Nickel-catalyzed cross-coupling reaction of grignard reagents with alkyl halides and tosylates: remarkable effect of 1,3-butadienes.
A new method for the cross-coupling reaction of Grignard reagents with alkyl chlorides, bromides, and tosylates has been developed by the use of a nickel catalyst in the presence of a diene as an additive. This reaction proceeds efficiently at 0-25 degrees C in THF using primary and secondary alkyl and aryl Grignard reagents. Nickel complexes bearing no phosphine ligands, such as NiCl2, Ni(acac)2, and Ni(COD)2, afford the coupling products in good yields, whereas NiCl2(PPh3)2 and NiCl2(dppp) were less effective. 1,3-Butadiene shows the highest activity as an additive for the present coupling reaction. A plausible reaction pathway was proposed.


Faecal microbiota transplantation-mediated jejunal microbiota changes halt high-fat diet-induced obesity in mice via retarding intestinal fat absorption.
Faecal Microbiota Transplantation (FMT) is considered as a promising technology to fight against obesity. Wild boar has leanermuscle and less fat in comparison to the domestic pig, which were thought to be related with microbiota. To investigate the function and mechanism of the wild boar microbiota on obesity, we first analysed the wild boar microbiota composition via 16S rDNA sequencing, which showed that Firmicutes and Proteobacteria were the dominant bacteria. Then, we established a high-fat diet (HFD)-induced obesity model, and transfer low and high concentrations of wild boar faecal suspension in mice for 9 weeks. The results showed that FMT prevented HFD-induced obesity and lipid metabolism disorders, and altered the jejunal microbiota composition especially increasing the abundance of the Lactobacillus and Romboutsia, which were negatively correlated with obesity-related indicators. Moreover, we found that the anti-obesity effect of wild boar faecal suspension was associated with jejunal N6-methyladenosine (m6 A) levels. Overall, these results suggest that FMT has a mitigating effect on HFD-induced obesity, which may be due to the impressive effects of FMT on the microbial composition and structure of the jejunum. These changes further alter intestinal lipid metabolism and m6 A levels to achieve resistance to obesity.


PUVA treatment of alopecia totalis.
40 patients with alopecia totalis have been treated with PUVA. 26 did not respond, 6 experienced a partial hair regrowth, while 8 got a complete regrowth. However, relapses were frequent, occurring at an early stage.


GENA: A knowledge graph for nutrition and mental health.
While a large number of knowledge graphs have previously been developed by automatically extracting and structuring knowledge from literature, there is currently no such knowledge graph that encodes relationships between food, biochemicals and mental illnesses, even though a large amount of knowledge about these relationships is available in the form of unstructured text in biomedical literature articles. To address this limitation, this article describes the development of GENA - (Graph of mEntal-health and Nutrition Association), a knowledge graph that represents relations between nutrition and mental health, extracted from biomedical abstracts. GENA is constructed from PubMed abstracts that contain keywords relating to chemicals, food, and health. A hybrid named entity recognition (NER) model is firstly applied to these abstracts to identify various entities of interest. Subsequently, a deep syntax-based relation extraction model is used to detect binary relations between the identified entities. Finally, the resulting relations are used to populate the GENA knowledge graph, whose relationships can be accessed in an intuitive and interpretable manner using the Neo4J Database Management System. To evaluate the reliability of GENA, two annotators manually assessed a subset of the extracted relations. The evaluation results show that our methods obtain high precision for the NER task and acceptable precision and relative recall for the relation extraction task. GENA consists of 43,367 relationships that encode information about nutrition and health, of which 94.04% are new relations that are not present in existing ontologies of food and diseases. GENA is constructed based on scientific principles, and has the potential to be used within further applications to contribute towards scientific research within the domain. It is a pioneering knowledge graph in nutrition and mental health, containing a diverse range of relationship types. All of our source code and results are publicly available at https://github.com/ddlinh/gena-db.


Hypertension control among newly treated patients before and after publication of the main ALLHAT results and JNC 7 guidelines.
Medication prescribing practice changed following the publications of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) in 2002 and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) in 2003. Few data are available on changes in hypertension control rates for patients initiating antihypertensive treatment before and after these publications. The authors compared systolic and diastolic blood pressure (SBP and DBP) levels and hypertension control (SBP <140 mm Hg and DBP <90 mm Hg) rates in patients initiating antihypertensive treatment in a large managed care organization during 2 time periods: July 1, 2001, to June 30, 2002 (n=322); and July 1, 2003, to June 30, 2004 (n=323). The blood pressure reduction associated with antihypertensive medication initiation was similar in 2001-2002 and 2003-2004 (-11.9 and -10.5 mm Hg, respectively, P=.251 for SBP; -6.9 and -5.9 mm Hg, respectively, P=.160 for DBP). The mean SBP and DBP prior to treatment were significantly lower in 2003-2004 vs 2001-2002 (145.4 vs 151.3 mm Hg, P<.001 for SBP; 87.6 vs 90.1 mm Hg, P<.002 for DBP). Hypertension control rates increased from 38.0% to 50.2% (P=.005) from 2001-2002 to 2003-2004. Lower pretreatment SBP and DBP explained hypertension control improvement over time. In this real-world clinic population, antihypertensive treatment was initiated at lower blood pressure levels following publication of ALLHAT and JNC 7, resulting in substantial improvements in hypertension control rates.


The increase in [3H]glutamate release associated with long-term potentiation in the dentate gyrus is blocked by commissural stimulation.
Previous findings have indicated that long-term potentiation (LTP) in the perforant path-granule cell synapses is accompanied by an increase in K+-stimulated, calcium-dependent release of [3H]glutamate 45 min after the induction of LTP. Here we report that release of [3H]glutamate is increased at 3 time intervals following induction of LTP, 2.5 min, 45 min and 3 h. Stimulation of the commissural input to the granule cells blocks the induction of LTP and the increase in [3H]glutamate release.


Control of cross-over by single-strand DNA resection.
Control of DNA cross-overs is necessary for meiotic recombination and genome integrity. The frequency of cross-overs is dependent on homology length and the conversion tract, but the mechanisms underlying the regulation of cross-overs remain unknown. We propose that 5'-end resection, a key intermediate in double-strand break repair, could determine the formation of cross-overs. Extensive DNA resection might favor gene conversion without cross-over by channeling recombination events through synthesis-dependent strand-annealing. In reactions with short regions of homology, resection beyond the homologous sequence would impede Holliday junction formation and, consequently, cross-over. Extensive DNA resection could be an effective mechanism to prevent reciprocal exchanges between dispersed DNA sequences, and thus contribute to the genome stability.


Controversies in defining death: a case for choice.
When a new, brain-based definition of death was proposed fifty years ago, no one realized that the issue would remain unresolved for so long. Recently, six new controversies have added to the debate: whether there is a right to refuse apnea testing, which set of criteria should be chosen to measure the death of the brain, how the problem of erroneous testing should be handled, whether any of the current criteria sets accurately measures the death of the brain, whether standard criteria include measurements of all brain functions, and how minorities who reject whole-brain-based definitions should be accommodated. These controversies leave little hope of consensus on how to define death for social and public policy purposes. Rather, there is persistent disagreement among proponents of three major groups of definitions of death: whole-brain, cardiocirculatory or somatic, and higher-brain. Given the persistence and reasonableness of each of these groups of definitions, public policy should permit individuals and their valid surrogates to choose among them.


Adipose tissue as a dedicated reservoir of functional mast cell progenitors.
White adipose tissue (WAT) is a heterogeneous tissue, found in various locations throughout the body, containing mature adipocytes and the stroma-vascular fraction (SVF). The SVF includes a large proportion of immune hematopoietic cells, among which, mast cells that contribute to diet-induced obesity. In this study, we asked whether mast cells present in mice adipose tissue could derive from hematopoietic stem/progenitor cells (HSPC) identified in the tissue. We therefore performed both in vitro and in vivo experiments dedicated to monitoring the progeny of WAT-derived HSPC. The entire study was conducted in parallel with bone marrow-derived cells, considered the gold standard for hematopoietic-lineage studies. Here, we demonstrate that adipose-derived HSPC contain a precursor-cell population committed to the mast cell lineage, and able to efficiently home to peripheral organs such as intestine and skin, where it acquires properties of functional tissue mast cells. Additionally, WAT contains a significant mast cell progenitor population, suggesting that the entire mast cell lineage process take place in WAT. Considering the quantitative importance of WAT in the adult organism and the increasing roles recently assigned to mast cells in physiopathology, WAT may represent an important source of mast cells in physiological and pathological situations.


[Effect of weight loss on adipose tissue distribution and insulin sensitivity].
To discuss the effect of weight reduction on fat distribution and parameters of insulin sensitivity. 12 Caucasian women with simple obesity, aged 21 to 65 years, were treated by low caloric and high protein diet for four weeks. A series of examinations were taken before and after the treat, using computerized tomography for visceral and subcutaneous fat, using euglycemic insulin clamp for parameters of insulin sensitivity. Weight loss was (6 +/- 2) kg (2-11 kg). body mass index (BMI), waist, total fat, visceral fat, and subcutaneous fat reduced significantly. However waist-hip rate, visceral-total fat rate, and subcutaneous-total fat rate did not change significantly. Fasting serum insulin, and fasting insulin-glucose rate decreased significantly. Insulin metabolic clearance rate and, insulin sensitive index increased significantly. Fasting peptide C did not change significantly. The low caloric and high protein diet can reduce visceral and subcutaneous fat. Weight loss can improve insulin sensitivity and increase insulin metabolic clearance rate.


Bioinspired microenvironment modulation of metal-organic framework-based catalysts for selective methane oxidation.
Inspiration from natural enzymes enabling creationary catalyst design is appealing yet remains extremely challenging for selective methane (CH4) oxidation. This study presents the construction of a biomimetic catalyst platform for CH4 oxidation, which is constructed by incorporating Fe-porphyrin into a robust metal-organic framework, UiO-66, furnished with saturated monocarboxylic fatty acid bearing different long alkyl chains. The catalysts demonstrate the high efficiency in the CH4 to methanol (CH3OH) conversion at 50 °C. Moreover, the selectivity to CH3OH can be effectively regulated and promoted through a fine-tuned microenvironment by hydrophobic modification around the Fe-porphyrin. The long-chain fatty acids anchored on the Zr-oxo cluster of UiO-66 can not only tune the electronic state of the Fe sites to improve CH4 adsorption, but also restrict the amount of H2O2 around the Fe sites to reduce the overoxidation. This behavior resembles the microenvironment regulation in methane monooxygenase, resulting in high CH3OH selectivity.


Random peptide libraries displayed on adeno-associated virus to select for targeted gene therapy vectors.
Characterizing the molecular diversity of the cell surface is critical for targeting gene therapy. Cell type-specific binding ligands can be used to target gene therapy vectors. However, targeting systems in which optimum eukaryotic vectors can be selected on the cells of interest are not available. Here, we introduce and validate a random adeno-associated virus (AAV) peptide library in which each virus particle displays a random peptide at the capsid surface. This library was generated in a three-step system that ensures encoding of displayed peptides by the packaged DNA. As proof-of-concept, we screened AAV-libraries on human coronary artery endothelial cells. We observed selection of particular peptide motifs. The selected peptides enhanced transduction in coronary endothelial cells but not in control nonendothelial cells. This vector targeting strategy has advantages over other combinatorial approaches such as phage display because selection occurs within the context of the capsid and may have a broad range of applications in biotechnology and medicine.


Noise Response Data Reveal Novel Controllability Gramian for Nonlinear Network Dynamics.
Control of nonlinear large-scale dynamical networks, e.g., collective behavior of agents interacting via a scale-free connection topology, is a central problem in many scientific and engineering fields. For the linear version of this problem, the so-called controllability Gramian has played an important role to quantify how effectively the dynamical states are reachable by a suitable driving input. In this paper, we first extend the notion of the controllability Gramian to nonlinear dynamics in terms of the Gibbs distribution. Next, we show that, when the networks are open to environmental noise, the newly defined Gramian is equal to the covariance matrix associated with randomly excited, but uncontrolled, dynamical state trajectories. This fact theoretically justifies a simple Monte Carlo simulation that can extract effectively controllable subdynamics in nonlinear complex networks. In addition, the result provides a novel insight into the relationship between controllability and statistical mechanics.


Differential HDAC1/2 network analysis reveals a role for prefoldin/CCT in HDAC1/2 complex assembly.
HDAC1 and HDAC2 are components of several corepressor complexes (NuRD, Sin3, CoREST and MiDAC) that regulate transcription by deacetylating histones resulting in a more compact chromatin environment. This limits access of transcriptional machinery to genes and silences transcription. While using an AP-MS approach to map HDAC1/2 protein interaction networks, we noticed that N-terminally tagged versions of HDAC1 and HDAC2 did not assemble into HDAC corepressor complexes as expected, but instead appeared to be stalled with components of the prefoldin-CCT chaperonin pathway. These N-terminally tagged HDACs were also catalytically inactive. In contrast to the N-terminally tagged HDACs, C-terminally tagged HDAC1 and HDAC2 captured complete histone deacetylase complexes and the purified proteins had deacetylation activity that could be inhibited by SAHA (Vorinostat), a Class I/II HDAC inhibitor. This tag-mediated reprogramming of the HDAC1/2 protein interaction network suggests a mechanism whereby HDAC1 is first loaded into the CCT complex by prefoldin to complete folding, and then assembled into active, functional HDAC complexes. Imaging revealed that the prefoldin subunit VBP1 colocalises with nuclear HDAC1, suggesting that delivery of HDAC1 to the CCT complex happens in the nucleus.


A new phenolic glycoside from the aerial parts of Dryopteris fragrans.
A new phenolic glycoside, 3,5-dimethyl-6-hydroxy-2-methoxy-4-O-D-glucopyranosyl-oxy-acetophenone (1), was isolated from the aerial parts of Dryopteris fragrans. The structure was elucidated on the basis of spectroscopic methods.


Thermodynamic properties of amyloid fibrils in equilibrium.
In this manuscript we use a two-dimensional coarse-grained model to study how amyloid fibrils grow towards an equilibrium state where they coexist with proteins dissolved in a solution. Free-energies to dissociate proteins from fibrils are estimated from the residual concentration of dissolved proteins. Consistent with experiments, the concentration of proteins in solution affects the growth rate of fibrils but not their equilibrium state. Also, studies of the temperature dependence of the equilibrium state can be used to estimate thermodynamic quantities, e.g., heat capacity and entropy.


Dissimilatory microbial sulfur and methane metabolism in the water column of a shallow meromictic lake.
Lake Harutori is a brackish meromictic lake with a steep physicochemical gradient in shallow water. Anoxic water below the chemocline has been characterized by high concentrations of sulfide (>10 mM) and methane (>1.5 mM). Previously, we reported that uncultured bacteria in the SEEP-SRB1 group were major sulfate reducers in the lake [21], but knowledge of sulfur oxidation and methane metabolism was scarce. In this current study, the Lake Harutori microbial community structure in the mixolimnion (at depths of 1.5 m and 3.0 m), upper chemocline (3.5 m), and monimolimnion (4.5 m) was further investigated by 16S rRNA gene amplicon sequencing and catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH). Reads of type I and II methanotrophs were retrieved mainly from 3.5 m and above. Methanotrophic bacteria detected by CARD-FISH accounted for 3.1% of DAPI-stained cells at 3.5 m. Detection frequencies of reads affiliated with the genera Sulfurimonas and Thiomicrorhabdus, which are known to comprise sulfur oxidizers, were relatively high at 3.5 m. Methanogenic archaeal reads were retrieved from the monimolimnion and they affiliated with the genus Methanosaeta. CARD-FISH counts indicated that the cells of Methanosaeta/Methanosarcina/Methanomicrobiales accounted for up to 0.8% of the DAPI-stained cells in the monimolimnion. On the other hand, many of the reads retrieved primarily from the monimolimnion were affiliated with phylogenetically novel uncultured groups.


Long-Term Diabetes Improvement After Duodenal Exclusion in Zucker Diabetic Fatty Rats Is Associated with Prevention of Strain-Specific Pancreatic Remodeling and Increased Beta Cell Proliferation.
Response to metabolic surgery is heterogeneous and the metabolic states that underpin weight loss and metabolic improvement are still unclear. In this study, we investigate parameters of post-bariatric fasting glucoregulation and leverage artificial intelligence-assisted whole-slide image analyses to characterize associated immunohistologic features of the pancreas. We performed either loop duodeno-jejunostomy (DJOS) with exclusion of 1/3 of total intestinal length, loop duodeno-ileostomy with exclusion of 2/3 of total intestinal length (DiOS), or a sham operation on 8-week-old male obese ZDF rats. Six months post-operative, we measured blood metabolites and hormones. Subsequently, pancreatic and intestinal tissue was removed, formalin fixed, and paraffin embedded. Immunohistologic (IHC) analyses included proliferating cell nuclear antigen (PCNA) to visualize the proliferation fraction and pancreatic and duodenal homeobox 1 (PDX 1) as a measure of pancreatic cell differentiation. For IHC quantification, all slides were digitalized and analyzed using QuPath. All analyzed slides were reviewed by two independent pathologists for correctness. DJOS and DiOS were associated with preserved fasting insulin production compared to sham. Histopathologic evaluation showed significantly higher numbers of beta cells and specifically of clustered cell organization in DJOS and DiOS compared to sham. Cell proliferation (PCNA) was significantly elevated in DJOS and DiOS compared to sham. In this interventional model of bariatric surgery in severe genetic diabetes, we demonstrate post-operative histologic and immunohistologic features of the pancreas associated with improved fasting glucose homeostasis.


Precision 're'arming of CD33 antibodies.
In this issue of Blood, Kung Sutherland et al report on the preclinical activity of SGN-CD33A, a humanized anti-CD33 antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer via a protease-cleavable linker, against acute myeloid leukemia (AML) cells in vitro and in vivo.


Demonstration of chip-based coupled degenerate optical parametric oscillators for realizing a nanophotonic spin-glass.
The need for solving optimization problems is prevalent in various physical applications, including neuroscience, network design, biological systems, socio-economics, and chemical reactions. Many of these are classified as non-deterministic polynomial-time hard and thus become intractable to solve as the system scales to a large number of elements. Recent research advances in photonics have sparked interest in using a network of coupled degenerate optical parametric oscillators (DOPOs) to effectively find the ground state of the Ising Hamiltonian, which can be used to solve other combinatorial optimization problems through polynomial-time mapping. Here, using the nanophotonic silicon-nitride platform, we demonstrate a spatial-multiplexed DOPO system using continuous-wave pumping. We experimentally demonstrate the generation and coupling of two microresonator-based DOPOs on a single chip. Through a reconfigurable phase link, we achieve both in-phase and out-of-phase operation, which can be deterministically achieved at a fast regeneration speed of 400 kHz with a large phase tolerance.


Location of the protease-inhibitory region of secretory leukocyte protease inhibitor.
Secretory leukocyte protease inhibitor (SLPI) is a two-domain protein that inhibits a wide range of proteases including chymotrypsin, leukocyte elastase, and trypsin. Based on its homology to other protease inhibitors and on x-ray crystallography of an SLPI-chymotrypsin complex it has been proposed that the elastase and chymotrypsin-inhibitory site is in the COOH-terminal domain and that the trypsin-inhibitory site is in the NH2-terminal domain. We have prepared muteins of SLPI by site-directed mutagenesis of a synthetic gene for the protein, followed by expression in Escherichia coli. The protease-inhibitory activities of these muteins indicate that leucine 72 in the COOH-terminal domain is at the inhibitory site for elastase and chymotrypsin. Unexpectedly, our measurements indicate that the trypsin-inhibitory site is not in the NH2-terminal domain. Instead they suggest that leucine 72 is also the inhibitory site for trypsin, even though the amino acid residues at the inhibitory sites of other trypsin inhibitors are almost always either lysine or arginine.


Construction of ureteral grafts by seeding bone marrow mesenchymal stem cells and smooth muscle cells into bladder acellular matrix.
Congenital or acquired abnormalities may cause an ureteral injury or defect. The main methods to reconstruct a long ureter often cause serious complications. In this study, we sought to construct a tissue-engineered graft by seeding bone marrow mesenchymal stem cells (MSCs) and smooth muscle cells (SMCs) into a bladder acellular matrix (BAM) for ureteral reconstruction. Isolated, proliferated, and in vitro identified rabbit bone marrow MSCs and SMCs were seeded into BAM as the experimental group. Grafts only seeding SMCs were the control group. Cell-seeded grafts were used to construct tissue-engineered tubular grafts (TETG) for transplantation into the rabbit's omentum for 2 weeks before ureteral reconstruction. Evolutionary histology was performed at 2, 4, 8, and 16 weeks postoperatively. Renal function and ureteral obstruction were evaluated using intravenous urography at 16 weeks. Flow cytometry demonstrated bone marrow MSCs to express CD29, CD44, CD90, but not CD34. Histological examination revealed consistent regeneration of TETG urothelium in the experimental group. At 8 and 16 weeks after TETG grafting in vivo, multilayer urothelium covered the entire lumen with visible neovascularization within the center. Organized smooth muscle bundles were observed. Intravenous urography demonstrated no ureteral stricture or hydronephrosis. The 5 rabbits were dead within 4 weeks postoperatively. Autopsy showed scar formation inside the graft with severe hydronephrosis. We successfully constructed a TETG by seeding bone marrow MSCs and SMCs into BAM for ureteral reconstruction. Thus bone marrow MSCs can potentially promote urothelial regeneration to achieve a tissue-engineered ureter.


Characterizing early detection of language difficulties in children born preterm.
The optimal age for assessing language difficulties in premature children remains unclear. To determine the most predictive and earliest screening tool for later language difficulties on children born preterm. A prospective population-based study in the Loire Infant Follow-up Team LIFT SUBJECTS: All children born <35weeks of gestation between 2003 and 2005 were assessed at corrected ages by four screening tools: the Ages & Stages Questionnaire (ASQ) communication scale at 18 and 24months, the language items of Brunet Lezine test at 24months, and the "Epreuves de Repérage des Troubles du Langage" (ERTL) at 4years. After 5years, the kindergarten teacher evaluated the vocabulary, grammar and pronunciation capacities of the child in comparison with the classroom performances. Among 1957 infants enrolled at discharge, 947 were assessed by their teacher with 12.2% (n=116) of language difficulties. Full data at all time points were available for 426 infants. The area under curve of the receiver operator characteristic curve obtained for the ASQ communication scale at 18months was significantly lower (0.65±0.09) than that obtained at 24months (0.77±0.08) and the languages items of Brunet Lezine test at 24months (0.77±0.08), and the ERTL at 4years (0.76±0.09). The optimal cut-off value for ASQ communication at 24months is ≤45 [sensitivity of 0.79 (95%CI: 0.70-0.86); specificity of 0.63 (95%CI: 0.59-0.66)]. The Ages & Stages Questionnaire communication scale at 24 corrected months appears as an acceptable test at an early time point to identify preterm children at risk of later language difficulties.


MicroRNA-206 in human cancer: Mechanistic and clinical perspectives.
MicroRNAs (miRNAs), small non-coding RNAs approximately 20-25 nt in length, play important roles via directly binding to the corresponding 3' UTR of target mRNAs. Recent research has shown that miRNAs cover a wide range of diseases, including several types of cancer. It is interesting to note that miR-206 operates as a tumor suppressor and is downregulated in abundant cancer types, such as breast cancer, lung cancer, colorectal cancer, and so forth. Interestingly, a growing number of studies have also reported that miR-206 could function as an oncogene and promote tumor cell proliferation. Thereby, miR-206 may act as either oncogenes or tumor suppressors under certain conditions. In addition, it was widely acknowledged that restoring tumor-suppressor miR-206 has emerged as an unconventional cancer therapy strategy. Therefore, miR-206 might be a newfangled procedure for achieving a more significant treatment outcome for cancer patients. This review summarizes the role of miR-206 in several cancer types and the contributions made between miR-206 and the diagnosis, treatment, and drug resistance of solid tumors.


Methods for analysis of calcium/calmodulin signaling in cilia and flagella.
The axonemal microtubules of cilia/flagella act as a scaffold for assembly of the protein complexes that ultimately regulate dynein activity to control the size and shape of ciliary bends. Despite our general understanding of the contribution of microtubule sliding to ciliary and flagellar motility, many questions regarding the regulation of dynein remain unanswered. For example, we know that the second messenger calcium plays an important role in modulating dynein activity in response to extracellular cues, but it remains unclear how calcium-binding proteins anchored to the axoneme contribute to this regulation. Recent work has focused on determining the identity and specific functions of these axonemal calcium-binding proteins. Here, we review our current knowledge of calcium-mediated motility and highlight key experiments that have substantially aided our understanding of calcium signaling within the axoneme.


Characterization of dissolved organic matter in reclaimed wastewater supplying urban rivers with a special focus on dissolved organic nitrogen: A seasonal study.
This study investigated the seasonal characterization of dissolved organic matter (DOM) in reclaimed wastewater (RW) with a special focus on dissolved organic nitrogen (DON) from two full-scale municipal wastewater reclamation plants (WRPs) where the produced RW was used to augment urban rivers. Results showed that the concentrations of DON in RW ranged from 0.32 mg/L to 1.21 mg/L. A higher seasonal mean value of DON in RW from both of the WRPs was observed in winter (p < 0.05, ANOVA). DON chemical characteristics analysis, including ultrahigh-resolution mass spectrometry and ultrafiltration fractionation, showed that DON in RW exhibits more lability during winter than during the other three seasons. This finding was also supported by the results of an algal bioassay experiment, in which DON bioavailabilities were 63.7 ± 3.0%, 53.0 ± 5.3%, 49.5 ± 0.5%, and 49.8 ± 0.2% for WRP-A and were 60.8 ± 2.4%, 43.7 ± 2.2%, 41.2 ± 1.7%, and 43.1 ± 1.1% for WRP-B in winter, spring, summer, and autumn, respectively. Accordingly, DON in RW during winter is more prone to stimulate natural algae and microorganisms, which gives rise to eutrophication in urban rivers. At the molecular level, the seasonal changes in DON are not coupled with those of DOC, which highlights the necessity of DON measurement to obtain a comprehensive understanding of the seasonal characteristics of DOM in RW and its effect on wastewater reuse in urban rivers.


Proteins associated with critical sperm functions and sperm head shape are differentially expressed in morphologically abnormal bovine sperm induced by scrotal insulation.
The objective was to investigate expression patterns of proteins in pyriform sperm, a common morphological abnormality in bull sperm. Ejaculates were collected from sexually mature Holstein bulls (n=3) twice weekly for 10 weeks (pre-thermal insult samples). Testicular temperature was elevated in all bulls by scrotal insulation for 72 consecutive hours during week 2. Total sperm proteins were extracted from pre- and post-thermal insult sperm samples and subjected to two-dimensional gel electrophoresis. Among the protein spots detected, 131 spots were significantly expressed (False Detection Rate <0.01) with ≥ 2 fold changes between normal and pyriform sperm. Among them, 25 spots with ≥ 4 fold difference in expression patterns were identified using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Expression of several proteins involved in sperm capacitation, sperm-egg interaction and sperm cytoskeletal structure was decreased in pyriform sperm, whereas proteins regulating antioxidant activity, apoptosis and metabolic activity were increased. Contents of reactive oxygen species and ubiquitinated proteins were higher in pyriform sperm. In addition to understanding the molecular basis of functional deficiencies in sperm with specific morphological abnormalities, comparing normal versus morphologically abnormal sperm appeared to be a suitable experimental model for identifying important sperm functional proteins. To our knowledge, this study is the first report on differential expression of proteins in pyriform bovine sperm versus morphologically normal sperm. We report that expression of several proteins involved in sperm capacitation, sperm-egg interaction and sperm cytoskeletal structure was decreased in pyriform sperm, whereas proteins which regulate antioxidant activity, apoptosis and metabolic activity were increased. Contents of reactive oxygen species and ubiquitinated proteins were higher in pyriform sperm. In addition to understanding the molecular basis of functional deficiencies in sperm with specific morphological abnormalities, our results suggest that comparing normal versus morphologically abnormal sperm appeared to be a suitable experimental model for identifying important sperm functional proteins.


Correction to: Tripeptides Restore the Number of Neuronal Spines under Conditions of In Vitro Modeled Alzheimer's Disease.
On the page 553 Acknowledgements should be as follows: The study was supported by the Russian Science Foundation (grant 14-25-00024-P).


Root system architecture and genomic plasticity to salinity provide insights into salt-tolerant traits in tall fescue.
Salinity is detrimental to soil health, plant growth, and crop productivity. Understanding salt tolerance mechanisms offers the potential to introduce superior crops, especially in coastal regions. Root system architecture (RSA) plasticity is vital for plant salt stress adaptation. Tall fescue is a promising forage grass in saline regions with scarce RSA studies. Here, we used the computer-integrated and -automated programs EZ-Rhizo II and ROOT-Vis II to analyze and identify natural RSA variations and adaptability to high salt stress at physiological and genetic levels in 17 global tall fescue accessions. Total root length rather than the number of lateral roots contribute more to water uptake and could be used to separate salt-tolerant (LS-11) and -sensitive accessions (PI531230). Comparative evaluation of LS-11 and PI531230 demonstrated that the lateral root length rather than the main root contributed more towards the total root length in LS-11. Also, high water uptake was associated with a larger lateral root vector and position while low water intake was associated with an insignificant correlation between root length, vector, and position. To examine candidate gene expression, we performed transcriptome and transcription analyses using high-throughput RNA sequencing and real-time quantitative PCR, respectively of the lateral and main roots. The main root displayed more differentially expressed genes than the lateral root. A Poisson comparison of LS-11 vs PI531230 demonstrated significant upregulation of PLASMA MEMBRANE AQUAPORIN 1 and AUXIN RESPONSE FACTOR 22 in both the main and lateral root, which are associated with transmembrane water transport and the auxin-activated signaling system, respectively. There is also an upregulation of BASIC HELIX-LOOP-HELIX 5 in the main root and a downregulation in the lateral root, which is ascribed to sodium ion transmembrane transport, as well as an upregulation of THE MEDIATOR COMPLEX 1 assigned to water transport in the lateral root and a downregulation in the main root. Gene-protein interaction analysis found that more genes interacting with aquaporins proteins were upregulated in the lateral root than in the main root. We inferred that deeper main roots with longer lateral roots emanating from the bottom of the main root were ideal for tall fescue water uptake and salt tolerance, rather than many shallow roots, and that, while both main lateral roots may play similar roles in salt sensing and water uptake, there are intrinsic genomic differences.


Labetalol as a hypotensive agent for middle ear microsurgery.
Labetalol, an alpha- and beta-adrenergic receptor-blocking agent, was studied as a hypotensive agent during halothane (mostly 0.5 vol.%)-N2O-fentanyl-d-tubocurarine anaesthesia with a head-up tilt of 5 degrees in 41 patients undergoing middle ear microsurgery. After the mean initial dose of 0.3 mg/kg, the mean need for labetalol ranged from 0.05 to 0.07 mg/kg at 30 +/- 5-min intervals. The mean duration of the hypotensive period was 102 min. During the hypotension, the average mean arterial pressure ranged from 59 to 62 mmHg (7.9-8.3 kPa) and the mean heart rate from 61 to 66 b.p.m. After labetalol the maximum cardiac output decrease was 7%. Before labetalol the mean PaO2 value was 158 mmHg (21.1 kPa) and during hypotension it ranged from 145 to 149 mmHg (19.3-19.9 kPa) when FiO2 was 40%. The only peroperative side effects were ECG changes (middle junctional rhythm and sinus bradycardia) which occurred in 10% of the patients. The mean value for the degree of haemostasis rated by the otologist on a visual analogue scale between poor (0 mm) and excellent (100 mm) was 91 mm. The patients were able to open their eyes and to give their names 8-9 min after the end of anaesthesia. After extubation the patients were normotensive and there were no clinically significant changes in the cardiovascular parameters during the 4-h recovery room period. Acid-base status showed slight metabolic acidosis. The most common postoperative side effects were nausea only and nausea + vomiting, which occurred in 39% and 20% of the patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Recurrence in patients with benign paroxysmal positional vertigo of the lateral semicircular canal.
There are 3 subtypes of lateral canal benign paroxysmal positional vertigo. Persistent geotropic positional nystagmus is due to a light cupula, heavy cupula produces apogeotropic positional nystagmus, and canalolithiasis accounts for transient geotropic positional nystagmus. The aims of this study were to determine the recurrence rate and to examine the number of times of recurrence in each of the 3 subtypes. Subjects were patients with light cupula (n = 47), heavy cupula (n = 48), and canalolithiasis (n = 45). We investigated the number of times of recurrence and determined the subtypes of a recurrent vertigo attack over the period of 5 years. The subtype of a recurrent vertigo attack was not always the same as the subtype at the first visit. The recurrence rate of light cupula group was 72.3%, that of heavy cupula group was 20.8%, and that of canalolithiasis group was 28.9%. Some patients experienced recurrence more than once. The mean value and standard deviation of the number of times of recurrence in light cupula group was 2.5 ± 1.3 times, that in heavy cupula group was 1.5 ± 0.7 times, and that in canalolithiasis group was 1.5 ± 0.7 times. The recurrence rate in patients with light cupula is much higher than that in patients with heavy cupula or canalolithiasis. The number of times of recurrence in patients with light cupula is greater than that in patients with heavy cupula or canalolithiasis.


Mechanism of vinorelbine-induced radiosensitization of human small cell lung cancer cells.
Vinorelbine (Navelbine, KW-2307), a semisynthetic vinca alkaloid, is a potent inhibitor of mitotic microtubule polymerization. The aims of this study were to demonstrate vinorelbine-induced radiosensitization of human small cell lung cancer (SCLC) SBC-3 cells and to elucidate the mechanisms of radiosensitization. A clonogenic assay demonstrated that SBC-3 cells were sensitized to radiation by vinorelbine using different schedules combining exposure to both. The sensitizer enhancement ratios (SERs) at a cell survival level of 10% were 1.42+/-0.21 to 1.33+/-0.06, and 1.22+/-0.07 depending on schedule. Vinorelbine-induced radiosensitization did not depend on the schedule of the combined exposure. Flow cytometric analyses showed that the cells did not accumulate in the radiosensitive G(2)/M phase of the cell cycle after concurrent treatment with vinorelbine and radiation. The results of an alkaline filter elution assay demonstrated that in the presence of vinorelbine at 1 n M radiation-induced DNA strand breaks were not completely repaired at 24 h postradiation. We conclude that human SCLC SBC-3 cells are sensitized to radiation by vinorelbine and that a possible mechanisms of vinorelbine-induced radiosensitization may at least in part be associated with impairment of DNA repair following radiation-induced DNA damage.


Risk Factors for Recurrence after Robot-Assisted Radical Hysterectomy for Early-Stage Cervical Cancer: A Multicenter Retrospective Study.
This retrospective analysis aimed to assess the risk factors for recurrence in patients diagnosed with early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009) undergoing robot-assisted radical hysterectomy in Spain and Portugal between 2009 and 2018. A second primary objective was to audit the oncological outcomes according to quality indicators (QI) proposed by the European Society of Gynecology Oncology (ESGO). The study population included 239 women. After a median follow-up of 51 months, recurrence occurred in 26 patients (10.9%). Independent factors for recurrence were clinical tumor size > 20 mm (hazard ratio (HR) 2.37), adenocarcinoma as histological type (HR 2.51), positive pelvic lymph nodes (HR 4.83), tumor grade 2 (HR 4.99), tumor grade 3 (HR 8.06), and having not performed sentinel lymph node biopsy (SLNB) (HR 4.08). All 5 QI selected were surpassed by our results. In patients with early-stage cervical cancer undergoing robotic radical hysterectomy, clinicians should be aware that tumor grade 2 and 3, tumor size > 20 mm, adenocarcinoma, positive pelvic nodes, and lack of performance of SLNB are risk factors for recurrence. Fulfillment of QI targets of the ESGO might be considered as an objective oncological outcome indicator supporting the minimally invasive approach for early-stage cervical cancer treatment.


Progesterone amplifies oxidative stress signal and promotes NO production via H2O2 in mouse kidney arterial endothelial cells.
The role of progesterone on the cardiovascular system is controversial. Our present research is to specify the effect of progesterone on arterial endothelial cells in response to oxidative stress. Our result showed that H2O2 (150 μM and 300 μM) induced cellular antioxidant response. Glutathione (GSH) production and the activity of Glutathione peroxidase (GPx) were increased in H2O2-treated group. The expression of glutamate cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) was induced in response to H2O2. However, progesterone absolutely abolished the antioxidant response through increasing ROS level, inhibiting the activity of Glutathione peroxidase (GPx), decreasing GSH level and reducing expression of GClC and GCLM. In our study, H2O2 induced nitrogen monoxide (NO) production and endothelial nitric oxide synthase (eNOS) expression, and progesterone promoted H2O2-induced NO production. Progesterone increased H2O2-induced expression of hypoxia inducible factor-α (HIFα) which in turn regulated eNOS expression and NO synthesis. Further study demonstrated that progesterone increased H2O2 concentration of culture medium which may contribute to NO synthesis. Exogenous GSH decreased the content of H2O2 of culture medium pretreated by progesterone combined with H2O2 or progesterone alone. GSH also inhibited expression of HIFα and eNOS, and abolished NO synthesis. Collectively, our study demonstrated for the first time that progesterone inhibited cellular antioxidant effect and increased oxidative stress, promoted NO production of arterial endothelial cells, which may be due to the increasing H2O2 concentration and amplified oxidative stress signal.


DNA-informed breeding of rosaceous crops: promises, progress and prospects.
Crops of the Rosaceae family provide valuable contributions to rural economies and human health and enjoyment. Sustained solutions to production challenges and market demands can be met with genetically improved new cultivars. Traditional rosaceous crop breeding is expensive and time-consuming and would benefit from improvements in efficiency and accuracy. Use of DNA information is becoming conventional in rosaceous crop breeding, contributing to many decisions and operations, but only after past decades of solved challenges and generation of sufficient resources. Successes in deployment of DNA-based knowledge and tools have arisen when the 'chasm' between genomics discoveries and practical application is bridged systematically. Key steps are establishing breeder desire for use of DNA information, adapting tools to local breeding utility, identifying efficient application schemes, accessing effective services in DNA-based diagnostics and gaining experience in integrating DNA information into breeding operations and decisions. DNA-informed germplasm characterization for revealing identity and relatedness has benefitted many programs and provides a compelling entry point to reaping benefits of genomics research. DNA-informed germplasm evaluation for predicting trait performance has enabled effective reallocation of breeding resources when applied in pioneering programs. DNA-based diagnostics is now expanding from specific loci to genome-wide considerations. Realizing the full potential of this expansion will require improved accuracy of predictions, multi-trait DNA profiling capabilities, streamlined breeding information management systems, strategies that overcome plant-based features that limit breeding progress and widespread training of current and future breeding personnel and allied scientists.


The importance of hydration for the kinetics and thermodynamics of protein folding: simplified lattice models.
Recent studies have proposed various sources for the origin of cooperativity in simplified protein folding models. Important contributions to cooperativity that have been discussed include backbone hydrogen bonding, sidechain packing and hydrophobic interactions. Related work has also focused on which interactions are responsible for making the free energy of the native structure a pronounced global minimum in the free energy landscape. In addition, two-flavor bead models have been found to exhibit poor folding cooperativity and often lack unique native structures. We propose a simple multibody description of hydration with expectations that it might modify the free energy surface in such a way as to increase the cooperativity of folding and improve the performance of two-flavor models. We study the thermodynamics and kinetics of folding for designed 36-mer sequences on a cubic lattice using both our solvation model and the corresponding model without solvation terms. Degeneracies of the native states are studied by enumerating the maximally compact states. The histogram Monte Carlo method is used to obtain folding temperatures, densities of states and heat capacity curves. Folding kinetics are examined by accumulating mean first-passage times versus temperature. Sequences in the proposed solvation model are found to have more unique ground states, fold faster and fold with more cooperativity than sequences in the nonsolvation model. We find that the addition of a multibody description of solvation can improve the poor performance of two-flavor lattice models and provide an additional source for more cooperative folding. Our results suggest that a better description of solvation will be important for future theoretical protein folding studies.


Gender difference in the composition of fecal flora in laboratory mice, as detected by denaturing gradient gel electrophoresis (DGGE).
The difference between genders in the composition of mouse fecal flora was examined. A polymerase chain reaction followed by denaturing gradient gel electrophoresis (DGGE) were performed on the V6-V8 regions of bacterial 16S rDNA obtained from fecal samples at 0, 1, 2, 3, 4, and 8 weeks after the introduction of mice into the laboratory from a mouse farm. Cluster analysis and non-metric multidimensional scaling (NMDS) were then performed. Male and female mice were distributed on opposite sides of the origin of the plane in NMDS at weeks 0, 2, 3, and 8. These results suggest a gender difference in the composition of intestinal flora in mice.


A cross-sectional comparison of ethanol-related cytokine expression in the hippocampus of young and aged Fischer 344 rats.
Our work in Sprague Dawley rats has shown rapid alterations in neuroimmune gene expression (RANGE) in the hippocampus and paraventricular nucleus of the hypothalamus (PVN). These manifest as increased interleukin (IL)-6 and IκBα, and suppressed IL-1β and tumor necrosis factor alpha during acute ethanol intoxication. The present studies tested these effects across the lifespan (young adulthood at 2-3 months; senescence at 18 and 24 months), as well as across strain (Fischer 344) and sex. The hippocampus revealed age-dependent shifts in cytokine expression (IL-6, IL-1β, and monocyte chemoattractant protein 1), but no changes were observed in the PVN at baseline or following ethanol. RANGE in adults was similar across sex and comparable with effects seen in Sprague Dawley rats. Plasma corticosterone levels increased with age, whereas the blood ethanol concentrations and loss of righting reflex were similar in all groups older than 2 months. These findings indicate that the RANGE effect is largely conserved across strain and is durable across age, even in the face of a shifting neuroimmune profile that emerges during immunosenescence.


Fate of MHCII in salmonids following 4WGD.
Major histocompatibility complex (MHC) genes are key players in the adaptive immunity providing a defense against invading pathogens. Although the basic structures are similar when comparing mammalian and teleost MHC class II (MHCII) molecules, there are also clear-cut differences. Based on structural requirements, the teleosts non-classical MHCII molecules do not comply with a function similar to the human HLA-DM and HLA-DO, i.e., assisting in peptide loading and editing of classical MHCII molecules. We have previously studied the evolution of teleost class II genes identifying various lineages and tracing their phylogenetic occurrence back to ancient ray-finned fishes. We found no syntenic MHCII regions shared between cyprinids, salmonids, and neoteleosts, suggesting regional instabilities. Salmonids have experienced a unique whole genome duplication 94 million years ago, providing them with the opportunity to experiment with gene duplicates. Many salmonid genomes have recently become available, and here we set out to investigate how MHCII has evolved in salmonids using Northern pike as a diploid sister phyla, that split from the salmonid lineage prior to the fourth whole genome duplication (4WGD) event. We identified 120 MHCII genes in pike and salmonids, ranging from 11 to 20 genes per species analyzed where DB-group genes had the most expansions. Comparing the MHC of Northern pike with that of Atlantic salmon and other salmonids species provides a tale of gene loss, translocations, and genome rearrangements.


Diagnostic and prognostic values of preoperative serum levels of YKL-40, HE-4 and DKK-3 in endometrial cancer.
The objective of this study is to determine the efficiency of YKL-40, HE-4 and DKK-3 levels in early diagnosis of patients with endometrial cancer and in the pre-operative estimation of the prognostic parameters such as stage, grade and the extension of the disease. In this prospective study, 50 patients diagnosed with endometrial cancer and 50 women as a control group, who applied to Dokuz Eylul University and Ege University Faculties of Medicine, Obstetrics and Gynecology Clinics between May 2011-May 2012 were included. CA125, HE-4, YKL-40 and DKK-3 serum levels were measured by ELISA and compared between two groups. The relation between serum levels and histopathological results, extension of disease and prognostic factors were analyzed. Preoperative serum CA125, HE-4 and YKL-40 levels were significantly higher in endometrial cancer group (p<0.001). Serum HE-4 levels were significantly higher in advanced stages (p=0.004). When we examined early stage patients, YKL-40 levels were significantly higher in non-endometrioid histology compared with endometrioid adenocarcinoma (p=0.022). We also examined the relation between the markers and prognostic factors. Different from other markers, HE-4 levels were significantly higher in endometrial cancer patients who had lymphovascular space involvement, lower uterine segment involvement, endocervical stromal involvement, and deep myometrial invasion. YKL-40 and HE-4 were significantly higher in patients with endometrial cancer. HE-4 seems to be superior to YKL-40 in discriminating early and advanced stages. Additionally, HE4 is significantly correlated with prognostic factors. HE-4 and YKL-40 may be successful in early determination of endometrial cancer and in detection of high risk subsets before surgery.


Impaired Bone Regenerative Effect of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells in Type 1 Diabetes.
Stem cell-derived exosomes have exhibited promise for applications in tissue regeneration. However, one major problem for stem cell-derived exosome therapies is identifying appropriate source cells. In the present study, we aimed to compare the bone regenerative effect of exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) derived from type 1 diabetes rats (dBMSC-exos) and exosomes secreted by BMSCs derived from normal rats (nBMSC-exos). BMSCs were isolated from rats with streptozotocin-induced diabetes and normal rats. dBMSC-exos and nBMSC-exos were isolated by an ultracentrifugation method and identified. The effects of dBMSC-exos and nBMSC-exos on the proliferation and migration of BMSCs and human umbilical vein endothelial cells (HUVECs) were investigated. The effects of exosomes on the osteogenic differentiation of BMSCs and the angiogenic activity of HUVECs were compared. Finally, a rat calvarial defect model was used to compare the effects of exosomes on bone regeneration and neovascularization in vivo. In vitro, dBMSC-exos and nBMSC-exos both enhanced the osteogenic differentiation of BMSCs and promoted the angiogenic activity of HUVECs, but nBMSC-exos had a greater effect than dBMSC-exos. Similarly, in vivo, both dBMSC-exos and nBMSC-exos promoted bone regeneration and neovascularization in rat calvarial defects, but the therapeutic effect of nBMSC-exos was superior to that of dBMSC-exos. The present study demonstrates for the first time that the bone regenerative effect of exosomes derived from BMSCs is impaired in type 1 diabetes, indicating that for patients with type 1 diabetes, the autologous transplantation of BMSC-exos to promote bone regeneration may be inappropriate. Stem Cells Translational Medicine 2019;8:593-605.


Ultrasmall, elementary and highly translational nanoparticle X-ray contrast media from amphiphilic iodinated statistical copolymers.
To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity, and well-defined spatial and temporal resolutions, a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media (nano-XRCM) as dual-modality imaging agents for positron emission tomography (PET) and computed tomography (CT) has been established. Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide) acrylate monomers, the amphiphilic statistical iodocopolymers (ICPs) could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations (>140 mg iodine/mL water) and comparable viscosities to conventional small molecule XRCM. The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca. 10 nm in water was confirmed by dynamic and static light scattering techniques. In a breast cancer mouse model, in vivo biodistribution studies revealed that the 64Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents. PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals, while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection, enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.


h-BN nanosheets as simple and effective additives to largely enhance the activity of Au/TiO2 plasmonic photocatalysts.
The activity of Au nanoparticle-loaded P25 TiO2 (Au/P25) plasmonic photocatalysts, evaluated by the oxidative decomposition of formic acid in water under visible light irradiation, was enhanced up to 3 times by simply mixing Au/P25 with photocatalytically inactive h-BN nanosheets as a result of electron transfer from photoexcited Au/TiO2 to the h-BN nanosheets and retardation of the charge recombination.


A physical map covering the nsv locus that confers resistance to Melon necrotic spot virus in melon (Cucumis melo L.).
Melon necrotic spot virus (MNSV) is a member of the genus Carmovirus, which produces severe yield losses in melon and cucumber crops. The nsv gene is the only known natural source of resistance against MNSV in melon, and confers protection against all widespread strains of this virus. nsv has been previously mapped in melon linkage group 11, in a region spanning 5.9 cM, saturated with RAPD and AFLP markers. To identify the nsv gene by positional cloning, we started construction of a high-resolution map for this locus. On the basis of the two mapping populations, F(2) and BC1, which share the same resistant parent PI 161375 (nsv/nsv), and using more than 3,000 offspring, a high-resolution genetic map has been constructed in the region around the nsv locus, spanning 3.2 cM between CAPS markers M 29 and M 132. The availability of two melon BAC libraries allowed for screening and the identification of new markers closer to the resistance gene, by means of BAC-end sequencing and mapping. We constructed a BAC contig in this region and identified the marker 52 K 20 sp 6, which co-segregates with nsv in 408 F(2) and 2.727 BC1 individuals in both mapping populations. We also identified a single 100 kb BAC that physically contains the resistance gene and covers a genetic distance of 0.73 cM between both BAC ends. These are the basis for the isolation of the nsv recessive-resistance gene.


Optimizing 3DCT image registration for interfractional changes in carbon-ion prostate radiotherapy.
To perform setup procedures including both positional and dosimetric information, we developed a CT-CT rigid image registration algorithm utilizing water equivalent pathlength (WEPL)-based image registration and compared the resulting dose distribution with those of two other algorithms, intensity-based image registration and target-based image registration, in prostate cancer radiotherapy using the carbon-ion pencil beam scanning technique. We used the data of the carbon ion therapy planning CT and the four-weekly treatment CTs of 19 prostate cancer cases. Three CT-CT registration algorithms were used to register the treatment CTs to the planning CT. Intensity-based image registration uses CT voxel intensity information. Target-based image registration uses target position on the treatment CTs to register it to that on the planning CT. WEPL-based image registration registers the treatment CTs to the planning CT using WEPL values. Initial dose distributions were calculated using the planning CT with the lateral beam angles. The treatment plan parameters were optimized to administer the prescribed dose to the PTV on the planning CT. Weekly dose distributions using the three different algorithms were calculated by applying the treatment plan parameters to the weekly CT data. Dosimetry, including the dose received by 95% of the clinical target volume (CTV-D95), rectal volumes receiving > 20 Gy (RBE) (V20), > 30 Gy (RBE) (V30), and > 40 Gy (RBE) (V40), were calculated. Statistical significance was assessed using the Wilcoxon signed-rank test. Interfractional CTV displacement over all patients was 6.0 ± 2.7 mm (19.3 mm maximum standard amount). WEPL differences between the planning CT and the treatment CT were 1.2 ± 0.6 mm-H2O (< 3.9 mm-H2O), 1.7 ± 0.9 mm-H2O (< 5.7 mm-H2O) and 1.5 ± 0.7 mm-H2O (< 3.6 mm-H2O maxima) with the intensity-based image registration, target-based image registration, and WEPL-based image registration, respectively. For CTV coverage, the D95 values on the planning CT were > 95% of the prescribed dose in all cases. The mean CTV-D95 values were 95.8 ± 11.5% and 98.8 ± 1.7% with the intensity-based image registration and target-based image registration, respectively. The WEPL-based image registration was CTV-D95 to 99.0 ± 0.4% and rectal Dmax to 51.9 ± 1.9 Gy (RBE) compared to 49.4 ± 9.1 Gy (RBE) with intensity-based image registration and 52.2 ± 1.8 Gy (RBE) with target-based image registration. The WEPL-based image registration algorithm improved the target coverage from the other algorithms and reduced rectal dose from the target-based image registration, even though the magnitude of the interfractional variation was increased.


Gene expression profiling of human melanoma cell lines with distinct metastatic potential identifies new progression markers.
Identification of markers associated with melanoma progression is crucial to identify new prognostic and/or therapeutic targets. By using DNA microarrays, two human melanoma cell lines, M4Be and Tw12, derived from the same tumor, but with different metastatic potential, were profiled. Western blot of cell lines, immunohistochemistry on melanoma biopsies and in silico analyses validated and extended our results. Thirty-six clones were differentially-expressed between the two cell lines, representing 33 named genes and 2 expressed sequence tags. The most up-regulated gene in the strongly metastatic clone Tw12 was CD10. Protein analysis with anti-CD1O antibody confirmed this finding in cell lines and clinical samples with expression being more frequent in metastatic compared to primary tumors. Many up-regulated genes were involved in angiogenesis, invasion, growth and apoptosis. Down-regulated genes included tumor suppressor genes and those were involved in differentiation. We identified several genes the expression of which is associated with metastatic progression in human melanoma cells. Although further analyses are warranted to clarify their exact role in tumor progression, they might lead to new prognostic markers and/or molecular therapeutic targets in metastatic melanoma.


Multinucleate cell angiohistiocytoma of the orbit.
A 31-year-old had a five-year history of painless progressive swelling of her right upper eyelid. A mass was removed from the superonasal aspect of the right orbit. The orbital mass was composed of a collagenous stroma with capillary channels and irregular giant cells. The findings were characteristic of multinucleate cell angiohistiocytoma. Multinucleate cell angiohistiocytoma should be included in the differential diagnosis of circumscribed orbital tumors.


A novel approach in breast reconstruction: The extended lateral thoracic flip-over flap combined with loops and lipofilling (ELT FOLL).
The use of the thoracodorsal musculocutaneous flap has been limited to donor site complications, whereas the thoracodorsal fasciocutaneous flap spares the muscle and limits morbidities. Our objective is to describe a new technique of breast reconstruction using an extended lateral thoracic (ELT) flip-over flap combined with loops and lipofilling (ELT FOLL) to achieve better breast remodeling. Between 2013 and 2018, 64 patients underwent breast reconstruction using an ELT FOLL. The flap is designed in an elliptical transverse pattern and extends 2 cm lateral to the back midline up to the breast axis at the level of the inframammary fold. The surgical technique consists of an infiltration and tunnelization of the breast recipient site and surrounding area, deepithelialization of the skin paddle, and additional preparation of the flaps and loops. Liposuction is performed using the power-assisted liposuction and lipofilling technique, and lipofilling is achieved throughout the thoracic cutaneous surface of the reconstructed site, particularly into the lower quadrant of the breast. Among the reconstructions, 73.4% was delayed and 92.2% was unilateral. A fourth of the patients were smokers, and 39.1% received radiotherapy. The total complication rate was 8.7%, the patient's shoulder function was not affected at long term, with the DASH score rising from 6.53 preoperatively to 11.32 at 6 weeks and 7.52 at 6 months. The average operative time was 57 min, and drains were removed at day one after surgery. The ELT FOLL should be considered a simple, safe, and reliable alternative for breast reconstruction.


ACF catalyses chromatosome movements in chromatin fibres.
Nucleosome-remodelling factors containing the ATPase ISWI, such as ACF, render DNA in chromatin accessible by promoting the sliding of histone octamers. Although the ATP-dependent repositioning of mononucleosomes is readily observable in vitro, it is unclear to which extent nucleosomes can be moved in physiological chromatin, where neighbouring nucleosomes, linker histones and the folding of the nucleosomal array restrict mobility. We assembled arrays consisting of 12 nucleosomes or 12 chromatosomes (nucleosomes plus linker histone) from defined components and subjected them to remodelling by ACF or the ATPase CHD1. Both factors increased the access to DNA in nucleosome arrays. ACF, but not CHD1, catalysed profound movements of nucleosomes throughout the array, suggesting different remodelling mechanisms. Linker histones inhibited remodelling by CHD1. Surprisingly, ACF catalysed significant repositioning of entire chromatosomes in chromatin containing saturating levels of linker histone H1. H1 inhibited the ATP-dependent generation of DNA accessibility by only about 50%. This first demonstration of catalysed chromatosome movements suggests that the bulk of interphase euchromatin may be rendered dynamic by dedicated nucleosome-remodelling factors.


Fabrication of bienzyme nanobiocomposite electrode using functionalized carbon nanotubes for biosensing applications.
Mediated biosensors consisting of an oxidase and peroxidase (POx) have attracted increasing attention because of their wider applicability. This work presents a novel approach to fabricate nanobiocomposite bienzymatic biosensor based on functionalized multiwalled carbon nanotubes (MWNTs) with the aim of evaluating their ability as sensing elements in amperometric transducers. Electrochemical behavior of the bienzymatic nanobiocomposite biosensor is investigated by Faradaic impedance spectroscopy and cyclic voltammetry. The results indicate that glucose oxidase (GOD) and horseradish peroxidase (HRP) are strongly adsorbed on the surface of the thionin (TH) functionalized MWNTs and demonstrate a facile electron transfer between immobilized GOD/HRP and the electrode via the functionalized MWNTs in a Nafion film. The functionalized carbon nanotubes act as molecular wires to allow efficient electron transfer between the underlying electrode and the redox centres of enzymes through TH. Linear ranges for these electrodes are from 10nM to 10mM for glucose and 17nM to 56mM for hydrogen peroxide with the detection limit of 3 and 6nM, respectively. A remarkable feature of the bienzyme electrode is the possibility to determine glucose and hydrogen peroxide at a very low applied potential where the noise level and interferences from other electroactive compounds are minimal. Performance of the biosensor is evaluated with respect to response time, detection limit, selectivity, temperature and pH as well as operating and storage stability.


Industrial development and urban spatial planning practices: The case of Galan and Dukem cities in Ethiopia.
Urbanization in developing countries like Ethiopia is taking place at an unprecedented rate. This, coupled with the rapid industrialization process, puts enormous pressure on preparing and implementing city spatial plans. As a result, most development in many cities is taking place without clear planning guidelines and lacks the institutional capacity to realize effectively the urban spatial plans. Galan and Dukem cities, located near the capital Addis Ababa, have attracted substantial industrial development investment in recent decades. This article examines the nexus between urban spatial planning and industrial development by analyzing the current urban structure plans of the two cities using institutionalist and political economy approaches. The research methodology involves key informant interviews, an expert survey, personal observation, and reviewing secondary sources. The data were analyzed using descriptive statistics and multivariate Exploratory Factor Analysis (EFA). The EFA identifies three latent variables that affect urban spatial planning performances, including the level of institutions' and actors' involvement, the state of spatial plan implementation, and the lack of public participation in planning and implementation processes. These three dimensions explain 75% of the total variations, with each accounting for 35%, 24%, and 16% respectively. The study argues that the lack of planned investment allocation and poor urban spatial plan-making and implementation hinder sustainable urban development and result in haphazard development. The successful implementation of urban spatial plans requires the involvement of various actors and strong institutional support. Therefore, urban spatial decisions need to receive policy attention to ensure efficient and sustainable urban and industrial development.


Toxicity of styrene and styrene oxide on chick embryos.
Styrene and styrene oxide were injected into the air space of fertilized chicken eggs at different times during an incubation period of 14 days. The toxicity of styrene and styrene oxide when injected on the fourth day of incubation revealed an LD50 of 40 mumol/egg and 1.5 mumol/egg, respectively. Malformations were found in 0-20% of the embryos, but never in the controls. The results obtained point to a need for further experimental, and possibly epidemiologic, studies on the consequences of styrene exposure.


Sequence of small cardioactive peptide A: a second member of a class of neuropeptides in Aplysia.
Previous studies have shown that the nervous system and other tissues of molluscs contain a number of peptides that potently excite molluscan hearts. Two such peptides, termed small cardioactive peptides A and B (SCPA and SCPB) are present in large quantities in the nervous system of Aplysia. These peptides are widely distributed within the CNS and peripheral tissues and have been found to be potent modulators of synaptic transmission in Aplysia. SCPB has previously been purified from nervous tissue and sequenced. In this paper, we report the purification of SCPA and propose its sequence. This sequence was confirmed by comparing the chromatographic properties of native SCPA (labelled in organ culture) with a synthetic peptide that has the proposed sequence. A significant proportion of the sequence of the two SCPs is conserved, indicating that they are members of the same peptide class, a finding that is consistent with the recent observation that the two peptide sequences are present in a single precursor.


A robust nine-gene prognostic signature associated with tumour doubling time for hepatocellular carcinoma.
Tumour doubling time (TDT) is an indicator reflecting tumour growth rate, however, the prognostic genes associated with the TDT in hepatocellular carcinoma (HCC) have not been fully identified. We obtained mRNA expression profiles and tumour doubling time from GSE54236 and used the Pearson correlation test to identify tumour doubling time-related genes (TDTRGs). We extracted TDTRGs from The Cancer Genome Atlas (TCGA) and identified prognostic genes using univariate Cox regression analysis and Kaplan-Meier survival analysis. Lasso and multivariate Cox regression analysis assisted in constructing the signature and International Cancer Genome Consortium (ICGC) served as an external validation. We identified a total of 296 genes associated with tumour doubling time and developed a prognostic signature consisting of 9 genes. Patients were divided into high- and low-risk groups according to the uniform cutoff (0.85). Regardless of the clinical characteristics of the patients, the group at high risk exhibited obviously lower overall survival (OS) than did the group with low risk in both TCGA and ICGC cohorts. The prognostic model showed superior accuracy in both TCGA and ICGC cohorts, as confirmed by receiver operating characteristic (ROC) curve analysis. The univariate together with multivariate Cox regression analysis further suggested the ability of the signature to predict prognosis independently. A novel prognostic signature for HCC was developed and validated in the study, which may be beneficial to improve the treatment strategy of HCC.


Binocular coordination of saccades in children with vertigo: dependency on the vergence state.
The present study examines the quality of binocular coordination of saccades at far and near distance in 15 children with symptoms of vertigo headache and equilibrium disorders; these children show normal vestibular function but abnormal convergence eye movements (e.g., long time preparation, slow execution and poor accuracy, see ). The results show normal binocular saccade coordination at far distance, but large abnormal disconjugacy for saccades at near distance. During combined saccade-vergence movements (studied in six of these children), convergence remains abnormally slow. This supports the interpretation according to which poor binocular yoking of the saccades is linked to the reduced ability to produce fast convergence during the saccade; a learning mechanism based on rapid vergence would help to reduce the abducting-adducting asymmetry of the saccades. An alternative interpretation would be reduced learning ability for monocular adjustment of the saccade signals.


[The meteorological influence on cases of acute glaucoma in French-speaking Switzerland in the years 1971-1976 (author's transl)].
The authors present a meteorological study of 45 cases of acute closed-angle glacuoma. Frontal type weather, especially that associated with an invasion of maritime air from the north-west following the passage of a cold front appears able to trigger off an attack in an anatomically predisposed subject.


Biosorption of cadmium by biomass of brown marine macroalgae.
Five different brown seaweeds, Bifurcaria bifurcata, Saccorhiza polyschides, Ascophyllum nodosum, Laminaria ochroleuca and Pelvetia caniculata were studied for their ability to remove cadmium from aqueous solution. Kinetics of cadmium adsorption by all the algae were relatively fast, with 90% of total adsorption occurring in less than 1h. These experiments could be accurately described by a pseudo-second-order rate equation, obtaining values between 1.66x10(-3) and 9.92x10(-3) g/mgmin for the sorption rate constant k. Several equilibrium adsorption isotherms were obtained for the quantitative description of cadmium uptake. The use of the Langmuir isotherm led to values between 64 and 95 mg/g for qmax and between 0.036 and 0.094 L/mg for b. The effect of pH on biosorption was also studied. Acid-base properties of algae were studied by potentiometry to determine pK values (from 3.54 to 3.98) and the total number of acid groups.


Spatial Distribution of Pollinating Butterflies in Yunnan Province, Southwest China with Resource Conservation Implications.
Pollinating butterflies are an important asset to agriculture, which still depends on wild resources. Yunnan Province in Southwest China is a region with typical montane agriculture, but this resource is poorly investigated. From literature reference and specimen examination, the present study identified 554 species of pollinating butterflies (50.8% of the total butterflies) from Yunnan, with family Nymphalidae possessing the least number of pollinators (80 species, 16.0%), while the remaining four families are pollinator-rich (>73%). Tropical lowlands and mountain-valley areas possess higher species richness than those with plain terrains. The species richness of pollinating butterflies in Yunnan does not simply decline with the increase of latitude, nor is significantly different between West and East Yunnan. Zonation of pollinating butterflies using the parsimony analysis of endemicity (PAE) identified nine distribution zones and ten subzones. Most areas of endemism (AOE) are found in lowlands or mountain-valley areas, complexity of terrains, climates, and vegetation types are believed to be the main causes of such endemicity. The potential pollinating service of these butterflies could be great to montane agriculture with expanding areas of cash crops and fruit horticulture. Conservation strategies for pollinating butterflies may consist of preserving habitats and establishing butterfly-friendly agriculture based on local traditions.


Sparse asynchronous cortical generators can produce measurable scalp EEG signals.
We investigate to what degree the synchronous activation of a smooth patch of cortex is necessary for observing EEG scalp activity. We perform extensive simulations to compare the activity generated on the scalp by different models of cortical activation, based on intracranial EEG findings reported in the literature. The spatial activation is modeled as a cortical patch of constant activation or as random sets of small generators (0.1 to 3cm(2) each) concentrated in a cortical region. Temporal activation models for the generation of oscillatory activity are either equal phase or random phase across the cortical patches. The results show that smooth or random spatial activation profiles produce scalp electric potential distributions with the same shape. Also, in the generation of oscillatory activity, multiple cortical generators with random phase produce scalp activity attenuated on average only 2 to 4 times compared to generators with equal phase. Sparse asynchronous cortical generators can produce measurable scalp EEG. This is a possible explanation for seemingly paradoxical observations of simultaneous disorganized intracranial activity and scalp EEG signals. Thus, the standard interpretation of scalp EEG might constitute an oversimplification of the underlying brain activity.


Methodology for digital radiography simulation using the Monte Carlo code MCNPX for industrial applications.
This work presents a methodology for digital radiography simulation for industrial applications using the MCNPX radiography tally. In order to perform the simulation, the energy-dependent response of a BaFBr imaging plate detector was modeled and introduced in the MCNPX radiography tally input. In addition, a post-processing program was used to convert the MCNPX radiography tally output into 16-bit digital images. Simulated and experimental images of a steel pipe containing corrosion alveoli and stress corrosion cracking were compared, and the results showed good agreement between both images.


Morphology of ventricular premature beats as an aid in the electrocardiographic diagnosis of myocardial infarction.
To determine whether morphologic analysis of ventricular premature beats (VPBs) can aid in the electrocardiographic diagnosis of myocardial infarction (MI), 12-lead electrocardiograms were evaluated in 760 consecutive patients who underwent cardiac catheterization, and 2-minute multiple-lead rhythm strips were evaluated in 515 of these patients. VPBs occurred in 58 patients; 21 had prior MI diagnosed by regional akinesia or dyskinesia on left ventricular cineangiography. Standard criteria were used to diagnose prior MI from the sinus beats of the electrocardiogram. Infarction was diagnosed from the morphology of a VPB when it had a QR or QRS pattern with Q wave greater than or equal to 0.04 second. Morphologic analysis of VPBs had a low sensitivity (29%) but high specificity (97%) and high predictive value (86%) for the diagnosis of MI. Sinus beats diagnosed MI with higher sensitivity (52%, and 69% if patients with left bundle branch block and left ventricular hypertrophy were excluded from analysis) than VPB morphologic analysis (p less than 0.05), but with similar specificity (97%) and predictive value (92%). Two patients with angiographic MI had no MI according to standard electrocardiographic criteria, but did have an MI manifest by VPB morphologic analysis. Despite low sensitivity, analysis of the morphology of VPBs may be useful for the diagnosis of MI when the morphology of sinus beats is not diagnostic. Therefore, VPB analysis is complementary to the standard electrocardiographic diagnosis of MI.


Can the pattern of neuropsychological improvement obtained with cholinergic drugs be used to infer a cholinergic mechanism in other nootropic drugs?
1. Enhancement of episodic memory and reduction of intrusion errors are considered as the most characteristic outcome of cholinergic drugs administration in AD patients. 2. Since the nootropic drugs Piracetam and Oxiracetam are deemed to act through a cholinergic mechanism, we checked whether AD patients treated with these drugs would show the same pattern of neuropsychological improvement. 3. Results were negative, since (a) episodic memory showed a similar degree of improvement both in patients treated with these drugs and in patients treated with placebo; (b) the number of intrusions tended to increase, rather than to decrease, after the treatment period.


Benefits of digital thoracic drainage systems.
A number of risks and complications are associated with traditional chest drainage systems. A trust decided to trial digital drainage systems, and found the new systems improved treatment time and patient mobility.


Water, sanitation, hygiene practices, health and nutritional status among children before and during the COVID-19 pandemic: longitudinal evidence from remote areas of Dailekh and Achham districts in Nepal.
The COVID-19 pandemic drew hygiene to the center of disease prevention. The provision of adequate water, sanitation, and hygiene (WASH) services is crucial to protect public health during a pandemic. Yet, access to levels of water supply that support adequate hygiene measures are deficient in many areas in Nepal. We examined WASH practices and their impact on child health and nutritional status in two districts before and during the COVID-19 pandemic. A longitudinal and mixed method study was conducted in March-May 2018 and November-December 2021. In total, 715 children aged 0-10 years were surveyed at baseline. Of these, 490 children were assessed at endline. Data collection methods included observations, a questionnaire, stool analysis, anthropometric measurements, water quality analysis, and an assessment of clinical signs of nutritional deficiencies. We conducted 10 in-depth interviews to understand major problems related to COVID-19. Most respondents (94.2%) had heard about COVID-19; however, they did not wear face masks or comply with any social distancing protocols. Almost 94.2% of the households self-reported handwashing with soap 5-10 times per day at endline, especially after defecation, compared to 19.6% at baseline. Water quality was better at endline than at baseline with median 12 to 29 CFU Escherichia coli/100 mL (interquartile range at baseline [IQR] = 4-101) at the point of collection and 34 to 51.5 CFU Escherichia coli/100 mL (IQR = 8-194) at the point of consumption. Fever (41.1-16.8%; p = 0.01), respiratory illness (14.3-4.3%; p = 0.002), diarrhea (19.6-9.5%; p = 0.01), and Giardia lamblia infections (34.2-6.5%, p = 0.01) decreased at endline. In contrast, nutritional deficiencies such as bitot's spots (26.7-40.2%; p = 0.01), pale conjunctiva (47.0-63.3%; p = 0.01), and dermatitis (64.8-81.4%; p = 0.01) increased at endline. The inadequacy of the harvest and the lack of household income to meet households' nutritional needs increased drastically (35.0-94.2%; p = 0.01). We found that improved water quality and handwashing practices were associated with a decrease in infectious diseases. However, food security also decreased resulting in a high prevalence of nutritional deficiencies. Our findings underline that disaster preparedness should consider access to adequate WASH, nutrition, and health supplies.


Calculation of oxygen pressures in tissue with anisotropic capillary orientation. I. Two-dimensional analytical solution for arbitrary capillary characteristics.
In tissue with a distinct orientation of the oxygen supplying structures, the capillaries, a mathematical description of oxygen transport is feasible in terms of two-dimensional diffusion in a plane perpendicular to the capillaries. Muscle tissue is an example of a highly anisotropic tissue. With some additional simplifying assumptions, a solution can be constructed in terms of capillary sources for arbitrary capillary characteristics, in particular, capillary locations. The solution includes facilitated diffusion by myoglobin in the tissue. For homogeneous tissue, the solution becomes explicit allowing direct calculation of tissue oxygen pressure at any location in a field of simple geometry (circular, rectangular). Also, the size of the area into which each capillary distributes its oxygen, the oxygen supply area, is readily calculated.


Use of pneumatic lithotripsy for managing difficult CBD calculi.
About 7-12% of patients who harbor gallbladder calculi concomitant common bile duct (CBD) calculi are present. The treatment of gallbladder calculi has standardized in the form of laparoscopic cholecystectomy but management of CBD calculi is still evolving. Endoscopic removal of CBD calculi <2 cm in diameter is successful in 90-100% of cases but patients harboring stones >2 cm in diameter high failure rates can be seen. Traditionally, laparoscopically one can achieve success rate comparable to endoscopic surgery but large and impacted calculi may cause failures. If one uses pneumatic lithotripsy during laparoscopic management of CBD calculi one can achieve 100% stone clearance irrespective of size, degree of hardness and impaction. This study evaluates the feasibility of using pneumatic lithotripsy for CBD calculi. To our knowledge this is the 1st reported series of using pneumatic lithotripsy for CBD calculi. From June 2002 to June 2010 96 laparoscopic CBD explorations (LCBDE) were done for CBD calculi. Patients having choledocholithiasis with CBD diameter of >10 mm were taken for LCBDE while in patients with CBD diameter of <10 mm were referred for endoscopic clearance. Additionally ERCP failure cases were also subjected to LCBDE. Rigid nephroscope was used for LCBDE and usually calculi were removed by forceps only. In patients having large, hard &/or impacted calculi pneumatic lithotripsy were used for fragmentation. Out of the 96 patients in 12 (12.5%) cases pneumatic lithotripsy was used for stone fragmentation. Out of these 12 cases 5 (41.6%) were ERCP failure cases. At a mean hospital stay of 2.5 days 100% stone clearance was achieved in all cases with no perioperative complication. The present study shows how successfully pneumatic lithotripsy can be used to fragment large, hard &/or impacted CBD calculi. Pneumatic lithotripsy being user friendly easily available can reliably fragment CBD calculi in one session.


Meningeal seeding from rhabdomyosarcoma of the head and neck with base of the skull invasion: recognition of the clinical evolution and suggestions for management.
Rhabdomyosarcomas of the head and neck may spread by diffuse local invasion, resulting in erosion of the base of the skull with possible extension to the leptomeninges, brain, and cranial nerves, as well as invasion of the ventricular system with possible intradural, extramedullary metastases anywhere along the neuraxis. Meningeal spread of tumor is difficult to eradicate, and nearly all patients reviewed died soon after meningeal disease was evident. Patients with erosion of the base of the skull or abnormal cranial nerve findings seem to have a risk of seeding the meninges with tumor. The clinical evolution of this pattern of metastatic spread is reviewed, diagnostic studies are recommended, and therapeutic considerations are discussed. Tentative treatment guidelines are also offered.


Current management of varicose veins.
There has been an increasing trend towards less invasive methods of treating varicose veins, e.g. foam sclerotherapy, radiofrequency ablation and endovenous laser ablation, which has led many to question the more conventional methods of treating varicose veins. This review focuses on current techniques of managing varicose veins.


Side-effects and adverse events of a shoulder- and back-support exoskeleton in workers: A systematic review.
While the biomechanical effects of exoskeletons are well studied, research about potential side-effects and adverse events are limited. The aim of this systematic review was to provide an overview of the side-effects and adverse events on shoulder- and back-support exoskeletons during work tasks. Four in-field studies and 32 laboratory studies were included in this review, reporting on n = 18 shoulder exoskeletons, n = 9 back exoskeletons, n = 1 full body with a supernumerary arm, and n = 1 combination of shoulder and back exoskeleton. The most frequent side-effect reported is discomfort (n = 30), followed by a limited usability of the exoskeleton (n = 16). Other identified side-effects and adverse events were changes in muscle activity, mobility, task performance, balance and posture, neurovascular supply, gait parameters and precision. An incorrect fit of the exoskeleton and the decreased degrees of freedom are most often reported as causes of these side-effects. Two studies did not find any side-effects. This review also showed that there are differences in the occurrence of side-effects in gender, age, and physical fitness. Most studies (89%) were conducted in a laboratory setting. Most studies (97%) measured short-term effects only. Psychological and social side-effects or adverse events were not reported. Side-effects and adverse events for active exoskeletons were understudied (n = 4). It was concluded that the evidence for side-effects and adverse events is limited. If available, it mainly consists of reports of mild discomfort and limited usability. Generalisation is limited because studies were conducted in lab settings and measured short term only, and most participants were young male workers.


Synthesis of terphenyl benzimidazoles as tubulin polymerization inhibitors.
A series of new terphenyl benzimidazoles (3a-z and 3aa-ad) were synthesized and evaluated for their anticancer activity. All the 30 compounds have shown moderate to good anticancer potency, however some of the compounds (3j, 3m-t and 3aa-ad) exhibited prominent anticancer potency with GI(50) values ranging from <0.1 to 9.72 μM. These compounds exhibit G2/M phase arrest and the analysis of tubulin by Western blot experiments in case of 3t and 3ad shows the disturbances that are caused in the ratio of soluble versus polymerized tubulin in cells. Compounds 3t and 3ad are the most promising candidates amongst the series and has the potential to be taken up for further detailed studies either alone or in combination with the existing therapies.


Seroprevalence of Hydatidosis in People Referring to Reference Laboratory of Gorgan, Golestan Province, Northern Iran 2017.
Hydatidosis is a neglected global zoonotic disease, caused by larval stage of the cestode Echinococcus granulosus in human and animal. Because of high economic and medical importance of the disease, this study was performed to find the seroprevalence of human hydatidosis in Gorgan City, Golestan Province, northern Iran. In this cross-sectional study, blood samples were collected from people referring to Reference laboratory of Golestan University of Medical sciences in 2017. A relevant questionnaire was completed for demographic data for each person. Echinococcus IgG antibody was investigated by ELISA using native antigen B. The data were analyzed using SPSS software applying logistic regression. Overall, 612 blood samples were collected. Cut-off was considered 0.29. Sixteen cases (2.6%) were seropositive for hydatidosis. The seroprevalence of hydatidosis was 2.3% and 4.7% among males and females, respectively. There was no statistically significant correlation between the hydatidosis and investigated variables such as sex, age, tribes, residence, education, etc. The prevalence of human hydatidosis shows approximately the same range as other regions of Iran. Although due to the neighboring the Mazandaran Province reported as the highest seroprevalence of hydatidosis, we expected more rate of seropositivity.


High-pressure chromatography of tobacco mosaic virus on Spheron gels.
High-pressure chromatography on Spheron 300 BTD and Spheron 1000 was used to separate tobacco mosaic virus from other components of an extract from infected tobacco leaves, including F1, a protein having a molecular weight of 0.58 X 10(6). Comparative experiments have shown that the virus is not adsorbed by the carrier and is eluted in the free volume of the column; the virus is free from contamination by vegetable-juice components and is regained quantitatively. The virus can be separated partially, but distinctly, from the F1 protein by using a column of microgranular Spheron 300. Polyhydric phenols in the vegetable extract are adsorbed on Spheron and eluted from the column after a delay.


Pathological differences in the bone healing processes between tooth extraction socket and femoral fracture.
Despite various reports on the bone healing processes of tooth extraction socket and long bone fracture, the differences of pathological changes during these healing processes remain elusive. This study aims to elucidate the underlying mechanisms behind the pathophysiology of bone regeneration between the tooth extraction socket and femoral fractures through a comparative study. Eight-week-old male mice were used in the experiments. The maxillary first molar was extracted, and intramedullary nailing femoral fracture (semistabilized fracture repair) was performed in the femur. Pathological changes in these bone injuries were investigated by micro-CT, histology, immunohistochemistry, and RT-PCR until day 7 post operation. Pathological changes in drill hole injury created in cortical bone of femur were also examined. Micro-CT analyses revealed increases in mineralized tissues in both the tooth extraction socket and femoral fracture. Histological examinations revealed that tooth socket was repaired by intramembranous ossification, and intramedullary nailing femoral fracture was healed by endochondral ossification. Immunohistochemical investigation revealed that tooth socket healing associated with Sp7-positive cells but not Sox9, aggrecan, and type II collagen, while femoral fracture models exhibited positive signals for all antibodies. RT-PCR analyses revealed the expression of Sp7, Col1a1, and Col2a1 in tooth socket healing, and the expression of Sp7, Col1a1, Runx2, Sox9, Acan, Col2a1, and Col10a1 in intramedullary nailing femoral fracture. Drill hole injury was repaired primarily by intramembranous ossification when the periosteum was removed before making the hole. The present study demonstrated that the absence of cartilage appearance during tooth extraction socket healing indicates it as distinctly different pathological features from the healing processes of semistabilized femoral fracture. This study contributes to the understanding of the molecular and cellular characteristics of bone healing among the different sites of bone injury.


Civil society organizations, the implementing partners of the Global Vaccine Action Plan.
The authors illustrate by way of civil society (CS) experiences in Pakistan, India, and Ghana how the guiding principles of CS and civil society organizations (CSOs) align with those of the Global Vaccine Action Plan (GVAP); (i.e., country ownership, shared responsibility and partnership, equity, integration, sustainability, and innovation). These experiences show how CS is contributing to GVAP goals such as global polio eradication and improving vaccination coverage by removing barriers and ultimately working toward achieving Millennium Development Goal (MDG) 4-reducing child mortality. A number of CSOs working in the field of child health share some of the objectives enlisted in GVAP: that immunization becomes a national health priority; individuals, families, communities understand the importance of immunization; benefits of immunization are equitably extended to all people; and vaccination systems are part of an integrated health system.


[Water-electrolyte balance and plasma corticosteroid level in patients with food poisoning and salmonellosis].
Altogether 57 patients with alimentary toxoinfections of obscure etiology and 39 patients with the gastrointestinal form of salmonellosis of average gravity were examined. Two methods were employed: rehydration and incorporation of indomethacin in the therapeutic scheme. The time course of the studied indices in the patients with salmonellosis was similar to dynamic changes in the patients with alimentary toxoinfections. The incorporation of indomethacin in the therapeutic scheme brought the indices of water-electrolyte metabolism and corticosteroid secretion more rapidly to normal.