortem sampling in 11.7% (20/171) of deceased children, including 13.2% (12/91) in whom MITS was done. Eighteen (90%) of 20 deaths with SARS-CoV-2 infection were <12 months age. COVID-19 was attributed in the causal pathway to death in 91.7% (11/12) and 87.5% (7/8) cases with and without MITS, respectively. Lung histopathologic features in COVID-19-related deaths included diffuse alveolar damage (n = 6, 54.5%), type 2 pneumocyte proliferation (n = 6, 54.5%) and hyaline membrane formation (n = 5, 36.4%). Culture-confirmed invasive bacterial disease was evident in 54.5% (6/11) of COVID-19 attributed deaths investigated with MITS. COVID-19 was in the causal pathway of 10.5% (18/171) of all childhood deaths under surveillance. The postmortem histopathologic features in fatal COVID-19 cases in children were consistent with reports on COVID-19 deaths in adults; although there was a high prevalence of invasive bacterial disease in the children.


Coherent THz Transient Spin Currents by Spin Pumping.
The generation of short spin current pulses is the basis for fast spintronic devices. In thin bilayer systems consisting of a nonmagnetic metal and a ferromagnet, a pure spin current is induced by a precessing magnetization into the nonmagnetic layer by spin pumping. This effect has been experimentally demonstrated at ferromagnetic resonance at GHz frequencies. Here, it is theoretically shown that transient magnetization dynamics efficiently generates short spin current pulses that exhibit two transient contributions. An effective coherent spin current generation is found far above the ferromagnetic resonance up to THz frequencies although dynamic magnetization amplitudes are very small in this regime. The results provide a concept for coherent THz spin current generation.


On the Importance of π-Hole Beryllium Bonds: Theoretical Study and Biological Implications.
In this study, the ability of beryllium compounds to establish π-hole bonding interactions has been evaluated at the RI-MP2/def2-TZVPD level of theory. A search of the Protein Data Bank revealed some X-ray crystal structures in which BeF3- moieties act as electron-acceptor entities. We have used [Mg(BeF3 )(HCOO)] (1) as a π-hole bond donor and CO, CH3 CN, NH3 , O(CH3 )2 , S(CH3 )2 , H3 PO, and glycine as electron-rich entities. In all cases, favorable binding energies were obtained, reflecting the attractive nature of the interaction involving the trivalent beryllium atom (-BeF3 moiety). In addition, we have used Bader's theory of "atoms in molecules" and noncovalent interaction (NCI) plot analysis to further investigate and characterize the π-hole complexes described herein. To the best of our knowledge, π-hole interactions involving beryllium have not hitherto been described in the literature.


Cyclic changes of the rate of phospholipid synthesis during synchronous growth of Escherichia coli.
The problem of the coordination between cyclic events in the DNA assembly line and the cell envelope assembly line was approached with the technique of synchronized cultures. Escherichia coli strains ML 30, K12 3300, K12 PC2, K12 BB2014 and B/rF were synchronized by repeated cycles of mass doubling followed by short phosphate starvation periods. Steady-state balanced growth was obtained by subsequent incubation in non-limiting growth conditions for one or more generation times. Several successive cell cycles were monitored for mass increase and cell number, while the rate of DNA synthesis and the rate of phospholipid synthesis were usually measured with more than one method. In all strains, and in strain ML 30 in five different growth media giving doubling times from 20-110 min, a discontinuity in the rate of synthesis of phosphatidylethanolamine and of phosphatidylglycerol was observed. These two major phospholipid components of inner and outer membranes were synthesized at a constant rate per cell for a large portion of the cell cycle and the rate of synthesis of both increased twofold at the same time. This cyclic program was reproducible not only in successive cell cycles, but also in separate experiments with the same strain, in the same medium. In contrast, differences in timing were observed with different strains, and in the same strain with different carbon sources. In particular, the simultaneity of the increase in phospholipid synthesis either with DNA initiation or with cell division could not be observed as a rule.


Current perspectives on the optimal management of infantile hemangioma.
Infantile hemangiomas (IHs) are the most common benign tumor of infancy. As our understanding of their pathobiology has evolved, treatment has become more focused and tailored to specifically treat IH while minimizing adverse effects. Propranolol has gained FDA approval as the first medical therapy for a traditionally surgical disease. This review provides readers with an overview of IH, treatment modalities, and addresses specific considerations in IH disease management.


Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor.
The study of immunodominance within microbe-specific CD8 T cell responses has been challenging. We used a previously undescribed approach to create unbiased panels of CD8 cytotoxic T lymphocyte clones specific for herpes simplex virus type 2, a pathogen with a complex genome encoding at least 85 polypeptides. Circulating herpes simplex virus type 2-specific cells were enriched and cloned after sorting for expression of the skin homing-associated receptor, cutaneous lymphocyte-associated antigen, bypassing restimulation with antigen. The specificity of the resultant cytotoxic clones was determined. Clonal frequencies were compared with each other and with the total number of cytotoxic clones. For each subject within the homing receptor-positive compartment, the CD8 cytotoxic response was dominated by T cells specific for only a few peptides. Previously undescribed antigens and epitopes in viral tegument, capsid, or scaffold proteins were immunodominant in some subjects. Clone enumeration analyses were confirmed in some subjects with dominance studies by using herpes simplex mutants, vaccinia recombinants, and/or enzyme-linked immune spots. We conclude that among circulating cells expressing a homing-associated receptor, during chronic herpes type 2 infection, the CD8 T cell response becomes quite focused despite the presence of many potential antigenic peptides.


Amplified-fragment length polymorphism as a complement to IS6110-based restriction fragment length polymorphism analysis for molecular typing of Mycobacterium tuberculosis.
The amplified-fragment length polymorphism (AFLP) technique was applied to clusters of Mycobacterium tuberculosis clinical isolates obtained by using IS6110-based restriction fragment length polymorphism (RFLP). Ten of the RFLP clusters showed identical AFLP patterns also, but the other 13 could be resolved into subclusters by AFLP. Our results suggest that some RFLP clusters may not be due to recent transmission and that AFLP may be a useful complementary technique.


Synergistic effect of electrical conductivity and biomolecules on human meniscal cell attachment, growth, and proliferation in poly-ε-caprolactone nanocomposite scaffolds.
Poly-ε-caprolactone (PCL)-based nanocomposite scaffolds with different concentrations of carbon nanofillers (carbon nanofibers (CNFs), nanographite, and exfoliated graphite) have been studied to investigate the effect of electrical conductivity and biomolecule supplementation for enhanced human meniscal cell attachment, growth, and proliferation. The incorporation of carbon nanofillers was found to improve the mechanical and electrical properties. CNF-based nanocomposite scaffolds showed the highest electrical conductivity with significant improvements in mechanical properties (more than 50% tensile strength increase than PCL with 10% (w/w) CNF). All nanocomposite scaffolds were subjected to cytotoxicity studies using primary meniscus cells. The nanocomposite scaffolds showing higher cell viability were selected and tested for meniscal cell attachment and proliferation assays such as total deoxyribonucleic acid content, extracellular matrix secretion, nuclear staining, and cell attachment studies using a scanning electron microscope. When an optimized combination of biomolecules is supplemented in the cell culture medium, a synergistic effect of the electrical conductivity and biomolecule combination is observed, especially in the case of highly conducting CNF (7.5% and 10% (w/w))-based nanocomposite scaffolds. Our findings suggest that electrically conductive scaffolds with optimized biomolecules in cell culture medium can potentially be used for successful human meniscal tissue engineering applications.


Speech utterance clustering based on the maximization of within-cluster homogeneity of speaker voice characteristics.
This paper investigates the problem of how to partition unknown speech utterances into a set of clusters, such that each cluster consists of utterances from only one speaker, and the number of clusters reflects the unknown speaker population size. The proposed method begins by specifying a certain number of clusters, corresponding to one of the possible speaker population sizes, and then maximizes the level of overall within-cluster homogeneity of the speakers' voice characteristics. The within-cluster homogeneity is characterized by the likelihood probability that a cluster model, trained using all the utterances within a cluster, matches each of the within-cluster utterances. To attain the maximal sum of likelihood probabilities for all utterances, the proposed method applies a genetic algorithm to determine the cluster in which each utterance should be located. For greater computational efficiency, also proposed is a clustering criterion that approximates the likelihood probability with a divergence-based model similarity between a cluster and each of the within-cluster utterances. The clustering method then examines various legitimate numbers of clusters by adapting the Bayesian information criterion to determine the most likely speaker population size. The experimental results show the superiority of the proposed method over conventional methods based on hierarchical clustering.


When size does matter: organelle size influences the properties of transport mediated by molecular motors.
Organelle transport is driven by the action of molecular motors. In this work, we studied the dynamics of organelles of different sizes with the aim of understanding the complex relation between organelle motion and microenvironment. We used single particle tracking to obtain trajectories of melanosomes (pigmented organelles in Xenopus laevis melanophores). In response to certain hormones, melanosomes disperse in the cytoplasm or aggregate in the perinuclear region by the combined action of microtubule and actin motors. Melanosome trajectories followed an anomalous diffusion model in which the anomalous diffusion exponent (α) provided information regarding the trajectories' topography and thus of the processes causing it. During aggregation, the directionality of big organelles was higher than that of small organelles and did not depend on the presence of either actin or intermediate filaments (IF). Depolymerization of IF significantly reduced α values of small organelles during aggregation but slightly affect their directionality during dispersion. Our results could be interpreted considering that the number of copies of active motors increases with organelle size. Transport of big organelles was not influenced by actin or IF during aggregation showing that these organelles are moved processively by the collective action of dynein motors. Also, we found that intermediate filaments enhance the directionality of small organelles suggesting that this network keeps organelles close to the tracks allowing their efficient reattachment. The higher directionality of small organelles during dispersion could be explained considering the better performance of kinesin-2 vs. dynein at the single molecule level.


Development of a Prognostic Nomogram for Acute Myeloid Leukemia on IGHD Gene Family.
Acute myeloid leukaemia (AML) is a common haematological disease in adults. The overall survival (OS) remains unsatisfactory. It is critical to identify potential prognostic biomarkers and develop a nomogram that predicts overall survival in patients with AML. We used gene expression dataset and clinical data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to identify differential expression analysis, survival analysis, and prognostic value of IGHD gene family (IGHDs) in AML patients. A risk score model was built through Lasso analysis and multivariate Cox regression. We also developed a nomogram and evaluated its accuracy with Harrell's Harmony Index (C-index) and calibration curve. Last, the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database was used for external validation. IGHD1-20 mRNA expression level was an independent prognostic factor for patients with AML by multivariate analysis. After Lasso analysis and multivariate Cox regression, we constructed a 3-gene model (IGHD1-1, IGHD1-20, IGHD3-16) associated with OS in AML. Risk score and age were validated as independent risk factors for prognosis and were used to build a nomogram. The C index and calibration curve results show that its ability to predict 1-year, 3-year and 5-year overall survival is accurate. The mRNA level of IGHDs was increased in AML patients. IGHD1-20 was an independent risk factor for OS in AML patients. The IGHDs risk model (IGHD1-1, IGHD1-20, IGHD3-16) relates to the OS of AML patients. The nomogram, including risk score and age, can conveniently and effectively predict the overall survival rate of patients.


Hydraulic structure design and downhole flow field optimization of geophysical drill bits in a limestone stratum.
The hydraulic structure of conventional geophysical drill bit is designed for the general stratum. When conventional geophysical drill bit pierces into a limestone stratum, the shape of cuttings is large because of the high brittleness of limestone. The cuttings are ground repeatedly; this phenomenon can reduce drilling efficiency and increase drilling costs. According to the characteristics of limestone cuttings, the numerical simulation method is used to research downhole flow field characteristics of conventional geophysical drill bit. First, the influence of key hydraulic structure parameters on cuttings removal performance is found. Then, the hydraulic structure is optimized. The flow field characteristics of the hydraulic structure of the geophysical drill bit before and after optimization in the flow path is analyzed, at the bottom of the bit and the annulus area of the shaft lining. The optimized downhole crossflow area increased from 50% to 98%. No vortex was observed at the exit of the flow path and cuttings groove. The downhole pressure gradient increased from 0.12 Mpa to 0.15 Mpa. The cutting removal space in the annulus area of the shaft lining is fully utilized. Field tests show that the cutting removal and drilling performance of optimized geophysical drill bit has improved and the drilling speed increases by 20.6%.


Physical Fitness and Dynamic Balance in Medication Naïve Turkish Children with ADHD.
This study investigated physical fitness levels and dynamic balance in medication-naïve children with Attention-Deficit/Hyperactivity Disorder (ADHD). Participants were 24 medication-naïve Turkish children with ADHD (4 girls, 20 boys) and 19 typically developing (TD) Turkish children (4 girls, 15 boys). We measured physical fitness levels with the Eurofit Test Battery, body composition with the Inbody 720 Body Composition Analyzer, cognitive attention with the Stroop Test, and dynamic balance with the Y-Balance Test. We found significantly poorer dynamic balance and both upper extremity and running fitness problems among the medication-naïve Turkish children with ADHD compared to the TD group (p = 0.002; p = 0.032; p = 0.002). It may be important to adress dynamic balance and physical fitness when treating children with ADHD.


Diatom Frustule Morphogenesis and Function: a Multidisciplinary Survey.
Diatoms represent the major component of phytoplankton and are responsible for about 20-25% of global primary production. Hundreds of millions of years of evolution led to tens of thousands of species differing in dimensions and morphologies. In particular, diatom porous silica cell walls, the frustules, are characterized by an extraordinary, species-specific diversity. It is of great interest, among the marine biologists and geneticists community, to shed light on the origin and evolutionary advantage of this variability of dimensions, geometries and pore distributions. In the present article the main reported data related to frustule morphogenesis and functionalities with contributions from fundamental biology, genetics, mathematics, geometry and physics are reviewed.


When surgery is not an option: is there a clinical need for transcatheter tricuspid valve therapies?
Severe functional tricuspid regurgitation (FTR) is frequent and carries a poor prognosis when left untreated. The strategy in symptomatic patients should be decided by a Heart Team who will choose between valve surgery, transcatheter intervention, heart transplantation or palliative medical therapy. The field of application of transcatheter tricuspid valve therapy will certainly focus on inoperable or high-risk patients first, especially those with FTR occurring late after left-sided valve surgery. If surgery is contraindicated because of multiple comorbidities interventions which are likely to be "futile" should be avoided. Conversely, if life expectancy is acceptable, it is attractive to envisage percutaneous intervention. Thus, there is a clinical need for transcatheter tricuspid valve therapies when surgery is not an option. Controlled clinical studies are necessary to show the safety profile and the performance of the new transcatheter procedures and define their potential role.


[Metastatic cancer of the kidney. What can be done today?].
Metastatic cancer of the kidney kills one half of the patients concerned within one year and there are no survivors two years later. All of the treatments used up until the present time have been disappointing. Nephrectomy does not prolong survival, does not induce regression of metastases and does not modify the mode of metastatic dissemination. It only has a palliative role. Lymphadenectomy associated with nephrectomy only has a prognostic value. Hormone therapy and chemotherapy are ineffective. Resection of a single metastasis is justified by 5-year survival rates of 30 to 50% in certain series. At the present time, the hopes for effective treatment are raised by the use of recombinant alpha interferon. Therapeutic trials obtain an overall complete response rate of 2.5% (disappearance of all signs of tumour for 4 weeks) and a partial response rate of 14% (decrease in the neoplastic lesions by at least 50%). The combination of interferon with vinblastine ensures much better results with complete and partial response rates of up to 43%. The characteristics of responder patients are discussed in terms of the natural history of renal cancer and the respective results of other treatments. There is a sub-population of patients with metastatic renal cancer suitable for this combination of interferon-vinblastine: they are young patients, in good general condition, previously nephrectomised and preferably suffering from lung metastases. The essential limiting factor of this treatment is the high cost of interferon.


A scanning tunneling microscope study on an ordered mixed monolayer of bis(4,5-dihydronaphtho[1,2-d])-tetrathiafulvalene and n-tetradecane on highly oriented pyrolytic graphite.
Tetrathiafulvalene (TTF) and its derivatives (TTFs) have been successfully used as building blocks to form charge transfer salts and organic semiconductors because of their special structures and rich electron nature. We report the formation of ordered mixed binary-component monolayer consisting of Bis(4,5-dihydronaphtho[1,2-d])tetrathiafulvalene (DH-TTF) and n-tetradecane (n-C14H30) molecules on highly oriented pyrolytic graphite (HOPG) surface. Scanning tunneling microscope (STM) imaging reveals that the two different kinds of molecules can spontaneously form ordered periodic phase separation structures on the substrate, in which ordered DH-TTF double- (or single-) lamella structures are periodically tuned by ordered n-C14H30 double- (or single-) lamella structures. Furthermore, scanning tunneling spectrum (STS) measurements by addressing the individual DH-TTF and n-C14H30 molecules in the ordered monolayer show that the two different kinds of molecules exhibit completely different I(V) characters on the HOPG substrate. The modulated arrangement of the TTF derivative by insulating molecules opens a possible route to construct organic conducting molecule ribbons for potential application in nanodevices.


A spatially invariant sediment rating curve and its temporal change following watershed management in the Chinese Loess Plateau.
Sediment rating curves have long been used as a tool for predicting sediment yield. In this study, the spatial and temporal variations of rating curves were examined in the loess area (~15,000km2) of the Wuding River basin of the Chinese Loess Plateau. Data of mean daily water discharge per unit area, Qd (m3s-1km2), and mean daily sediment discharge per unit area, SDd (kgs-1km2), were compiled for three periods of 1959-1971, 1972-1989, and 2006-2013. Soil conservation measures were rarely implemented for the pre-1971 period but were intensively implemented for the latter periods. The proportional function, i.e. SDd=CdQd, fitted the rating curve well for all periods. The coefficient, Cd, is an approximation of the mean sediment concentration of surface runoff (MSCSR). Contrary to the usual belief, Cd was ca. 730kgm-3 whatever the location for the pre-1971 period; examinations at the instantaneous and the event time scales further demonstrated the spatial invariant MSCSR across six orders of magnitude in drainage area sizes (from 0.006 up to 3893km2). The spatial invariant MSCSR forms as a result of the ready availability of mass-wasted materials in headwaters and holds on as a result of the minimal in-stream erosion and sedimentation along the stream channel. For the post-1971 periods, both Cd and its spatial invariability decreased in a non-monotonous way, which was related to the check-dam (i.e., sediment trapping dams) constructions but not to the implementation of revegetation and terracing measures. As a result, the non-monotonous temporal trends of Cd and its spatial coefficient of variation both captured the intermittency of the check-dam construction well. Temporal changes in MSCSR or the sediment rating curve, which is less disturbed by rainfall, provides important insights into anthropogenic impacts on river systems.


Socioeconomic status affects oral and manual exploration across the first year.
Oral and manual exploration are part of the foundation of problem solving and cognition in infancy. How these develop in an at-risk population, infants in poverty, is unknown. The current study tested exploratory behaviors longitudinally at 6, 9, and 12 months in infants from high- and low-socioeconomic (SES) families. Oral exploration consisted of passive and active mouthing and looks after active mouthing. Manual exploration consisted of frequency of fingering, rotating, and transferring the object. High-SES infants replicated the trajectory previously reported in the literature, showing a decrease in mouthing and fingering and an increase in rotating and transferring (e.g., Palmer, 1989). In contrast, low-SES infants showed no change in any of the manual exploratory behaviors over the first year, thus demonstrating reduced overall levels of exploration as well as a different developmental trajectory. Results are discussed in terms of attention, potential physiological mechanisms, and implications for later problem solving.


In vivo evidence that defects in the transcriptional elongation factors RPB2, TFIIS, and SPT5 enhance upstream poly(A) site utilization.
While a number of proteins are involved in elongation processes, the mechanism for action of most of these factors remains unclear primarily because of the lack of suitable in vivo model systems. We identified in yeast several genes that contain internal poly(A) sites whose full-length mRNA formation is reduced by mutations in RNA polymerase II subunit RPB2, elongation factor SPT5, or TFIIS. RPB2 and SPT5 defects also promoted the utilization of upstream poly(A) sites for genes that contain multiple 3' poly(A) signaling sequences, supporting a role for elongation in differential poly(A) site choice. Our data suggest that elongation defects cause increased transcriptional pausing or arrest that results in increased utilization of internal or upstream poly(A) sites. Transcriptional pausing or arrest can therefore be visualized in vivo if a gene contains internal poly(A) sites, allowing biochemical and genetic study of the elongation process.


Observation of B(+/-) --> p(-)pK(+/-).
We report the observation of the decay mode B(+/-) --> p(-)pK(+/-)based on an analysis of 29.4 fb(-1) of data collected by the Belle detector at KEKB. This is the first example of a b-->s transition with baryons in the final state. The p(-)p mass spectrum in this decay is inconsistent with phase space and is peaked at low mass. The branching fraction for this decay is measured to be B(B+/--->p(-)pK+/-) = [4.3(+1.1)(-0.9)(stat)+/-0.5(syst)]x 10(-6). We also report upper limits for the decays B(0)-->p(-)pK(S) and B(+/-)-->p(-)p pi(+/-).


Increased serum levels of the carrier molecules of the carbohydrate antigen sialyl Lewis X in liver diseases.
The serum levels of the carbohydrate antigen sialyl Lewis X (SLEX) increase in liver diseases (Sunayama T, Okada Y, Tsuji T., J Hepatol 1994; 19: 451-458). However, it is not known whether the increased serum SLEX levels are associated with the increased levels of its carrier molecules and/or the increased density of SLEX per carrier molecule. By using of rabbit antibody against an SLEX-positive fraction from HepG2 culture supernatant, we developed an enzyme-linked immunosorbent assay to determine the serum levels of the carrier molecules of SLEX (CMSLEX). The CMSLEX-levels in patients with hepatocellular carcinoma were significantly higher than those of normal controls (P < 0.001) and benign chronic liver diseases, i.e., chronic active hepatitis, mild and severe form, and liver cirrhosis (P < 0.05). Patients with chronic persistent hepatitis and chronic active hepatitis, mild form, had higher CMSLEX-levels than normal controls (P < 0.05). The serum CMSLEX-levels did not differ significantly among benign liver diseases. We concluded that serum CMSLEX-levels increase nonspecifically in liver diseases. This is a possible molecular mechanism for the increased serum SLEX levels in liver diseases.


NEW INSIGHT INTO THE MACULAR DEEP VASCULAR PLEXUS IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
To describe the macular deep capillary plexus (DCP) in normal eyes using optical coherence tomography angiography. Retrospective study including 41 consecutive normal eyes imaged using optical coherence tomography angiography (RTVue XR Avanti; Optovue Inc). Default autosegmentation of the superficial capillary plexus (SCP) and DCP, and manual adjustments of "deep settings" were used to analyze the organization of the normal macular microvascularization and to investigate in vivo the connection between these capillary networks. Mean age was 31 years (range, 22-55 years). The SCP and DCP had 2 different organizations, but the plexus autosegmentation was imperfect: In 68% of cases, the image of the SCP variably superimposed on the DCP, interfering with its analysis. The SCP was composed on average of 7 pairs of arterioles and venules obvious on each 3-mm × 3-mm optical coherence tomography angiography scanning area. The DCP was composed of a capillary vortex arrangement, whose centers were aligned along the course of the macular superficial venules. The SCP and DCP had two different topographic organizations. The pattern of the capillary units converging into capillary vortexes highly suggests that they drain into the superficial venules. The different structural properties of the SCP and DCP could explain the differences in flow resistance and perfusion.


Increased Cdx protein dose effects upon axial patterning in transgenic lines of mice.
To investigate the link between Cdx protein concentration and axial patterning in embryos, we made lines of mice OE1, OE2 and OE4 that overexpress each of the Cdx genes Cdx1, Cdx2 and Cdx4, respectively. The lines carry Cdx transgenes under the transcriptional control of their own promoter/enhancer elements. Transgenic embryos show Cdx transcription at 8.5 to 8.7 days within normal spatial domains for Cdx expression (primitive streak/tailbud), yet, overall, they contain elevated levels of Cdx proteins. Increased doses of Cdx proteins result in homeotic shifts in vertebral types along most of the vertebral column, with transformations being most obvious within the cervical region. Most of the shifts are anterior-to-posterior transformations and the anterior limits of these are commonly skull/vertebra 1 (v1) for OE1, v1/v2 for OE2 and v7 for OE4. OE embryos display anterior shifts in the expression of a Hoxa7/lacZ reporter within neural, paraxial and lateral plate mesoderm tissues. Hoxa7/lacZ expression commences at the normal time in OE1 and OE4 embryos. OE2 embryos display a forward shift in the gradient of Cdx2 protein along the axis, suggesting that a Cdx morphogen gradient model could account, at least in part, for the homeotic shifts in vertebral types. OE mice display additional defects: forelimb deficiencies in OE1, multiple tail axes, vertebral mis-alignments and axial truncations in OE2.


Communication: Strong laser alignment of solvent-solute aggregates in the gas-phase.
Strong quasi-adiabatic laser alignment of the indole-water-dimer clusters, an amino-acid chromophore bound to a single water molecule through a hydrogen bond, was experimentally realized. The alignment was visualized through ion and electron imaging following strong-field ionization. Molecular-frame photoelectron angular distributions showed a clear suppression of the electron yield in the plane of the ionizing laser's polarization, which was analyzed as strong alignment of the molecular cluster with ⟨cos2 θ2D⟩ ≥ 0.9.


The transmissibility of noroviruses: Statistical modeling of outbreak events with known route of transmission in Japan.
In Japan, the fraction of norovirus outbreaks attributable to human-to-human transmission has increased with time, and the timing of the increased fraction has coincided with the increase in the observed fraction of genogroup II genotype 4 (GII.4). The present study aimed to estimate the time-dependent changes in the transmissibility of noroviruses. The effective reproduction number (Ry), for year y, was estimated by analyzing the time series surveillance data for outbreak events from 2000 to 2016. Ry was estimated by using the fraction of outbreak events that were attributable to human-to-human transmission and by employing three different statistical models that are considered to mechanistically capture the possible data-generating process in different ways. The Ry estimates ranged from 0.14 to 4.15 in value, revealing an overall increasing trend (p<0.05 for all three models). The proportion of outbreaks caused by GII and GII.4 viruses among the total events also increased with time, and positive correlations were identified between transmissibility and these proportions. Parametric modeling of Ry indicated that the time-dependent patterns of Ry were better described by a step function plus linear trend rather than the step function alone that reflects the widespread use of reverse transcriptase PCR (RT-PCR) in and after 2007 for laboratory diagnosis. Accordingly, we conclude that norovirus transmissibility has increased over the past 16 years in Japan. The change is at least partially explained by the time-dependent domination of the contagious GII genogroup (e.g., GII.4), indicating that noroviruses better fitted to humans have selectively caused the human-to-human transmissions, thereby altering the epidemiology of this pathogen.


The Resilience of Microbial Community under Drying and Rewetting Cycles of Three Forest Soils.
Forest soil ecosystems are associated with large pools and fluxes of carbon (C) and nitrogen (N), which could be strongly affected by variation in rainfall events under current climate change. Understanding how dry and wet cycle events might influence the metabolic state of indigenous soil microbes is crucial for predicting forest soil responses to environmental change. We used 454 pyrosequencing and quantitative PCR to address how present (DNA-based) and potentially active (RNA-based) soil bacterial communities might response to the changes in water availability across three different forest types located in two continents (Africa and Asia) under controlled drying and rewetting cycles. Sequencing of rRNA gene and transcript indicated that Proteobacteria, Actinobacteria, and Acidobacteria were the most responsive phyla to changes in water availability. We defined the ratio of rRNA transcript to rRNA gene abundance as a key indicator of potential microbial activity and we found that this ratio was increased following soil dry-down process whereas it decreased after soil rewetting. Following rewetting Crenarchaeota-like 16S rRNA gene transcript increased in some forest soils and this was linked to increases in soil nitrate levels suggesting greater nitrification rates under higher soil water availability. Changes in the relative abundance of (1) different microbial phyla and classes, and (2) 16S and amoA genes were found to be site- and taxa-specific and might have been driven by different life-strategies. Overall, we found that, after rewetting, the structure of the present and potentially active bacterial community structure as well as the abundance of bacterial (16S), archaeal (16S) and ammonia oxidizers (amoA), all returned to pre-dry-down levels. This suggests that microbial taxa have the ability to recover from desiccation, a critical response, which will contribute to maintaining microbial biodiversity in harsh ecosystems under environmental perturbations, such as significant changes in water availability.


Campylobacter immunity and quantitative excretion rates in Thai children.
Campylobacter species were isolated from 61 (15%) of 416 Thai children < 5 years old with diarrhea. Although the baseline levels of Campylobacter-specific antibody increased with age, 80.3% of Campylobacter-infected children seroconverted compared with 12.9% of 45 Shigella-infected patients used as controls. The response to acute infection was greatest in the 6- to 12-month-old group. Nonseroconverters had higher initial IgG levels than did seroconverters (P = .001). Quantitative cultures showed a range of 1-8 log10 Campylobacter cfu/g of stool (median, 6.0 log10), and the seroconversion rate was highest in those with the highest Campylobacter excretion. Fecal Campylobacter excretion was inversely related to age (chi 2 for trend, P = .03). These studies indicate that endemic Campylobacter exposure frequently induces seroconversion in young children, whether Campylobacter is isolated as a single pathogen or one of multiple pathogens, and that fecal excretion of the organism is inversely related to the age-related immune response to infection.


Restoration of terahertz continuous wave image obtained by continuous scan mode with large time constant.
Abstract-continuous scan mode offers a relatively higher data achievement rate than the step scan mode, so it is often used in continuous-wave terahertz imaging to improve the imaging efficiency. The large time constant of lock-in amplifiers also provides good noise attenuation; however, it might bring motion blur to some extent in continuous scan mode. To cope with the problem, an imaging restoration method, which identifies the motion-point spread function of the motion blur, was proposed. A modified spatial filter was used to restore the blurred image. The image quality is better than that obtained by a conventional Wiener filter evaluated by a modified no-reference motion blur metric.


Demographic analyses of the effects of carvedilol vs metoprolol on glycemic control and insulin sensitivity in patients with type 2 diabetes and hypertension in the Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) study.
In the Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial, carvedilol added to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers had neutral or beneficial effects on glycemic measures compared with metoprolol tartrate. For the 1235 diabetic hypertensive GEMINI patients, the authors assessed treatment differences by race (white/black/other), age (continuous variable), and sex on hemoglobin A(1c), insulin resistance (homeostasis model assessment-insulin resistance [HOMA-IR]), and blood pressure. Both treatments significantly reduced blood pressure in all subgroups, but the metabolic effects of carvedilol were more beneficial in subgroups of race and sex. Carvedilol did not affect hemoglobin A(1c) but improved HOMA-IR results in all subgroups, significantly in males and "other race" subgroups. Metoprolol significantly increased hemoglobin A(1c) in all subgroups except "other race," with no effect on HOMA-IR findings. Differences vs metoprolol significantly favored carvedilol for hemoglobin A(1c) in white and female subgroups and favored carvedilol for HOMA-IR in black, "other race," and male subgroups. Carvedilol effects were favorable to adjustment of age as a covariate. In hypertensive patients with diabetes, carvedilol may be a more appropriate choice when beta-blockade is indicated.


Airway responsiveness to adenosine 5'-monophosphate and exhaled nitric oxide measurements: predictive value as markers for reducing the dose of inhaled corticosteroids in asthmatic subjects.
To investigate the utility of the determination of airway responsiveness to inhaled adenosine 5'-monophosphate (AMP) and exhaled nitric oxide (ENO) levels as markers for safely reducing the dose of inhaled corticosteroids (ICS) in patients with asthma well controlled with a moderately high ICS dose. A total of 37 patients with asthma well controlled for at least 3 months by treatment with a moderately high ICS dose (beclomethasone dipropionate, 500 to 1,000 microg or equivalent daily) were included in the study. Patients were treated for a 2-week run-in (baseline) period with their usual dose of ICS. For the next 12 weeks, patients were treated with ICS at half the previous dose, maintaining the same inhalation device. At the end of the baseline period and after 2 weeks, 8 weeks, and 12 weeks of treatment with a reduced dose of ICS, measurements were made in the following order: ENO, spirometry, and AMP challenge. Furthermore, patients completed a diary twice daily recording peak expiratory flow, daytime and nighttime symptoms, and use of rescue albuterol. Ten patients had an asthma exacerbation. Using a Kaplan-Meier survival analysis, the significant predictors of a failure of ICS reduction were having both bronchoconstriction in response to AMP and ENO levels > or = 15 parts per billion (ppb) at baseline (p = 0.006), as well as having both bronchoconstriction in response to AMP and ENO levels > or = 20 ppb at baseline (p = 0.033). Having a decrease in the provocative concentration of AMP causing a 20% fall in FEV(1) of at least one doubling concentration 2 weeks after the dose of ICS was halved was a borderline significant predictor for failure of ICS reduction (p = 0.062). These observations suggest that in asthmatic patients well controlled with ICS, the determination of AMP responsiveness and ENO levels may be useful to identifying those subjects whose condition will or will not deteriorate when the dose of ICS is reduced.


Ultrasound-Guided Continuous Thoracic Erector Spinae Plane Block Within an Enhanced Recovery Program Is Associated with Decreased Opioid Consumption and Improved Patient Postoperative Rehabilitation After Open Cardiac Surgery-A Patient-Matched, Controlled Before-and-After Study.
Open cardiac surgery may cause severe postoperative pain. The authors hypothesized that patients receiving a bundle of care using continuous erector spinae plane blocks (ESPB) would have decreased perioperative opioid consumption and improved early outcome parameters compared with standard perioperative management. A consecutive, patient-matched, controlled before-and-after study. Two tertiary teaching hospitals. The study comprised 67 consecutive patients undergoing elective cardiac surgery with cardiopulmonary bypass. In a controlled before-and-after trial, this study compared a historical group of 20 consecutive open cardiac surgery patients matched with a prospective group of 47 consecutive patients receiving continuous bilateral ESPB (0.25 mL/kg/side of ropivacaine 0.5%) after general anesthesia induction. For postoperative analgesia, both groups received paracetamol. The control group received intravenous (IV) morphine, 0.5 mg/h, and IV nefopam, 100 mg/24 h. In the ESPB group, 8 hours after the loading dose, catheters were connected to a pump infusing intermittent automatic boluses of ropivacaine 0.2% every 6 hours. If needed, for both groups, rescue analgesia was provided with IV ketorolac, 30 mg, and IV morphine, 30 µg/kg. Morphine consumption in the first 48 hours was significantly decreased in the ESPB group (40 [25-45] mg in the control group compared with 0 [0-0] mg in the ESPB group [p < 0.001]) as was intraoperative sufentanil (0.8 [0.6-0.9] µg/kg/h and 0.2 [0.16-0.3] µg/kg/h, respectively; p < 0.001). Times to chest tube removal, first mobilization, pain (Visual Analogue Scale) values 2 hours after chest tube removal, pain values at rest 1 month after surgery, and postoperative adverse events were significantly decreased in the ESPB group. There was no difference for extubation time and pain during first mobilization. The authors report for the first time that the use of a bundle of care including a continuous bilateral ESPB is associated with a significant decrease in intraoperative and postoperative opioid consumption, optimized rapid patient mobilization, and chest tube removal after open cardiac surgery.


A heterologous prime-boost vaccination strategy comprising the Francisella tularensis live vaccine strain capB mutant and recombinant attenuated Listeria monocytogenes expressing F. tularensis IglC induces potent protective immunity in mice against virulent F. tularensis aerosol challenge.
Francisella tularensis, the causative agent of tularemia, is a category A bioterrorism agent. A vaccine that is safer and more effective than the currently available unlicensed F. tularensis live vaccine strain (LVS) is needed to protect against intentional release of aerosolized F. tularensis, the most dangerous type of exposure. In this study, we employed a heterologous prime-boost vaccination strategy comprising intradermally administered LVS ΔcapB (highly attenuated capB-deficient LVS mutant) as the primer vaccine and rLm/iglC (recombinant attenuated Listeria monocytogenes expressing the F. tularensis immunoprotective antigen IglC) as the booster vaccine. Boosting LVS ΔcapB-primed mice with rLm/iglC significantly enhanced T cell immunity; their splenic T cells secreted significantly more gamma interferon (IFN-γ) and had significantly more cytokine (IFN-γ and/or tumor necrosis factor [TNF] and/or interleukin-2 [IL-2])-producing CD4(+) and CD8(+) T cells upon in vitro IglC stimulation. Importantly, mice primed with LVS ΔcapB or rLVS ΔcapB/IglC, boosted with rLm/iglC, and subsequently challenged with 10 50% lethal doses (LD50) of aerosolized highly virulent F. tularensis Schu S4 had a significantly higher survival rate and mean survival time than mice immunized with only LVS ΔcapB (P < 0.0001); moreover, compared with mice immunized once with LVS, primed-boosted mice had a higher survival rate (75% versus 62.5%) and mean survival time during the first 21 days postchallenge (19 and 20 days for mice boosted after being primed with LVS ΔcapB and rLVS ΔcapB/IglC, respectively, versus 17 days for mice immunized with LVS) and maintained their weight significantly better (P < 0.01). Thus, the LVS ΔcapB-rLm/iglC prime-boost vaccination strategy holds substantial promise for a vaccine that is safer and at least as potent as LVS.


Crystal structure analysis of phosphatidylcholine-GM2-activator product complexes: evidence for hydrolase activity.
GM2-activator protein (GM2AP) is a lysosomal lipid transfer protein with important biological roles in ganglioside catabolism, phospholipid metabolism, and T-cell activation. Previous studies of crystal structures of GM2AP complexed with the physiological ligand GM2 and platelet activating factor (PAF) have shown binding at two specific locations within the spacious apolar pocket and an ordering effect of endogenous resident lipids. To investigate the structural basis of phospholipid binding further, GM2AP was cocrystallized with phosphatidylcholine (PC), known to interact with GM2AP. Analysis of three crystal forms revealed binding of single chain lipids and fatty acids only and surprisingly not intact PC. The regions of best defined electron density are consistent with the presence of lyso-PC and oleic acid, which constitute deacylation products of PC. Their acyl tails are in stacking contact with shorter, less well-defined stretches of electron density that may represent resident fatty acids. The GM2AP associated hydrolytic activity that generates lyso-PC was further confirmed by mass spectrometry and enzymatic assays. In addition, we report the structures of (i) mutant Y137S, assessing the role of Tyr137 in lipid transfer via the hydrophobic cleft, and (ii) apo-mouse GM2AP, revealing a hydrophobic pocket with a constricted opening. Our structural results provide new insights into the biological functions of GM2AP. The combined effect of hydrolytic and lipid transfer properties has profound implications in cellular signaling.


Using complex networks for refining survival prognosis in prostate cancer patient.
Complex network theory has been used, during the last decade, to understand the structures behind complex biological problems, yielding new knowledge in a large number of situations. Nevertheless, such knowledge has remained mostly qualitative. In this contribution, I show how information extracted from a network representation can be used in a quantitative way, to improve the score of a classification task. As a test bed, I consider a dataset corresponding to patients suffering from prostate cancer, and the task of successfully prognosing their survival. When information from a complex network representation is added on top of a simple classification model, the error is reduced from 27.9% to 23.8%. This confirms that network theory can be used to synthesize information that may not readily be accessible by standard data mining algorithms.


Nanocolloids in Natural Water: Isolation, Characterization, and Toxicity.
Nanocolloids are widespread in natural water systems, but their characterization and ecological risks are largely unknown. Herein, tangential flow ultrafiltration (TFU) was used to separate and concentrate nanocolloids from surface waters. Unexpectedly, nanocolloids were present in high concentrations ranging from 3.7 to 7.2 mg/L in the surface waters of the Harihe River in Tianjin City, China. Most of the nanocolloids were 10-40 nm in size, contained various trace metals and polycyclic aromatic hydrocarbons, and exhibited fluorescence properties. Envelopment effects and aggregation of Chlorella vulgaris in the presence of nanocolloids were observed. Nanocolloids entered cells and nanocolloid-exposed cells exhibited stronger plasmolysis, chloroplast damage and more starch grains than the control cells. Moreover, nanocolloids inhibited the cell growth, promoted reactive oxygen species (ROS), reduce the chlorophyll a content and increased the cell permeability. The genotoxicity of nanocolloids was also observed. The metabolomics analysis revealed a significant ( p < 0.05) downregulation of amino acids and upregulation of fatty acids contributing to ROS increase, chlorophyll a decrease and plasmolysis. The present work reveals that nanocolloids, which are different from specific, engineered nanoparticles (e.g., Ag nanoparticles), are present at high concentrations, exhibit an obvious toxicity in environments, and deserve more attention in the future.


Carriage of colistin-resistant, extended-spectrum β-lactamase-producing Escherichia coli harboring the mcr-1 resistance gene after short-term international travel to Vietnam.
Due to increasing colistin usage, the dissemination of the colistin-resistant gene mcr-1 has been increasingly investigated. The aim of this study was to determine whether a traveler on a short-term international trip to a developing country could bring mcr-1 back to their home country. Thirty-four travel events from Japan to Vietnam encompassing 19 travelers were assessed. A fecal specimen was collected from each traveler before and after each travel event and was inoculated on CHROMagar containing cefotaxime (CTX). Three to seven colonies exhibiting the characteristics of Escherichia coli were collected. Susceptibility to antibiotics and extended-spectrum β-lactamase (ESBL) production were determined by the disk diffusion method and the double-disk synergy test, respectively. ESBL-encoding genes were genotyped, and phylogenetic groupings were determined by multiplex polymerase chain reaction (PCR). The presence of mcr-1 was also confirmed by PCR and sequencing. A total of 175 ESBL-producing E. coli isolated before and up to 2 weeks after traveling to Vietnam were analyzed. Genotyping of ESBL-producing isolates showed that blaCTX-M-1/blaTEM (27.7%) and blaCTX-M-9 (45.9%) were the most prevalent genotypes, while the most frequently detected phylogenetic group was D (41.9%) followed by B2 (23.0%). In a significant number of travel events, travelers brought ESBL-producing E. coli back to Japan and three events by three travelers carried mcr-1. ESBL-producing E. coli isolates harboring mcr-1 were identified as those carrying both blaCTX-M-14 or blaCTX-M-55 and mcr-1. Using Vietnam as an example, we have shown that even a short-term trip to some countries may result in ESBL-producing mcr-1-positive E. coli carriage by international travelers.


A Role for the Left Angular Gyrus in Episodic Simulation and Memory.
Functional magnetic resonance imaging (fMRI) studies indicate that episodic simulation (i.e., imagining specific future experiences) and episodic memory (i.e., remembering specific past experiences) are associated with enhanced activity in a common set of neural regions referred to as the core network. This network comprises the hippocampus, medial prefrontal cortex, and left angular gyrus, among other regions. Because fMRI data are correlational, it is unknown whether activity increases in core network regions are critical for episodic simulation and episodic memory. In the current study, we used MRI-guided transcranial magnetic stimulation (TMS) to assess whether temporary disruption of the left angular gyrus would impair both episodic simulation and memory (16 participants, 10 females). Relative to TMS to a control site (vertex), disruption of the left angular gyrus significantly reduced the number of internal (i.e., episodic) details produced during the simulation and memory tasks, with a concomitant increase in external detail production (i.e., semantic, repetitive, or off-topic information), reflected by a significant detail by TMS site interaction. Difficulty in the simulation and memory tasks also increased after TMS to the left angular gyrus relative to the vertex. In contrast, performance in a nonepisodic control task did not differ statistically as a function of TMS site (i.e., number of free associates produced or difficulty in performing the free associate task). Together, these results are the first to demonstrate that the left angular gyrus is critical for both episodic simulation and episodic memory.SIGNIFICANCE STATEMENT Humans have the ability to imagine future episodes (i.e., episodic simulation) and remember episodes from the past (i.e., episodic memory). A wealth of neuroimaging studies have revealed that these abilities are associated with enhanced activity in a core network of neural regions, including the hippocampus, medial prefrontal cortex, and left angular gyrus. However, neuroimaging data are correlational and do not tell us whether core regions support critical processes for simulation and memory. In the current study, we used transcranial magnetic stimulation and demonstrated that temporary disruption of the left angular gyrus leads to impairments in simulation and memory. The present study provides the first causal evidence to indicate that this region is critical for these fundamental abilities.


Comparative Analysis of Prepectoral versus Subpectoral Implant-based Breast Reconstruction.
Recent advances in mastectomy and reconstruction have allowed for an evolution in implant-based breast reconstruction to a muscle-sparing, prepectoral approach. Advantages of this technique may include reductions in postoperative pain, shorter hospitalization, less narcotic usage, and improved aesthetic outcomes. Postoperative complication rates are described as comparable to subpectoral techniques; however, little comparative data exist to adequately assess prepectoral versus subpectoral implant placement. To address this knowledge gap, we performed a single institution retrospective review of 186 (83 prepectoral, 103 subpectoral) consecutive immediate breast reconstructions. All cases were tracked for a minimum of 2 years between 2016 and 2021. Prepectoral patients demonstrated an overall higher seroma rate (P = 0.001), with all other postoperative complications being comparable. Prepectoral patients tolerated higher intraoperative tissue expander fill volumes (P < 0.001), shorter hospital stays (P = 0.007), fewer clinic visits for tissue expansion (P < 0.001), and experienced less animation deformity (P = 0.005). Both groups demonstrated similar pain scores (P = 0.65) and needs for narcotics (P = 0.8) as well as comparable scores of capsular contracture (P = 0.791). Our comparative analysis of consecutive immediate implant-based breast reconstructions finds prepectoral reconstruction to be safe and effective. Compared with subpectoral reconstruction, the prepectoral approach may offer quicker tissue expansion, less postoperative office visits, less need for muscle relaxants, and a shorter hospital stay with a comparable complication profile.


Mechanistic insights into H2 evolution via water splitting at the expense of B2(OH)4: a theoretical study.
H2 has been comprehensively deemed a promising potential candidate to replace traditional fossil fuel-based energy. Typically, the hydrolysis of most hydrogen-rich boron hydrides (e.g. NaBH4, NH3BH3 and Me2NHBH3) catalyzed by nanomaterials generates H2 with only one H atom supplied by water and the other one by a hydrogen-rich boron hydride. Interestingly, both H atoms of produced H2 are provided by water upon hydrolysis of B2(OH)4. Herein, the catalytic mechanisms of H2 evolution upon water splitting at the expense of B2(OH)4 in its hydrolysis reactions catalyzed by acid, base or metal nanoparticles have been investigated by density functional theory (DFT) calculations. By computational studies, the mechanisms of catalysis by base and metal nanoparticles are basically the same as those speculated from our previous experiments. The previously proposed acid catalytic mechanism has been overturned, however. This study not only provides important insights into the catalytic mechanism for water splitting at the expense of B2(OH)4, but also opens up an exciting opportunity to use water to store H2.


Meta-analysis of prognostic role of Ki-67 labeling index in gastric carcinoma.
This meta-analysis aimed to elucidate the prognostic role of the Ki-67 labeling index (LI) in gastric cancer (GC). The current study included 3,615 GC patients in 20 eligible studies, and evaluated the prognostic role of Ki-67 LI in GC. Subgroup analysis was conducted based on depth of invasion and cutoff value for high Ki-67 LI. A high Ki-67 LI correlated significantly with worse survival (hazard ratio [HR] = 1.214, 95% confidence interval [CI], 1.004-1.468). However, there was no significant correlation between high Ki-67 LI and worse survival in advanced GC (HR = 1.252, 95% CI, 0.801-1.956). The subgroup with cutoff value ≤25% showed a significant correlation with worse survival, but this was not seen in the subgroup with cutoff >25% (HR = 1.433, 95% CI, 1.094-1.876 vs. HR = 1.005, 95% CI, 0.801-1.262). In addition, in the 10% <Ki-67 LI ≤ 20% range, there was a significant correlation between high Ki-67 LI and worse overall survival (HR = 1.931, 95% CI, 1.013-3.310). A high Ki-67 LI correlated significantly with a worse prognosis in GC patients. Further cumulative studies for the optimal cutoff value for high Ki-67 LI are needed before application in clinical practice.


Demands of World Cup Competitions in Elite Women's Road Cycling.
To describe the demand of recent World Cup (WC) races comparing top-10 (T10) and non-top-10 (N-T10) performances using power data. Race data were collected in 1-d World Cup races during the 2012-2015 road cycling seasons. Seven female cyclists completed 49 WC races, finishing 25 times in T10 and 24 times in N-T10. Peak power (1 s) and maximal mean power (MMP) for durations of 5, 10, 20, and 30 s and 1, 2, 5, 10, 20, 30, and 60 min expressed as power to weight ratio were analyzed in T10 and N-T10. The percentage of total race time spent at different power bands was compared between T10 and N-T10 using 0.75-W·kg-1 power bands, ranging from <0.75 to >7.50 W·kg-1. The number of efforts in which the power output remained above 7.50 W·kg-1 for at least 10 s was recorded. MMPs were significantly higher in T10 than in N-T10, with a large effect size for durations between 10 s and 5 min. N-T10 spent more time in the 3.01- to 3.75-W·kg-1 power band when compared to T10 (P = .011); conversely, T10 spent more time in the 6.75- to 7.50- and >7.50-W·kg-1 power bands (P = .009 and .005, respectively) than N-T10. A significantly higher number of short and high-intensity efforts (≥10 s, >7.5 W·kg-1) was ridden by T10 than N-T10 (P = .002), specifically, 46 ± 20 and 30 ± 15 efforts for T10 and N-T10, respectively. The ability to ride at high intensity was determinant for successful road-cycling performances in WC races.


Increased risk profile in the treatment of patients with symptomatic degenerative aortic valve stenosis over the last 10 years.
Currently, Cardiology Centres are overfilled with patients with degenerative aortic valve stenosis (DAS), usually eldery, with severe concommittant comorbidities, who are referred for further decisions and possible intervention. To evaluate changes in the risk profile of patients with severe DAS admitted to the cardiology department a decade ago compared with patients currently being admitted. We retrospectively evaluated all patients admitted with confirmed severe DAS, hospitalized during 2005-2006 (group I: 140 patients) and in 2016 (group II: 152 patients), admitted for aortic valve intervention. A standard transthoracic echocardiogram, cardiovascular symptom and risk factor distribution, perioperative risk with the logistic EuroSCORE II and STS mortality scores were obtained. Patients in group II were significantly older (p < 0.001), had more cardiovascular risk factors, and more often presented with atrial fibrillation (27% vs. 11.4%, p = 0.001), renal impairment (34.9% vs. 22.8%; p = 0.024), severe lung disease (17.1% vs. 2.1%, p < 0.001), and extracardiac arteriopathy (40.1% vs. 17.8%, p < 0.001). The aortic valve area (AVA) (p = 0.356), mean-transvalvular pressure gradient (p = 0.215), and left ventricular ejection fraction (p = 0.768) were similar in both groups. However, the prevalence of pulmonary hypertension, severe mitral regurgitation, and low-flow, low-gradient DAS were 3.1-, 8.4- and 1.84-fold more frequent in group II than group I. The percentages of subjects with EuroSCORE II and STS scores ≥ 4% in 2005-2006 were 7.1% and 6.4%, as compared to 27% and 26.3% in 2016 (both p < 0.001). 22% of patients in 2016, as compared to 31% in 2005/2006, were considered ineligible for DAS intervention. In just a decade, the risk profile of patients admitted with DAS has increased hugely, mainly due to older age, accumulation of comorbidities and more advanced disease at presentation. Although transcatheter aortic valve intervention has expanded the indications for intervention in high-risk patients, the number of patients disqualified from interventional treatment remains high.


The endocrine mechanism of sex reversal in the protandrous black porgy, Acanthopagrus schlegeli: a review.
Black porgy, Acanthopagrus schlegeli Bleeker, a marine protandrous hermaphrodite, is a functional male for the first 2 years of life but begin to sexually reverse to female after the third year. This sex pattern provides a very good model to study the mechanism of sex reversal in fish. The gonad at 5 month of age consisted of testicular tissue with few primary oocytes at 5 month of age. The ovarian tissue became dominant at 18 months of age during the non-spawning season. Testicular and ovarian tissues were separated by connective tissue. Plasma estradiol-17 beta(E2), vitellogenin and 11-ketotestosterone (11-KT) profiles in males were significantly different from those in the 3-year-old reversing females. Peak levels of plasma E2 in the reversing females occurred during the early prespawning season (in October). Lower levels of plasma E2 were, however, observed in the males. Plasma 11-KT levels significant decreased but no changes of plasma testosterone were detected in the reversing females. Exogenous E2 suppressed the testicular development but induced the gonadal aromatase activity, ovarian development and sex reversal in 2-year-old black porgy. Exogenous T and LHRH analog did not have effects on the sex reversal. Higher concentrations of pituitary GtH II and mRNA of GtH II-beta subunit were detected in the reversed females. These data suggested that E2 and gonadal aromatase closely associated to the occurrence of sex reversal. A working model of the sex reversal in black porgy is proposed.


Gentamicin-Impregnated Collagen Sponge: Effectiveness in Preventing Sternal Wound Infection in High-Risk Cardiac Surgery.
Sternal wound infections represent one of the most frequent complications after cardiac surgery and are associated with high postoperative mortality. Several preventive methods have been introduced, and recently, gentamicin-impregnated collagen sponges (GICSs) have shown a promising effect in reducing the incidence of this type of complications. Gentamicin is an aminoglycoside antibiotic that has been widely used to treat infections caused by multiresistant bacteria; despite its effectiveness, its systemic use carries a risk of toxicity. GICSs appear to overcome this side effect, topically delivering high antibiotic concentrations to the wound and thus reducing the toxic-related events. Although several retrospective analyses and randomized controlled trials have studied the use of GICSs in cardiac surgery, conclusions regarding their efficacy in preventing sternal wound infection are inconsistent. We have reviewed the current literature focusing on high-risk patients.


Genome-wide identification and expression profiling of the YUCCA gene family in Malus domestica.
The plant hormone auxin is essential for plant growth and development. YUCCA proteins catalyse the rate-limiting step for endogenous auxin biosynthesis. In this study, we isolated 20 MdYUCCA genes from apple genome. MdYUCCA6a, MdYUCCA8a, and MdYUCCA10a were expressed in most organs and could support whole plant basal auxin synthesis. MdYUCCA4a, MdYUCCA10b, and MdYUCCA11a expression indicated roles for these genes in auxin biosynthesis in vegetative organs. MdYUCCA2b, MdYUCCA11b, and MdYUCCA11d were mainly expressed in flower organs. High temperature induced the expression of MdYUCCA4a, MdYUCCA6a, MdYUCCA8a, and MdYUCCA10a, and down-regulated the expression of MdYUCCA2b and MdYUCCA6b. Dual-luciferase assay indicated that MdPIF4 could trans-activate the MdYUCCA8a promoter. Overexpression of MdYUCCA8a increased IAA content, increased stem height, enhanced apical dominance, and led to silique malformation. These results provide a foundation for further investigation of the biological functions of apple MdYUCCAs.


Factors influencing the short-term outcome following thoracic surgery in 98 dogs.
To evaluate the factors influencing the short-term (<14 days) outcome of thoracic surgery in dogs. A retrospective review of 98 dogs undergoing thoracotomy over a five-year period was undertaken. A pre-operative diagnosis was achieved in 69 per cent of cases. Intrathoraic neoplasia had the lowest pre-operative diagnosis rate (5.5 per cent). Mortality rates of 21 per cent were recorded and were significantly higher for intrathoracic neoplasia (50 per cent) and significantly lower for persistent ductus arteriosus (7.4 per cent) and vascular ring anomaly (0 per cent). Median sternotomy was the preferred approach for pyothorax (85 per cent) and penetrating thoracic injuries (66 per cent). Intercostal thoracotomy was the preferred approach for all other diseases. Postoperative complications occurred in 39 per cent of cases. Wound complications were more common for pyothorax (45 per cent) and following median sternotomy (71 per cent). Thoracic drains were placed in 77 per cent of cases and complications were recorded in 23 per cent. Pyothorax and chylothorax had thoracic drains maintained for significantly longer periods of time. Longer thoracic drain duration was correlated significantly with increased complication rates. The short-term outcome following thoracic surgery is influenced by diagnosis. The thoracic approach is determined by intrathoracic disease, but may influence outcome by affecting the incidence of postoperative wound complications. The risk of thoracic drain complications increases with drain duration, which is influenced by the underlying disease. Drains should be maintained for the minimal amount of time possible.


Dynamic Stability of Tensegrity Structures-Part II: The Periodic External Load.
The paper contains a parametric analysis of tensegrity structures subjected to periodic loads. The analysis focuses on determining the main region of dynamic instability. When load parameters fall within this region, the resulting vibration amplitudes increase, posing a risk to the durability of structures. The study considers structures built using commonly used modules. The influence of the initial prestress on the distribution of the instability regions is examined. Additional prestress can significantly reduce the extent of instability regions, potentially narrowing them by up to 99%. A nondimensional parameter is introduced to accurately assess changes in the extent of the instability region. A geometrically non-linear model is employed to evaluate the behavior of the analyzed structures.


A strategy for the synthesis of hydrophobic proteins and glycoproteins.
Our synthetic strategy for the hydrophobic glycoprotein is summarized. The reverse-polarity protection strategy, in which the side chain carboxy group is protected as a basic picolyl ester, combined with the O-acylisopeptide method proved to be efficient for the preparation of the hydrophobic glycoprotein by ligation methods, and would be applicable for the synthesis of membrane proteins in the future.


Geometric analysis of root canals prepared by single twisted file in three different operation modes.
The aim of this study was to evaluate and compare the effects of a single twisted file (TF) instrument in three different operation modes on the preparation of curved root canals in human molars and to explore a new possible method in canal shaping in the clinic setting. A total of 105 selected root canals with an angle of curvature ranging from 20° to 35° were divided into the following three groups with 35 samples each according to the different operation mode in canal preparation: "continuous rotation-500" (CR, 500 rpm), reciprocating movement-300 (RM-300 rpm) and CR-300 rpm. Root canals were prepared by single file (a size 25/0.06 TF). The pre- and post-instrumented images of the sections were scanned using a cone-beam computed tomography scanner to measure the root transportation and centering ratio. The data were evaluated at 1.5 mm, 3.0 mm and 6.0 mm positions from the apex. The significance level was set at P < 0.05. The results showed a statistically significant difference in root transportation that was only found in cross-sections 3.0 mm from the anatomic apex between group "CR-500" and group "CR-300." In addition, a significant difference in centering ratio was found between group "RM-300" and group "CR-300." There was no significant difference in the two indices among the three groups at cross-sections 1.5 mm and 6 mm from the apex. Under the three conditions of this study, the continuous rotation mode has better shaping ability in root canal preparation than the RM mode when used with a TF single file (size 25/0.06).


Enantioselective total synthesis of lycopodine.
The first enantioselective total synthesis of lycopodine has been completed. Key steps include a highly diastereoselective organocatalyzed cyclization of a keto sulfone to establish the key C7 and C8 stereocenters and a tandem 1,3-sulfonyl shift/intramolecular Mannich cyclization to form the tricyclic core.


Recent Research in the Genetics of Exercise Training Adaptation.
In the present review, we focus on evaluating the state of the literature in the area of genetic aspects of exercise training adaptation, in particular focusing on findings published since 2009. Our focus is primarily on studies examining genetic polymorphisms and their association with variability in training responses for a number of exercise-related traits, including aerobic fitness, hemodynamic variables, metabolic traits, body composition and obesity, and muscular strength and size. Very few large-scale studies are available to provide the quality scientific evidence needed to conclusively identify specific genetic factors that contribute to exercise training adaptations. As such, despite years of effort by a number of groups, the search continues for specific genes and combinations of genetic factors that contribute to the interindividual variability observed in phenotype adaptations to exercise training interventions.


Epidemiological analysis of 556 procedures of open thoracoabdominal aortic aneurysm repair in the Public Health System in the largest Brazilian city.
Despite the development of endovascular procedures, open repair remains the gold standard for the treatment of aortic thoracoabdominal aneurysms and some type B dissections, with well-established good outcomes and long-term durability at high-volume centers. The present study described and analyzed public data from patients treated in the public system in a 12-year interval, in a city where more than 5 million inhabitants depend on the Public Health System. Public data from procedures performed between 2008 and 2019 were extracted using web scraping techniques. The variables available in the database include sex, age, elective or emergency hospital admission, number of surgeries, in-hospital mortality, length of stay, and information on reimbursement values. A total of 556 procedures were analyzed. Of these, 60.79% patients were men, and 41.18% were 65 years of age or older. Approximately 60% had a residential address registered in the municipality. Of all surgeries, 65.83% were elective cases. There were 178 in-hospital deaths (mortality of 32%). In the elective context, there were 98 deaths 26.78% versus 80 deaths (42.10%) in the emergency context (p=0.174). Mortality was lower in the hospitals that performed more surgeries. A total of USD 3,038,753.92 was paid, an average of USD 5,406.95 for elective surgery and USD 5,074.76 for emergency surgery (p=0.536). Mortality was no different between groups, and hospitals with higher volume presented more favorable outcomes. Specialized referral centers should be considered by health policy makers.


Patient-Targeted Googling by New Zealand Mental Health Professionals: A New Field of Ethical Consideration in the Internet Age.
Patient-targeted Googling (PTG) describes the searching on the Internet by healthcare professionals for information about patients with or without their knowledge. Little research has been conducted into PTG internationally. PTG can have particular ethical implications within the field of mental health. This study was undertaken to identify the extent of PTG by New Zealand mental healthcare professionals and needs for further guidance regarding this issue. All (1,850) psychiatrists, clinical psychologists, and psychotherapists working in New Zealand were electronically surveyed about their experience of PTG and knowledge about the associated practice of therapist-targeted Googling (TTG) using a questionnaire that had previously been developed with a German sample. Due to ethics and advertising restrictions, only one indirect approach was made to potential participants. Eighty-eight clinicians (5%) responded to the survey invitation. More than half (53.4%, N = 47) of respondents reportedly being engaged in PTG, but only a minority (10.3%, N = 9) had ever received any education about the subject. Reasons for undertaking PTG included facilitating the therapeutic process, information being in the public domain, and mitigating risks. Reasons against undertaking PTG included impairment of therapeutic relationship, unethical invasion of privacy, and concerns regarding the accuracy and clinical relevance of online information. Two-thirds of participants reported being the subject of TTG. New Zealand psychiatrists, clinical psychologists, and psychotherapists are engaging in PTG with limited education and professional guidance. Further discussion and research are required, and so, PTG is undertaken in a manner that is safe and useful for patients and health practitioners.


Traveller behaviour in public transport in the early stages of the COVID-19 pandemic in the Netherlands.
With a few exceptions, public transport ridership around the world has been hit hard by the COVID-19 pandemic. Travellers are now likely to adapt their behaviour with a focus on factors that contribute to the risk of COVID-19 transmission. Given the unprecedented spatial and temporal scale of this crisis, these changes in behaviour may even be sustained after the pandemic. To evaluate travellers' behaviour in public transport networks during these times and assess how they will respond to future changes in the pandemic, we conduct a stated choice experiment with train travellers in the Netherlands at the end of the first infection wave. We specifically assess behaviour related to three criteria affecting the risk of COVID-19 transmission: (i) crowding, (ii) exposure duration, and (iii) prevalent infection rate. Observed choices are analysed using a latent class choice model which reveals two, nearly equally sized latent traveller segments: 'COVID Conscious' and 'Infection Indifferent'. The former has a significantly higher valuation of crowding, accepting, on average 8.75 min extra waiting time (average total travel time in the choice scenarios was about 40 min) to reduce one person on-board. Moreover, this class indicates a strong desire to sit without anybody in the neighbouring seat and is quite sensitive to changes in the prevalent infection rate. By contrast, the Infection Indifferent class has a value of crowding (1.04 waiting time minutes/person) that is only slightly higher than pre-pandemic estimates and is relatively unaffected by infection rates. We find that older and female travellers are more likely to be COVD Conscious while those reporting to use the trains more frequently during the pandemic tend to be Infection Indifferent. Further analysis also reveals differences between the two segments in attitudes towards the pandemic and self-reported rule-following behaviour. We believe that the behavioural insights from this study will not only contribute to better demand forecasting for service planning but will also inform public transport policy decisions aimed at curbing the shift to private modes.


Rehabilitation of lower limb tendinopathies.
Tendon rehabilitation requires an extensive assessment, and identification of deficits that impact on sporting performance. Rehabilitation must address all these deficits and may take several months. Return to sport may require short- or long-term load modification. Surgery also requires a long recovery time, and may not guarantee a return to sport.


Secondary structure analysis of the scrapie-associated protein PrP 27-30 in water by infrared spectroscopy.
A protease-resistant form of the protein PrP (PrP-res) accumulates in tissues of mammals infected with scrapie, Creutzfeldt-Jakob disease, and related transmissible neurodegenerative diseases. This abnormal form of PrP can aggregate into insoluble amyloid-like fibrils and plaques and has been identified as the major component of brain fractions enriched for scrapie infectivity. Using a recently developed technique in Fourier transform infrared spectroscopy which allows protein conformational analysis in aqueous media, we have studied the secondary structure of the proteinase K resistant core of PrP-res (PrP-res 27-30) as it exists in highly infectious fibril preparations. Second-derivative analysis of the infrared spectra has enabled us to quantitate the relative amounts of different secondary structures in the PrP-res aggregates. The analysis indicated that PrP-res 27-30 is predominantly composed of beta-sheet (47%), which is consistent with its amyloid-like properties. In addition, significant amounts of turn (31%) and alpha-helix (17%) were identified, indicating that amyloid-like fibrils need not be exclusively beta-sheet. The infrared-based secondary structure compositions were then used as constraints to improve the theoretical localization of the secondary structures within PrP-res 27-30.


Energetics and behavior of coral reef fishes during oscillatory swimming in a simulated wave surge.
Oxygen consumption rates were measured for coral reef fishes during swimming in a bidirectional, oscillatory pattern to simulate station-holding in wave-induced, shallow-water flows. For all species examined, increases in wave intensity, as simulated by increases in frequency and amplitude of oscillation, yielded increased metabolic rates and net costs of swimming (NCOS; swimming metabolic rate minus standard metabolic rate). Comparing species with different swimming modes, the caudal fin swimming Kuhlia spp. (Kuhliidae) and simultaneous pectoral-caudal fin swimming Amphiprion ocellaris (Pomacentridae) turned around to face the direction of swimming most of the time, whereas the median-paired fin (MPF) swimmers, the pectoral fin swimming Ctenochaetus strigosus (Acanthuridae) and dorsal-anal fin swimming Sufflamen bursa (Balistidae), more frequently swam in reverse for one half of the oscillation to avoid turning. Contrary to expectations, the body-caudal fin (BCF) swimming Kuhlia spp. had the lowest overall NCOS in the oscillatory swimming regime compared with the MPF swimmers. However, when examining the effect of increasing frequency of oscillation at similar average velocities, Kuhlia spp. showed a 24% increase in NCOS with a 50% increase in direction changes and accelerations. The two strict MPF swimmers had lower increases on average, suggestive of reduced added costs with increasing frequency of direction changes with this swimming mode. Further studies are needed on the costs of unsteady swimming to determine whether these differences can explain the observed prevalence of fishes using the MPF pectoral fin swimming mode in reef habitats exposed to high, wave-surge-induced water flows.


[Astrovirus infection among hospitalized children with acute diarrhea in seven regions of China, 1998-2005].
To study the epidemiology and strain variations of astrovirus infection among children under 5 years of age, hospitalized for acute diarrhea in China. Inpatients under 5 years of age with acute diarrhea in hospitals of seven provinces between 1998 and 2005 were enrolled in the study Stool specimens were collected and tested for astrovirus using the Dako Amplified IDEIA Astrovirus kits or reverse-transcription polymerase chain reaction (RT-PCR). Genetic identities of the strains were determined using RT-PCR with serotype-specific primers and confirmed by sequencing of the RT-PCR products. A total of 1668 diarrheal stool samples tested for both rotavirus and calicivirus negative were examined. The detection rate of astrovirus infection was 5.5% (91/1668) and the diarrhea cases caused by astrovirus infection could be found in any season of the year but mainly occurred in cold season from October to next January. Astrovirus detection-rates were: 7.4% among infants aged 9-11 months followed by 6.1% in 12-17 month-olds, and 6-8 months 5.6% & 0-2 months 5.6% before 8 months. Over 95% of astrovirus infections occurred in children before 2 years of age. Among 49 strains, typed, serotype 1(45/91) was most commonly seen while serotype 5 was in two cases and serotype 3 and 8 were detected in only one case respectively. Astrovirus seemed an important etiologic agent in young children with acute diarrhea in China and Serotype 1 was the most prevalent one.


Phytotoxicity of major constituents of the volatile oil from leaves of Artemisia scoparia Waldst. & Kit.
The phytotoxicity of the three major monoterpene constituents of the essential oil from leaves of Artemisia scoparia Waldst. & Kit. (redstem wormwood) was investigated. GC/GC-MS analysis revealed that the essential oil (yield 0.84%) is a complex mixture containing 19 monoterpenes, 7 sesquiterpenes and 15 other compounds--aliphatic alcohols, ketones, aromatic hydrocarbons and esters. The three major monoterpenes were beta-myrcene (30.2%), p-cymene (12.8%) and dl-limonene (12.4%). The essential oil and the three monoterpenes exhibited phytotoxicity and reduced germination, seedling growth, chlorophyll content and percent respiration of Avena sativa and Triticum aestivum in a dose-response manner. The inhibitory effect of monoterpenes was comparatively smaller than of the crude essential oil and beta-myrcene was most toxic followed by p-cymene, whereas limonene was least toxic. The study suggests that A. scoparia oil and beta-myrcene can be explored for phytotoxicity against weeds.


Photocatalytic Azetidine Synthesis by Aerobic Dehydrogenative [2 + 2] Cycloadditions of Amines with Alkenes.
Photocatalytic dehydrogenative [2 + 2] cycloadditions between amines and alkenes were developed that allow for the stereoselective and high-yielding synthesis of functionalized azetidines. The oxidative formal Aza Paternò-Büchi reactions are induced by photoredox-catalyzed aerobic oxidation of dihydroquinoxalinones 1 as the amines, and in the presence of structurally diverse alkenes 3 intermolecular [2 + 2] cyclization to dihydro-1H-azeto[1,2-a]quinoxalin-3(4H)-ones 4 occurs. The utility of the method is illustrated by the selective conversion of amino acid derived dihydroquinoxalinones 1, including oxidation-prone lysine and tryptophan derivatives.


Anterior cruciate ligament reconstruction. The effect of tibial tunnel placement on range of motion.
In 111 patients who had anterior cruciate ligament reconstructions, postoperative radiographic measurements of anterior to posterior and medial to lateral location of the tibial tunnels were correlated with the final range of motion achieved. In the 25 patients with extension deficits of 10 degrees or more, placement of the tibial tunnel was more anterior (average, anterior 23% of the tibia) than in the remaining 86 patients with extension deficits of < 10 degrees (average, anterior 29% of tibia). This difference was statistically significant with P < 0.001. Logistic regression analysis revealed that the more anterior the placement of the tibial tunnel, the greater the loss of both flexion (P = 0.01) and extension (P = 0.002). In the 21 patients with full extension but flexion < 130 degrees, placement of the tibial tunnel tended to be more medial (average, medial 40% of the tibia) than in the 65 patients without flexion deficit (average, medial 45% of the tibia). We conclude that placement of the tibial tunnel in the "eccentric," anteromedial position may contribute to the development of flexion and extension deficits after anterior cruciate ligament reconstruction.


Effect of galanin on arginine-stimulated pancreatic hormone release from isolated perifused rat islets.
The effect of galanin on pancreatic hormone release was studied using isolated perifused rat pancreatic islets. In the presence of 100 mg/dl glucose, 10(-8) mol/L galanin significantly inhibited the basal somatostatin release compared with the perifusion without galanin, whereas there was no significant change in the basal insulin and glucagon release. However, under stimulation of 20 mmol/L arginine, 10(-8) mol/L galanin significantly enhanced glucagon release and suppressed insulin and somatostatin release. These effects disappeared immediately after cessation of galanin infusion. Additionally, 10(-8) mol/L galanin significantly enhanced the first and second phase of glucagon release stimulated by arginine, whereas arginine-stimulated insulin and somatostatin releases were significantly inhibited in both phases. In the cysteamine-treated rat islets, neither enhancement of glucagon release nor suppression of insulin release by galanin was reproducible. These findings indicate two possible explanations. First, it is suggested that the effects of galanin on insulin and glucagon release may be direct and reversed by non-specific effect of cycteamine. Secondly, it seems likely that galanin-enhanced glucagon release may be indirect and in part due to the concomitant somatostatin suppression. Galanin may have an important regulatory function on endocrine pancreas.