Individual characteristics and management decisions affect outcome of anticoagulated patients with intracranial hemorrhage.
Anticoagulated patients with intracranial hemorrhage represent a major management challenge. Our goal is to determine how patient characteristics and management decisions influence outcome. A systematic review of the literature identified relevant reported cases. Variables describing patient characteristics, management, and outcome were extracted. Statistical analyses were carried out using analysis of variance and Fisher's exact test. A total of 242 patients from our updated dataset met inclusion criteria. Tissue plane of the hemorrhage (P < 0.0001), indication for anticoagulation (P < 0.0001), type of anticoagulant (P = 0.0173), and history of hypertension (P = 0.0418) were significantly associated with outcome. Older age (P < 0.0001), supratentorial index hemorrhages (P = 0.0018), failure to restart anticoagulation (P < 0.0001), and larger hematoma volume (P < 0.0001) were associated with worse outcome. Surgical evacuation was associated with improved outcome (P = 0.0011). There was a trend toward an association between the occurrence of a hemorrhagic or thromboembolic complication and risk of death (P = 0.0882). Sex and sidedness of the index hemorrhage were not significantly associated with outcome. Our results provide prognostic information that may assist management of these patients. Our results also suggest that it may be unwise to withhold anticoagulation indefinitely after an index hemorrhage. As thromboembolic or hemorrhagic complications may be associated with worse outcome, efforts to avoid them may be wise. The studies that comprise our dataset have important limitations and a prospective study will be required to confirm these results.


Intranuclear inclusions in the developing neurons of the rat cuneate nuclei.
The ultrastructure of intranuclear rodlets, microtubules, fibrillar lattices and membranous inclusions found in the developing cuneate nuclei of rats is described. Rodlets, ranging in diameter from 96--312 nm and in length from 1--2 micrometer, are made up of tightly packed straight filaments measuring 5--8 nm in diameter. Microtubules with a diameter of 26 nm are clustered together. Fibrillar lattices are made up of fibrils with a diameter of 9 nm arranged in layers or sets. Two to nine sets make up a lattice, with a maximum width of 68 nm, in which the adjacent sets are arranged at an angle to each other. Rodlets and fibrillar lattices occur in 6.8% of the neurons. Membranous inclusions, reported here for the first time in normal neurons, are of 2 types: small vesicles of 0.1--0.6 micrometer and large vacuoles measuring 1--2 micrometer. Both types are bounded by either a single or a double membrane and generally have an electron lucent content. Membranous inclusions occur in 25.3% of the neurons. Changes in the frequency of occurrence of the various intranuclear inclusions in the course of postnatal development are also reported.


Comparison of cost efficiencies of nuclear power and renewable energy generation in mitigating CO2 emissions.
The objective of this study is to compare the cost efficiencies of nuclear power and renewable energy generation in reducing CO2 emissions. To achieve this objective, we estimate the relationship between CO2 emissions and both nuclear power and renewable energy generation in 16 major nuclear power-generating countries, and compare the costs of both energy generation methods in reducing CO2 emissions by the same amount. The results show that, to reduce CO2 emissions by 1%, nuclear power and renewable energy generation should be increased by 2.907% and 4.902%, respectively. This implies that if the current amount of electricity generation is one megawatt-hour, the cost of mitigating CO2 emissions by 1% is $3.044 for nuclear power generation and $7.097 for renewable energy generation. That is, the total generation costs are approximately $1.70 billion for the nuclear power and $3.97 billion for renewable energy to mitigate 1% of CO2 emissions at the average amount of electricity generation of 0.56 billion MWh in 2014 in the sample countries. Hence, we can conclude that nuclear power generation is more cost-efficient than is renewable energy generation in mitigating CO2 emissions, even with the external costs of accidents and health impact risks associated with nuclear power generation.


Tucatinib promotes immune activation and synergizes with programmed cell death-1 and programmed cell death-ligand 1 inhibition in HER2-positive breast cancer.
Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors have poor efficacy in patients with trastuzumab-resistant advanced HER2-positive breast cancer. Tucatinib is a potent, selective anti-HER2 tyrosine kinase inhibitor with proven clinical benefit in the advanced setting in patients with trastuzumab resistance. We investigated if tucatinib can alter the tumor microenvironment and if this could be harnessed for therapeutic efficacy. We investigated the antitumor efficacy and contribution of the immune response of tucatinib using 2 immunocompetent, HER2-positive murine breast cancer models (trastuzumab-sensitive H2N113; trastuzumab-resistant Fo5) and the efficacy of tucatinib with trastuzumab and PD-1 or PD-L1 checkpoint inhibitors. In both models, tucatinib statistically significantly inhibited tumor growth and demonstrated dose-dependent efficacy. Ex vivo analysis by flow cytometry of tumor-infiltrating lymphocytes in mice treated with tucatinib showed increased frequency, higher proliferation, and enhanced effector function of CD8+ effector memory T cells. Tucatinib treatment also increased frequency of CD8+PD-1+ and CD8+TIM3+ T cells, CD49+ natural killer cells, monocytes, and major histocompatibility complex II expression on dendritic cells and macrophages and a decrease in myeloid-derived suppressor cells. Gene expression analysis revealed statistically significant enrichment in pathways associated with immune activation, type I and II interferon response, adaptive immune response, and antigen receptor signaling. In vivo, tucatinib and α-PD-L1 or α-PD-1 demonstrated statistically significantly increased efficacy and improved survival of mice compared with tucatinib alone. Tucatinib modulates the immune microenvironment favorably, and combination treatment with α-PD-L1 or α-PD-1 demonstrated increased efficacy in preclinical HER2-positive tumor models. These findings provide a rationale for investigation of tucatinib and immune checkpoint inhibition in the clinic.


Preexisting physical activity level and cardiovascular responses across the Valsalva maneuver.
To determine the effect of preexisting physical activity level on resting cardiovascular measures and the intensity of cardiovascular responses across the Valsalva Maneuver (VM), 131 young (30-55 years) and 67 older (greater than 55 years) healthy adults, classified into sedentary, active, semitrained, or trained groups, were studied. Resting heart rate (HR) was lower in all trained subjects. In contrast, resting diastolic blood pressure was lower in young but not older trained subjects. During the VM, the expected fall in systolic blood pressure (SBP) from baseline during strain was less in young trained but not older trained subjects. Physical training significantly lessened the intensity of SBP and HR responses during the overshoot phase of the VM only in young subjects, most often in young males.


Undercarboxylated osteocalcin correlates with insulin secretion in Japanese individuals with diabetes.
Undercarboxylated osteocalcin (ucOC) is a secreted protein produced by osteoblasts that regulates insulin secretion and insulin sensitivity in rodents. However, the significance of these effects on glucose metabolism in human remains unknown. Moreover, the pathophysiological roles of ucOC on varying degrees of glucose intolerance, including diabetes need to be elucidated. In the present study, correlations between ucOC and indices of insulin secretion and sensitivity were analyzed in normal glucose tolerance (NGT), impaired glucose metabolism (IGM), and diabetes mellitus (DM) groups. Based on 75 g OGTT data in Japanese individuals without diabetic medication, or medications which may affect ucOC levels, individuals were classified as having normal glucose tolerance (NGT), impaired glucose metabolism (IGM), or diabetes (DM). In each group, 25 individuals were consecutively recruited [total 75 individuals, age: 65 ± 11 (mean ± SD); BMI: 24.9 ± 3.8 kg/m2]. QUICKI and Matsuda index (MI) were calculated as insulin sensitivity indices. Homeostasis model assessment (HOMA)-β and insulinogenic index (IGI) were calculated as insulin secretion indices. UcOC was measured using ECLIA. Normally-distributed loge-transformed (ln-) values were used for ucOC, HOMA-β, IGI, and MI. The ucOC was not significantly different among the three groups. The results of multiple regression analysis showed that ln-ucOC did not significantly correlate with age, sex, BMI, waist circumference, fasting plasma glucose, plasma glucose 120 min after glucose loading, fasting plasma immunoreactive insulin, ln-HOMA-β, QUICKI, or ln-MI in any of the three groups. Interestingly, ln-ucOC correlated with ln-IGI (r = 0.422, P = 0.0354) and HbA1c (r = - 0.574, P = 0.0027) only in the DM group. There was no significant correlation between ln-IGI and age, sex, BMI, or HbA1c in the DM group. Further, the results of multiple regression analysis showed that ln-IGI could be independently predicted by BMI (β = 0.598, P = 0.0014) and ln-ucOC (β = 0.641, P = 0.0007) in the DM group (R2 = 0.488, P = 0.0006). In our study, ucOC positively correlated with insulin secretion independently of BMI in Japanese individuals with diabetes. These results suggest that ucOC plays more important roles in insulin secretion than in insulin sensitivity in individuals with diabetes.


Can quantitative MRI be used in the clinical setting to quantify the impact of intra-articular glucocorticoid injection on synovial disease activity in juvenile idiopathic arthritis?
Juvenile idiopathic arthritis (JIA), the most common chronic rheumatic disease of childhood, is characterised by synovitis. Clinical assessments of synovitis are imperfect, relying on composite and indirect measures of disease activity including clinician-reported measures, patient-reported measures and blood markers. Contrast-enhanced MRI is a more sensitive synovitis assessment technique but clinical utility is currently limited by availability and inter-observer variation. Improved quantitative MRI techniques may enable future development of more stringent MRI-defined remission criteria. The objective of this study was to determine the utility and feasibility of quantitative MRI measurement of synovial volume and vascularity in JIA before and twelve weeks after intra-articular glucocorticoid injection (IAGI) of the knee and to assess the acceptability of MRI to participating families. Children and young people with JIA and a new episode of knee synovitis requiring IAGI were recruited from the Great North Children's Hospital in Newcastle upon Tyne. Quantitative contrast-enhanced MRI was performed prior to and twelve weeks after IAGI, in addition to standard clinical assessment tools, including the three-variable clinical juvenile arthritis disease activity score (cJADAS) and active joint count. Eleven young people (5 male, median age 13 years, range 7-16) with JIA knee flare were recruited and 10 completed follow-up assessment. Following IAGI, the median (interquartile range) cJADAS improved from 8.5 (2.7) to 1.6 (3.9), whilst the median synovial volume improved from 38.5cm3 (82.1cm3) to 0.0cm3 (0.2cm3). Six patients presented with frank synovitis outside normal limits on routine MRI reporting. A further three had baseline MRI reports within normal limits but the quantitative measurements identified measurable synovial uptake. Post-IAGI quantitative measurements highlighted significant improvements in 9 patients. IAGI led to a marked reduction in synovial volume, with quantitative MRI identifying more patients with an improved synovial volume than routine qualitative clinical reporting. Improvements in cJADAS scores were more variable with the patient/parent global assessment component contributing most to the scores. Further work is indicated, exploring the utility of quantitative MRI in the assessment of less accessible joints and comparing the impact of different treatment modalities.


Physicochemical characterization and antioxidant activity of polysaccharides from Chlorella sp. by microwave-assisted enzymatic extraction.
Microwave-assisted enzymatic extraction (MAEE) was used for the separation of polysaccharides from micro-Chlorella. The extraction condition of MAEE was optimized by Box-Behnken design and response surface methodology. Results showed that the optimal condition for the extraction of Chlorella sp. crude polysaccharides (CSCP) was at 50°C for 2.3 h with 380 W of microwave power and 0.31% of enzyme dosage. Under the optimal extraction condition, the extraction yield of CSCP reached 0.72%. Similarly, the α-amylase modification conditions of the CSCP were also optimized, in which the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging rate was used as the response value. The scavenging rate of DPPH free radicals was 17.58% when enzyme dosage was 271 U/g at 51°C for 14 min. Moreover, the enzyme-modified CSCP presented a typical heteropolysaccharide mainly including glucose (48.84%), ribose (13.57%) and mannose (11.30%). MAEE used in this work achieved a high extraction yield of CSCP, which provides an efficient method for the extraction of CSCP from Chlorella sp.


Molecular epidemiology of Pseudomonas aeruginosa in adult patients with cystic fibrosis in Northern Ireland.
Isolates (n = 51) of Pseudomonas aeruginosa obtained from the sputa of 29 adult patients attending the Regional Cystic Fibrosis Centre in Northern Ireland were compared using an enterobacterial repetitive intergenic consensus sequence (ERIC2) primer in a random amplification of polymorphic DNA (RAPD) polymerase chain reaction (PCR) method. Resulting banding patterns showed a high degree of genetic heterogeneity among all isolates from the patients examined, suggesting a non-clonal relationship between isolates from these patients, when employing this genotyping technique.


Scintigraphic localization of lymphatic leakage site after oral administration of iodine-123-IPPA.
Chylothorax can occur secondary to traumatic lesions of the thoracic duct caused by chest injuries, surgical procedures involving the pleural space, neoplasms or malformations of the lymphatics. Lymphatic leakage sites were localized by scintigraphy after oral administration of the 123I-labeled long-chain fatty acid derivative iodophenyl pentadecanoic acid (IPPA). We report on three patients with different lymphatic leakage sites and on one normal control subject. IPPA scintigraphy localized the lymphatic leakage site correctly in all three patients. In two of them, the method even guided the successful surgical treatment of the leakage. This approach is suitable for detecting lymphatic leakages of intestinal origin.


Mean platelet volume predicts embolic complications and prognosis in infective endocarditis.
This study was designed to examine the change in mean platelet volume (MPV) over the course of infective endocarditis (IE) and also the association between MPV and complications including embolic events in IE. Forty patients (26 male, mean age 46±15 years) who were hospitalized with a diagnosis of IE at the Department of Cardiology, Erciyes University, from March 2005 to August 2008, were retrospectively evaluated. The diagnosis of IE was made clinically and was confirmed with Duke's criteria. The erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hs-CRP), and MPV were measured before treatment and periodically during the follow-up period, until discharge. There were 27 cases of native valve endocarditis and 13 of prosthetic valve endocarditis. While 31 patients were treated medically, an operation was performed in nine patients because of unsuccessful medical therapy. On admission, mean MPV was 10.8±1.1 fl, ESR was 82±26mm/h, and hs-CRP was 110±72mg/l. Seven patients died: one intraoperatively, three patients postoperatively, and three patients during medical treatment. With the exception of these seven patients, ESR and hs-CRP were significantly reduced in all patients at discharge compared to levels at hospitalization (ESR 82±26 to 32±22, p=0.001 and hs-CRP 110±72 to 25±15, p=0.001). Similarly, we detected a significant decrease in MPV from hospitalization to discharge, i.e., from the active period of the disease to recovery (10.8±1.1 to 9.7±0.8 fl, p=0.002). In addition, MPV was found to be significantly higher in patients with observed embolic complications (11.5 vs. 10.3 fl, p=0.001), other complications (11.0 vs. 10.2 fl, p=0.001), and death (11.1 vs. 10.4 fl, p=0.005). MPV can be used as an activity criterion in IE, like ESR and hs-CRP. Also, high MPV is associated with a poor prognosis and adverse outcomes, and predicts complications including embolic events.


Renewed interest in cancer immunotherapy with the tumor necrosis factor superfamily molecules.
Molecules belonging to the Tumor Necrosis Factor (TNF) and TNF receptor superfamilies have explosively expanded through the era of genomics and bioinformatics. Biological investigations of these molecules have explored their potency as attractive targets for cancer therapy. Anti-tumor mechanisms mediated by TNF superfamily molecules (TNFSF) could be classified into direct actions onto tumor cells and indirect effects through immune or non-immune components of tumor-bearing host. In this review, we focus on TRAIL, CD40, 4-1BB (CD137), and LIGHT as promising molecules to mediate powerful and selective anti-tumor responses, and summarize their unique effector mechanisms. In addition, optimal approaches to manipulate these molecules for cancer therapy are also discussed. We try to provide an insight into a role of TNFSF in cancer therapeutics and highlight each of their potency to be an important player in anti-cancer strategies.


βLact-Pred: A Predictor Developed for Identification of Beta-Lactamases Using Statistical Moments and PseAAC via 5-Step Rule.
Beta-lactamase (β-lactamase) produced by different bacteria confers resistance against β-lactam-containing drugs. The gene encoding β-lactamase is plasmid-borne and can easily be transferred from one bacterium to another during conjugation. By such transformations, the recipient also acquires resistance against the drugs of the β-lactam family. β-Lactam antibiotics play a vital significance in clinical treatment of disastrous diseases like soft tissue infections, gonorrhoea, skin infections, urinary tract infections, and bronchitis. Herein, we report a prediction classifier named as βLact-Pred for the identification of β-lactamase proteins. The computational model uses the primary amino acid sequence structure as its input. Various metrics are derived from the primary structure to form a feature vector. Experimentally determined data of positive and negative beta-lactamases are collected and transformed into feature vectors. An operating algorithm based on the artificial neural network is used by integrating the position relative features and sequence statistical moments in PseAAC for training the neural networks. The results for the proposed computational model were validated by employing numerous types of approach, i.e., self-consistency testing, jackknife testing, cross-validation, and independent testing. The overall accuracy of the predictor for self-consistency, jackknife testing, cross-validation, and independent testing presents 99.76%, 96.07%, 94.20%, and 91.65%, respectively, for the proposed model. Stupendous experimental results demonstrated that the proposed predictor "βLact-Pred" has surpassed results from the existing methods.


Case report of transient mcr-1-haboring Escherichia coli with concurrent Staphylococcus aureus bacteremia in Long Beach, California.
A 55-year-old man with history of chronic hepatitis B cirrhosis presented to an emergency department in California with abdominal pain, constipation, and jaundice. The patient developed methicillin-susceptible S. aureus bacteremia with a concurrent transient E. coli. This organism carried mcr-1 in a plasmid similar to other mcr-1-carrying plasmids from the USA. The spread of mcr-1 into carbapenem-resistant isolates is of great concern and monitoring of this resistance mechanism is important.


Brain mitochondrial cytochrome P-450scc: spectral and catalytic properties.
The cytochrome P-450-dependent cholesterol side chain cleavage system of the brain has been studied using nonsynaptic mitochondria as the source of enzymatic activity. The system has been found to bind cholesterol and 11-deoxycorticosterone, producing type I difference spectra, whereas the binding of pregnenolone induced a reverse type I difference spectrum. Inhibitors of cytochrome P-450-linked monooxygenase activities produced type II spectra. The formation of labeled pregnenolone after incubation of brain mitochondria with [4-14C]cholesterol has been obtained, and this formation was inhibited by glutethimide, a specific inhibitor of cytochrome P-450scc. The functional significance of this enzymatic activity is discussed.


Current controversies in oral lichen planus: report of an international consensus meeting. Part 2. Clinical management and malignant transformation.
Despite recent advances in understanding the immunopathogenesis of oral lichen planus (LP), the initial triggers of lesion formation and the essential pathogenic pathways are unknown. It is therefore not surprising that the clinical management of oral LP poses considerable difficulties to the dermatologist and the oral physician. A consensus meeting was held in France in March 2003 to discuss the most controversial aspects of oral LP. Part 1 of the meeting report focused on (1) the relationship between oral LP and viral infection, with special emphasis on hepatitis C virus (HCV), and (2) oral LP pathogenesis, in particular the immune mechanisms resulting in lymphocyte infiltration and keratinocyte apoptosis. Part 2 focuses on patient management and therapeutic approaches and includes discussion on malignant transformation of oral LP.


Effects of antisera on human sperm penetration of zona-free hamster ova.
Human sperm, after treatment with a 10% concentration of rabbit or rhesus monkey normal sera and antisera, were evaluated for fertilizing potential by incidence of zona-free hamster ova penetrated by the sperm as evidenced by the presence of swollen sperm heads and male pronuclei. Compared with the basic medium alone, treating sperm with normal sera tended to increase the percentage of ova penetrated whereas antisera against sperm, sperm extract, and testis caused significant decreases in ova penetrated. A Fab preparation of these antisera exhibited similar inhibitory effects. Antisera Fab treatment of the zona-free ova prior to exposure to sperm had no effect on penetration rate.


Antibacterial activity of tannin constituents from Phaseolus vulgaris, Fagoypyrum esculentum, Corylus avellana and Juglans nigra.
Tannins were fractionated from acetonic extract preparations of phenolic compounds from Phaseolus vulgaris, Fagoypyrum esculentum, Corylus avellana and Juglans nigra. Wide variations in antibacterial activities ranging from MICs of 62.5 to 500 microg/ml were apparent. Of particular note was a relatively high level of activity (62.5 to 125 microg/ml) for all extracts against Listeria monocytogenes.


Genome integrity, stem cells and hyaluronan.
Faithful preservation of genome integrity is the critical mission of stem cells as well as of germ cells. Reviewed are the following mechanisms involved in protecting DNA in these cells: (a) The efflux machinery that can pump out variety of genotoxins in ATP-dependent manner; (b) the mechanisms maintaining minimal metabolic activity which reduces generation of reactive oxidants, by-products of aerobic respiration; (c) the role of hypoxic niche of stem cells providing a gradient of variable oxygen tension; (d)(e) the presence of hyaluronan (HA) and HA receptors on stem cells and in the niche; (f) the role of role of HA in protecting DNA from oxidative damage; (g) the specific role of HA that may play a role protecting DNA in stem cells; (h) the interactions of HA with sperm cells and oocytes that also may shield their DNA from oxidative damage, and (e) mechanisms by which HA exerts the anti-oxidant activity. While HA has multitude of functions its anti-oxidant capabilities are often overlooked but may be of significance in preservation of integrity of stem and germ cells genome.


Attitudes about palliative care: a comparison of pediatric critical care and oncology providers.
Pediatric critical care and oncology providers care for patients who have life-threatening or serious illness, yet they receive little palliative care education. Compare oncology and critical care providers' attitudes regarding palliative care. An electronic survey assessed respondents' opinions of whether, when, and why palliative care should be utilized. Response rate was 49%. Critical care physicians were more likely to incorporate palliative care for psychosocial support; oncologists for symptom control. Those with palliative care education were more likely to involve in palliative care, did so earlier and for reasons other than end-of-life planning. Oncology and critical care providers utilized palliative care for different reasons.


Diverse Molecular Mechanisms Underlying Pathogenic Protein Mutations: Beyond the Loss-of-Function Paradigm.
Most known disease-causing mutations occur in protein-coding regions of DNA. While some of these involve a loss of protein function (e.g., through premature stop codons or missense changes that destabilize protein folding), many act via alternative molecular mechanisms and have dominant-negative or gain-of-function effects. In nearly all cases, these non-loss-of-function mutations can be understood by considering interactions of the wild-type and mutant protein with other molecules, such as proteins, nucleic acids, or small ligands and substrates. Here, we review the diverse molecular mechanisms by which pathogenic mutations can have non-loss-of-function effects, including by disrupting interactions, increasing binding affinity, changing binding specificity, causing assembly-mediated dominant-negative and dominant-positive effects, creating novel interactions, and promoting aggregation and phase separation. We believe that increased awareness of these diverse molecular disease mechanisms will lead to improved diagnosis (and ultimately treatment) of human genetic disorders.


Comparisons of psychomotor performance between the upper and lower extremities in three age groups.
Decreasing speed of foot movement is a serious perceptual-motor impairment for older individuals such as in walking and driving. The present study examined the relationship between age and psychomotor performance for upper vs lower extremities. A visual stimulus was used to measure the speed of finger and foot movement responses, i.e., choice reaction time and total response time. 32 healthy persons, ranging in age from 9 to 75 years, were divided into three groups: ages 9-10, ages 20-30, and age 60 and above. A 3 (age group) x 2 (test: finger vs foot) two-way analysis of variance on converted Z scores indicated a significant effect on age group and an interaction between test and age group. While the elderly group showed poorest over-all performance, their lower extremity response was identified to be relatively slower than their upper-extremity response.


Characterisation of hydrogels: Linking the nano to the microscale.
Hydrogels are water enriched soft materials widely used for applications as varied as super absorbents, breast implants and contact lenses. Hydrogels have also been designed for smart functional devices including drug delivery, tissue engineering and diagnostics such as blood typing. The hydrogel properties and functionality depend on their crosslinking density, water holding capacity and fibre/polymer composition, strength and internal structure. Determining these parameters and properties are challenging. This review presents the main characterisation methods providing both qualitative and quantitative information of the structures and compositions of hydrogel. The length scale of interest ranges from the nano to the micro scale and the techniques and results are analysed in relationship to the hydrogel macroscopic applications. The characterisation methods examined aim at quantifying swelling, mechanical strength, mesh size, bound and free water content, pore structure, chemical composition, strength of chemical bonds and mechanical strength. These hydrogel parameters enable us to understand the fundamental mechanisms of hydrogel formation, to control their structure and functionality, and to optimize and tailor specific hydrogel properties to engineer particular applications.


Sorting of major cargo glycoproteins into clathrin-coated vesicles.
The AP-1 and AP-2 complexes are the most abundant adaptors in clathrin-coated vesicles (CCVs), but clathrin-mediated trafficking can still occur in the absence of any detectable AP-1 or AP-2. To find out whether adaptor abundance reflects cargo abundance, we used lectin pulldowns to identify the major membrane glycoproteins in CCVs from human placenta and rat liver. Both preparations contained three prominent high molecular-weight proteins: the cation-independent mannose 6-phosphate receptor (CIMPR), carboxypeptidase D (CPD) and low-density lipoprotein receptor-related protein 1 (LRP1). To investigate how these proteins are sorted, we constructed and stably transfected CD8 chimeras into HeLa cells. CD8-CIMPR localized mainly to early/tubular endosomes, CD8-CPD to the trans Golgi network and CD8-LRP1 to late/multivesicular endosomes. All three constructs redistributed to the plasma membrane when clathrin was depleted by siRNA. CD8-CIMPR was also strongly affected by AP-2 depletion. CD8-CPD was moderately affected by AP-2 depletion but strongly affected by depleting AP-1 and AP-2 together. CD8-LRP1 was only slightly affected by AP-2 depletion; however, mutating an NPXY motif in the LRP1 tail caused it to become AP-2 dependent. These results indicate that all three proteins have AP-dependent sorting signals, which may help to explain the relative abundance of AP complexes in CCVs. However, the relatively low abundance of cargo proteins in CCV preparations suggests either that some of the APs may be empty or that the preparations may be dominated by empty coats.


Mutagenesis of the regulatory subunit of yeast cAMP-dependent protein kinase. Isolation of site-directed mutants with altered binding affinity for catalytic subunit.
Oligonucleotide-directed mutagenesis was used to produce mutants in the hinge region of the regulatory subunit (R) of the Saccharomyces cerevisiae cAMP-dependent protein kinase. The mutant proteins were expressed in Escherichia coli, purified, urea treated to produce cAMP-free regulatory (R), and analyzed in vitro for catalytic (C) subunit inhibitory activity in the presence and absence of cAMP. When assayed in the absence of cAMP, wild type R dimer inhibited C with an IC50 of 40 nM. Replacement of amino acid residue Ser-145 (the autophosphorylation site of yeast R) with Ala or Gly produced mutants which were 2-10-fold better inhibitors of C, while replacement with Glu, Asp, Lys, or Thr produced mutants which were 2-5-fold worse inhibitors of C relative to wild type R. When assayed in the presence of cAMP, all R subunits had a decreased affinity for C subunit, with Ser-145 and Thr-145 undergoing autophosphorylation. These results suggest that the amino acid at position 145 of R contributes to R-C interaction and therefore influences the equilibrium of yeast protein kinase subunits in vitro.


Increasing women's engagement in vector control: a report from Accelerate To Equal project workshops.
Workshops with academic, national and local government, and community stakeholders were held in Kenya (2017) and Indonesia (2018) to understand the role and perceptions of women in vector control and to identify strategies for accelerating involvement of women in sustained support for vector control interventions at multiple levels/sectors.


Can listeners hear who is singing? Part B--experienced listeners.
Previous research has shown that inexperienced listeners have a more difficult time identifying an oddball singer in a three-note task where two sung stimuli are produced by the same singer and one sung stimulus is produced by an oddball singer than they do in a six-note task where five sung stimuli are produced by the same singer and one sung stimulus is produced by the oddball singer. Such results support the idea that timbre should be understood as a transformation that connects the different sounds of one source, that a "rich" set of sounds is necessary to discover the trajectory. The role of listener experience in perceiving the trajectory, however, is unknown. This paper investigated the ability of experienced listeners to identify which pitch in an ascending or descending sequence of three or six stimuli was sung by a different singer. For three-note sequences, listeners for the most part chose the most dissimilarly pitched stimulus as coming from the oddball singer. For six-note sequences, the detection of the oddball singer was much improved. In all tasks, experienced listeners were better able to detect the oddball singer than were inexperienced listeners. These results support the idea that while listener experience is an important factor in singer discrimination, experienced and inexperienced listeners alike benefit from a "rich" set of exemplars from which to abstract the timbre transformation.


Hemiparasite abundance in an alpine treeline ecotone increases in response to atmospheric CO(2) enrichment.
Populations of the annual hemiparasites Melampyrum pratense L. and Melampyrum sylvaticum L. were studied at the treeline in the Swiss Alps after 3 years of in situ CO(2) enrichment. The total density of Melampyrum doubled to an average of 44 individuals per square meter at elevated CO(2) compared to ambient CO(2). In response to elevated CO(2), the height of the more abundant and more evenly distributed M. pratense increased by 20%, the number of seeds per fruit by 21%, and the total seed dry mass per fruit by 27%, but the individual seed size did not change. These results suggest that rising atmospheric CO(2) may stimulate the reproductive output and increase the abundance of Melampyrum in the alpine treeline ecotone. Because hemiparasites can have important effects on community dynamics and ecosystem processes, notably the N cycle, changing Melampyrum abundance may potentially influence the functioning of alpine ecosystems in a future CO(2)-rich atmosphere.


Knee joint reconstruction after hemiarticular resection using pedicled patella and vascularized fibular graft.
Between 1999 and 2005, seven patients had resection of tumors around the knee joint that involved half of the articular surface of the femoral or tibial side. Average age of the patients was 28 years (range, 14-40). Tumor pathology was giant cell tumor in four patients, osteoblastoma in two, and benign fibrous histocytoma in one patient. Two patients had recurrent tumors. The tumor was located in the distal femur in five patients and in the proximal tibia in the remaining two. The ipsilateral patella pedicled on the infrapatellar fat pad was used to substitute the resected articular surface and a vascularized fibula osteoseptocutaneous flap was used to reconstruct the metaphyseal defect. Average follow-up period was 6.5 years (range, 3.5-10 years). All flaps survived. Average time to bone union was 3.5 months (range, 3-4 months), and average time to full weight-bearing was 5 months (range, 4-6 months). No radiological signs of avascular necrosis of the patella were observed in any patient. Two patients required secondary procedures for correction of instability. One patient had local recurrence. At final follow-up, the median range of knee motion was from 10° to 100°. The average Knee Society Score (KSS) was 76 points (range; 50-85 points), and the average KSS functional score was 76.6 points (range, 70-90 points). In conclusion, the procedure is a reliable option for after resection of tumors that involve half the articular surface of the femur or the tibia.


Chronic recurrent multifocal osteomyelitis: report of a case with epiphyseal and metaphyseal involvement.
Chronic recurrent osteomyelitis is a recognized clinicopathological entity with typical radiographic findings in the metaphyses of the long bones. Epiphyseal lesions usually are small and may easily be overlooked. Bone scintigraphy is helpful in identifying multiple lesions whether symptomatic or not. The diagnosis is one of exclusion without pathognomonic findings. Recognition of the condition is important to avoid treatment with antibiotics and repeated operations.


Electromagnetic articulography: use of alternating magnetic fields for tracking movements of multiple points inside and outside the vocal tract.
The purpose of this paper is to present a new electromagnetic device which uses alternating magnetic fields for tracking movements of multiple points inside and outside the vocal tract. It is biologically safe, noninvasive, it does not interfere with speech movements, allows for multiple recording in the same subject, and for easy collection of large amounts of data. It is especially suitable for evaluation of patients with speech motor impairments.


Malignant struma ovarii: a case report.
Malignant struma ovarii is a rare form of the ovarian germ cell tumors. Hence, diagnosis and management of malignant struma ovarii have not been clearly defined. We present the case of a 34-year-old woman with papillary carcinoma arising in struma ovarii. The malignant component of this tumor was detected after laparoscopic removal, and a re-staging operation was performed afterwards. There was no evidence of clinical malignancy or metastases. In this paper, clinical features, treatment guidelines, diagnostic features, and immunohistochemical characteristics of this tumor are reviewed.


Immortalized equivalent human epidermis as a platform to evaluation hair dyes toxicity: Efficiency comparison between 3D and monolayer culture.
The use of 3D models in various scientific applications is becoming more popular to replace traditional monolayers models. In this work, we used a three-dimensional in-house model of epidermis using HaCaT immortalized cells to evaluate the dermal toxicity induced by Basic Blue 99 and Basic Red 51, both present in commercial hair dye formulations. Our data show that cells cultured in the 3D model respond differently to those cultured in monolayer. Basic Red 51 dye induces apoptosis an DNA breaks in both models, however, these effects is more pronounced in cells cultured in monolayer. The toxic mode of action of Basic Blue 99 seems to be the induction of cell death, without genotoxic effects, but while the necrotic pathway is observed in HaCaT monolayer cell culture, was apoptosis seen in the Equivalent Human Epidermis (EHE) model. We could also confirm that cells in EHE model, an environment that could better mimic human effects, react differently to chemical stressors than the cells cultivated in 2D.


Analysis of recurrence patterns associated with toxoplasmic retinochoroiditis.
Toxoplasmic retinochoroiditis is thought to recur randomly. We sought to determine whether there is, instead, a longitudinal pattern of recurrences and to identify risk factors for recurrence. Longitudinal cohort study. We collected the following data for 143 patients with toxoplasmic retinochoroiditis in The Netherlands: gender, first affected eye, age at first episode, mode of Toxoplasma gondii infection (congenital vs postnatal), treatment history, and presence of retinal scars at initial examination. For each episode, we determined age, duration since first episode, and interval since previous episode. We estimated the relationship between disease-free interval after an episode and recurrence risk. The influence of host and disease factors on recurrence risk was analyzed using Cox regression with frailty modeling for correlated intrapatient recurrence times. We performed a Monte Carlo test for occurrence of clusters after prolonged disease-free intervals. Follow-up ranged from 0.3 to 41 years (323 episodes in first-affected eyes). Recurrence risk was highest immediately after an episode, then decreased with increasing disease-free intervals, a pattern consistent with clustering. Relative risk (RR) of recurrence declined 72% (RR, 0.28; 95% confidence interval [CI], 0.22 to 0.36; P < .001) with each 10-year interval since first episode, and declined 15% (RR, 0.85; 95% CI, 0.71 to 1.01; P = .06) for each 10-year increase in age at first episode. Patients more than 40 years of age were at higher risk of recurrence than younger patients (RR, 1.74; 95% CI, 1.06 to 2.86; P = .03). Clusters of episodes occurred after prolonged disease-free intervals. Toxoplasmic retinochoroiditis occurs in clusters over time. Recurrence risk is influenced by patient age and duration of infection.


Functioning free gracilis transfer to reconstruct elbow flexion and quality of life in global brachial plexus injured patients.
In the study, the functional recovery and relative comprehensive quality of life of cases of global brachial plexus treated with free functioning muscle transfers were investigated. Patients who received functioning gracilis muscle transfer between August 1999 and October 2014 to reconstruct elbow flexion, wrist and fingers extension were recruited. The mean age of the patients was 26.36 (range, 16-42) years. The mean period of time from gracilis transfer to the last follow-up was 54.5 months (range, 12-185 months). Muscle power, active range of motion of the elbow flexion, wrist extension, and total active fingers extension were recorded. SDS, SAS and DASH questionnaires were given to estimate patients' quality of life. 35.71% reported good elbow flexion and 50.00% reported excellent elbow flexion. The average ROM of the elbow flexion was 106.5° (range, 0-142°) and was 17.00° (range, 0-72°) for wrist extension. The average DASH score was 51.14 (range, 17.5-90.8). The prevalence of anxiety and depression were 42.86% and 45.24%. Thrombosis and bowstringing were the most common short and long-term complications. Based on these findings, free gracilis transfer using accessory nerve as donor nerve is a satisfactory treatment to reconstruct the elbow flexion and wrist extension in global-brachial-plexus-injured patients.


Optimisation study of alpha-cyclotron production of At-211/Po-211g for high-LET metabolic radiotherapy purposes.
The production of no-carrier-added (NCA) alpha-emitter (211)At/(211g)Po radionuclides for high-LET targeted radiotherapy and immunoradiotherapy, through the (209)Bi(alpha,2n) reaction, together with the required wet radiochemistry and radioanalytical quality controls carried out at LASA is described, through dedicated irradiation experiments at the MC-40 cyclotron of JRC-Ispra. The amount of both the gamma-emitter (210)At and its long half-lived alpha-emitting daughter (210)Po is optimised and minimised by appropriate choice of energy and energy loss of alpha particle beam. The measured excitation functions for production of the main radioisotopic impurity (210)At-->(210)Po are compared with theoretical predictions from model calculations performed at ENEA.


Comparison of the specificity of PCR and the histopathological detection of leishmania for the diagnosis of American cutaneous leishmaniasis.
More precise and rapid diagnostic methods for American cutaneous leishmaniasis (ACL) are necessary because of the growing number of cases observed in Brazil, including the northeastern region of the State of São Paulo. We applied PCR to 54 skin or mucosal biopsies from patients with a clinical and/or laboratory diagnosis of ACL using primers 13A and 13B, with positive results being obtained for 82% of the samples. When the PCR results were compared to those of histopathological leishmania detection, PCR showed superior results with 81.5% sensitivity and 95% CI of 68.0-95.1%. The Montenegro skin test (MST) was positive in 88.7% of patients. Since MST cannot be used as a diagnostic tool in endemic areas, the present results strongly suggest the use of PCR for the etiological confirmation of ACL, with emphasis on the mucosal form.


The impact of environmental fluctuations on structured discrete time population models: resonance, synchrony and threshold behaviour.
External forcing of a discrete time ecological system does not just add variation to existing dynamics but can change the dynamics. We study the mechanisms that can bring this about, focusing on the key concepts of excitation and suppression which emerge when analysing the power spectra of the system in linear approximation. Excitation, through resonance between the system dynamics and the external forcing, is the greater the closer the system is to the boundary of the stability region. This amplification means that the extinction of populations becomes possible sooner than expected and, conversely, invasion can be significantly delayed. Suppression and the consequent redistribution of power within the spectrum proves to be a function both of the connectivity of the network graph of the system and the way that external forcing is applied to the system. It is also established that colour in stochastic forcing can have a major impact, by enhancing resonance and by greater redistribution of power. This can mean a higher risk of extinction through larger fluctuations in population numbers and a higher degree of synchrony between populations. The implications of external forcing for stage-structured species, for populations in competition and for trophic web systems are studied using the tools and concepts developed in the paper.


Clinical experiences of ICSI-ET thawing cycles with embryos cryopreserved at different developmental stages.
The aim of our study was to analyze factors including survival, implantation and pregnancy rate, patients' age and BMI, abortions and extra uterine pregnancies that might influence the outcome of ICSI-ET thawing cycles. A total of 147 cycles with embryos cryopreserved at different developmental stages were retrospectively evaluated. No difference was found in the survival, implantation and pregnancy rates of embryos cryopreserved on Day 2-3 and 5. However, in the pregnant group significantly higher implantation rate was observed with Day 5 blastocysts then with Day 2 or 3 early embryos. We found no difference in the number of abortions and extra uterine pregnancies between fresh and frozen ICSI-ET cycles. Higher BMI was found in the pregnant than in the nonpregnant group. However, the age of patient had no effect on the results. Developmental stage of embryo and patients' BMI influences the success of ICSI-ET thawing cycles.


Removal of Calcium Hydroxide Pastes Containing N-Methyl-2-Pyrrolidone, Local Anaesthesia, Glycerine, and Methylcellulose from Artificial Radicular Grooves: An In-vitro Study.
To compare the removal of calcium hydroxide (CaOH) pastes containing N-Methyl-2-pyrrolidone (NMP), lidocaine, glycerine, methylcellulose, or water from artificially created grooves. In this study, 115 human single-rooted maxillary incisors with single and straight root canals were prepared using a rotary file up to size 40/.04 and split longitudinally. A longitudinal groove was created from 2 to 5 mm from the apex and filled with CaOH combined with different vehicles. The specimens were divided among 5 experimental groups according to the vehicle as follows: distilled water, lidocaine, glycerine, methylcellulose, and NMP. The two halves were re-attached, and the canals were flushed with 10 ml of 17% EDTA for 60 seconds. The residual amount of CaOH was scored using a stereomicroscope at 8× magnification. Statistical significance was set at P<0.05. The NMP-based group exhibited significantly less residual medicament compared to the distilled water (P<0.05), while there were no statistically significant differences among the methylcellulose-, lidocaine-, and glycerine-based groups and distilled water (P>0.05). The vehicle is an important factor in the successful removal of CaOH medicament from the root canals. Within the limitations of the present study, the NMP-based CaOH medicament exhibited better removal efficacy than the distilled water. However, the cleaning success of the methylcellulose-, lidocaine-, and glycerine-based groups was similar to that of distilled water.


3-(2,3-Di-meth-oxy-phen-yl)-2,3-di-hydro-1H-benzo[f]chromen-1-one.
In the title compound, C21H18O4, the central pyran ring is in an envelope conformation and the dihedral angle between the benzene ring and naphthalene ring system is 88.31 (1)°. The meth-oxy groups at the ortho and meta positions of the benzene ring are tilted to the ring with C-C-O-C torsion angles of 105.9 (4) and 9.5 (5)°, respectively. In the crystal, pairwise C-H⋯O hydrogen bonds form R 2 2(14) inversion dimers, which are linked by another pair of C-H⋯O hydrogen bonds to form [210] chains in the crystal.


Endoscopic resection and suturing methods for non-ampullary duodenal submucosal tumors: "mini-invasive" treatments that should never be underestimated.
To evaluate the effectiveness and safety of endoscopic resection and various suturing methods to treat non-ampullary duodenal submucosal tumors (NAD-SMTs). We performed a retrospective observational study of patients with NAD-SMTs who underwent endoscopic resection at Zhongshan Hospital, Fudan University, China, between June 2017 and December 2020. Data on patient characteristics, treatments and follow-up results were collected. The association between clinicopathologic characteristics and different suturing methods or adverse events were analyzed. Of 128 patients analyzed, 26 underwent endoscopic mucosal resection (EMR), 64 underwent endoscopic submucosal excavation (ESE), and 38 underwent endoscopic full-thickness resection (EFTR). EMR and ESR are both appropriate for non-full-thickness lesions, whereas ESE is more appropriate for tumors located in the bulb or descending duodenum. Gastric tube drainage is more strongly recommended after ESE. Satisfactory suturing is also vital endoscopic resection of NAD-SMTs. Metallic clips are often used in EMR or ESE of non-full-thickness lesions. The pathological findings revealed that the full-thickness lesions were predominantly gastrointestinal stromal tumors (GIST), Brunner's tumor or lipoma, and the surgeons usually used purse-string sutures to close the wounds. The operation time was longer for purse-string suture closure than metallic clip closure. Eleven patients had complications. Risk factors for adverse events included large-diameter tumor (≥ 2 cm), location in the descending part of the duodenum, involvement of the fourth layer of the duodenal wall, EFTR, and GIST. Endoscopic resection of NAD-SMTs is effective but is associated with a high incidence of complications due to their anatomical peculiarities. Preoperative diagnosis is quite important. Careful selection of treatment and suturing methods are necessary to reduce the risk of adverse effects. Given the increased frequency of severe complications during or following duodenal endoscopic resection, this procedure should be performed by experienced endoscopists.


Rotman Lens-Based Circular Array for Generating Five-mode OAM Radio Beams.
Recently, vortex beam carrying orbital angular momentum (OAM) for radio communications has attracted much attention for its potential of transmitting multiple signals simultaneously at the same frequency, which can be used to increase the channel capacity. However, most of the methods for getting multi-mode OAM radio beams remain up to now mainly at simulation level, since their implementations are of complicated structure and very high cost. This paper provides an effective design of generating five-mode OAM radio beams by using the Rotman lens-fed antenna array. The Rotman lens is a viable beamforming approach instead of electronically scanned arrays for its low cost and the ease of implementation. The lens-fed array employs a two-layer structure for size reduction, and the lens body and the antenna array are segregated by a common ground plane to eliminate spurious radiation and thus improve the performance of the OAM beams. The measured results coincide with the simulated ones, which verified the effectiveness of the proposed design for generating multi-mode OAM beams.


Effect of pH on effluent organic matter removal in hybrid process of magnetic ion-exchange resin adsorption and ozonation.
It is essential to mitigate the risk of exposure to effluent organic matter (EfOM) in aquatic environments to ensure safe wastewater recycling. Magnetic ion-exchange (MIEX) resin adsorption combined with ozonation could provide EfOM removal. However, the poor understanding of the influences of the parameters and mechanisms in the hybrid process has restricted the applications. In this study, the response surface methodology was used to reveal the interactions of the major operation parameters. The degradation behaviour of the EfOM was investigated by using spectroscopy combined with mathematical methods. The effect of the pH on the EfOM removal was also analysed. The maximum efficiency of the removal of dissolved organic carbon (DOC) was 59.77% at the optimal MIEX resin dosage of 7.97 mL/L, ozone concentration of 8 mg/L, agitation speed of 199.84 r/min, and pH of 9.98. The ozonation was superior to resin adsorption in the removal of 1054-Da compounds, while the resin adsorption was advantageous in the removal of 4168-Da compounds. Three fluorescent components (C1, C2, and C3) were more easily subjected to external perturbation than the DOC and ultraviolet absorbance at 254 nm in the oxidation processes. The MIEX resin exhibited low efficiencies of removal of the fluorescent substances. A synchronous fluorescence analysis coupled with a two-dimensional correlation analysis revealed that the variation in EfOM followed the order of fulvic-to humic-like substances in the hybrid process of MIEX and the following ozonation. The pH was the most significant influencing factor in the hybrid process.


Spread of potentials along the network of horizontal cells in the retina of the turtle.
The spread of potentials along electrically-coupled horizontal cell networks in the turtle retina was studied at different levels of illumination. The mean values of the stationary space constant, lambda st, measured by the steady-state responses to a bar of light moved along the retina, is about 0.13 mm for the LII horizontal cell response and 0.35 mm for the LI response. lambda st is quite stable in the physiological range of membrane potentials. The dynamic space constant, lambda (t), measured at different intervals after the onset of the light bar, transiently increased during the rising phase of the on-response. Such a transient change of lambda (t) is absent or less apparent for depolarizing responses to the offset of the light bar. Ba2+ ions strongly enhanced the transient increase of lambda (t) for hyperpolarizing responses without affecting lambda (t) for depolarizing responses. Possible mechanisms of the transient increase of the dynamic space constant are discussed.


Effects of des-Asp-angiotensin I on the contractile action of angiotensin II and angiotensin III.
Nanomolar concentrations of des-Asp-angiotensin I potentiated the contractile action of angiotensin II on the rabbit aortic ring but attenuated the contractile action of angiotensin III in the same tissue. Indomethacin had no effect on the potentiation of angiotensin II but inhibited the attenuation of angiotensin III. The action of angiotensin II, angiotensin III and des-Asp-angiotensin I was not inhibited by (S)-1-}[4-(dimethylamino)-3-methylphenyl]methyl}-5-(diphenylacetyl )-4,5,6, 7-tetrahydro-1H-imidazo-[4,5-c]pyridine-6-carboxylic acid, ditrifluoroacetate, dihydrate (PD123319), an angiotensin AT2 receptor antagonist. The data show that angiotensin II and angiotensin III act on different subclasses of angiotensin receptors and that their actions are differentially modulated by des-Asp-angiotensin I. The data also indicate the possibility that des-Asp-angiotensin I is a functional peptide that modulates the contractile action of the two angiotensins at sub-nanomolar concentrations.


Perinatal outcomes in dichorionic diamniotic twins with multifetal pregnancy reduction versus expectant management: A systematic review and meta-analysis.
Published findings on perinatal outcomes of multifetal pregnancy reduction (MPR) of dichorionic diamniotic (DCDA) twin pregnancy to singleton are controversial. We performed a meta-analysis to appraise the effects of MPR of DCDA twin pregnancy versus expectant management on perinatal outcomes. Four electronic databases were searched from their inception to June 15, 2019, to identify publications that appraised MPR before 15 weeks of gestation. Studies reporting perinatal outcomes of both MPR of DCDA twin pregnancy to singleton and expectant management were considered. The relative risks (RRs) and mean differences with 95% confidence intervals (CIs) were pooled using a random-effects model. Six studies involving 7398 participants showed that MPR of DCDA twin pregnancy to singleton was associated with a lower risk of preterm birth (5 studies with 7297 participants; RR: 0.30, 95% CI: 0.22-0.40; P < .001) and higher birth weight (4 studies with 5763 participants; mean differences: 548.10 g, 95% CI: 424.04-672.15; P < .001) than expectant management; there was no difference in the occurrence of miscarriages (5 studies with 7355 participants; RR: 1.57, 95% CI: 0.90-2.75; P = .11). Sensitivity analysis showed that all the results were stable and reliable, with the omission of 2 studies with serious risk of bias. Compared to expectant management, MPR of DCDA twin pregnancy to singleton prevents preterm birth and low birth weight, without increasing the risk of miscarriages. Regarding perinatal morbidity related to preterm birth, MPR can be reserved as a remediation measure to improve the perinatal outcomes of DCDA twin pregnancies.


Clinical Outcomes of Patients with Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer with Leptomeningeal Metastasis in the Modern Target Therapy Era.
Leptomeningeal metastasis (LM) is a severe complication in patients with non-small-cell lung cancer (NSCLC) and the optimal treatment strategy remains a challenge. This study aimed to investigate the treatment strategies and clinical outcomes in these patients. We retrospectively reviewed the data of 44 patients with epidermal growth factor receptor (EGFR)-mutated NSCLC with LM between 2014 and 2020 at our institute. The patient characteristics, treatment approaches, LM progression-free survival (LMPFS) and overall survival (OS) after the diagnosis of LM (OSLM) were analyzed. The median OSLM was 16.0 months and the 3-year OS rate was 22.5%. The PFSLM in EGFR T790M-positive NSCLC patients with leptomeingeal disease was significantly improved by initiation of third-generation tyrosine kinase inhibitors (TKIs) compared with that of patients who were T790M negative (14.0 vs. 7.0 months; P = 0.030). A significantly higher LM disease control rate was shown in patients who received third-generation TKIs compared with previous generations of TKIs (90.1% vs. 60.0%; P = 0.024). Better Eastern Cooperative Oncology Group performance status, EGFR exon 19del, and clinical improvement of LM after therapy were independently associated with better OS. The survival of patients with NSCLC with LM has improved in the target therapy era. Our study provided real-world clinical evidence that patients with EGFR-mutated NSCLC who developed LM from previous TKIs can be benefit from third-generation EGFR-TKIs, especially for patients with EGFR T790M-positive.


Limb chondrogenesis is compromised in the versican deficient hdf mouse.
It has been suggested that the matrix proteoglycan, versican, may perform a functional role during early events of limb skeletogenesis largely by virtue of its spatiotemporal expression pattern in precartilage mesenchymal aggregations. The versican-deficient hdf transgenic mouse has provided the first model to explore the implications of a null mature versican on limb chondrogenesis. Due to lethality of hdf homozygous embryos prior to limb cartilage differentiation, high-density micromass cultures were employed to compare the chondrogenic capacity of hdf mutant limb mesenchyme to that of wild-type. In homozygous hdf mesenchyme, aggregation was severely compromised and neither cartilage-characteristic Type II collagen nor alcian blue positive foci were detected during a 6-day period of culture. Three-dimensional culture of hdf mutant mesenchyme, however, showed that in a permissive environment mutant cells also expressed Type II collagen. Results strongly suggest that mature versican proteoglycan is essential for precartilage aggregation and subsequent cartilage differentiation.


Meta-analysis at middle age: a personal history.
The 40-year history of meta-analysis is traced from the vantage point of one of its originators. Research syntheses leading to the first examples of meta-analysis are identified. Early meta-analyses of the literature on psychotherapy outcomes and school class size are recounted. The influence on the development of meta-analysis of several statisticians and psychologists is described. Finally, some directions for future development of research synthesis methods are suggested.


Optimization studies of BTX removal by magnetite coated oleic acid obtained from microwave-assisted synthesis using response surface methodology.
Benzene, toluene and xylene (BTX) are volatile organic compounds released into the environment, that require urgent removal to avoid adverse health effects. In this work, the modelling and optimization of the preparation factors for magnetite coated oleic acid (MNP-OA) composite from microwave synthesis using response surface methodology were conducted to maximize BTX removal, and iron content. The influence of five crucial preparation variables: the Fe3+/Fe2+ solution volumes, microwave power, volume of ammonia water (VAW), reaction time and volume of oleic acid (VOA) on the iron content (% Fe), and BTX adsorption capacity were investigated. The analysis of variance results revealed that VOA and VAW were the most influential factors for high % Fe content, and improved BTX removal. The % Fe, and BTX adsorption capacity for MNP-OA composite at optimized experimental conditions were estimated to be 85.57%, 90.02 mg/g (benzene), 90.07 mg/g (toluene), and 96.31 mg/g (xylene).


Preparation, characterization and photocatalytic activity of AgBr/BiVO4 composite photocatalyst.
The AgBr/BiVO4 heterostructure were synthesized. The heterostructure materials were characterized by XRD, DRS, SEM-EDS, TEM, XPS and TG-DSC. In order to investigate the photocatalytic activity of AgBr/BiVO4 heterostructures, the methylene blue (MB) dye was used as a model compound. The result suggested that under visible light irradiation, the degradation efficiency of AgBr/BiVO4 reached 83.1% within 2.5 h, which was higher than that of the pure BiVO4. The presence of AgBr significantly increased the photocatalytic activity of the composites. The photocatalytic mechanism was also discussed.


Differential expression of heat shock proteins in Drosophila embryonic cells following metal ion exposure.
Drosophila embryonic cells were exposed to a number of metal ions that have been previously reported to act as teratogens in mammalian systems, including some known to induce heat shock (stress) proteins in a variety of model systems. This study examined the effects of these ions both on differentiation of muscles and neurons and on the induction of heat shock proteins. Metals such as arsenate, cadmium, and mercury all inhibited neuron and/or muscle differentiation in Drosophila embryonic cultures, while they also induced the entire set of heat shock proteins. Two metal ions, nickel and zinc, were shown to induce only the 22- and 23-K proteins, a pattern similar to that seen in "classical" teratogens reported previously. None of the metals tested induced only the 26- and 27-K proteins. These results suggest that there exist different regulatory mechanisms responsible for the heat shock response.


Tumor dosimetry using 177Lu: influence of background activity, measurement method and reconstruction algorithm.
Image-based tumor dosimetry after radionuclide therapy, using the isotope 177Lu, finds application e.g., for tumor-to-organ dose comparison and for dose response evaluation. When the tumor extent is not much larger than the image resolution, and when 177Lu is found in nearby organs or other tumors, an accurate determination of tumor dose is particularly challenging. Here a quantitative evaluation of three different methods for determining the 177Lu activity concentration in a phantom is performed, and the dependence on a variety of parameters is described. The phantom (NEMA IEC body phantom) has spheres of different size in a background volume, and sphere-to-background 177Lu activity concentration ratios of infinity, 9.5, 5.0 and 2.7 are applied. The methods are simple to implement and well-known from the literature. They are based on (1) a large VOI encompassing the whole sphere, without background activity and with volume information from other sources, (2) a small VOI located in the sphere center, and (3) a VOI consisting of voxels with voxel value above a certain percentage of the maximum voxel value. The determined activity concentration varies significantly with sphere size, sphere-to-background ratio, SPECT reconstruction method and method for determining the concentration. Based on the phantom study, criteria are identified under which the activity concentration can be determined with a maximal error of 40% even in the presence of background activity. Tumor dosimetry is feasible in the presence of background activity using the above-mentioned methods, provided appropriate SPECT reconstructions are applied and tumors are selected for dosimetry analysis according to the following criteria for the three methods: (1) solitary tumor with diameter > 15 mm, (2) tumor diameter > 30 mm and tumor-to-background ratio > 2, and (3) tumor diameter > 30 mm and tumor-to-background ratio > 3.


Efficacy of risk-reducing salpingo-oophorectomy in women with BRCA-1 and BRCA-2 mutations.
Recognizing the emerging role of genetics in clinical care, in 1996 the American Society of Clinical Oncology established a Task Force on Cancer Genetics Education to develop educational opportunities and resources for its members. These efforts, and recent advances in the understanding of genetic predisposition to breast and ovarian cancers, have resulted in growing numbers of women participating in genetic testing protocols. The first prospective clinical trial involving women with known BRCA-1 and BRCA-2 mutations was recently published. In a prospective study involving 170 BRCA-1 and BRCA-2 mutation carriers and a mean follow-up of 2 years, the estimated 5-year cancer-free estimates were 96% for the 98 women choosing prophylactic bilateral salpingo-oophorectomy and 69% for the 72 women choosing intensive surveillance (p=0.006). Three cases of stage I ovarian cancers were diagnosed at the time of prophylactic surgery. These results are consistent with published literature and data from the Prevention and Observation of Surgical Endpoints (PROSE) study group, which reported a 96% reduction in ovarian cancer risk and a 53% reduction in breast cancer risk among BRCA-1 and BRCA-2 mutation carriers who had prophylactic bilateral oophorectomy compared to matched controls. Thus prophylactic bilateral salpingo-oophorectomy can be regarded as an effective risk-reducing procedure that permits early diagnosis of ovarian cancer at the time of surgery and significantly reduces the risk of breast and ovarian cancer in women with germ-line mutations in the BRCA-1 and BRCA-2 genes.


Synthesis of full-length cDNAs from partially purified human procollagen mRNAs.
Partially purified human procollagen mRNAs have been copied using reverse transcriptase from avian myeloblastosis virus. Under standard conditions, using a high deoxynucleotide concentration, only incomplete cDNAs corresponding to one-fifth to one-half of the template could be synthesized. Addition of a ribonuclease inhibitor from human placenta in the reaction mixture allowed the synthesis of full-length cDNA copies from extremely long procollagen mRNA.


Expression of epstein-barr virus nuclear antigen 1 is associated with enhanced expression of CD25 in the Hodgkin cell line L428.
Epstein-Barr virus is associated with several human malignancies including Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease (HD). To examine the effect of Epstein-Barr virus nuclear antigen 1 (EBNA-1) in the pathogenesis of HD, we transfected the gene into the HD cell line L428. EBNA-1 expression was associated with significantly enhanced CD25 expression (interleukin 2 [IL-2]-receptor alpha chain) in transient and stably transfected L428 cells but did not affect the expression of IL-2 receptor beta and gamma chains. There was no up-regulation of the B-cell activation molecules CD23, CD30, CD39, CD40, CD44, CD71, and CD54 (intercellular adhesion molecule 1) or enhanced production of IL-6, IL-10, lymphotoxin alpha, and the soluble form of CD25. Stable EBNA-1-expressing L428 cells were nontumorigenic in SCID mice but showed enhanced lymphoma development in nonobese diabetic-SCID mice compared to mock-transfected cells.


Bilateral compared with unilateral sacral nerve stimulation for faecal incontinence: results of a randomized, single-blinded crossover study.
This randomized single-blinded crossover study aimed to investigate whether bilateral sacral nerve stimulation (SNS) is more efficient than unilateral stimulation for faecal incontinence (FI). Patients with FI who responded during a unilateral test stimulation, with a minimum improvement of 50% were eligible. Twenty-seven patients who were accepted to enter the trial were bilaterally implanted with two permanent leads and pacemakers. Patients were randomized into three periods of 4 weeks' stimulation including unilateral right, unilateral left and bilateral stimulation. Symptoms scores and bowel habit diaries were collected at baseline and in each study period. A 1-week washout was introduced between each study period. Twenty-seven (25 female) patients with a median age of 63 (36-84) years were bilaterally implanted from May 2009 to June 2012. The median number of episodes of FI per 3 weeks significantly decreased from 17 (3-54) at baseline to 2 (0-20) during stimulation on the right side, 2 (0-42) during stimulation on the left side and 1 (0-25) during bilateral stimulation. The Wexner incontinence score improved significantly from a median of 16 (10-20) at baseline to 9 (0-14) with right-side stimulation, 10 (0-15) with left-side stimulation and 9 (0-14) with bilateral stimulation. The differences between unilateral right or unilateral left and bilateral stimulation were non-significant, for FI episodes (P = 0.3) or for Wexner incontinence score (P = 0.9). Bilateral SNS therapy for FI is not superior to standard unilateral stimulation in the short term. Equal functional results can be obtained regardless of the side of implantation.


Droplets as reaction compartments for protein nanotechnology.
Extreme miniaturization of biological and chemical reactions in pico- to nanoliter microdroplets is emerging as an experimental paradigm that enables more experiments to be carried out with much lower sample consumption, paving the way for high-throughput experiments. This review provides the protein scientist with an experimental framework for (a) formation of polydisperse droplets by emulsification or, alternatively, of monodisperse droplets using microfluidic devices; (b) construction of experimental rigs and microfluidic chips for this purpose; and (c) handling and analysis of droplets.


Prolonged activation of cAMP-dependent protein kinase during conditioning induces long-term memory in honeybees.
To investigate the function cAMP-dependent protein kinase (PKA) exerts in the induction of long-term memory, changes in PKA activity induced by associative learning in vivo were measured in the antennal lobes (ALs) of honeybees. The temporal dynamics of PKA activation depend on both the sequence of conditioned and unconditioned stimuli and the number of conditioning trials. Only multiple-trial conditioning, which induces long-term memory (LTM), leads to a profound prolongation of PKA activation mediated by the NO/cGMP system. Imitation of this prolonged PKA activation in the ALs in combination with single-trial conditioning is sufficient to induce LTM. These findings not only demonstrate the close connection between conditioning procedure and temporal dynamics in PKA activation but also reveal that already during conditioning a distinct temporal pattern of PKA activation is critical for LTM induction in intact animals.


Reactions of 1-bromo-2-[14C]pinacolone with acetylcholinesterase from Torpedo nobiliana. Effects of 5-trimethylammonio-2-pentanone and diisopropyl fluorophosphate.
1-Bromo-2-[14C]pinacolone, (CH3)3C14COCH2Br [( 14C]BrPin), was prepared from [1-14C]acetyl chloride and tert-butylmagnesium chloride with cuprous chloride catalyst, followed by bromination. It was examined as an active-site directed label for acetylcholinesterase (acetylcholine acetylhydrolase, EC 18.104.22.168) (AcChE). AcChE, isolated from Torpedo nobiliana, has k(cat) = (4.00 +/- 0.04).10(3) s-1, Km = 0.055 +/- 0.008 mM in hydrolysis of acetylthiocholine, and k(cat) = (5.6 +/- 0.2).10(3) s-1, Km = 0.051 +/- 0.003 mM in hydrolysis of acetylcholine. BrPin, binding in the trimethyl cavity, acts initially as a reversible competitive inhibitor, Ki = 0.20 +/- 0.09 mM, and, with time, as an irreversible covalently bound inactivator. Introduction of 14C from [14C]BrPin into Torpedo AcChE at pH 7.0 was followed by SDS-PAGE, autoradiography and scintillation counting, in the absence and presence of 5-trimethylammonio-2-pentanone (TAP), a competitive inhibitor (Ki = 0.075 +/- 0.001 mM) isosteric with acetylcholine; 1.8-1.9 14C was incorporated per inactivated enzyme unit at 50% inactivation. TAP retarded inactivation by [14C]BrPin, and prevented introduction of 0.9-1.1 14C per unit of enzyme protected. Prior inactivation of AcChE by BrPin prevents reaction with [3H]diisopropyl fluorophosphate [( 3H]DFP). Prior inactivation by DFP or [3H]DFP does not prevent reaction with [14C]BrPin, and this subsequent reaction with BrPin does not displace the [3H] moiety. [14C]BrPin alkylates a nucleophile in the active site, and this reaction does not alkylate or utilize the serine-hydroxyl.


Chest shielding in preterm neonates under phototherapy-a randomised control trial.
Shielding the precordium can effect manifestation of haemodynamically significant patent ductus arteriosus (hsPDA). Preterm neonates born at ≤ 32 weeks of gestation if needed phototherapy within 72 h of birth and had no echocardiographically proven hsPDA were eligible to be enrolled in this open-label randomised controlled trial. In chest shielding group, in addition to the standard care, left side of the chest was covered using food grade aluminium foil during phototherapy while control group received standard care. Mean gestational age (weeks; 30.1 ± 1.5 vs 30.1 ± 1.6) was comparable in the two groups. However, neonates in the chest shield group had lower birth weight (g; 1281 ± 259 vs 1422 ± 307) and were more likely to be small-for-gestational age (21.6% vs 8.0%). It was seen that 4 (7.8%) babies in the chest shield group and 5 (10%) babies in the standard group developed hsPDA after starting phototherapy with relative risk (RR) of 0.78 (95% CI 0.22-2.75). The left atrium to aortic ratio was significantly different in the two groups with 1.5 ± 0.1 in the chest shield group and 1.8 ± 0.2 in standard group (p value 0.03).Conclusion: Chest shielding of preterm babies during phototherapy has no effect on the incidence of haemodynamically significant patent ductus arteriosus.Trial registration: Trial was registered with Clinical trial registry of India (CTRI/2018/01/011069). What is Known: • Chest shielding in preterm neonates under phototherapy has inconclusive effect on the manifestation of patent ductus arteriosus. What is New: • Preterm neonates under phototherapy have no significant difference in manifestation of haemodynamically significant patent ductus arteriosus if precordium is shielded.


The absolute configuration of SU 23397: a novel neuroleptic agent.
The absolute configuration of a novel chiral neuroleptic agent SU 23397 (I) was determined by ORD comparison of (+)-5-methoxy dihydro coumarilic acid (VIII), a synthetic precursor of SU 23397 (I), with (+)-dihydro coumarilic acid, whose absolute configuration is known. This assignment was confirmed by oxidative degradation of (+)-5-methoxy dihydro coumarilic acid VIII to D-(+)-malic acid.


Influence of predator density on nonindependent effects of multiple predator species.
Interactions between multiple predator species are frequent in natural communities and can have important implications for shared prey survival. Predator density may be an important component of these interactions between predator species, as the frequency of interactions between species is largely determined by species density. Here we experimentally examine the importance of predator density for interactions between predator species and subsequent impacts on prey. We show that aggressive interactions between the predatory shore crabs Carcinus maenas and Hemigrapsus sanguineus increased with predator density, yet did not increase as fast as negative interactions between conspecifics. At low density, interactions between conspecific and heterospecific predators had similar inhibitory impacts on predator function, whereas conspecific interference was greater than interference from heterospecifics at high predator density. Thus the impact of conspecific interference at high predator density was sufficient in itself that interactions with a second predator species had no additional impact on per capita predation. Spatial and temporal variability in predator density is a ubiquitous characteristic of natural systems that should be considered in studies of multiple predator species.


Broadband temporal stimuli decrease the integration time of neurons in cat striate cortex.
We have studied the responses of striate cortical neurons to stimuli whose contrast is modulated in time by either a single sinusoid or by the sum of eight sinusoids. The sum-of-sinusoids stimulus resembles white noise and has been used to study the linear and nonlinear dynamics of retinal ganglion cells (Victor et al., 1977). In cortical neurons, we have found different linear and second-order responses to single-sinusoid and sum-of-sinusoids inputs. Specifically, while the responsivity near the optimal temporal frequency is lower for the sum-of-sinusoids stimulus, the responsivity at higher temporal frequencies is relatively greater. Along with this change in the response amplitudes, there is a systematic change in the time course of responses. For complex cells, the integration time, the effective delay due to a combination of actual delays and low-pass filter stages, changes from a median of 85 ms with single sinusoids to 57 ms with a sum of sinusoids. For simple cells, the integration times for single sinusoids range from 44-100 ms, but cluster tightly around 40 ms for the sum-of-sinusoids stimulus. The change in time constant would argue that the increased sensitivity to high frequencies cannot be explained by a static threshold, but must be caused by a fundamental alteration in the response dynamics. These effects are not seen in the retina (Shapley & Victor, 1981) and are most likely cortical in origin.


Site-directed modification of adenoviral vector with combined DNA assembly and restriction-ligation cloning.
Commonly used and well accepted approaches are lacking for site-directed modification of adenoviral vectors. Here, we attempt to introduce an easy-to-implement strategy for such purpose with an example of establishing a replication competent adenoviral vector system from pKAd5 plasmid, an infectious clone of human adenovirus 5 (HAdV-5). PCR products of GFP expression cassette and plasmid backbone were fused with the EcoRI/NdeI-digested fragment of pKAd5 to generate a modified intermediate plasmid pMDXE3GA by DNA assembly. NdeI-digested fragment of pMDXE3GA was brought back to pKAd5 to form the adenoviral plasmid pKAd5XE3GA by restriction-ligation cloning. Recombinant adenovirus HAdV5-XE3GA was rescued, amplified and purified. The expression of GFP and the propagation of virus in adherent HEp-2 and suspension K562 cells were investigated. Expression of target gene was significantly enhanced in both cell lines infected with HAdV5-XE3GA due to virus replication. However, propagation of virus could not sustain in culture of K562 cells. Shuttle plasmid pSh5RC-GFP was constructed to facilitate exchange of transgene. In summary, the strategy of combined DNA assembly and restriction-ligation cloning is functional, cost-effective and suitable for genetic modification of adenovirus.


Fluorine magnetic resonance studies of fluorine-substituted benzoyl chymotrypsins.
The fluorine magnetic resonance spectra of 4-fluorobenzoyl and 3,5-di(trifluoromethyl)benzoyl-alpha-chymotrypsins and the corresponding methyl esters were determined. An unusually large downfield displacement of the chemical shift (-10 ppm) was observed for the 4-fluorobenzoyl-alpha-chymotrypsin compared to the free acid in water. The shift of the ethyl ester was displaced upfield on going from a partly aqueous solvent to dioxane or methanol. The line broadening of the fluorine resonance of the 3,5-di(trifluoromethyl)benzoyl-alpha-chymotrypsin was minimal and there was no evidence of two peaks in the spectrum. The resonance was displaced only slightly downfield from the corresponding acid in water. Unusual chemical shifts for fluorinated acylchymotrypsins have been reported for other acyl groups and they appear to be unrelated to the anomalous deacylation rates observed for some fluorine substituted acylenzymes.


Computed tomography in urologic patients: preliminary assessment.
Computed tomography (CT) body scanning has specific application to the precise diagnosis of urologic disease. The advantage of visualizing the density of normal and abnormal tissue provides new accuracy in evaluation of renal, retroperitoneal, and pelvic masses. The penetration of the pelvic cavity allows the urologist to assess local, nodal, and skeletal involvement from prostatic and bladder neoplasms in a single diagnostic examination. Cost/efficacy analysis and the role of computed tomography in patient managment must await further review and experience.


Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study.
To test the prognostic value of emerging biomarkers in the Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial. Circulating cardiac [N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT)], neurohumoral [mid-regional pro-adrenomedullin (MR-proADM) and copeptin], renal (cystatin C), and inflammatory [high-sensitivity C-reactive protein (hsCRP)] biomarkers were measured at randomization in 1853 participants with complete data. The relationship between these biomarkers and the primary composite endpoint of heart failure hospitalization or cardiovascular death over 28 months of follow-up (n = 834) was evaluated using Cox proportional hazards regression, the c-statistic and the net reclassification index (NRI). After adjustment, the hazard ratio (HR) for the composite outcome in the top tertile of the distribution compared to the lowest tertile for each biomarker was: NT-proBNP 3.96 (95% CI 3.16-4.98), hsTnT 3.09 (95% CI 2.47-3.88), MR-proADM 2.28 (95% CI 1.83-2.84), copeptin 1.66 (95% CI 1.35-2.04), cystatin C 1.92 (95% CI 1.55-2.37), and hsCRP 1.51 (95% CI 1.27-1.80). A basic clinical prediction model was improved on addition of each biomarker individually, most strongly by NT-proBNP (NRI +62.3%, P < 0.001), but thereafter was only improved marginally by addition of hsTnT (NRI +33.1%, P = 0.004). Further addition of biomarkers did not improve discrimination further. Findings were similar for all-cause mortality. Once NT-proBNP is included, only hsTnT moderately further improved risk stratification in this group of chronic heart failure with reduced ejection fraction patients with moderate anaemia. NT-proBNP and hsTnT far outperform other emerging biomarkers in prediction of adverse outcome.


Acquired immune deficiency syndrome (AIDS) manifesting as anogenital herpes zoster eruption: demonstration of virus-like particles in lymphocytes.
A case of AIDS manifesting as a necrotic, haemorrhagic anogenital herpes zoster and lymphadenopathy, is described. Investigations of T-lymphocyte subsets showed decreased T4 and slight increase of T8. Electronmicroscopy revealed tubuloreticular virus-like structures in lymphocytes.


[Comparative study of barium enema, computed tomography and magnetic resonance imaging in preoperative diagnosis of colorectal carcinoma].
To compare the diagnostic value of barium enema (BE), computed tomography (CT) and magnetic resonance imaging(MRI) in primary colorectal carcinoma. A total of 64 patients with suspected colorectal carcinoma received BE (n=39), spiral CT (n=31) and MRI (n=42). The detective results were compared with the surgical results. Among 64 patients, 54 cases were pathologically proved as colorectal carcinoma. The diagnostic sensitivity of BE,CT and MRI was 96.9% ,96.2% and 97.1% ,and the overall accuracy was 92.3% 83.9 % and 90.5% respectively. The overall accuracy of CT and MRI for tumor T staging was 73.1% and 82.9% respectively. BE can be considered as a primary approach for diagnosing colorectal carcinoma, CT and MRI be necessary diagnostic approaches. Combined BE with MRI is the best choice for diagnosing of colorectal carcinoma.


A first-generation physical map of the human genome.
Sets of ordered overlapping cloned genomic DNA fragments that span each of the human chromosomes are urgently needed for identification of human disease genes. Such a physical map also provides unique material to study the structure and function of the genome. We have therefore exhaustively analysed the CEPH yeast artificial chromosome (YAC) library, which contains 33,000 clones, whose insert size was individually determined. These YACs have an average length of 0.9 megabases and cover the equivalent of 10 haploid genomes. Several mapping techniques were combined to provide multiple sources of structural information for most of these clones. Finally, the library was screened with more than 2,000 genetic markers quasiuniformly distributed over 90% of the genome. These results should allow the scientific community to construct detailed maps of all human chromosomes. Moreover, we propose a data analysis strategy that produces a first-generation integrated map covering most of the human genome.


Learning Equations from Biological Data with Limited Time Samples.
Equation learning methods present a promising tool to aid scientists in the modeling process for biological data. Previous equation learning studies have demonstrated that these methods can infer models from rich datasets; however, the performance of these methods in the presence of common challenges from biological data has not been thoroughly explored. We present an equation learning methodology comprised of data denoising, equation learning, model selection and post-processing steps that infers a dynamical systems model from noisy spatiotemporal data. The performance of this methodology is thoroughly investigated in the face of several common challenges presented by biological data, namely, sparse data sampling, large noise levels, and heterogeneity between datasets. We find that this methodology can accurately infer the correct underlying equation and predict unobserved system dynamics from a small number of time samples when the data are sampled over a time interval exhibiting both linear and nonlinear dynamics. Our findings suggest that equation learning methods can be used for model discovery and selection in many areas of biology when an informative dataset is used. We focus on glioblastoma multiforme modeling as a case study in this work to highlight how these results are informative for data-driven modeling-based tumor invasion predictions.


Giant cell tumor of metacarpal treated by cryosurgery.
We report the case of a 44-year-old woman with a giant cell tumor of the fourth metacarpal head of her dominant left hand that was treated with cryoprobe freezing, curettage and bone grafting. Three years after operation the metacarpophalangeal joint remained normal both functionally and radiologically. The tumor has not recurred. Cryoprobe killing of giant cell tumors of the hand can offer effective direct tumor eradication, as well as maintaining normal bone architecture and preserving full function.


Au nanoparticles-anchored defective metal-organic frameworks for photocatalytic transformation of amines to imines under visible light.
Designing efficient metal organic frameworks (MOF)-based photocatalysts has recently attracted wide attention. In this work, Au nanoparticles(NPs)-decorated defective DUT-67(Zr) (Au@DUT-67(Zr)) with enlarged channels was successfully fabricated and achieved 7.5 times higher conversion than Au NPs-decorated UiO-66(Zr) (Au@UiO-66(Zr)) for photocatalytic selective oxidation of amines to imines driven by visible light. Au NPs are more effectively fixed on DUT-67(Zr) due to its partially hollow structure. Au@DUT-67(Zr) possesses more active sites including unsaturated Zr atoms and oxygen vacancies (VO) than Au@UiO-66(Zr). In situ Fourier transform infrared (FTIR) spectrum reveals that benzylamine is activated on unsaturated Zr sites via HN…Zr species, facilitating deprotonation of -CH2 in benzylamine. VO can not only adsorb and activate oxygen (O2) but also capture plasmonic hot electrons, enhancing the forming of superoxide radical (O2-). Plasmonic hot holes assisted with O2- effectively achieve the selective oxidation of benzylamine. Finally, a possible synergetic mechanism combining the plasmon with the molecular activation is presented to illustrate the photocatalytic pathway at the molecular level.


The role of deimination in ATP5b mRNA transport in a transgenic mouse model of multiple sclerosis.
Deimination refers to conversion of protein-bound arginine into citrulline. An mRNA carrier, RNA binding export factor (REF), present on mitochondria undergoes loss of deimination with impaired ATP5b mRNA transport in ND4 mice (model of multiple sclerosis) compared with the controls. We present evidence of (1) reduced ATP5b mRNA binding strength of non-deiminated REF compared with deiminated REF, (2) impaired ATP5b mRNA transport in ND4 mice and (3) reduced mitochondrial ATP synthase activity on inhibition of deimination in PC12 cells. Impaired deimination of REF and defect in mitochondrial mRNA transport are critical factors in mitochondrial dysfunction in ND4 mice.


A step too far or a step in the wrong direction? A critique of the 2014 Amendment to the Belgian Euthanasia Act.
In 2014, Article 3 of the the Belgian Euthanasia Act (2002) (the Euthanasia Act) was amended ('the Amendment') to include the 'capacity for discernment' requirement. This paper explores the implications of this highly controversial Amendment. I remain unconvinced of the benefits for children < 12 years old suffering chronic or terminal illnesses. In Part One, I argue that the phrase 'capacity for discernment' is problematic and vulnerable to abuse; neither a consistent, widely accepted definition of the phrase has been established nor a standardised method or procedure to adequately gauge a minor's capacity for discernment. In Part Two I advance the argument that specifically for children < 12 years, aggressive and sophisticated paediatric palliative care treatment, which risks, but does not intend death, is more ethically justified than Euthanasia treatment. A definition of a child's interests is best achieved through a care-based ethics framework; namely, the child's relationship with their parents and family members, their doctors and medical practitioners is held to be an interest of crucial importance for the child. I conclude that paediatric palliative care arguably better promotes and upholds this interest.


cAMP-induced Epac-Rap activation inhibits epithelial cell migration by modulating focal adhesion and leading edge dynamics.
Epithelial cell migration is a complex process crucial for embryonic development, wound healing and tumor metastasis. It depends on alterations in cell-cell adhesion and integrin-extracellular matrix interactions and on actomyosin-driven, polarized leading edge protrusion. The small GTPase Rap is a known regulator of integrins and cadherins that has also been implicated in the regulation of actin and myosin, but a direct role in cell migration has not been investigated. Here, we report that activation of endogenous Rap by cAMP results in an inhibition of HGF- and TGFbeta-induced epithelial cell migration in several model systems, irrespective of the presence of E-cadherin adhesion. We show that Rap activation slows the dynamics of focal adhesions and inhibits polarized membrane protrusion. Importantly, forced integrin activation by antibodies does not mimic these effects of Rap on cell motility, even though it does mimic Rap effects in short-term cell adhesion assays. From these results, we conclude that Rap inhibits epithelial cell migration, by modulating focal adhesion dynamics and leading edge activity. This extends beyond the effect of integrin affinity modulation and argues for an additional function of Rap in controlling the migration machinery of epithelial cells.


Fetus as an allograft: noncytotoxic maternal antibodies to HLA-linked paternal antigens.
A cellular enzyme-linked immunospecific assay (CELISA) was used to monitor maternal humoral responses in human pregnancy. Non-cytotoxic IgG antibodies to paternal lymphocytes were detected in sera from 6 of 20 normal first trimester primigravidae and 6 of 13 multiparae. No antibody activity against lymphocytes from their partners was detected in sera from any of the 15 nulliparous women. The differences in antibody response between primigravidae and nulliparae (P = 0.024) and between multiparae and nulliparae (P = 0.005) were statistically significant. Lymphocytotoic antibodies to T- and B-lymphocytes were present in sera from three multiparae, but from none of the women in the other two groups. Family studies indicated that the non-cytotoxic pregnancy-associated maternal antibodies were directed to HLA-linked antigens (P less than 0.001). Evidence obtained using cell panels and platelet absorption suggested, however, that these antibodies were not directed to the currently recognized HLA specificities (HLA-A, -B, -C, or -DR).


An exploratory analysis of the nature of informal knowledge underlying theories of planned action used for public health oriented knowledge translation.
Informal knowledge is used in public health practice to make sense of research findings. Although knowledge translation theories highlight the importance of informal knowledge, it is not clear to what extent the same literature provides guidance in terms of how to use it in practice. The objective of this study was to address this gap by exploring what planned action theories suggest in terms of using three types of informal knowledge: local, experiential and expert. We carried out an exploratory secondary analysis of the planned action theories that informed the development of a popular knowledge translation theory. Our sample included twenty-nine (n = 29) papers. We extracted information from these papers about sources of and guidance for using informal knowledge, and then carried out a thematic analysis. We found that theories of planned action provide guidance (including sources of, methods for identifying, and suggestions for use) for using local, experiential and expert knowledge. This study builds on previous knowledge translation related work to provide insight into the practical use of informal knowledge. Public health practitioners can refer to the guidance summarized in this paper to inform their decision-making. Further research about how to use informal knowledge in public health practice is needed given the value being accorded to using informal knowledge in public health decision-making processes.


Myxomas of soft tissues and the facial skeleton.
Myxomas in the head and neck may be intraosseous or in soft tissues. In each site, their microscopic appearance and biologic activity are similar. Recurrences of myxomas are more the consequence of incomplete excision than intrinsic aggressiveness.