Effects of road de-icing salt (NaCl) on larval wood frogs (Rana sylvatica).
Vast networks of roads cover the earth and have numerous environmental effects including pollution. A major component of road runoff in northern countries is salt (mostly NaCl) used as a winter de-icing agent, but few studies of effects of road salts on aquatic organisms exist. Amphibians require aquatic habitats and chemical pollution is implicated as a major factor in global population declines. We exposed wood frog tadpoles to NaCl. Tests revealed 96-h LC50 values of 2,636 and 5,109 mg/l and tadpoles experienced reduced activity, weight, and displayed physical abnormalities. A 90 d chronic experiment revealed significantly lower survivorship, decreased time to metamorphosis, reduced weight and activity, and increased physical abnormalities with increasing salt concentration (0.00, 0.39, 77.50, 1,030.00 mg/l). Road salts had toxic effects on larvae at environmentally realistic concentrations with potentially far-ranging ecological impacts. More studies on the effects of road salts are warranted.


Unusual fucoidin-binding properties of chymotrypsinogen and trypsinogen.
Previous work (Jones, R. (1987) Cell Biol. Int. Reports 11, 833 and Jones et al. (1988) Development 102, 781-792) has shown that sperm proacrosin (the zymogen form of the acrosomal proteinase acrosin, EC 18.104.22.168) has the capacity to recognize and bind sulphated polysaccharides and that this property is important for the initial stages of fertilization in mammals. To investigate whether this behaviour is specific to proacrosin, a variety of other proteinases (chymotrypsinogen, trypsinogen, thrombin, elastase, plasminogen, pepsin, Streptomyces griseus proteinase and V8 proteinase from Staphylococcus aureus) were immobilized on nitrocellulose and probed with [125I]fucoidin. Only chymotrypsinogen and trypsinogen retained significant amounts of the probe with Kd values of 1.4.10(-6) M and 3.0.10(-5) M, respectively. Proteinase inhibitors were ineffective as blocking agents suggesting that enzymic activity is not involved in recognition. However, the tertiary structure of the proteins is important, since cleavage of intramolecular disulphide bonds with 2-mercaptoethanol reduced binding by 50-60%. Competition experiments with a variety of mono- and polysaccharides suggest that the number and disposition of sulphate groups is critical for interaction with basic residues on the protein. It is concluded that, like proacrosin, chymotrypsinogen and trypsinogen are bifunctional proteins.


Niche Differentiation of Biofilm Microorganisms in a Full-scale Municipal Drinking Water Distribution System in China and Their Implication for Biofilm Control.
Biofilms on the inner surface of a drinking water distribution system (DWDS) affect water quality and stability. Understanding the niche differentiation of biofilm microbial communities is necessary for the efficient control of DWDS biofilms. However, biofilm studies are difficult to conduct in the actual DWDS because of inaccessibility to the pipes buried underground. Taking the opportunity of infrastructure construction and relevant pipeline replacement in China, biofilms in a DWDS (a water main and its branch pipes) were collected in situ, followed by analysis on the abundances and community structures of bacterial and archaeal using quantitative PCR and high-throughput sequencing, respectively. Results showed that archaea were detected only in the biofilms of the water main, with a range of 9.4×103~1.1×105 copies/cm2. By contrast, bacteria were detected in the biofilms of branch pipes and the distal part of the water main, with a range of 8.8×103~9.6×106 copies/cm2. Among the biofilm samples, the archaeal community in the central part of the water main showed the highest richness and diversity. Nitrosopumilus was found to be predominant (86.22%) in the biofilms of the proximal part of the water main. However, Methanobrevibacter (87.15%) predominated in the distal part of the water main. The bacterial community of the water main and branch pipes was primarily composed of Firmicutes and Proteobacteria at the phylum level, respectively. Regardless of archaea or bacteria, only few operational taxonomic units (OTUs) (<0.5% of total OTUs) were shared by all the biofilms, indicating the niche differentiation of biofilm microorganisms. Moreover, the high Mn content in the biofilms of the distal sampling location (D3) in the water main was linked to the predominance of Bacillus. Functional gene prediction revealed that the proportion of infectious disease-related genes was 0.44-0.67% in the tested biofilms. Furthermore, functional genes related to the resistance of the bacterial community to disinfections and antibiotics were detected in all the samples, that is, glutathione metabolism-relating genes (0.14-0.65%) and beta-lactam resistance gene (0.01-0.05%). The results of this study indicate the ubiquity of archaea and bacteria in the biofilms of water main and branch pipes, respectively, and pipe diameters could be a major influencing factor on bacterial community structure. In the water main, the key finding was the predominant existence of archaea, particularly Nitrosopumilus and methanogen. Hence, their routine monitoring and probable influences on water quality in pipelines with large diameter should be given more attention. Besides, since Mn-related Bacillus and suspected pathogenic Enterococcus were detected in the biofilm, supplementation of disinfectant may be a feasible strategy for inhibiting their growth and ensuring water quality. In addition, the monitoring on their abundance variation could help to determine the frequency and methods of pipeline maintenance.


Blockade of vasospastic attacks by alpha 2-adrenergic but not alpha 1-adrenergic antagonists in idiopathic Raynaud's disease.
Idiopathic Raynaud's disease is characterized by cold-induced digital vasospasms, but its origin has not been established. Previous research has shown that peripheral vascular alpha 2-adrenergic receptors are hypersensitive to local cooling in these patients, but the role of alpha 1-adrenergic receptors is not clear. Moreover, the role of adrenergic receptors in the production of actual vasospastic symptoms has not been investigated. We studied 23 patients with idiopathic Raynaud's disease who were screened using conservative criteria. They were randomly assigned to receive brachial artery infusions of an alpha 1-antagonist, an alpha 2-antagonist, or both while vasospastic attacks were induced by cooling in the laboratory. Each patient's hands were photographed, and the number of attacks in the infused hand was compared with the number in the contralateral hand. The number of fingers (mean +/- SEM) with attacks in infused hands was yohimbine 0.3 +/- 0.3, prazosin 2.3 +/- 0.3, and both drugs 0.6 +/- 0.2. The difference between prazosin and the other two drug groups was significant (P < .001). These findings demonstrate that activation of alpha 2-adrenergic receptors but not alpha 1-adrenergic receptors is necessary for the production of vasospastic attacks in idiopathic Raynaud's disease.


Quality-of-life indicators and falls due to vitamin D deficiency.
To determine whether the number of falls and quality-of-life indicators relate to serum levels of vitamin D, parathyroid hormone (PTH), and calcium levels. A prospective study. Patients being admitted with a fall with or without sustaining a fragility fracture post fall. Measured frequency of falling, SF-12 questionnaire, serum concentrations of 25-hydroxyvitamin D, calcium, and PTH levels before and after treatment with vitamin D supplementation. The mean age (N=38) of the cohort was 80.2±12. In all, 76.3% of the cohort had sustained a fragility fracture after the fall. The cohort was vitamin D deficient with the pretreatment mean value of 24.2±17 nmol/L and posttreatment mean value of 99±40 nmol/L with a statistically significant mean difference of 74.7 nmol/L (confidence interval [CI] 61.27-88.3), P=0.001. The levels of calcium and PTH were statistically significant after treatment with a mean difference of 0.16 (CI 0.1-0.2), P=0.001, and 3.7 (CI -4.8 to -2.5), P=0.001, respectively. After treatment, the mean difference of physical component score (PCS) and mental component score for the whole cohort was 2.9 (CI -0.69 to 6.6), P=0.10, and 1.05 (CI -2.6 to 4.7), P=0.56, respectively. However, a subgroup analysis for cohort aged ≤70 years provided a statistically significant effect on PCS with a mean difference of 8.9 (CI 1.3-16.4), P=0.03, but a statistically insignificant improvement in mental component score with a mean difference of 6.0 (CI -17 to -5.0), P=0.20. However, a statistically significant improvement in PCS SF-12 was observed in patients ≤70 years of age 2.9 (1.3-16.4), P=0.03. The mean number of falls for the whole cohort pre- and posttreatment was 1.11±0.92 vs 0.97±0.99 (P=0.68), respectively. Patients who had fallen and sustained fragility fracture had lower serum 25-dihydroxyvitamin D and higher serum PTH levels. Our study demonstrates that there is no statistically significant improvement in the number of falls after treatment with vitamin D. Overall, vitamin D levels improved significantly, this is despite quality-of-life indicators showing a mean increase in PCS but not a statistically significant improvement. However, statistically significant improvement in PCS was observed in group aged ≤70 years after vitamin D supplementation.


Chemotherapy in the treatment of cancer of the pancreas.
Opinions about the value of chemotherapy in pancreatic cancer vary from the idea that its use should be abandoned because of lack of proven efficacy and considerable toxicity to the idea that it may produce clinically meaningful responses correlated with improved survival. A systematic review of the available literature-based evidence was undertaken. The results are discussed in relation to supportive evidence from recent studies focusing on patient benefit. Six randomized trials of chemotherapy in advanced disease and two in the adjuvant setting with a no-active treatment group were identified. All eight trials were small, and the methodology was not always what is currently desirable. One of four palliative trials reported during the early 1980s, and both trials completed during the 1990s showed a slight survival benefit with chemotherapy. In one of the trials, quality of life (QoL) was also more often improved after 5-fluorouracil-based chemotherapy than after best supportive care. Supportive evidence for a slight prolongation of survival and a clinical benefit also comes from trials comparing different drugs. No standard regimen is defined, although one drug, gemcitabine, has been approved in some countries for the treatment of advanced pancreatic cancer. The two randomized adjuvant trials included a very small number of patients, and, although a survival benefit was seen, conclusive evidence supporting the use of adjuvant chemo (radio) therapy is still lacking. Chemotherapy has low activity in advanced pancreatic cancer, but it can improve survival and well-being in some patients.


Preconditioning-induced ischemic tolerance stimulates growth factor expression and neurogenesis in adult rat hippocampus.
Preconditioning (PC) is a phenomenon in which a brief ischemic insult induces tolerance against a subsequent severe ischemic insult. Recent studies showed that cerebral ischemia in adult rat upregulates progenitor cell proliferation in the hippocampal dentate gyrus. We presently evaluated whether PC can also stimulate progenitor cell proliferation in rat brain. Middle cerebral artery was transiently occluded in spontaneously hypertensive rats for 10 min to induce PC and 1h to induce focal ischemia. Progenitor cell proliferation (defined as BrdU(+) cell number) significantly increased after focal ischemia (by 3.9-fold; p<0.05) as well as PC (by 2.7-fold; p<0.05) compared to sham. PC 3 days prior had neither an inhibitory nor an additive effect on focal ischemia-induced progenitor cell proliferation. In both ischemia and PC groups, approximately 45% of the progenitor cells proliferated in week 1 survived to the end of week 3 and approximately 21% of those matured into NeuN(+) neurons. Furthermore, cerebral mRNA expression of the growth factors IGF1, FGF2, TGFbeta1, EGF and PDGF-A was significantly elevated after PC. Thus, we show that the beneficial effects of PC extend beyond providing neuroprotection during the acute phase after ischemia. Induction of growth factor expression and neurogenesis by PC might be a positive adaptation for an efficient repair and plasticity in the event of an ischemic insult.


Integrin β1 mediates epithelial growth factor-induced invasion in human ovarian cancer cells.
Integrins function as cell-extracellular matrix adhesion proteins and have been implicated in tumor progression. In ovarian tumors, elevated integrin β1 expression correlates with high clinical stage and poor patient survival. In this study, we report that EGF treatment up-regulated integrin β1 mRNA and protein levels in ovarian cancer cells. Moreover, pharmacological inhibition of MEK totally abolished EGF-induced integrin β1 up-regulation and cell invasion suggesting that MAPK/ERK signaling is required for EGF-induced integrin β1 up-regulation and cell invasion. Furthermore, we found that knockdown of integrin β1 expression reduced the intrinsic invasiveness of ovarian cancer cells and the EGF-induced cell invasion. Finally, we found that overexpression of integrin β1 was sufficient to promote ovarian cancer cell invasion. This study demonstrates that integrin β1 mediates EGF-induced cell invasion in ovarian cancer.


The expression of podocyte-specific proteins in parietal epithelial cells is regulated by protein degradation.
The role of parietal epithelial cells (PECs) in glomerular disease is unclear because they also express podocyte proteins under pathophysiological conditions. To help resolve this, we established a novel PEC isolation technique in rats and mice to investigate which regulatory mechanisms lead to podocyte protein expression in PECs. This pure pool of naive PECs was then compared with PECs in primary culture and immortalized PECs in permanent culture. The naive PECs expressed low levels of podocyte-specific mRNA. Accordingly, in crescentic glomerulonephritis, single PECs activated the podocin promoter in vivo. In primary culture, PECs expressed a distinct morphology from podocytes but with high transcript and protein levels of PEC markers. In contrast to naive PECs, cultured PECs also expressed podocyte proteins, and this correlated with reduced proteolytic activity but not with increased transcript levels. Activation of autophagy or proteasomal degradation decreased the levels of podocyte proteins in PECs, whereas inhibition of proteasomal degradation led to the stabilization of podocyte proteins in PECs. Thus, naive PECs express podocyte transcripts physiologically and these podocyte proteins are stable under pathological conditions through decreased proteolysis.


46,XX/46,XX,8p- mosaicism in a phenotypically normal female.
A phenotypically normal female was found to have a chromosome 8 short arm deletion in a low percentage of the cells. The reduced proportion of monosomic cells in relationship with proband's age are discussed.


In-depth genetic analysis reveals conditioning of polyphenol oxidase activity in wheat grains by cis regulation of TaPPO2A-1 expression level.
Time-dependent darkening and discoloration of wheat product caused by high polyphenol oxidase enzymes (PPO) activity is the most undesirable character in wheat processing industry. We performed GWAS of PPO activity in wheat grains utilizing an association panel and identified 22 significant SNPs. The most significant GWAS peak on chromosome 2A was verified by QTL analysis of PPO activity. The candidate gene for this GWAS peak was identified as TaPPO2A-1, which was the highest expressed PPO gene in wheat grains. The expression level of TaPPO2A-1 was significantly correlated with PPO activity. The most significant association signal for GWAS of the expression values of TaPPO2A-1 pinpointed to the genomic region containing TaPPO2A-1. The results suggested that cis regulation of TaPPO2A-1 expression is the key factor in regulation of PPO activity in wheat grains. The conclusion was further enhanced by haplotype analysis of seven SNPs in the promoter of TaPPO2A-1.


Re-examining the relationship between interpersonal reactivity index sub-scales and mental well-being: Implications of the pandemic.
The pandemic has severely impacted people's Mental Well-being (MWB) globally. Pre-pandemic studies have widely linked MWB with empathy. Against the backdrop of pandemic, we intend to re-examine this association between empathy, as widely measured by the Interpersonal Reactivity Index (IRI) sub-scales: perspective taking, empathic concerns, and personal distress with MWB. For this, a survey using a non-experimental research design was carried out during the 2020 lockdown. We used the Structural Equation Modeling approach to analyse the data. All the standardized scales have been tested for unidimensionality, reliability, and validity. We also resort to a self-administered questionnaire consisting of questions related to day-to-day activities to support the empirical findings. Results demonstrate a positive relationship between perspective taking and empathic concern with MWB and a negative relationship between personal distress and MWB. The response to the self-administered questionnaire corroborates with our model results and presents the scope of interpreting the findings. In continuation, limitations, contributions, and future scope conclude this essay.


Translating Imaging Into 3D Printed Cardiovascular Phantoms: A Systematic Review of Applications, Technologies, and Validation.
Translation of imaging into 3-dimensional (3D) printed patient-specific phantoms (3DPSPs) can help visualize complex cardiovascular anatomy and enable tailoring of therapy. The aim of this paper is to review the entire process of phantom production, including imaging, materials, 3D printing technologies, and the validation of 3DPSPs. A systematic review of published research was conducted using Embase and MEDLINE, including studies that investigated 3DPSPs in cardiovascular medicine. Among 2,534 screened papers, 212 fulfilled inclusion criteria and described 3DPSPs as a valuable adjunct for planning and guiding interventions (n = 108 [51%]), simulation of physiological or pathological conditions (n = 19 [9%]), teaching of health care professionals (n = 23 [11%]), patient education (n = 3 [1.4%]), outcome prediction (n = 6 [2.8%]), or other purposes (n = 53 [25%]). The most common imaging modalities to enable 3D printing were cardiac computed tomography (n = 131 [61.8%]) and cardiac magnetic resonance (n = 26 [12.3%]). The printing process was conducted mostly by material jetting (n = 54 [25.5%]) or stereolithography (n = 43 [20.3%]). The 10 largest studies that evaluated the geometric accuracy of 3DPSPs described a mean bias <±1 mm; however, the validation process was very heterogeneous among the studies. Three-dimensional printed patient-specific phantoms are highly accurate, used for teaching, and applied to guide cardiovascular therapy. Systematic comparison of imaging and printing modalities following a standardized validation process is warranted to allow conclusions on the optimal production process of 3DPSPs in the field of cardiovascular medicine.


[Difficulties in the diagnosis of acute intestinal obstruction].
The experience with treatment of 679 patients admitted with diagnosis of acute ileus is summarized. In complex examination, the diagnosis was confirmed in 237 patients, in remaining, the other diseases were revealed.


Quantitative biochemical phenotypic heterogeneity of macrophages after myelin debris phagocytosis at a single cell level by synchrotron radiation fourier transform infrared microspectroscopy.
During the immuno-inflammatory pathophysiological process of spinal cord injury, traumatic brain injury, and ischemic stroke, macrophages play an important role in phagocytizing and clearing degenerated myelin debris. After phagocytizing myelin debris, the biochemical phenotypes related to the biological function of macrophages show vast heterogeneity; however, it is not fully understood. Detecting biochemical changes after myelin debris phagocytosis by macrophages at a single-cell level is helpful to characterize phenotypic and functional heterogeneity. In this study, based on the cell model of myelin debris phagocytosis by macrophages in vitro, the biochemical changes in macrophages were investigated using Synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy. Infrared spectrum fluctuations, principal component analysis, and cell-to-cell Euclidean distance statistical analysis of specific spectrum regions revealed dynamic and significant changes in proteins and lipids within macrophages after myelin debris phagocytosis. Thus, SR-FTIR microspectroscopy is a powerful identification toolkit for exploring biochemical phenotype heterogeneity transformation that may be of great importance to providing an evaluation strategy for studying cell functions related to cellular substance distribution and metabolism.


Survey data on Vietnamese propensity to attend periodic general health examinations.
As general living standards rise, so does the demand for periodic general health examinations (GHEs). Research on the subject, however, has reached opposing conclusions on the value of GHEs, although methodological limitations in previous works make these differences hard to resolve. Here, we present data from a socio-demographic survey of behaviours and tendencies concerning periodic GHE attendance in Vietnam. These data are shown to be suitable for evaluating the impact of demographic and socio-economic elements on regular health examinations. By presenting the methods used in this survey and by describing the enquiries mentioned in the dataset, this article aims to promote data-collecting methodologies that can help policy-makers and health communicators derive practical conclusions.


Specific modification of the functional arginine residue in soybean trypsin inhibitor (Kunitz) by peptidylarginine deiminase.
In order to elucidate the specificity of rabbit muscle peptidylarginine deiminase, which catalyzes the conversion of arginyl to citrullyl residues (Takahara, H., Oikawa, Y., and Sugawara, K. (1983) J. Biochem. (Tokyo) 94, 1945-1953), we examined the action of this enzyme on a variety of trypsin inhibitors by assay of residual trypsin-inhibiting activity. The enzyme rapidly abolished the activity of soybean trypsin inhibitor (Kunitz) (STI) in a process that was pseudo-first order with the rate dependent on enzyme concentration (second order rate constant = 5.0 X 10(4) M-1 S-1), whereas no detectable changes in activity were noted for other inhibitors tested. Inactivation of STI was due to the conversion of 1 arginine to a citrulline residue and was accompanied with a 0.2 unit decrease of the isoelectric point. There was no alteration of the molecular size and overall conformation of STI. Furthermore, analysis of modified STI indicated that arginine 63, known as the reactive site of STI, is the residue modified by peptidylarginine deiminase. Thus, peptidylarginine deiminase selectively catalyzes the deimination of the functional arginine residue of STI.


Gene expression analysis using a high-resolution DNA microarray of peripheral whole blood immediately before and after leukocytapheresis for rheumatoid arthritis.
Leukocytapheresis (LCAP) is a safe, unique therapy pertaining to intractable rheumatoid arthritis (RA) even in cases of drug allergy or infectious states. To investigate how to represent LCAP efficacy, we have conducted gene expression analyses from the peripheral blood of RA patients treated with non-woven polyethylene terephthalate filters. Peripheral blood samples were collected immediately before and after treatment from eight RA patients who received LCAP. Among these patients, all of them achieved 20% improvement in the core set of the American College of Rheumatology (ACR20), and thus, they were confirmed as LCAP responders. Gene expression analysis was done with a high-resolution DNA microarray. The results of each of the two groups' gene expression values (immediately before and after LCAP) were calculated using Welch's t-test. Calculations were performed with a statistical software R.basic package: if the P-value was less than 0.05, this was seen as a significant change. In a comparison of 25,370 gene expressions, the number of genes showing a P-value < 0.05 in the upregulating group was 2110, and in the downregulating group it was 1864. The results of pathway analysis using the MetaCore program indicate that gene groups work for cytoskeletal remodeling are upregulated, and genes related to immune responses, such as antigens presenting via major histocompatibility complex class I and II, are downregulated just after LCAP. These findings may relate to LCAP efficacy for RA patients, but this needs further investigation.


Estimated Incidence of Coronavirus Disease 2019 (COVID-19) Illness and Hospitalization-United States, February-September 2020.
In the United States, laboratory-confirmed coronavirus disease 2019 (COVID-19) is nationally notifiable. However, reported case counts are recognized to be less than the true number of cases because detection and reporting are incomplete and can vary by disease severity, geography, and over time. To estimate the cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, symptomatic illnesses, and hospitalizations, we adapted a simple probabilistic multiplier model. Laboratory-confirmed case counts that were reported nationally were adjusted for sources of underdetection based on testing practices in inpatient and outpatient settings and assay sensitivity. We estimated that through the end of September, 1 of every 2.5 (95% uncertainty interval [UI]: 2.0-3.1) hospitalized infections and 1 of every 7.1 (95% UI: 5.8-9.0) nonhospitalized illnesses may have been nationally reported. Applying these multipliers to reported SARS-CoV-2 cases along with data on the prevalence of asymptomatic infection from published systematic reviews, we estimate that 2.4 million hospitalizations, 44.8 million symptomatic illnesses, and 52.9 million total infections may have occurred in the US population from 27 February-30 September 2020. These preliminary estimates help demonstrate the societal and healthcare burdens of the COVID-19 pandemic and can help inform resource allocation and mitigation planning.


Sensillum development in the absence of cell division: the sensillum phenotype of the Drosophila mutant string.
We have investigated sensillum development in Drosophila embryos homozygous for mutations in the locus string (stg). In these embryos, cell division is blocked following blastoderm formation. This permits a study of the differentiative fate of undivided precursor cells, in particular those giving rise to the larval sensory organs (sensilla). Of the different cell fates normally represented in the sensilla (i.e., sensory neuron, thecogen cell, trichogen cell, tormogen cell, glia cell), only the phenotype of sensory neurons is expressed morphologically in stg embryos, suggesting that the neuronal fate predominates over the fates of the nonneuronal accessory cells. Consistent with this finding, the P element-lacZ insertion A1-2nd-29, which is a marker for trichogen and tormogen cells in the wild-type embryo, is not expressed in the body wall of the stg embryo. Some sensillum precursor cells appear to express a mixed fate in stg mutants: They express antigens (recognized by the monoclonal antibodies 22C10 and 21A6) which in the wild-type appear in separate cells (sensory neurons and thecogen cell, respectively). The differentiation of undivided cells in stg embryos is not restricted to the peripheral nervous system; in all types of tissues analyzed in this study (e.g., epidermis, intestine, muscle, CNS), precursor cells express characteristics normally exhibited by their progeny.


Climate: how unusual is today's solar activity?
To put global warming into context requires knowledge about past changes in solar activity and the role of the Sun in climate change. Solanki et al. propose that solar activity during recent decades was exceptionally high compared with that over the preceding 8,000 years. However, our extended analysis of the radiocarbon record reveals several periods during past centuries in which the strength of the magnetic field in the solar wind was similar to, or even higher than, that of today.


Intracellular signal transduction pathways in sponges.
Sponges are the lowest multicellular eukaryotic organisms. Due to the relatively low specialization, and concomitantly the high differentiation and dedifferentiation potency of their cells, the sponge cell system has proven to be a useful model to study the mechanism of cell-cell adhesion on molecular levels. Results of detailed biochemical and cell biological studies with the main cell adhesion molecules, the aggregation factor (AF) and the aggregation receptor, led to the formation of the modulation theory of cell adhesion. The events of cell adhesion are contigent on a multiplicity of precisely coordinated intracellular signal transduction pathways. Using the marine sponge Geodia cydonium we showed that during the initial phase of cell-cell contact the AF causes a rapid stimulation of the phosphatidylinositol pathway, resulting in an activation of protein kinase C and a subsequent phosphorylation of DNA topoisomerase II. As one consequence of these processes, the cells undergo a phase of high DNA synthesis. However, at later stages, the AF loses its mitogenic activity; this function is then taken over by the matrix lectin. During this switch, the lectin receptor associates in the plasma membrane with the ras oncogene product. The description of these processes is subject of this review article.


Distinct models of induced hyperactivity in zebrafish larvae.
The analysis of behavioural hyperactivity can provide insights into how perturbations in normal activity may be linked to the altered function of the nervous system and possibly the symptoms of disease. As a small vertebrate zebrafish have numerous experimental advantages that are making them a powerful model for these types of studies. While the majority of behavioural studies have focused on adult zebrafish, it has become apparent that larvae can also display complex stereotypical patterns of behaviour. Here we have used three compounds (pentylenetetrazole (PTZ), aconitine and 4-aminopyridine) that have different neuronal targets (GABA, sodium and potassium channels), to induce distinct patterns of hyperactivity in larvae. Our studies have revealed that each compound produces a number of distinct concentration-dependent activity patterns. This work has shown for the first time that at sub-convulsive concentrations, PTZ can reverse the normal behavioural response to alternating periods of light and dark in zebrafish larvae. It also appears that both PTZ and 4-aminopyridine produce distinct changes in the normal startle response patterns immediately following light/dark transitions that may be the result of an elevation in stress/anxiety. Aconitine produces a general elevation in activity that eliminates the normal response to light and dark. In addition to differences in the patterns of behaviour each compound also produces a unique pattern of c-fos (an immediate early gene) expression in the brain. While more work is required to make direct links between region specific neuronal activity and individual behaviours, these models provide a framework with which to study and compare mechanistically different types of inducible behaviours.


Characterization of store-operated Ca2+ channels in pancreatic duct epithelia.
Store-operated Ca2+ channels (SOCs) are activated by depletion of intracellular Ca2+ stores following agonist-mediated Ca2+ release. Previously we demonstrated that Ca2+ influx through SOCs elicits exocytosis efficiently in pancreatic duct epithelial cells (PDEC). Here we describe the biophysical, pharmacological, and molecular properties of the duct epithelial SOCs using Ca2+ imaging, whole-cell patch-clamp, and molecular biology. In PDEC, agonists of purinergic, muscarinic, and adrenergic receptors coupled to phospholipase C activated SOC-mediated Ca2+ influx as Ca2+ was released from intracellular stores. Direct measurement of [Ca2+] in the ER showed that SOCs greatly slowed depletion of the ER. Using IP3 or thapsigargin in the patch pipette elicited inwardly rectifying SOC currents. The currents increased ∼8-fold after removal of extracellular divalent cations, suggesting competitive permeation between mono- and divalent cations. The current was completely blocked by high doses of La3+ and 2-aminoethoxydiphenyl borate (2-APB) but only partially depressed by SKF-96365. In polarized PDEC, SOCs were localized specifically to the basolateral membrane. RT-PCR screening revealed the expression of both STIM and Orai proteins for the formation of SOCs in PDEC. By expression of fluorescent STIM1 and Orai1 proteins in PDEC, we confirmed that colocalization of the two proteins increases after store depletion. In conclusion, basolateral Ca2+ entry through SOCs fills internal Ca2+ stores depleted by external stimuli and will facilitate cellular processes dependent on cytoplasmic Ca2+ such as salt and mucin secretion from the exocrine pancreatic ducts.


PROMIS Physical Function Short Forms Display Item- and Scale-Level Characteristics at Least as Good as the Roland Morris Disability Questionnaire in Patients With Chronic Low Back Pain.
To compare dimensionality, item-level characteristics, scale-level reliability, and construct validity of PROMIS Physical Function short forms (PROMIS-PF) and 24-item Roland Morris Disability Questionnaire (RMDQ-24) in patients with chronic low back pain (LBP). Cross-sectional study. Secondary care center for rehabilitation and rheumatology. Patients with nonspecific LBP ≥3 months (N=768). Mean age was 49±13 years, 77% were female, and 54% displayed pain for more than 5 years. Not applicable. Dutch versions of the 4-, 6-, 8-, 10-, and 20-item PROMIS-PF and of the RMDQ-24. PROMIS-PF-6, PROMIS-PF-8, and RMDQ-24 exhibited sufficient unidimensionality (confirmatory factor analysis: comparative fit index>0.950, Tucker-Lewis index>0.950, root means square error of approximation<0.060), whereas the other instruments did not. All instruments were free of local dependence except PROMIS-PF-20 with 4 item pairs with clear residual correlations. Mokken scale analysis found 1 nonmonotone item for PROMIS-PF-20 and 8 for RMDQ-24 (ie, the probability of endorsing these items was not increasing with increasing level on the underlying construct). PROMIS-PF-20 displayed 2 misfitting items (S-χ2P value>.001). Two-parameter item response theory models found 2 items with low discrimination for RMDQ-24. All other instruments had adequate fit statistics and item parameters. PROMIS-PF-20 displayed the best scale-level reliability. Construct validity was sufficient for all instruments as all hypotheses on expected correlations with other instruments and differences between relevant subgroups were met. PROMIS-PF-6, PROMIS-PF-8, and RMDQ-24 exhibited better unidimensionality, whereas PROMIS-PF-4, PROMIS-PF-6, PROMIS-PF-8, and PROMIS-PF-10 showed superior item-level characteristics. PROMIS-PF-20 was the instrument with the best scale-level reliability. This study warrants assessment of other measurement properties of PROMIS-PF short forms in comparison with disease-specific physical functioning instruments in LBP.


Comparing domestic versus imported apples: a focus on energy use.
The issue of whether food miles are a relevant indicator for the environmental impacts associated with foods has received significant attention in recent years. It is suggested here that issues other than the distance travelled need to be considered. The argument is presented by illustrating the case for the provision of apples. The effects of variability in primary energy requirements for apple cultivation and for other life cycle stages, seasonality (timing of consumption) and loss of produce during storage are studied in this paper, by comparing apples from different supplier countries for consumption in Europe. Data sources for primary energy use (PEU) of apple production are identified ranging from 0.4-3.8 MJ/kg apples for European and Southern American countries and 0.4-0.7 MJ/kg for New Zealand. This variability is related to different yields and producer management practices in the different countries. Storage loss may range from 5% to 40% for storage periods between 4 and 10 months, and this has a significant effect on the results (e.g. increasing the total PEU by 8-16% when stored for 5-9 months in Europe as compared with a no loss and no storage situation). The storage periods and related storage losses change markedly through the year for imported (i.e. non-European) versus European apples. The timing of consumption and related storage losses need to be included in the assessment, as this affects the order of preference for locally sourced versus imported apples. The variability in energy requirements in different life cycle stages, but particularly for the fruit production stage, is also significant in this comparative analysis. Overall, it seems that there are similarities in the total PEU ranges for European and New Zealand apples during the Southern Hemisphere's apple season (European spring and summer). However, during the European autumn and winter (Northern Hemisphere apple season) PEU values are generally higher for apples imported from the Southern Hemisphere compared with European apples consumed in Europe. However, this latter observation may not hold true where apples for consumption in one European country are imported from another European country, because energy use for road transportation has a significant influence on the result. Future studies comparing alternative sources of fresh produce need to account for ranges of data for the fruit production and storage stages, which reflect the seasonality of production.


Trans-fatty acid content of food products in Spain in 2015.
To ascertain the content of trans-fatty acids (TFA) in food products in Spain in 2015 and assess trends in TFA content since 2010. We analysed the fat content of 277 food products purchased in Spanish supermarkets in 2015 and calculated both the total fat and TFA content and the proportion of TFA to total fats. The results obtained in 2015 were compared to those yielded by a similar study in 2010. In 2015, the majority of food products studied had a TFA content of less than 0.2g/100g product, and a TFA/total fat ratio of less than 2%. No significant increases were found compared to 2010. Food groups with a higher TFA content were dairy products of possible natural origin. TFA content in Spain is low and has significantly fallen since 2010.


Periocular hidradenoma papilliferum.
Hidradenoma is a benign adnexal neoplasm originating from the apocrine sweat gland, and is almost exclusively detectable in the skin of the anogenital area of middle-aged white females after puberty. Ectopic hidradenoma papilliferum, which involves the skin away from the anogenital region, is exceedingly rare, and can also affect males. We report a female patient with a lesion (dating back to childhood) close to the medial end of the left eyebrow and overriding the anterior medial part of superior orbital rim. The lesion was completely excised and had not reoccurred during over four years of follow-up.


Otoacoustic emissions for monitoring aminoglycoside-induced ototoxicity in children with cystic fibrosis.
To investigate whether transient-evoked and distortion-product (DP) otoacoustic emissions (OAEs) are more sensitive than pure-tone audiometry (PTA) in revealing gentamicin-induced ototoxicity in children with cystic fibrosis (CF). Prospective case-control study. Tertiary referral audiologic center in conjunction with an academic pediatric CF unit. The study group consisted of a consecutive sample of 12 audiologically normal children with CF and a history of gentamicin exposure (CF-gentamicin group). The control groups consisted of 8 age-matched children with CF and 11 age-matched healthy volunteers. No member of the control groups had a history of aminoglycoside exposure. Members of the CF-gentamicin study group received 4 mg/kg of gentamicin per day for a mean of 14.2 days (range, 11-29 days). The PTA thresholds (250-8000 Hz) were the criterion standard. Transient-evoked OAEs' reproducibility at 5 frequency bands (800, 1600, 2400, 3200, and 4000 Hz) and total emission level were measured, as were DP-audiogram (DP-gram) amplitude (1001-6299 Hz), input-output function dynamic range, and detection thresholds at 4004, 6006, and 7996 Hz. Baseline measurements were compared between groups examining the effect of CF and previous gentamicin exposure (2-way analysis of variance). For the CF-gentamicin group, baseline measurements were compared with those at the end of the last gentamicin treatment (paired t test). The PTA findings were normal for all groups at baseline and remained normal in the CF-gentamicin group after treatment. The CF-gentamicin group had significantly lower transient-evoked OAEs total emission level, DP-gram amplitude at 5042 Hz, and input-output dynamic ranges with higher detection thresholds in all frequencies compared with both control groups, which was attributed completely to previous gentamicin exposure (P<.05). After treatment, further decreases in total emission levels, DP-gram amplitudes (>3000 Hz), and dynamic ranges were noted, with increased detection thresholds (P<.05). Otoacoustic emissions measurement (especially of DP OAEs) proved more sensitive than PTA in revealing minor cochlear dysfunction after gentamicin exposure. They should be used for monitoring patients receiving ototoxic factors such as aminoglycosides.


Another interpretation of the Goldman-Hodgkin-Katz equation based on Ling's adsorption theory.
According to standard membrane theory, the generation of membrane potential is attributed to transmembrane ion transport. However, there have been a number of reports of membrane behavior in conflict with the membrane theory of cellular potential. Putting aside the membrane theory, we scrutinized the generation mechanism of membrane potential from the view of the long-dismissed adsorption theory of Ling. Ling's adsorption theory attributes the membrane potential generation to mobile ion adsorption. Although Ling's adsorption theory conflicts with the broadly accepted membrane theory, we found that it well reproduces experimentally observed membrane potential behavior. Our theoretical analysis finds that the potential formula based on the GHK eq., which is a fundamental concept of membrane theory, coincides with the potential formula based on Ling's adsorption theory. Reinterpreting the permeability coefficient in the GHK eq. as the association constant between the mobile ion and adsorption site, the GHK eq. turns into the potential formula from Ling's adsorption theory. We conclude that the membrane potential is generated by ion adsorption as Ling's adsorption theory states and that the membrane theory of cellular potential should be amended even if not discarded.


Gelatin-thrombin-based hemostatic sealant for intraoperative bleeding in vascular surgery.
Vascular surgical procedures may be prolonged because of intraoperative bleeding that is not easily controlled by cautery or suture ligation. This trial compared the ability of a new hemostat, FloSealTM Matrix (FM), with a known hemostat, Gelfoam(R) plus thrombin (GT), to control intraoperative bleeding. Patients undergoing vascular surgery procedures at four institutions were entered in the trial. After a bleeding site was identified, patients were randomized to one of the study agents: (1) FM, a cross-linked gelatin of bovine origin combined with thrombin, or (2) GT. The assigned agent was applied and the site observed for bleeding at 1, 2, 3, 6, and 10 min. The primary end point was cessation of bleeding within 10 min for the first identified site treated. Secondary end points were cessation of bleeding within 10 min for all sites and time to cessation of bleeding. Patients were assessed for morbidity at 30 days and 6-8 weeks after the operation. Analysis was performed on an intent-to-treat basis for analysis of hemostasis at 10 min and on protocol-valid patients for analysis of time to hemostasis. From our results we concluded that for patients undergoing vascular surgery procedures, the new topical hemostat, FloSeal Matrix, provides more rapid and effective hemostasis than Gelfoam plus thrombin.


Correction: 'We are the change'-An innovative community-based response to address self-stigma: A pilot study focusing on people living with HIV in Zimbabwe.
[This corrects the article DOI: 10.1371/journal.pone.0210152.].


Dopamine deficiency increases synchronized activity in the rat subthalamic nucleus.
Abnormal neuronal activity in the subthalamic nucleus (STN) plays a crucial role in the pathophysiology of Parkinson's disease (PD). In this study we investigated changes in rat STN neuronal activity after 28days following the injection of 6-OHDA in the substantia nigra pars compacta (SNc). This drug provoked a lesion of SNc that induced a dopamine (DA) depletion assessed by changes in rotating capacity in response to apomorphine injection and by histological analysis. By means of extracellular recordings and waveshape spike sorting it was possible to analyze simultaneous spike trains and compute the crosscorrelations. Based on the analysis of the autocorrelograms we classified four types of firing patterns: regular (Poissonian-like), oscillatory (in the range 4-12Hz), bursty and cells characterized by a long refractoriness. The distribution of unit types in the control (n=61) and lesioned (n=83) groups was similar, as well as the firing rate. In 6-OHDA treated rats we observed a significant increase (from 26% to 48%) in the number of pairs with synchronous firing. These data suggest that the synchronous activity of STN cells, provoked by loss of DA cells in SNc, is likely to be among the most significant dysfunctions in the basal ganglia of Parkinsonian patients. We raise the hypothesis that in normal conditions, DA maintains a balance between funneling information via the hyperdirect cortico-subthalamic pathway and parallel processing through the parallel cortico-basal ganglia-subthalamic pathways, both of which are necessary for selected motor behaviors. This article is part of a Special Issue entitled 'Neural Coding'.


Rheumatologic manifestations of gastrointestinal diseases.
One of the most significant extraintestinal manifestations of gastrointestinal diseases is rheumatologic disorders. The gastrointestinal diseases with rheumatologic manifestations can be divided into two major categories: intestinal disorders and disorders of the liver, biliary tree, and pancreas. The cause of diseases in each of these categories is different. Although intestinal permeability and immune responsiveness are frequently implicated in disorders of the intestine, diseases of the liver, biliary tree, and pancreas usually involve the production of autoantibodies, cytokines, or enzymes. Treatment of rheumatologic complications frequently involves therapy directed at the underlying gastrointestinal disease.


Heat shock protein 90 (Hsp90) regulates the stability of transforming growth factor beta-activated kinase 1 (TAK1) in interleukin-1beta-induced cell signaling.
Heat shock protein 90 (Hsp90) is an abundantly and ubiquitously expressed chaperone with majority of client proteins which act as signal molecules. Transforming growth factor beta-activated kinase 1 (TAK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK), and is essential in interleukin-1beta (IL-1beta) triggered signaling pathways. In the present study, we found that Hsp90 plays an important role in regulating IL-1beta signaling by keeping TAK1 stability. The results showed that the specific inhibitor geldanamycin (GA) of Hsp90 dramatically inhibited IL-1beta stimulated TAK1-MAPKs and TAK1-nuclear factor-kappaB (NF-kappaB) activation, resulting in the decrease of cyclooxygenase-2 (COX-2) protein expression. Silencing Hsp90 expression through RNA interference (RNAi) also down-regulated TAK1, as well as attenuated IL-1beta induced phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and p38 MAPKs, and degradation of IkappaBalpha. The same results were obtained in T6RZC stable cells which initiated IL-1beta-induced cell signaling at the level of the oligomerization and ubquitination of TNF receptor-associated factor 6 (TRAF6). We further found that Hsp90 formed a complex with TAK1 via its N-terminal domain and GA destabilized TAK1 and induced TAK1 degradation through proteasome pathway. Taken together our results demonstrate that Hsp90 regulates IL-1beta-induced signaling by interacting with TAK1 and maintaining the stability of TAK1, suggesting that Hsp90 might act as the chaperone of TAK1 in immune and inflammatory responses related with IL-1 signal cascades.


PLXNA1 and PLXNA3 cooperate to pattern the nasal axons that guide gonadotropin-releasing hormone neurons.
Gonadotropin-releasing hormone (GnRH) neurons regulate puberty onset and sexual reproduction by secreting GnRH to activate and maintain the hypothalamic-pituitary-gonadal axis. During embryonic development, GnRH neurons migrate along olfactory and vomeronasal axons through the nose into the brain, where they project to the median eminence to release GnRH. The secreted glycoprotein SEMA3A binds its receptors neuropilin (NRP) 1 or NRP2 to position these axons for correct GnRH neuron migration, with an additional role for the NRP co-receptor PLXNA1. Accordingly, mutations in SEMA3A, NRP1, NRP2 and PLXNA1 have been linked to defective GnRH neuron development in mice and inherited GnRH deficiency in humans. Here, we show that only the combined loss of PLXNA1 and PLXNA3 phenocopied the full spectrum of nasal axon and GnRH neuron defects of SEMA3A knockout mice. Together with Plxna1, the human orthologue of Plxna3 should therefore be investigated as a candidate gene for inherited GnRH deficiency.


High-frequency ultrasound treatment of sludge: combined effect of surfactants removal and floc disintegration.
Ultrasounds represent an effective technology in many research fields. In sewage sludge treatment, low-frequency ultrasound, particularly at 20 kHz, are widely used for sludge disintegration before the anaerobic digestion, while in the last years novel application of high-frequency ultrasound regards the decontamination of water and wastewater through sonochemical reactions. The innovative approach presented in this paper is the treatment of sewage sludge with ultrasound at 200 kHz for obtaining efficient sludge disintegration and the removal of the linear alkylbenzenesulphonates (LAS) at the same time. Results of the sonolysis experiments showed that native LAS degradation up to 40% can be achieved with low power input in less than 1h. The degradation pattern was different for each LAS homologue (from C10 to C13), because of their physical-chemical properties, in particular as regards the alkyl chain length. This high-frequency ultrasound irradiation resulted effective also in terms of floc disintegration and soluble organic matter release, in particular for energy inputs higher than 30,000 kJ/kg TS. The disrupting effect of the 200 kHz treatment was also evaluated by microscope analyses and determination of the extracellular polymeric substances release in the liquid phase.


Ethics of human testing.
What should one do, and why? Anyone asking such questions--and everyone does so hundreds of time each day--is concerned with ethics. Product development and testing raise many ethical questions. Particularly since the rise of 'green consumerism', these are of increasing concern to people outside the cosmetics industry, and so should be of interest to those inside it. The major problem seems to be that of reaching agreement on moral and ethical issues. Overcoming this problem involves investigating what is meant by 'ethics', and how decisions depend not on facts but on 'facts-as-perceived'. These in turn depend on many factors, with one's philosophy being the most fundamental. The range of philosophical options is reviewed and it is proposed that wider discussion is the only just way to achieve agreement. Yet some things are not negotiable. There are certain key moral concepts in terms of which discussion must take place for it to be relevant. In ethics of human testing, 'respect for others', that is, avoiding exploitation, is the principal one. Some synthesis of the key moral concepts like that of Immanuel Kant is therefore recommended as the soundest and most widely acceptable basis for the necessary discussion. Defining the responsible use of human subjects covers a range of issues, moral, historical, legal and professional. For example, there may be ethical difficulties in deliberate damage induction as in SPF and irritancy testing. But above all, to avoid exploitation, there is a moral and also a legal requirement that subjects are truly volunteers. This is the basis of the concept of 'informed consent', required but not generally explained in current professional codes of practice. It is unjustified to exploit those who may be under duress, such as 'in-house volunteers' and those with low incomes. Hence in conclusion, criteria for obtaining valid informed consent are briefly reviewed. By considering issues such as these, we can help ensure that cosmetic scientists are true professionals, that is, those who recognise and are concerned with the ethical basis of their work.


A randomized double blind study of two oral contraceptives.
To study the question of whether one brand of oral contraceptives may be as acceptable as another for use of publicly-assisted family planning programs, a double blind study of two well-known brands, Ovral and Norinyl, was undertaken in Costa Rica and Trinidad. The pills were randomly assigned to 1,200 women. Common side effects - nausea, dizziness, vomiting, headaches - were associated with both Norinyl and Ovral. Differences in event rates for these conditions were much more marked by country than by the pill used. Ovral was associated with increases in skin problems, notably chloasma, in Cost Rica. A higher percentage of women using Norinyl reported intermenstrual bleeding and spotting in both countries. In Costa Rica continuation rates for Norinyl were adversely affected by this. With these exceptions there appear to be no important differences between the brands that would affect their use in family planning programs.


Histopathologic grading and DNA ploidy in relation to survival among 206 adult astrocytic tumor patients.
The authors studied the benefit of performing histopathologic grading and DNA ploidy characterization with respect to patient survival in a series of 206 astrocytomas (AST) for which they obtained 134 complete clinical follow-ups. The material analyzed came from archival material, i.e., formalin-fixed paraffin-embedded tissues. DNA ploidy was assessed by means of a cell image processor computing the integrated optical density (IOD) on Feulgen-stained nuclei. Results showed that histopathologic diagnosis in three grades, i.e., AST, anaplastic astrocytoma (ANA), and glioblastoma multiforme (GBM), had a significant prognostic value. Patients with AST showed a mean survival time (between histopathologic diagnosis and death) of more than 36 +/- 6 months (AST versus ANA or GBM) (P less than 0.001). Patients with ANA and GBM showed a mean survival time of 15 +/- 2 and 10 +/- 1 months, respectively, (ANA versus GBM) (P less than 0.05). Patient age strongly correlated with survival. Patients younger than 40 years of age had a mean survival time of 20 +/- 4 months. Patients between 41 and 60 years of age had a mean survival time of 12 +/- 2 months, and patients older than 60 years of age had a mean survival time of 11 +/- 1 months. Considering DNA ploidy characterization, the authors noticed that aneuploid ANA (DNA index [DI] more than 1.30) were associated with a significantly higher mean patient survival time compared with that associated with euploid ANA. In contrast, the authors did not find this in either of the groups with AST and GBM. Recognizing six DNA histogram types (diploid, triploid, tetraploid, hyperdiploid, hypertriploid, and polymorphic), the authors observed that hypertriploid tumors were associated with greater patient survival compared with what happened in the cases of the five other DNA histogram types. This was true with respect to the three AST histopathologic types. Thus, DNA ploidy determination seemed helpful in characterizing aggressiveness in adult AST.


Mosaic tetracycline resistance genes and their flanking regions in Bifidobacterium thermophilum and Lactobacillus johnsonii.
For the first time, mosaic tetracycline resistance genes were identified in Lactobacillus johnsonii and in Bifidobacterium thermophilum strains. The L. johnsonii strain investigated contains a complex hybrid gene, tet(O/W/32/O/W/O), whereas the five bifidobacterial strains possess two different mosaic tet genes: i.e., tet(W/32/O) and tet(O/W). As reported by others, the crossover points of the mosaic tet gene segments were found at similar positions within the genes, suggesting a hot spot for recombination. Analysis of the sequences flanking these genes revealed that the upstream part corresponds to the 5' end of the mosaic open reading frame. In contrast, the downstream region was shown to be more variable. Surprisingly, in one of the B. thermophilum strains a third tet determinant was identified, coding for the efflux pump Tet(L).


[Clinical efficiency of candesatran depends on angiotension II receptor, type 1 gene polymorphism].
Frequency of A and C alleles of the polymorphic gene (A1166C) of first type angiotension II receptor in healthy men of Poltava region was 68% and 32% accordingly, the AA, AC and CC genotypes made up 51%,34% and 15% correspondingly. The patients with essential hypertension had the following figures: 44% and 56%; 23%, 52% and 25% accordingly. The presence of C allele has been established to lead to more severe course and an early development of essential hypertension. Candesatran monoterapy is more effective for treatment patients having C allele.


Multiple pulmonary arterial aneurysms in Behçet's disease: clinical and radiologic remission after cyclophosphamide and corticosteroid therapy.
Behçet's disease (BD) with pulmonary arterial aneurysm is rare and often associated with a poor prognosis. But there is also a chance that the aneurysm may completely resolve with medical therapy. A 39-year-old man presented with fever, malaise, bilateral chest pain, recurrent oral ulcers, and hemoptysis. The chest radiograph showed a round opacity in the right hilum. Computed tomography and magnetic resonance angiography (MRA) further revealed multiple, bilateral pulmonary arterial aneurysms consistent with the diagnosis of BD. The patient was started on a course of cyclophosphamide and corticosteroid therapy that resulted in cessation of his symptoms and complete resolution of radiologic findings. The chest radiograph and MRA reverted to normal on long-term follow-up. He is still alive and symptom-free 20 months after diagnosis.


Utilization of Carica papaya latex on coating of SPIONs for dye removal and drug delivery.
Latex, a milky substance found in a variety of plants which is a natural source of biologically active compounds. In this study, Latex was collected from raw Carica papaya and was characterized using UV-Vis, FTIR and GC-MS analyses. Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) were synthesized, coated with C. papaya latex (PL-Sp) and characterized using UV-Vis, FT-IR, SEM-EDX, XRD, VSM and Zeta potential analyses. SPIONs and latex coated SPIONs (PL-Sp) were used in batch adsorption study for effective removal of Methylene blue (MB) dye, where (PL-Sp) removed MB dye effectively. Further the PL-Sp was used to produce a nanoconjugate loaded with curcumin and it was characterized using UV-Vis spectrophotometer, FT-IR, SEM-EDX, XRD, VSM and Zeta potential. It showed a sustained drug release pattern and also found to have good antibacterial and anticancer activity.


Efficacy of regional blocks or local anaesthetic infiltration for analgesia after caesarean delivery: a network meta-analysis of randomised controlled trials.
Caesarean delivery is common and can cause severe postoperative pain but injection of local anaesthetic at various sites for regional blocks or local anaesthetic infiltration may reduce this. We aimed to compare and rank these sites. We searched PubMed, Google Scholar, EMBASE and CENTRAL to June 2021 for randomised controlled trials and performed a random-effects Bayesian model network meta-analysis. The primary outcome was dose of parenteral morphine equivalents in the first 24 postoperative hours. We used surface under cumulative ranking probabilities to order techniques. We analysed 114 trials (8730 participants). The ordered mean (95% credible interval) reduction in morphine equivalents, from 34 mg with placebo, were as follows: ilio-inguinal 15 (1-32) mg; ilio-inguinal-iliohypogastric 13 (6-19) mg; transversalis fascia 11 (4-26) mg; erector spinae 11 (10-32); transverse abdominis 9 (4-13) mg; wound catheter infusion 8 (2-15) mg; quadratus lumborum 8 (1-15) mg; wound infiltration 8 (2-13) mg; and no intervention -4 (-10 to 2) mg. Ordered efficacies for injection sites were different for other relevant outcomes, including pain (to 4-6 h and to 24 h) and time to rescue analgesia: there was no single preferred route of injection. The ordered mean (95% credible interval) reduction in dynamic pain scores (0-10 scale) at 24 h compared with placebo were as follows: wound infusion 1.2 (0.2-2.1); erector spinae 1.3 (-0.5 to 3.1); quadratus lumborum 1.0 (0.1-1.8); ilio-inguinal-iliohypogastric 0.6 (-0.5 to 1.8); transverse abdominis 0.6 (-0.1 to 1.2); wound infiltration 0.5 (-0.3 to 1.3); transversalis fascia -0.8 (-3.4 to 1.9); ilio-inguinal -0.9 (-3.6 to 1.7); and no intervention -0.8 (-1.8 to 0.2). We categorised our confidence in effect sizes as low or very low.


Electrophysiological evidence for axonal sprouting of cerebellothalamic neurons in kittens after neonatal hemicerebellectomy.
Changes in cerebello-cerebral responses after hemicerebellectomy were investigated in 19 kittens by laminar field potential analysis in the cerebral cortex. In all of 11 kittens operated on before 11 days of age and kept for more than 16 days after surgery, marked cerebello-cerebral responses were evoked not only contralaterally as in intact animals but also ipsilaterally. In none of 16 intact kittens ranging in age from 2 to 14 days was there a detectable response in the cerebral cortex to stimulation of the ipsilateral cerebellar nucleus. Pathways responsible for the ipsilateral cerebello-cerebral responses were investigated by destruction of the thalamic VL nucleus and by unitary recordings from cerebellar nuclear neurons with antidromic activation on stimulation of the thalamus. From the latter investigation, a remarkable increase in the number of neurons with bilateral projections upon the thalamus was seen in the surgically treated kittens. Stimulation of the VL thalamic nucleus contralateral to the remaining hemicerebellum induced a marked response in the frontal cortex not only ipsilaterally as in intact animals but also contralaterally. The latter response was considered to be mediated by an axon reflex of the bilateral projection neurons. Destruction of that VL nucleus abolished the contralateral cerebello-cerebral response whereas the ipsilateral cerebello-cerebral response remained unchanged. It is concluded, that in kittens, hemicerebellectomized in the early postnatal period, nuclear neurons in the remaining cerebellum sprout axon collaterals growing into the thalamus ipsilateral to the spared hemicerebellum and that these sprouting axon collaterals make synpases on the thalamic neurons projecting upon the cerebral cortex.


An Individualized, Data-Driven Biological Approach to Attention-Deficit/Hyperactivity Disorder (ADHD) Heterogeneity.
Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed mental health disorder in childhood, however, there is well-established heterogeneity in both the presentation of ADHD symptoms and secondary characteristics across the literature. Existing Diagnostic and Statistical Manual of Mental Disorders (DSM-5) nosology has been ineffective in explaining such heterogeneity in terms of both pathophysiology and clinical trajectories. The current study investigated ADHD heterogeneity via a biologically-based, data-driven approach (k-Means algorithm). Specifically, unique biological profiles (derived from patterns of parasympathetic and sympathetic functioning) were identified and utilized as predictors of clinical presentations. Two hundred eighty-nine participants (167 youth with ADHD), ages 5 to 13 years, completed an emotion-based task while indexes of parasympathetic (i.e., respiratory sinus arrhythmia [RSA]) and sympathetic (i.e., electrodermal activity [EDA]) activity were obtained. Overall, results suggest that three distinct biological profiles among youth with ADHD are evident, with biological profiles differing in regulation and arousal levels during emotionally evocative contexts: (Profile 1) underregulated, hyperaroused (negative contexts only), (Profile 2) typically regulated, underaroused, and (Profile 3) overregulated (positive contexts only), hyperaroused. Results are supported by several dopaminergic- and reward-based theories, integrating differing concepts across the literature, and adds biological support for existing models. Behaviorally, results may translate into differing clinical presentations, however, further work is needed. In general, youth with ADHD are heterogenous in autonomic functioning, which could have implications for synthesizing across differing theories within the literature, predicting clinical presentations, and developing targeted treatments.


Use of a chemiluminescence detector for quantitation of nitric oxide produced in assays of denitrifying enzymes.
We have developed a closed-flow system that continuously sweeps away gases evolved in enzyme assay mixtures into a commercially available oxides of nitrogen (NOx) analyzer for the quantitation of any nitric oxide present in these gases. The system enabled us to study both the stoichiometry and the kinetics of NO production by a copper-containing nitrite reductase (EC 184.108.40.206) purified from Achromobacter cycloclastes IAM 1013. In addition to its much greater sensitivity in comparison with standard gas chromatographic (GC) techniques, the method offers the advantage that NO, a very reactive free radical, is immediately swept away and quantitated, obviating the necessity for periodic manipulations and disturbances of the reaction mixture characteristic of other GC quantitations. The characteristics of the system are discussed and its utility in studies of the kinetics and stoichiometry of NO production from nitrite is confirmed by comparison with results obtained using manometric and GC techniques.


Noninvasive assessment of valvular heart disease: surgery without catheterization.
Forty-one patients underwent valve surgery at our institution based solely on clinical, M-mode echocardiographic, phonocardiographic, and external pulse recording findings without preoperative cardiac catheterization. Patients with clinical evidence of coronary artery disease were excluded from the study. Preoperatively, 83% of the patients were New York Heart Association functional class III or IV. In all patients, the noninvasive evaluation was considered sufficiently diagnostic of the nature and severity of valvular heart disease to allow surgery without preoperative catheterization. In 23 of 41 cases (group 1), cardiac catheterization was not performed due to the patients' unstable hemodynamic condition at the time surgery was being considered. In the remaining 18 patients (group 2), the probability of obtaining data at catheterization that would significantly affect management decisions was thought to be low, thus not justifying the cost and potential morbidity of this procedure. In all cases, the noninvasive diagnosis was corroborated at operation; there were no unexpected findings nor deaths related to incomplete or incorrect diagnoses. Over a followup period of 4.5 +/- 1.4 years, no patient experienced signs or symptoms of ischemic heart disease. In selected patients without anginal chest pain syndromes, appropriate and successful valve surgery may be performed on the basis of combined clinical and noninvasive evaluation without the need for cardiac catheterization.


The differential effects of intravenous anesthetics on myofilament Ca2+ sensitivity in pulmonary venous smooth muscle.
Pulmonary venous contraction can increase pulmonary capillary pressure and pulmonary edema. In the present study, we investigated the direct effects of ketamine, etomidate, thiopental, and midazolam on pulmonary venous contraction and myofilament Ca2+ sensitivity in permeabilized pulmonary venous smooth muscle (PVSM). The effects of these IV anesthetics on acetylcholine contraction were assessed in isolated canine pulmonary vein rings. Tension and [Ca2+]i were measured simultaneously in fura-2 loaded endothelium-denuded PVSM strips after being permeabilized with alpha-toxin. The effects of the IV anesthetics on tension ([Ca2+]i remains constant) in the absence or the presence of muscarinic receptor activation (acetylcholine) were assessed. The immunofluorescence technique and confocal microscopy were used to localize the cellular distribution of protein kinase C (PKC) isoforms in PVSM cells before and after the addition of ketamine. Ketamine, etomidate, and midazolam each attenuated acetylcholine contraction dose-dependently, whereas thiopental had no effect. None of the IV anesthetics alone had an effect on tension in strips at constant [Ca2+]i (i.e., they had no direct effect on myofilament Ca2+ sensitivity). Acetylcholine increased tension by 56% +/- 7% at constant [Ca2+]i. In acetylcholine-stimulated strips, etomidate, midazolam, and thiopental had no additional effect on tension at constant [Ca2+]i, whereas ketamine decreased tension by 33% +/- 3%. Activation with acetylcholine induced translocation of PKC from cytoplasm to membrane, and this effect was blocked by ketamine. Ketamine, etomidate, and midazolam each attenuated acetylcholine-induced pulmonary venous contraction. Ketamine attenuates acetylcholine contraction by inhibiting the acetylcholine-induced increase in myofilament Ca2+ sensitivity and the acetylcholine-induced translocation of PKCalpha.


[Identification of the components and products of hydrolysis in acetylleucomycin by LC-MS].
To identify the components of acetylleucomycin and its hydrolytic products by LC-MS. Acetylleucomycin was separated on a Diamonsil C18 column with 0.1 mol x L(-1) ammonium acetate-acetontrile (35 : 65) as mobile phase. The LC-MS was equipped with an electorspray ion source (ESI), which was set at the positive ion mode, and the mass spectra of each component in chromatogram were obtained with difference cone voltage. The components of acetylleucomycin and its hydrolytic products can be separated by HPLC. The components were identified according to the molecular weight and its major mass fragment ions. The major components identified in domastic acetylleucomycin were acetylleucomycin A4, A5; acetylleucomycin A1, A3; acetylleucomycin A6, A7, and acetylleucomycin A13. The hydrolytic products of acetylleucomycin were not kitasamycin, but some non-complete hydrolytic product. The method is rapid, sensitive and specific. It' s suitable to application in the fields of multi-components antibiotics analysis.


Lethal gastric rupture caused by acute gastric ulcer in a 6-year-old girl.
Gastric rupture is extremely rare in childhood beyond the neonatal period. We describe a previously healthy 6-year-old girl with a large laceration along the greater curvature on the posterior wall of the stomach. The patient was admitted to a neighboring hospital because of vertigo with 1-day history of intractable vomiting and epigastric pain. Although abdominal distension was noticed during the physical examination, muscular rigidity was not detected on palpation. Laboratory data showed severe hypotonic dehydration and moderate metabolic acidosis with hyperkalemia. She suddenly developed cardiac arrest within an hour after admission. After resuscitation, surgical consultation was obtained. Abdominal X-ray and ultrasound revealed abdominal free air and massive cloudy ascites. At laparotomy, there was a large laceration on the greater curvature of the stomach. Pathology of the gastric wall showed mucosal necrosis while the musculature remained intact consistent with an acute gastric ulcer. Since clinical condition of gastric rupture deteriorates rapidly, early diagnosis and appropriate treatment is essential for good prognosis. One should consider that ulcer formation might cause gastric rupture in childhood.


Specific transduction of the leading edge cells of migrating epithelia demonstrates that they are replaced during healing.
As wounds in stratified epithelia close, the numbers of cells at the leading edge of migration decreases. It is not known whether cells at the leading edge are continually replaced or whether some retain their position at the leading edge over time. Replication-deficient adenovirus carrying the green fluorescent protein gene was applied to corneal epithelial wounds in mice and it was found that they primarily infect the leading edge cells of healing epithelium. Eighteen hr after viral transduction, green fluorescent protein expressing cells were located in the apical layer at varying distances behind the leading edge. These data indicate that leading edge cells are replaced during healing of stratified epithelia.


Impact of cumulative risk factors for expanded criteria donors on early survival after liver transplantation.
There are various options to help overcome the organ shortage, including performing transplants using grafts from marginal donors with characteristics previously described as unacceptable because of the high risk of graft failure. Nowadays, expanded criteria donors for liver transplantation (OLT) is a strategy used routinely by many teams. Some donor features have been suggested to jeopardize initial function or survival; when these features are aggregated, they may impact prognosis. The aim of this study was to evaluate the impact of donor risk factors on early patient survival and retransplantation. Donor risk factors were considered to be older than 60 years, body mass index > 30, serum sodium level > 155 mEq/L, cold ischemia time > 12 hours, and intensive care unit stay > 4 days. We prospectively recorded data from 139 patients who underwent 152 OLT from March 2003 to May 2007. Patients were classified into four groups: I, no risk factors; II, one risk factor; III, two risk factors; IV, three or more risk factors. Retransplantation or OLT due to acute liver failure was considered to be an exclusion criterion. Early overall survival rate was 83.76%; 12 retransplantations were required (10.25%). Comparing the four groups, patient survivals (P = .41) and retransplantation rates (P = .518) were similar. In conclusion, cumulative risk factors showed no impact on early (30-day) recipient survival and or on the necessity of retransplantation after OLT.


A meta-analysis of the cumulative incidence, risk factors, and clinical outcomes associated with chronic kidney disease after liver transplantation.
Chronic kidney disease (CKD) remains a relatively common complication after liver transplantation (LT), and significantly impacts overall survival. We sought to assess the cumulative incidence, risk factors and mortality associated with post-LT CKD. CKD was defined as eGFR <60 ml/min/1.73 m2 as estimated by the Modified Diet in Renal Disease (MDRD) formula. Single-arm meta-analysis was done to evaluate the cumulative incidence of CKD at 1-, 3-, and 5-year timepoints post-LT. Risk factors for CKD were evaluated using hazard ratios (HR). Twenty-one studies involving 44 383 patients were included. Cumulative incidence of stage 3-5 CKD was 31.44% (CI 0.182-0.447), 36.71% (CI 0.188-0.546), and 43.52% (CI 0.296-0.574) at 1, 3, and 5 years after LT, respectively. Stage 5 CKD cumulative incidence increased from 0.274% (CI 0.001-0.005) at 1 year to 2.06% (CI 0.009-0.045) at 5 years post-LT. Age, female sex, diabetes, and peri-operative acute kidney injury (AKI) were significant risk factors for CKD. Stage 4-5 CKD was associated with a decrease in overall survival (HR 3.23, 95% CI 1.74-5.98, P < 0.01). CKD after LT is relatively common, and is associated with significantly reduced overall survival. Identification of patients at high risk of developing CKD allows physicians to prophylactically use renal-sparing immunosuppression which may be crucial in achieving desirable clinical outcomes.


Mixed Plasmodium falciparum infections and its clinical implications in four areas of the Brazilian Amazon region.
The aim of this study was to assess the prevalence pattern of mixed-Plasmodium falciparum malaria infections in Brazil by molecular diagnosis and to address its clinically important features. DNA was extracted from 115 thick blood film P. falciparum human blood positive samples using the phenol-chloroform method, followed by a semi-nested PCR protocol with species-specific primers. Seventy-three percent of P. falciparum single infections and 26.95% of mixed infections were found. Amongst mixed infections, the majority was double infection (96.77%). Our results suggest that the prevalence of one species over the other can be important on weakening P. falciparum malaria clinical symptoms. We confirm that P. falciparum co-infections frequently occur in Brazilian malaria endemic areas, with underestimated diagnosis. The results point to the need of improving microscopy or changing for another accurate diagnosis technique to differentiate among human malaria species, as this is essential to choose the best treatment and control measure for malaria. More investigations are necessary in order to clarify the role of mixed-infections in the severity of P. falciparum disease.


In situ studies on crassulacean acid metabolism in Sedum acre L. and Sedum mite Gil.
CO2 exchange, the diurnal variations in the levels of malic, citric and isocitric acid, and the labelling pattern after 14CO2 fixation were measured in Sedum acre and Sedum mite growing in situ. As predicted from laboratory experiments, drought changed the gas exchange pattern from a C3 type to a crassulacean acid metabolism (CAM) type. This shift correlated with the development of a diurnal rhythm in the malic acid content. The results of 14CO2 pulse-chase experiments suggest that in well-watered plants a CAM pattern of carbon flow already exists; hence water stress might enhance latent CAM rather than induce it. The in situ CAM performance by the Sedum species appeared to be highly susceptible to modulation by season and external factors, particularly light and temperature.CAM did not substantially contribute to total carbon gain in S. acre and S. mite. During most of their lifecycles the plants grow under conditions that favour CO2 uptake by the C3 pathway rather than by CAM. Hence, despite a capability to feature CAM, the δ13C values found in S. acre and S. mite are those of C3 plants.


Identification of a novel non-ATP-competitive protein kinase inhibitor of PGK1 from marine nature products.
Phosphoglycerate kinase 1 (PGK1) acts as both a glycolytic enzyme and a protein kinase playing critical roles in cancer progression, thereby being regarded as an attractive therapeutic target for cancer treatment. However, no effective inhibitor of PGK1 has been reported. Here, we demonstrate that GQQ-792, a thiodiketopiperazine derivative from marine nature products, is a non-ATP-competitive inhibitor of PGK1 with the disulfide group within the structure of GQQ-792 as a key pharmacophore. The disulfide group of GQQ-792 binds to Cys379 and Cys380 of PGK1, resulting in occlusion of ATP from binding to PGK1. GQQ-792 treatment blocks hypoxic condition- and EGF stimulation-enhanced protein kinase activity of PGK1 that phosphorylates PDHK1 at T338 in glioblastoma cells; this treatment leads to decreased lactate production and glucose uptake, and subsequent apoptosis of glioblastoma cells. Animal studies reveal that GQQ-792 significantly inhibits the growth of tumor derived from glioblastoma cells. These findings underscore the potential of GQQ-792 as a promising anticancer agent and pave an avenue to further optimize the structure of GQQ-792 basing on its target molecule and pharmacophore in future.


Scalable Fabrication of Quasi-Three-Dimensional Chiral Plasmonic Oligomers Based on Stepwise Colloid Sphere Lithography Technology.
We report a simple and scalable method for the fabrication of spiral-type chiral plasmonic oligomers based on the stepwise colloid sphere lithography technology. Through carefully adjusting the azimuthal angle Φ of polystyrene (PS) sphere array monolayer and the deposition thickness k n , the chiral plasmonic oligomers composed of four achiral particles can be successfully fabricated on a desired substrate. And their chiral sign, i.e., left-hand or right-hand, is dependent on the anticlockwise or clockwise deposition sequence of the achiral particles. The measured results show a large chiroptical resonance in the visible region, and this resonance can be easily adjusted by using different sizes of PS spheres. Our in-depth theoretical and experimental researches further reveal that the obtained chiral plasmonic oligomers are indeed a kind of quasi-three-dimensional chiral nanostructures, which own a three-dimensional geometrical morphology, but with nonreciprocity chiroptical effect. The ease and scalability (>1 cm(2)) of the fabrication method make chiral plasmonic oligomers promising candidates for many applications, such as chiral biosensor and catalysis.


Relation of cell type and cell density in tissue culture to the isoaccepting spectra of the nucleoside Q containing tRNAs: tRNATyr, tRNAHis, tRNAAsn and tRNAAsp.
An examination, using reversed-phase chromatography and cyanogen bromide treatment, of tRNATyr, tRNAHis, tRNAAsn, and tRNAAsp from SV40-transformed mouse fibroblasts grown to different cell densities, untransformed cells grown to confluence, and mouse liver indicates that: (1) The tissue cultured mouse fibroblasts examined here are hypomodified with respect to nucleoside Q, while liver tRNA is almost completely modified with respect to Q. (2) Cell density and/or proliferative state do not present as major variables in controlling the expression of Q in the present system. (3) SV40 virus transformation is not a major variable controlling the expression of Q in the present system. The present results support previous use of cyanogen bromide effected shifts in chromatographic elution as an assay for nucleoside Q.


The reproductive performance of women at 40 years and over.
Adverse pregnancy outcome and increased operative deliveries have been reported in women of advanced maternal age. The objective of our study was to evaluate the reproductive performance of our women 40 years and over, and assess if they were at increased risk for adverse pregnancy outcome compared to younger women. A retrospective study of all women 40 years and over who delivered singleton pregnancies at Maternity Hospital, Kuwait, from 1 January 2000 through 30 June 2002, was undertaken. One-hundred and sixty-eight women formed the study group while 160 women aged 25-30 years served as the control group. The antenatal records, the intrapartum and postpartum events, and the perinatal outcome were extracted and analysed. Statistical analysis was done by Chi-square test, Fisher exact two-tailed test and the Welch t-test. The mean age of the study and control groups were 41.46+/-1.38 (range 40-47) and 27.40+/-1.67 (range 25-30) years, respectively. The mean parity of the study group, 4.24+/-2.35 was statistically higher than for the control group, 1.69+/-1.39, P < 0.0001. The past history of previous preterm delivery (10.1% versus 4.4%) and previous caesarean section (24.4% versus 11.9%) were more significant in the study group, P = 0.0562 and 0.0053, respectively. Women of 40 years and over presented significantly more medical complications. The incidence of caesarean section in the study group was significantly higher (31.0% versus 16.3%), P = 0.0027, OR 2.310, CI 1.356-3.935. The overall maternal and perinatal outcomes in both groups were comparable and satisfactory. Advanced maternal age of 40 years and over was not associated with adverse maternal and perinatal outcome, although the incidence of caesarean section was significantly increased in these women.


Assessing the Methodology for Calculating Platelet Contribution to Clot Strength (Platelet Component) in Thromboelastometry and Thrombelastography.
The viscoelastic properties of blood clot have been studied most commonly using thrombelastography (TEG) and thromboelastometry (ROTEM). ROTEM-based bleeding treatment algorithms recommend administering platelets to patients with low EXTEM clot strength (e.g., clot amplitude at 10 minutes [A10] <40 mm) once clot strength of the ROTEM® fibrin-based test (FIBTEM) is corrected. Algorithms based on TEG typically use a low value of maximum amplitude (e.g., <50 mm) as a trigger for administering platelets. However, this parameter reflects the contributions of various blood components to the clot, including platelets and fibrin/fibrinogen. The platelet component of clot strength may provide a more sensitive indication of platelet deficiency than clot amplitude from a whole blood TEG or ROTEM® assay. The platelet component of the formed clot is derived from the results of TEG/ROTEM® tests performed with and without platelet inhibition. In this article, we review the basis for why this calculation should be based on clot elasticity (e.g., the E parameter with TEG and the CE parameter with ROTEM®) as opposed to clot amplitude (e.g., the A parameter with TEG or ROTEM®). This is because clot elasticity, unlike clot amplitude, reflects the force with which the blood clot resists rotation within the device, and the relationship between clot amplitude (variable X) and clot elasticity (variable Y) is nonlinear. A specific increment of X (ΔX) will be associated with different increments of Y (ΔY), depending on the initial value of X. When calculated correctly, using clot elasticity data, the platelet component of the clot can provide a valuable insight into platelet deficiency in emergency bleeding.


Editorial Commentary: The Medial Patellar Ligaments: A Step Closer to the Knee Surgeon's "Rubik's Cube" Solution.
Recent cadaveric research analyzing the medial patellar ligaments and their contribution to patellar stability points out not only the need for reconstruction of the medial patellofemoral ligament, but also the medial tibiofemoral ligament to restore normal patellar stability and biomechanics.


Electronic modulation of nickel selenide by copper doping and in situ carbon coating towards high-rate and high-energy density lithium ion half/full batteries.
Over the past decades, metal selenides have drawn considerable attention due to their high theoretical specific capacity. However, huge volume changes and sluggish electrochemical transfer kinetics hinder their applications in energy storage and conversion. In this work, we demonstrate an efficient and ingenious synthesis strategy to regulate nickel selenide electrodes by the introduction of copper and in situ coating with carbon (Cu-NiSe2@C). When used as anodes for lithium-ion batteries, the as-synthesized Cu-NiSe2@C delivered a high capacity of 1630 mA h g-1 at 1.0 A g-1 after 200 cycles and excellent rate performance as well as long-term cycling stability with a high capacity of 489 mA h g-1 at 10 A g-1 after 20 000 cycles. When coupled with a commercial LiFePO4 cathode, the full cells showed a high capacity of 463 mA h g-1 at 0.2 A g-1. Their superior electrochemical performance can be attributed to the synergistic effect of the in situ carbon coating and copper doping, which can promote the electron/ion transfer kinetics, as well as alleviate the volume expansion during cycling. This work will open new opportunities for the development of high-performance anodes for lithium storage.


Aurora kinase inhibitor VX‑680 suppresses the proliferation and migration of HUVECs and angiogenesis.
Angiogenesis serves a key role in tumor growth and metastasis. VX‑680, a potent inhibitor targeting the Aurora kinase family, is widely used in the inhibition of tumor progression. However, the effect of VX‑680 on angiogenesis remains unknown. The present study identified that VX‑680 inhibited human umbilical vein endothelial cell (HUVEC) proliferation and promoted HUVEC apoptosis by inducing the cleavage of PARP and caspase‑3. VX‑680 also markedly decreased the migration and tube formation of HUVECs in a dose‑dependent manner. In addition, VX‑680 significantly suppressed the formation of blood vessels in a dose‑dependent manner confirmed by a chicken embryo chorioallantoic membrane assay in vivo. Furthermore, VX‑680 inhibited the expression levels of vascular endothelial growth factor and phosphorylated RAC‑α serine/threonine‑protein kinase in HUVECs. These results suggested that VX‑680 suppressed angiogenesis and may be a potential novel anti‑angiogenic agent.


Prospective study of the effects of ventilation tubes on hearing after radiotherapy for carcinoma of nasopharynx.
In patients with nasopharyngeal carcinoma, deafness sometimes occurs following radiotherapy. It is usually conductive, but may be sensorineural. Tinnitus is present frequently and usually is distressing. The role of ventilation tubes (grommets) in relieving these problems was assessed in a prospective randomized controlled trial of 115 patients. In the group with grommets, there was an improvement in hearing, with a reduction of the averaged air-bone gap (p less than .01). This was not found in the control group without ventilation tubes, who developed a larger conductive loss (p less than .01) and, in addition, a slight deterioration of the averaged bone conduction threshold (p less than .01). Surprisingly, the group with grommets did not develop this sensorineural loss (p less than .01). In addition, tinnitus was improved significantly by the insertion of ventilation tubes (p less than .01). Neither necrosis nor stenosis of the external auditory meatus was found in either group.


Radiotherapy of T4 bladder carcinoma.
A 16% 5-year crude survival was observed in 159 irradiated patients with T4NXMO bladder carcinoma. The presence of a T4a tumour and a good performance status were important prognostic parameters. The combination of radiotherapy and weekly injections of 5-FUra (12 mg/kg) resulted in a significant 2-year survival increase. New regimens of combined radiotherapy/chemotherapy should be developed for patients with T4NXMO bladder carcinoma. The palliation effect of radiotherapy should further be evaluated, preferably in prospective studies comparing radiotherapy with other types of palliation treatment.


An untapped resource: characteristics of thrombus recovered from intermediate or high risk pulmonary embolus patients.
Response to anticoagulation varies during management of acute hospitalized pulmonary embolism. We aimed to study thrombus histology in pulmonary embolism samples removed during acute surgical embolectomy to evaluate whether thrombus morphology was similar between patients and whether there was an association with duration of symptoms and/or resolution on follow up imaging. This was a retrospective observational single center study at the University of Rochester Medical Center. We evaluated patients that underwent acute surgical embolectomy and followed up in our clinic 2 - 4 months after the event with Ventilation/Perfusion (V/Q) scan obtained for all regardless of symptoms. Thromboemboli were formalin fixed and processed for light microscopy in the hospital histopathology laboratory. Four-micron thick sections were stained with hematoxylin and eosin, Masson trichrome, and Verhoeff elastic tissue stains. Immunohistochemistry was performed using anti-CD31 and anti-CD68. Slides were independently evaluated for time-dependent microscopic changes using Irniger's classification by two blinded pathologists. Sixteen patients underwent embolectomy with fifteen having V/Q imaging at follow up. The majority of patients were female. Samples showed a generally similar overall architecture that included a central core composed primarily of red blood cells and fibrin and an outer layer of platelets and monocytes. Two samples had evidence of fibrosis and recanalization. We found heterogeneous histopathology in samples obtained during acute embolectomy. Further prospective studies should systematically characterize clot morphology and evaluate treatment response and outcomes. Careful thrombus specimen measurement and consistent sampling for sections will be required to draw firm conclusions.


Obstruction of defunctionalized loop ten years after jejunoileal bypass for morbid obesity.
We have reported a case of obstruction due to volvulus of the ileosigmoid anastomosis ten years after jejunoileal bypass. Revision of the ileosigmoid anastomosis with drainage of the defunctionalized limb into the cecum relieved the obstruction.


Neurological recovery after cardiac arrest: clinical feasibility trial of calcium blockers.
In order to determine whether the calcium blockers verapamil and/or magnesium sulfate decrease neurological morbidity after cardiac arrest, all out-of-hospital cardiac arrests (290) occurring during a nine-month period in five participating hospitals were retrospectively studied. Twenty-nine patients met the criteria for inclusion in this study. Each had an unwitnessed, out-of-hospital cardiac arrest and was comatose (no purposeful response to pain) 20 minutes after the restoration of spontaneous circulation (ROSC). Eighteen patients (calcium blocker group) received verapamil and/or magnesium sulfate at some point after ROSC, while eleven patients received standard ACLS therapy (control group). Age, arrest time, cardiopulmonary resuscitation (CPR) time, and cerebral ischemic time were comparable in the two groups. In the calcium blocker group, seven of 18 patients regained consciousness, and six of these seven survived. All six survivors appeared neurologically normal upon discharge and at three and six months of follow-up. While no demonstrably adverse effects were seen after the administration of magnesium sulfate, 56% of the patients who received verapamil had a significant drop in blood pressure. In the control group, three of 11 patients regained consciousness and two of the three left the hospital alive. Both survivors were disabled--one severely and one moderately. Follow-up after three and six months revealed no significant improvement in their disability. Overall, six of 18 patients experienced clinically complete neurological recovery in the calcium blocker group, while none of the 11 patients in the control group made a complete neurological recovery (P = 0.06).


Nanoprobes for two-photon excitation time-resolved imaging of living animals: In situ analysis of tumor-targeting dynamics of nanocarriers.
Great challenges remain in the noninvasive luminescence imaging analysis of tumor-targeting dynamics of nanocarriers in living animals which is of significance for the development of anti-cancer nanomedicine. In this work, luminescent nanoparticles Eu(tta)3bpt@SMA (dav = 15 nm), which exhibited good water dispersion stability and high yields of red Eu-luminescence under near-infrared two-photon excitation, were prepared by a modified microfluidic mixing method in the absence of surfactants. Tumor-targeting agents, Arg-Gly-Asp-D-Phe-Lys (cRGD) polypeptide or transferrin (Tf), were then anchored on the nanoparticle surfaces to form the desired nanocarriers Eu@SMA-RGD or Eu@SMA-Tf. The tumor-targeting processes of the prepared nanocarriers in intact living mice were analyzed on a home-built two-photon excitation time-resolved (TPE-TR) imaging apparatus having a wide view filed. The TPE-TR strategy could effectively suppress the interference from biological autofluorescence, which allowed the targeted domains to be visualized with a high signal-to-noise ratio. It was found that the tumor-tissue trapping efficacy of Eu@SMA-RGD was much higher than that of Eu@SMA-Tf, and the desorption process from the tumor tissues of Eu@SMA-RGD was slower than that of Eu@SMA-Tf. The methods developed in this work pave a way to investigate the in vivo tumor-targeting dynamics of nanocarriers by noninvasive luminescence imaging of living animals.


Relationship between 5' UTR length and gene expression pattern in chicken.
The chicken (Gallus gallus) is an important model organism that bridges the evolutionary gap between mammals and non-amniote vertebrates. Here, we carried out a systematic study of the relationship between 5' UTR length and gene expression pattern in the chicken genome. We found that gene 5' UTRs lengths show a negative correlation with gene expression levels and gene expression breadths significantly. The relevance of 5' UTR length to expression pattern can not be a consequence of transcription-associated mutations. We also found that gene 5' UTR length shows a weakly positive correlation with gene tissue specificity. Another intriguing finding is that genes with 5' UTR length <30 bp have highest expression level, highest expression breadth, and lowest tissue specificity in chicken. We argued that selection is likely involved in shaping 5' UTR length in the chicken genome.