Quality control methods for linear accelerator radiation and mechanical axes alignment.
The delivery accuracy of highly conformal dose distributions generated using intensity modulation and collimator, gantry, and couch degrees of freedom is directly affected by the quality of the alignment between the radiation beam and the mechanical axes of a linear accelerator. For this purpose, quality control (QC) guidelines recommend a tolerance of ±1 mm for the coincidence of the radiation and mechanical isocenters. Traditional QC methods for assessment of radiation and mechanical axes alignment (based on pointer alignment) are time consuming and complex tasks that provide limited accuracy. In this work, an automated test suite based on an analytical model of the linear accelerator motions was developed to streamline the QC of radiation and mechanical axes alignment. The proposed method used the automated analysis of megavoltage images of two simple task-specific phantoms acquired at different linear accelerator settings to determine the coincidence of the radiation and mechanical isocenters. The sensitivity and accuracy of the test suite were validated by introducing actual misalignments on a linear accelerator between the radiation axis and the mechanical axes using both beam steering and mechanical adjustments of the gantry and couch. The validation demonstrated that the new QC method can detect sub-millimeter misalignment between the radiation axis and the three mechanical axes of rotation. A displacement of the radiation source of 0.2 mm using beam steering parameters was easily detectable with the proposed collimator rotation axis test. Mechanical misalignments of the gantry and couch rotation axes of the same magnitude (0.2 mm) were also detectable using the new gantry and couch rotation axis tests. For the couch rotation axis, the phantom and test design allow detection of both translational and tilt misalignments with the radiation beam axis. For the collimator rotation axis, the test can isolate the misalignment between the beam radiation axis and the mechanical collimator rotation axis from the impact of field size asymmetry. The test suite can be performed in a reasonable time (30-35 min) due to simple phantom setup, prescription-based beam delivery, and automated image analysis. As well, it provides a clear description of the relationship between axes. After testing the sensitivity of the test suite to beam steering and mechanical errors, the results of the test suite were used to reduce the misalignment errors of the linac to less than 0.7-mm radius for all axes. The proposed test suite offers sub-millimeter assessment of the coincidence of the radiation and mechanical isocenters and the test automation reduces complexity with improved efficiency. The test suite results can be used to optimize the linear accelerator's radiation to mechanical isocenter alignment by beam steering and mechanical adjustment of gantry and couch.


In vivo visualization of the neuromuscular junction before and after autologous nerve transfer in the rat.
In vivo visualization of the neuromuscular junction with epifluorescence imaging techniques has become a successful method of observing the ongoing process of re-occupation by regenerating motor axons of former post-synaptic sites after nerve injury. By using a light-integrating video camera for digital documentation, all parts of the neuromuscular junction can be visualized, as detailed as when documented with high-speed film, but with a minimum light intensity to prevent damage of neural or muscular structures. Results from comparisons of pre- and post-synaptic staining indicate a non-reoccupation rate up to 37 percent at a 55-day interval after nerve transfer, and up to 34 percent at a 66-day postoperative interval. Morphologic findings suggest that these high non-reoccupation rates are caused jointly by intramuscular missprouting, an insufficient intramuscular guidance apparatus, and intramuscular microneuroma formation at the insufficient neuromuscular junction.


Current status of radical systematic lymphadenectomy in pancreatic cancer--a review of the literature.
Pancreatic cancer is the fourth most common cause of death in malignancies with an incidence of 8-12 cases per 100000 in western world. In spite of numerous modifications in therapeutical approaches, prognosis has not improved. In the last few years numerous studies have been performed to reduce tumor mortality with more radical surgical procedures. Several articles of the last 15 years have been investigated to objectivate the benefit of extended lymphadenectomy in pancreatic surgery. Staging of the cancers, prognostic factors, technique and interpretation of lymphadenectomy have been analysed All studies document a lowered perioperative mortality in pancreatic resections. The procedure is counted as a standardized and safe one. However, several controversies exist. The distinct staging systems in Japan and the western world aggravate the comparison in all studies. Japanese authors in mostly retrospective analyses seem to document a survival benefit by radical surgery. Similar results could not be achieved by western authors. Over all, a significant benefit in extreme radical surgery could not bee found. However, there are indications of subgroups of patients in whom extended lymphadenectomy might be beneficial. This subgroup should be defined only by large multicentric, prospective, randomized studies.


Risk factors of hepatitis B virus infection in Turkey: A population-based, case-control study: Risk Factors for HBV Infection.
Although the World Health Organization (WHO) classifies Turkey as a country with a moderate-high prevalence of hepatitis B virus (HBV) infection, there is little data on HBV transmission in this country. To identify risk factors for HBV infection, we performed a retrospective case-control study between January 2007 and December 2009. Acute HBV patients and population controls were selected, and data from these groups were analyzed by logistic regression method. The study included 129 patients with acute HBV infection and 219 controls. Hemodialysis (OR:8.2, 95% CI: 4.17-16.61, p < 0.05), having an HBsAg (+) spouse (OR: 4.3, 95% CI:2.17-8.53, p < 0.05), living with an HBsAg (+) parent(s) (OR: 3.25, 95% CI:1.73-6.12, p < 0.05), and being male (OR: 1.34, 95% CI: 0.82-2.21, p < 0.05) were independent risk factors that were potentially associated with HBV infection. More than one-third of female patients had a significantly higher risk (34.5% vs. 13.5%, p < 0.05) of acquiring HBV from their sexual partners. Hemodialysis was the most frequent risk factor (46.9% vs. 20%, x (2) = 10.45, p < 0.05) for patients aged over 31 years, and living with HBsAg (+) parents was a significantly higher risk factor (28.8% vs. 10.2%, x (2) = 6.15, p < 0.05) that is more likely to lead to HBVin patients aged under 30 years. This study suggests that persons in Turkey who undergo hemodialysis are at high risk for acquiring HBV. Having an HBsAg (+) spouse (sexual transmission) or living with HBsAg (+) parents (household transmission) are significant risk factors for HBV transmission. Vaccination appears to be better preventive method against the spread of HBV.


Chiral selectivity of guanosine media in capillary electrophoresis.
Gels formed by self-association of monomeric guanosine compounds join numerous other agents such as cyclodextrins, crown ethers, chiral surfactants, antibiotics, proteins, and polysaccharides for chiral separations. Guanosine gels (G-gels) are self-assembled networks of hydrogen-bonded tetrads formed by guanosine nucleotides and their derivatives. The tetrads stack upon themselves to form columnar, helical aggregates that are stabilized by π-π interactions and centrally located cations. Previous work showed the effectiveness of G-gels formed by guanosine-5'-monophophate for separation of the enantiomers of the cationic drug propranolol using capillary electrophoresis. Subsequently, it was found that not all chiral compounds could be resolved into their enantiomers, leading us to investigate in this work the structural features that appear to be correlated to enantiomerically selective interactions of chiral compounds with G-gels. For those compounds (anionic 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate and zwitterionic tryptophan) for which enantiomeric resolution was achieved, the effects of experimental conditions and G-gel composition were examined. For other compounds with no net charge (hydrobenzoin and zwitterionic amino acids and derivatives), the migration times were used as an indicator of the extent of interaction with the G-gel run buffer. It was found that the extent of interaction alone does not determine the chiral selectivity of the G-gel, indicating that the mechanism of chiral separation involves particular structural characteristics of the chiral compounds.


Sjögren's syndrome and ranula development.
We hypothesized that the extravasation of saliva from damaged ducts with lymphocytic infiltration in patients with Sjögren's syndrome causes ranulas. There are too many uncertainties to support this hypothesis. The aim of this study was to investigate whether there is an association between Sjögren's syndrome and ranulas. We observed three cases of patients with ranulas who were also diagnosed with Sjögren's syndrome at the same facility. These cases led to the question of whether there are other such cases, and thus, an exhaustive literature search was conducted. Three cases in two case reports of mucocele of the floor of the mouth associated with adult Sjögren's syndrome were noted. Including our cases, until now, there have been six cases of ranula with adult Sjögren's syndrome. It could be useful to investigate whether patients presenting with a ranula are also affected by Sjögren's syndrome and, conversely, investigate patients with Sjögren's syndrome longitudinally to see whether they develop ranulas.


Ornithine decarboxylase gene (CaODC1) is specifically induced during TMV-mediated but salicylate-independent resistant response in hot pepper.
A gene encoding putative ornithine decarboxylase (ODC) has been isolated by differential screening of a cDNA library from the resistant hot pepper (Capsicum annuum L.) inoculated with avirulent tobacco mosaic virus (TMV) pathotype P0. In hot pepper plants, transcripts of the CaODC1 (C. annuum ODC1) gene started to accumulate at 24 h post-inoculation of TMV-P0 and the signal was spread systemically. The transcript level of CaODC1 was increased rapidly in a hot pepper resistant to Xanthomonas campestris pv. vesicatoria (Xcv) but not in a susceptible hot pepper after inoculation. These results suggest possible role(s) for CaODC1 in plant defense against a broad range of pathogens including viruses and bacteria.


Fluorogenic substrates and pre-column derivatization for monitoring the activity of bile salt hydrolase from Clostridium perfringens.
The bile acid pool has a profound impact on human health and disease. The intestinal microbiota initiates the metabolism of conjugated bile acids through a critical first step catalyzed by bacterial bile salt hydrolase (BSH) and provides unique contributions to the diversity of bile acids. There has been great interest in surveying BSH activity. We compared two substrates with either 2-(7-amino-4-methyl-coumarinyl)acetic acid or 7-amino-4-methyl-coumarin as fluorescent reporters of BSH activity. The BSH-catalyzed conversion of the natural substrate taurocholic acid was followed through an HPLC-based assay by applying 7-nitrobenzo[c][1,2,5]oxadiazole as scavenger for taurine, released in the enzymatic reaction. Hence, a new opportunity to monitor the activity of bile salt hydrolases was introduced.


Stereochemical course in water addition during LUP1-catalyzed triterpene cyclization.
Arabidopsis thaliana LUP1 (At1g78970) catalyzes the cyclization of oxidosqualene into lupeol and 3beta,20-dihydroxylupane (lupanediol). The stereochemical course of water addition to the lupanyl cation was studied. The X-ray crystal structure of lupanylepoxide 3,5-dinitrobenzoate established the configuration of epoxide as 20S. LiAlD4 reduction of the epoxide enabled the chemical shift assignment of prochiral methyl groups at C20 of lupanediol. Correlation of these methyl groups with biosynthetic lupanediol from [1,2-(13)C(2)] acetate established the stereochemical course of water addition. [reaction: see text].


Core decompression of the femoral head for osteonecrosis using percutaneous multiple small-diameter drilling.
Osteonecrosis is a disease with a wide ranging etiology and poorly understood pathogenesis seen commonly in young patients. Core decompression has historically been used in patients with small-sized or medium-sized precollapse lesions in an attempt to forestall disease progression. Typically, an 8-10 mm wide cannula trephine is used to do this procedure. The authors report on a new technique using multiple small drillings with a 3-mm Steinman pin to effectuate the core decompression. In this report, there were 32 of 45 hips (71%; 35 patients) with a successful clinical result at a mean followup of 2 years (range, 20-39 months). Twenty four of 30 Stage I hips (80%; 23 patients) had successful outcomes compared with 8 of 15 Stage II hips (57%; 12 patients) with no surgical complications occurring with this technique. This procedure is technically straightforward and led to minimal morbidity with no surgical complications. It may be effective in delaying the need for total hip arthroplasty in young patients with early (precollapse) stages of femoral head osteonecrosis.


Injecting drug users and their health seeking behavior: a cross-sectional study in dhaka, bangladesh.
Introduction and Aim. Injecting drug users (IDUs) are amongst the most vulnerable people to acquisition of HIV/AIDS. This study aims to collect information on IDUs and their health seeking behavior in Bangladesh. Design and Methods. A cross-sectional study was conducted among 120 IDUs attending a drug rehabilitation center in Dhaka, Bangladesh. Data were collected on sociodemographics, drug use, health seeking behavior, knowledge of injecting drugs, and sexual behavior. Results. The mean ± SD and median (IQR) age of the participants were 32.5 ± 21.3 and 33 (27-38) years, respectively, with only 9.2% females. Injection buprenorphine was the drug of choice for 40% of participants, and 58% of the participants first started drug use with smoking cannabis. 73.3% of participants shared needles sometimes and 57.5% were willing to use the needle exchange programs. 60% of the participants had no knowledge about the diseases spread by injection. Condom use during the last intercourse with regular partners was 11.7% and with any partners 15.8%. Conclusion. IDUs in Bangladesh are a high-risk group for HIV/AIDS due to lack of knowledge and risky behaviors. Education and interventions specifically aimed at IDUs are needed, because traditional education may not reach IDUs or influence their behavior.


Staging lung cancer: role of endobronchial ultrasound.
Accurate staging is the first step in the management of lung cancer. Nodal staging is quite important for physicians to be able to judge the primary operability of patients harboring no distant metastasis. For many years, mediastinoscopy has been considered a "gold standard" modality for nodal staging. Mediastinoscopy is known to be a highly sensitive procedure for mediastinal staging and has been performed worldwide, but is invasive. Because of this, clinicians have sought a less invasive modality for nodal staging. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive modality for diagnosis and staging of lung cancer. EBUS-TBNA is a needle biopsy procedure that has accessibility compatible with the reach of the convex-probe EBUS scope, so N1 nodes are also assessable. The diagnostic yield is similar to that of mediastinoscopy, and the core obtained by the dedicated needle biopsy can be used for histological assessment to determine the subtypes of lung cancer. The samples can also be used to test for various biomarkers using immunohistochemistry, polymerase chain reaction for DNA/complementary DNA, and in situ hybridization, and the technique is useful for selecting candidates for specific molecular-targeted therapeutic agents. According to the newly published American College of Chest Physicians guideline, EBUS-TBNA is now considered "the best first test" for nodal staging in patients with radiologically suspicious nodes. Appropriate training and thorough clinical experience is required to be able to perform correct nodal staging using this procedure.


Two-stage method to remove population- and individual-level outliers from longitudinal data in a primary care database.
PURPOSE: In the UK, primary care databases include repeated measurements of health indicators at the individual level. As these databases encompass a large population, some individuals have extreme values, but some values may also be recorded incorrectly. The challenge for researchers is to distinguish between records that are due to incorrect recording and those which represent true but extreme values. This study evaluated different methods to identify outliers. METHODS: Ten percent of practices were selected at random to evaluate the recording of 513,367 height measurements. Population-level outliers were identified using boundaries defined using Health Survey for England data. Individual-level outliers were identified by fitting a random-effects model with subject-specific slopes for height measurements adjusted for age and sex. Any height measurements with a patient-level standardised residual more extreme than ±10 were identified as an outlier and excluded. The model was subsequently refitted twice after removing outliers at each stage. This method was compared with existing methods of removing outliers. RESULTS: Most outliers were identified at the population level using the boundaries defined using Health Survey for England (1550 of 1643). Once these were removed from the database, fitting the random-effects model to the remaining data successfully identified only 75 further outliers. This method was more efficient at identifying true outliers compared with existing methods. CONCLUSIONS: We propose a new, two-stage approach in identifying outliers in longitudinal data and show that it can successfully identify outliers at both population and individual level. Copyright © 2011 John Wiley & Sons, Ltd.


PIDD mediates NF-kappaB activation in response to DNA damage.
Activation of NF-kappaB following genotoxic stress allows time for DNA-damage repair and ensures cell survival accounting for acquired chemoresistance, an impediment to effective cancer therapy. Despite this clinical relevance, little is known about pathways that enable genotoxic-stress-induced NF-kappaB induction. Previously, we reported a role for the p53-inducible death-domain-containing protein, PIDD, in caspase-2 activation and apoptosis in response to DNA damage. We now demonstrate that PIDD plays a critical role in DNA-damage-induced NF-kappaB activation. Upon genotoxic stress, a complex between PIDD, the kinase RIP1, and a component of the NF-kappaB-activating kinase complex, NEMO, is formed. PIDD expression enhances genotoxic-stress-induced NF-kappaB activation through augmented sumoylation and ubiquitination of NEMO. Depletion of PIDD and RIP1, but not caspase-2, abrogates DNA-damage-induced NEMO modification and NF-kappaB activation. We propose that PIDD acts as a molecular switch, controlling the balance between life and death upon DNA damage.


The protein phosphatases involved in cellular regulation. 2. Purification, subunit structure and properties of protein phosphatases-2A0, 2A1, and 2A2 from rabbit skeletal muscle.
Protein phosphatases-2A0, 2A1 and 2A2 have been purified to homogeneity from rabbit skeletal muscle. Approximately 1 mg of phosphatase-2A0 and 2A1, and 0.5 mg of phosphatase-2A2, was isolated from 4000 g muscle within 10 days. Protein phosphatases-2A0 and 2A1 each comprised three subunits, termed A, B' and C (2A0) or A, B and C (2A1), while phosphatase-2A2 contained only two subunits, A and C. The A and C components of phosphatases-2A0, 2A1 and 2A2 had indistinguishable mobilities on sodium dodecyl sulphate/polyacrylamide gels and identical peptide maps. By these criteria, the C component was also identical to the catalytic subunit of phosphatase-2A purified from ethanol-treated muscle extracts. The electrophoretic mobilities of the B and B' subunits were slightly different, and their peptide maps were distinct. The molecular masses of the native enzymes determined by sedimentation equilibrium centrifugation were 181 +/- 6 kDa (2A0), 202 +/- 6 kDa (2A1) and 107 +/- 5 kDa (2A2), while those of the subunits estimated by sodium dodecyl sulphate/polyacrylamide gel electrophoresis were 60 kDa (A), 55 kDa (B), 54 kDa (B') and 36 kDa (C). These values, in conjunction with molar ratios estimated by densitometric analyses of the gels, suggest that the subunit structures of the enzymes are AB'C2 (2A0), ABC2 (2A1) and AC (2A2). Protein phosphatase-2A2 appears to be derived from 2A0 and/or 2A1 during purification through degradation or dissociation of the B' and/or B subunits. Protein phosphatases-2A0, 2A1 and 2A2 were the only phosphorylase phosphatases in rabbit skeletal muscle that were activated by the basic proteins, protamine (A0.5 = 0.25 microM), histone H1 (A0.5 = 0.3 microM) and polylysine (A0.5 = 0.04 microM). Activation by protamine varied over 5-20-fold for phosphatase-2A0 and 5-7-fold for phosphatases-2A1 and 2A2. The dephosphorylation of glycogen synthase was activated by basic proteins in a similar manner to the phosphorylase phosphatase activity. The isolated C subunit was also stimulated by histone H1 and protamine, but 5-10-fold higher concentrations were required, and with phosphorylase as substrate, maximum activation was only about 2-fold. Activation by basic proteins appears to involve their interaction with the A and/or C subunits, but not with the B or B' subunits, or substrates phosphorylase and glycogen synthase.


Genes, variant genes, and pseudogenes of the human tRNA(Val) gene family are differentially expressed in HeLa cells and in human placenta.
Pre-tRNAs(Val) were identified in unfractionated tRNA preparations from HeLa cells and human placenta and their 5' leader structures were deduced from the nucleotide sequences of the corresponding cDNAs. Several of these precursors can be assigned to nine out of the eleven members of the human tRNA(Val) gene family characterized so far, which demonstrates that these gene loci are actively transcribed in vivo. Among the expressed genes there are (a) genes for the two known tRNA(Val) isoacceptor species from human placenta, (b) gene variants that exhibit sequence alterations as compared to conventional genes, and (c) pseudogenes that produce processing-deficient precursors which are not matured to tRNAs. The transcription products of several yet unknown tRNA(Val) genes have also been detected. Furthermore, different expression patterns are observed in the two cell types studied. These data allow for the first time an insight into the in vivo expression of a human tRNA gene family.


Variability and vulnerability at the ecological level: implications for understanding the social determinants of health.
We examined variability in disease rates to gain understanding of the complex interactions between contextual socioeconomic factors and health. We compared mortality rates between New York and California counties in the lowest and highest quartiles of socioeconomic status (SES), assessed rate variability between counties for various outcomes, and examined correlations between outcomes' sensitivity to SES and their variability. Outcomes with mortality rates that differed most by county SES were among those whose variability across counties was high (e.g., AIDS, homicide, cirrhosis). Lower-SES counties manifested greater variability among outcome measures. Differences in health outcome variability reflect differences in SES impact on health. Health variability at the ecological level might reflect the impact of stressors on vulnerable populations.


Differential expression of antioxidant system genes in honey bee (Apis mellifera L.) caste development mitigates ROS-mediated oxidative damage in queen larvae.
The expression of morphological differences between the castes of social bees is triggered by dietary regimes that differentially activate nutrient-sensing pathways and the endocrine system, resulting in differential gene expression during larval development. In the honey bee, Apis mellifera, mitochondrial activity in the larval fat body has been postulated as a link that integrates nutrient-sensing via hypoxia signaling. To understand regulatory mechanisms in this link, we measured reactive oxygen species (ROS) levels, oxidative damage to proteins, the cellular redox environment, and the expression of genes encoding antioxidant factors in the fat body of queen and worker larvae. Despite higher mean H2O2 levels in queens, there were no differences in ROS-mediated protein carboxylation levels between the two castes. This can be explained by their higher expression of antioxidant genes (MnSOD, CuZnSOD, catalase, and Gst1) and the lower ratio between reduced and oxidized glutathione (GSH/GSSG). In worker larvae, the GSG/GSSH ratio is elevated and antioxidant gene expression is delayed. Hence, the higher ROS production resulting from the higher respiratory metabolism in queen larvae is effectively counterbalanced by the up-regulation of antioxidant genes, avoiding oxidative damage. In contrast, the delay in antioxidant gene expression in worker larvae may explain their endogenous hypoxia response.


Tissue Imprinting on 2D Nanoflakes-Capped Silicon Nanowires for Lipidomic Mass Spectrometry Imaging and Cancer Diagnosis.
Spatially resolved tissue lipidomics is essential for accurate intraoperative and postoperative cancer diagnosis by revealing molecular information in the tumor microenvironment. Matrix-free laser desorption ionization mass spectrometry imaging (LDI-MSI) is an emerging attractive technology for label-free visualization of metabolites distributions in biological specimens. However, the development of LDI-MSI technology that could conveniently and authentically reveal molecular distribution on tissue samples is still a challenge. Herein, we present a tissue imprinting technology by retaining tissue lipids on 2D nanoflakes-capped silicon nanowires (SiNWs) for further mass spectrometry imaging and cancer diagnosis. The 2D nanoflakes were prepared by liquid exfoliation of molybdenum disulfide (MoS2) with nitrogen-doped graphene quantum dots (NGQDs), which serve as both intercalation agent and dispersant. The obtained NGQD@MoS2 nanoflakes were then decorated on the tip of vertical SiNWs, forming a hybrid NGQD@MoS2/SiNWs nanostructure, which display excellent lipid extraction ability, enhanced LDI efficiency and molecule imaging capability. The peak number and total ion intensity of different lipids species on animal lung tissues obtained by tissue imprinting LDI-MSI on NGQD@MoS2/SiNWs were ∼4-5 times greater than those on SiNWs substrate. As a proof-of-concept demonstration, the NGQD@MoS2/SiNWs nanostructure was further applied to visualize phospholipids on sliced non small cell lung cancer (NSCLC) tissue along with the adjacent normal tissue. On the basis of selected feature lipids and machine learning algorithm, a prediction model was constructed to discriminate NSCLC tissues from the adjacent normal tissues with an accuracy of 100% for the discovery cohort and 91.7% for the independent validation cohort.


[The feasibility of application of reverse docking method to the selectivity studies of protein kinase inhibitors].
This investigation is to explore the feasibility of applying reverse docking method to the selectivity studies of protein kinase inhibitors. Firstly, a database that consists of 422 protein kinase structures was established through collecting the reported crystal structures or homology modeling. Then a reverse docking based method of protein kinase target screening was established, followed by the optimization of related parameters and scoring functions. Finally, seven typical selective kinase inhibitors were used to test the established method. The results show that the selective targets of these inhibitors have relatively high scoring function values (ranking in the first 35% of the tested kinase targets according to the scoring function values). This implies that the reverse docking method can be applied to the virtual screening of kinase targets and further to the selectivity studies of protein kinase inhibitors.


Mechanically flexible and multifunctional polymer-based graphene foams for elastic conductors and oil-water separators.
We present a novel strategy for the fabrication of ordered and flexible polymer-based graphene foams by self-assembly of graphene sheets on a 3D polymer skeleton. The obtained graphene foams show excellent mechanical, electrical, and hydrophobic properties, thus holding great potential as elastic conductors and oil-water separators.


Quantitative mapping of the per-axon diffusion coefficients in brain white matter.
This article presents a simple method for estimating the effective diffusion coefficients parallel and perpendicular to the axons unconfounded by the intravoxel fiber orientation distribution. We also call these parameters the per-axon or microscopic diffusion coefficients. Diffusion MR imaging is used to probe the underlying tissue material. The key observation is that for a fixed b-value the spherical mean of the diffusion signal over the gradient directions does not depend on the axon orientation distribution. By exploiting this invariance property, we propose a simple, fast, and robust estimator of the per-axon diffusion coefficients, which we refer to as the spherical mean technique. We demonstrate quantitative maps of the axon-scale diffusion process, which has factored out the effects due to fiber dispersion and crossing, in human brain white matter. These microscopic diffusion coefficients are estimated in vivo using a widely available off-the-shelf pulse sequence featuring multiple b-shells and high-angular gradient resolution. The estimation of the per-axon diffusion coefficients is essential for the accurate recovery of the fiber orientation distribution. In addition, the spherical mean technique enables us to discriminate microscopic tissue features from fiber dispersion, which potentially improves the sensitivity and/or specificity to various neurological conditions. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc.


High-intensity statin therapy in patients with chronic kidney disease: a systematic review and meta-analysis.
To evaluate the efficacy and safety of high-intensity statin therapy in patients with chronic kidney disease (CKD). A systematic review and meta-analysis. Randomised controlled trials (RCTs) comparing high-intensity statin therapy (atorvastatin 80 mg or rosuvastatin 20/40 mg) with moderate/mild statin treatment or placebo were derived from the databases (PubMed, Embase, Ovid, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, and ISI Web of Knowledge). Primary end points: clinical events (all-cause mortality, stroke, myocardial infarction and heart failure); secondary end points: serum lipid, renal function changes and adverse events. A total of six RCTs with 10,993 adult patients with CKD were included. A significant decrease in stroke was observed in the high-intensity statin therapy group (RR 0.69, 95% CI 0.56 to 0.85). However, the roles of high-intensity statin in decreasing all-cause mortality (RR 0.85, 95% CI 0.67 to 1.09), myocardial infarction (RR 0.69, 95% CI 0.40 to 1.18) and heart failure (RR 0.73, 95% CI 0.48 to 1.13) remain unclear with low evidence. High-intensity statin also had obvious effects on lowering the LDL-C level but no clear effects on renal protection. Although pooled results showed no significant difference between the intervention and control groups in adverse event occurrences, it was still insufficient to put off the doubts that high-intensity statin might increase adverse events because of limited data sources and low quality evidences. High-intensity statin therapy could effectively reduce the risk of stroke in patients with CKD. However, its effects on all-cause mortality, myocardial infarction, heart failure and renal protection remain unclear. Moreover, it is hard to draw conclusions on the safety assessment of intensive statin treatment in this particular population. More studies are needed to credibly evaluate the effects of high-intensity statin therapy in patients with CKD.


Effects of mechanical weeding on soil fertility and microbial community structure in star anise (Illicium verum Hook.f.) plantations.
Recently, the effects of weed control on crop yield, quality and soil fertility have been increasingly investigated. However, soil microorganism diversity under weed control, especially for aromatic plants, is little studied. Mechanical weeding effects on soil fertility and microbial diversity in star anise plantations remain unknown, limiting improvements in crop quality and yield through weed control. Therefore, mechanical weeding (MW) and no weeding (NW) zones were randomly designed in the same star anise plantation to study the mechanical weeding impacts on soil biological properties and microbial diversity. The phosphatase activity of MW soil was significantly higher than that of NW soil; however, aminopeptidase activity was significantly lower than that under NW. There was no significant difference in β-glucosidase activity between MW and NW. Moreover, soil microbial biomass C and N in MW soil were significantly higher than those of NW, but soil microbial biomass P was significantly lower than that of NW. Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, Planctomycetes, WPS-2, Firmicutes and Verrucomicrobia were the predominant bacterial phyla in MW and NW soils. Specifically, Bacteroidetes was enriched in MW soil, being the unique dominant bacteria. Ascomycota, Basidiomycota, unclassified_k_Fungi, Rozellomycota and Mortierellomycota were the predominant fungi in MW and NW soils. The numbers of dominant bacterial genera (> 1%) were 26 and 23 for NW and MW soils, respectively. Among them, norank_f__norank_o__norank_c__Subgroup_6, 1921-2 and norank_f__norank_o__B12-WMSP1 went undetected in MW soil. Moreover, the numbers of dominant fungi in soils of star anise plantations were 11 and 9 for NW and MW, respectively. Among them, only unclassified_f__Clavicipitaceae and Mortierella went undetected in MW soils. Thus, soil microbial community structures are not significantly altered by mechanical weeding. The above results suggest that soil fertility can be improved and soil heath can be maintained by mechanical weeding in star anise plantations. Moreover, soil-borne diseases maybe easily occurred under NW treatment in star anise plantation.


[Clinical data mining by exploring public MIMIC-II intensive care database].
This paper introduces a free and publicly open ICU database: multi-parameter intelligent monitoring in intensive care II: MIMIC-II, which has been built up and maintained by the laboratory of computational physiology at the Massachusetts Institute Technology, Beth Israel Deaconess Medical Center and Philips Healthcare over the past decade. This paper briefly introduces its infrastructure, implementation and applications in clinical studies. Clinical study pertaining to circadian variation in heart rate and blood pressure during sepsis is shown as a typical example of research performed with MIMIC-II. In this study, it was found there was significant difference in circadian variation in both heart rate and blood pressure between survival and non-survival groups in septic patients. This study tackled several important techniques necessary for the investigation of the circadian rhythm.


Molecular simulation of liquid water confined inside graphite channels: thermodynamics and structural properties.
We carried out molecular dynamics simulations to describe the properties of water inside a narrow graphite channel. Two stable phases were found: a low-density one made of water clusters adsorbed on the graphite sheets and a liquid one that fills the entire channel, forming several layers around a bulk-like region. We analyzed the interfacial structure, orientational order, water residence times in several regions, and hydrogen bonding of this last water phase, calculating also a quantity of electrochemical interest, the probability of electron tunneling through interfacial water. The results are in good qualitative agreement with the available experimental data.


Triiodothyronine improves age-induced glucose intolerance and increases the expression of sirtuin-1 and glucose transporter-4 in skeletal muscle of aged rats.
To evaluate the potential beneficial impact and to clarify the underlying mechanisms of triiodothyronine (T3) on glucose intolerance in aged rats. Rats were divided into adult group, aged group, and T3-treated aged group (T3-aged). T3 was administered at a dose of 8 µg/kg body weight for 2 weeks. In comparison to adult group, aged rats presented significant higher levels of fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR). Glucose area under the curve (AUC), and peak glycemia, estimated from oral glucose tolerance curve, were significantly increased along with decreased mRNA expression of skeletal muscle sirtuin-1, glucose transporter-4 (GLUT-4) and uncoupling protein-3 (UCP-3) in aged versus adult group. T3 administration significantly decreased the serum levels of fasting insulin, HOMA-IR, glucose AUC, and peak glycemia in T3-aged versus aged rats. Skeletal muscle mRNA expression of sirtuin-1 and GLUT-4 were increased, whereas UCP-3 was not changed by T3 administration. T3 administration improved glucose intolerance, and decreased insulin resistance in aged rats. This was associated with upregulation of skeletal muscle sirtuin-1 and GLUT-4 which could mediate such beneficial effect.


Mouse monoclonal antibody to embryonic antigen: development, cross-reactivity with rodent and human tumors, and preliminary polypeptide characterization.
Hybridomas producing IgM and IgG monoclonal antibodies (MoAb) to embryonic or fetal antigens (EA) were obtained in a completely syngeneic system. Lethally irradiated, 13-day-gestation, C57BL/6N mouse fetal cells or KCI extracts of these fetal cells obtained from primaparous donors were used as immunogens in several regimens to induce splenocytes in C57BL/6N mice that were utilized to form the hybridomas following fusion with a mouse myeloma line. Successful growth and cloning of the IgM-producing hybridomas required supplementation with factor(s) produced in the growth medium of the macrophage cell line RAW 264.7. An enzyme-linked immunosorbent assay (ELISA) was employed to screen the primary fusion hybridomas for antibody directed against fetal cell or adult cell determinants with the use of freshly explanted tissues. Glutaraldehyde-fixed fetal cells as well as crude fetal cell membranes were used as EA+ target cells (i.e., cell lines known to activate T-lymphocyte-mediated tumor resistance) in a solid-phase ELISA to perform quantitative ELISA adsorption tests of the MoAb. The anti-EA monoclonal IgM and the IgG detected common, embryo-specific antigen(s) on mouse, hamster, and human fetuses. Term fetal cells and adult normal tissues of the mouse, hamster, and human did not express cross-reactive determinants for the MoAb by absorption analysis and/or by direct binding in ELISA. EA expression as oncofetal antigens could also be detected with the monoclones on several rodent tumor cell lines tested as well as on a variety of human carcinomas but not on a spectrum of normal human tissues with the use of indirect ELISA absorption and affinity gel and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses. Fluorescence analysis with the monoclones demonstrated specific reactivity with the surface of EA+ tumor cells in the FACS IV flow cytometer. The responsible antigen was carried on a 44- and a 200-kilodalton polypeptide.


Observation of peak neoclassical toroidal viscous force in the DIII-D tokamak.
Observation of a theoretically predicted peak in the neoclassical toroidal viscosity (NTV) force as a function of toroidal plasma rotation rate Ω is reported. The NTV was generated by applying n=3 magnetic fields from internal coils to low Ω plasmas produced with nearly balanced neutral beam injection. Locally, the peak corresponds to a toroidal rotation rate Ω(0) where the radial electric field E(r) is near zero as determined by radial ion force balance.


Chemically Modified Cpf1-CRISPR RNAs Mediate Efficient Genome Editing in Mammalian Cells.
CRISPR-based gene editing is a powerful technology for engineering mammalian genomes. It holds the potential as a therapeutic, although much-needed in vivo delivery systems have yet to be established. Here, using the Cpf1-crRNA (CRISPR RNA) crystal structure as a guide, we synthesized a series of systematically truncated and chemically modified crRNAs, and identify positions that are amenable to modification while retaining gene-editing activity. Modified crRNAs were designed with the same modifications that provide protection against nucleases and enable wide distribution in vivo. We show crRNAs with chemically modified terminal nucleotides are exonuclease resistant while retaining gene-editing activity. Chemically modified or DNA-substituted nucleotides at select positions and up to 70% of the crRNA DNA specificity region are also well tolerated. In addition, gene-editing activity is maintained with phosphorothioate backbone substitutions in the crRNA DNA specificity region. Finally, we demonstrate that 42-mer synthetic crRNAs from the similar CRISPR-Cas9 system are taken up by cells, an attractive property for in vivo delivery. Our study is the first to show that chemically modified crRNAs of the CRISPR-Cpf1 system can functionally replace and mediate comparable gene editing to the natural crRNA, which holds the potential for enhancing both viral- and non-viral-mediated in vivo gene editing.


Heterogeneous k-core versus bootstrap percolation on complex networks.
We introduce the heterogeneous k-core, which generalizes the k-core, and contrast it with bootstrap percolation. Vertices have a threshold r(i), that may be different at each vertex. If a vertex has fewer than r(i) neighbors it is pruned from the network. The heterogeneous k-core is the subgraph remaining after no further vertices can be pruned. If the thresholds r(i) are 1 with probability f, or k ≥ 3 with probability 1-f, the process can be thought of as a pruning process counterpart to ordinary bootstrap percolation, which is an activation process. We show that there are two types of transitions in this heterogeneous k-core process: the giant heterogeneous k-core may appear with a continuous transition and there may be a second discontinuous hybrid transition. We compare critical phenomena, critical clusters, and avalanches at the heterogeneous k-core and bootstrap percolation transitions. We also show that the network structure has a crucial effect on these processes, with the giant heterogeneous k-core appearing immediately at a finite value for any f>0 when the degree distribution tends to a power law P(q)~q(-γ) with γ<3.


Perivascular epithelioid cell tumor of the lacrimal gland.
A 33-year-old lady was referred to our clinic with a history of left upper eyelid swelling and difficulty to open her left eye for more than 4 years. Her globe was in infero-nasal displacement, and ocular movement was not full, with restriction to every direction. No clinical sign including eye redness, pain or visual loss was found on examination. Exophthalmometry confirmed 2 mm of left-sided proptosis. Computed tomography (CT) imaging of the orbit obtained in axial and coronal planes depicted an irregular and heterogeneous soft-tissue density mass in the left lacrimal gland, measuring 25 × 17 mm. Magnetic resonance imaging (MRI) revealed the mass of slightly longer T1 and slightly longer/shorter T2 signal, and Gd-enhanced MRI showed a significant enhancement. The tumor was first presumably diagnosed of pleomorphic adenomas. A surgery was applied to remove the tumor completely. Histopathological evaluation led to the diagnosis of PEComa.


Treatment strategies and indications for interventional management of pseudoaneurysms.
Pseudoaneurysms (PAs) are common vascular abnormalities predominantly arising from a disruption in the integrity of the arterial wall. The potential complications of PAs are usually unpredictable and carry high rates of morbidity and mortality. This paper presents our experience with various treatment strategies for PAs. Fifty-four patients with 55 PAs were diagnosed by non-invasive imaging examination. The etiology of PAs included trauma (33/55), infection (5/55), iatrogenic (6/55), and idiopathic (11/55). Different procedures including ultrasound (US)-guided compression, endovascular treatment, and surgery were performed depending on the location of PAs, size of the sac and neck, and characteristics of the donor artery. The methods of endovascular treatment included embolization of parent artery, the PA sac, or implantation of a stent-graft. Follow-up was performed using US or CT and ranged from 1 day to 24 months (average 16.7 months). In all 54 patients, 3 patients with superficial PAs were treated by US-guided compression, while 44 patients with 45 PAs located in the head and neck (n = 20), viscera (n = 10) or extremities (n = 15) were treated by endovascular treatment. Nine patients with PAs located in the head and neck (n = 2) or extremities (n = 7) were treated by surgery. Among them, one patient underwent endovascular treatment combined with surgery and 1 was treated by surgery after unsuccessful US-guided compression. In the 3 patients treated with US-guided compression, 2 were successfully treated while the remaining patient required additional surgery. Primary technical success of endovascular management was 97.7% (43/44) and the cure rate was 95.5% (42/44). In the surgery group, 4 patients recovered well, 1 patient was cured by endovascular treatment combined with surgery, 2 cases underwent amputation, 1 patient died of multi-organ failure and 1 patient was paralysed. Minimally invasive interventional techniques are established treatment methods for PA with favorable success rates and minimal morbidity. The therapeutic options should be tailored to the location, size and rupture risk of PA, condition of the donor artery and existing comorbidity.


Feeding intolerance: a concept analysis.
Feeding intolerance is a well-known phenomenon in the NICU and is linked to morbidity and mortality in the premature infant. However, a universal definition for this concept is lacking. Properly defining a concept is a key step in a successful research project. A concept analysis is an examination of the fundamental elements of a concept to bring clarification and definition to the topic of interest. The purpose of this concept analysis was to clarify the phenomenon of feeding intolerance in the premature infant and to provide a universal conceptual and operational definition for researchers and clinicians to use in practice theory.


The influence of sex hormones on ocular blood flow in women.
To investigate the influence of sex hormones on ocular haemodynamics, blood flow velocities in the ophthalmic and central retinal arteries and serum levels of sex hormones were measured in pre- and postmenopausal women. Colour Doppler imaging (CDI) was used to determine the flow velocities (peak systolic velocity [PSV] and end-diastolic velocity [EDV]) and the resistive index (RI) in the ophthalmic and central retinal arteries in 22 premenopausal and 32 postmenopausal women, who had never received hormone replacement therapy. Serum levels were measured for oestradiol, free testosterone and follicle-stimulating hormone. The CDI parameters were compared between the two groups and the influence of serum levels of oestradiol and testosterone on blood flow velocities and the resistive indices were analysed. After correcting for age and mean arterial blood pressure, an analysis of covariance disclosed a significantly lower EDV (p=0.02) and a significantly higher RI (p=0.01) in the central retinal artery of postmenopausal women compared with premenopausal women. Partial correlation analysis, controlling for age, revealed significant correlations between the CDI parameters and serum levels of oestradiol and testosterone. For premenopausal women, PSV (r=0.58, p=0.04) and EDV (r=0.73, p=0.006) in the ophthalmic artery correlated positively with serum oestradiol levels. The RI in the central retinal artery decreased with increasing oestradiol levels in both groups (premenopausal r= -0.40, p=0.04; postmenopausal r= -0.32, p=0.05). Peak systolic velocity in the central retinal artery correlated negatively (r= -0.49, p=0.04), whereas the RI correlated positively (r=0.53, p=0.02) with testosterone levels in the premenopausal group. Postmenopausal women with higher testosterone levels had lower EDV (r= -0.53, p=0.007) in the central retinal artery and higher RI in both vessels (ophthalmic artery r=0.48, p=0.01; central retinal artery r=0.61, p=0.002). Our data provide evidence of a relationship between serum sex hormone levels and blood flow velocities and resistive indices in retrobulbar arteries. Oestradiol appears to have beneficial effects on ocular haemodynamics, whereas testosterone may act as an antagonistic to the effects of oestrogen.


Phosphorus-modified two-dimensional graphdiyne (CnH2n-2)/ZnCdS forms S-scheme heterojunctions for photocatalytic hydrogen production.
Graphdiyne (GDY) is a new type of carbon allotrope material with a network structure composed of sp- and sp2-hybridized carbon, and its excellent photoelectrochemical properties have an extraordinary impact on energy materials. In this work, a graphite alkyne material was calcined and used as an anchor substrate to fix bimetallic sulfide-zinc-cadmium sulfide to form a phosphorus-doped graphdiyne (GDY-P)/zinc-cadmium sulfide (ZnCdS) heterojunction photocatalyst. The close contact between the 2D/0D binary heterojunction interfaces produced a strong interfacial force, and the final hydrogen evolution rate of the GDY-P/ZnCdS structure reached 10 395.57 μmol g-1 h-1, which was 2.57 and 240 times those of ZnCdS and GDY, respectively. The S-scheme heterojunction constructed by GDY-P and ZnCdS accelerates the formation of electron-hole pairs, improves the utilization of strongly reduced electrons, and overcomes the self-agglomeration of ZnCdS, ensuring the high hydrogen evolution activity of the binary structure. This work provides a new application paradigm for the construction of S-scheme heterojunctions for hydrogen evolution using new carbon materials in the field of photocatalysis.


[Sudden suffocation by clogging up of the respiratory tract with foreign bodies--case report].
The study presents a case of death by clogging up of the respiratory system by foreign bodies. The autopsy revealed among others the presence of a cigarette lighter and a piece of an aluminum spoon in the throat, and a cut-and-stab wound on the front surface of the neck with accompanying trial incisions, penetrating into the respiratory tract, clogged by a substantial amount of blood, focuses of aspiration in the lungs, and symptoms of lung distension. Histopathological examinations of inner organ samples revealed the presence of extravasations of blood in the air space as well as symptoms of acute lung distension, confirming the autopsy diagnosis. Toxicological examinations revealed that the victim in the moment of death was in a state of deep alcoholic intoxication. The conducted interrogations of possible witnesses/suspects of the incident turned out insufficient for the reconstruction of events. The authors of the study therefore attempt a reconstruction of the incident based on executed examinations.


Triterpenoidal alkaloids from Buxus natalensis and their acetylcholinesterase inhibitory activity.
Acetylcholinesterase (AChE) inhibition-directed phytochemical studies on the methanolic extract of Buxus natalensis, collected in South Africa, resulted in the isolation of 12 compounds: O(2)-natafuranamine (1), O(10)-natafuranamine (2), cyclonataminol (3), 31-demethylbuxaminol A (4), buxaminol A (5), buxafuranamide (6), buxalongifolamidine (7), buxamine A (8), cyclobuxophylline K (9), buxaminol C (10), methyl syringate (11), and p-coumaroylputrescine (12). Compounds 1-4 were new alkaloids, and compound 5 was isolated for the first time as a natural product. Their structures were elucidated with the aid of extensive NMR and mass spectroscopic studies. Compounds 1 and 2 are members of a rarely occurring class of Buxus alkaloids, having a tetrahydrofuran ring incorporated in their structures. Compounds 1-12 exhibited strong to moderate AChE inhibitory activity.


More robust detection of motifs in coexpressed genes by using phylogenetic information.
Several motif detection algorithms have been developed to discover overrepresented motifs in sets of coexpressed genes. However, in a noisy gene list, the number of genes containing the motif versus the number lacking the motif might not be sufficiently high to allow detection by classical motif detection tools. To still recover motifs which are not significantly enriched but still present, we developed a procedure in which we use phylogenetic footprinting to first delineate all potential motifs in each gene. Then we mutually compare all detected motifs and identify the ones that are shared by at least a few genes in the data set as potential candidates. We applied our methodology to a compiled test data set containing known regulatory motifs and to two biological data sets derived from genome wide expression studies. By executing four consecutive steps of 1) identifying conserved regions in orthologous intergenic regions, 2) aligning these conserved regions, 3) clustering the conserved regions containing similar regulatory regions followed by extraction of the regulatory motifs and 4) screening the input intergenic sequences with detected regulatory motif models, our methodology proves to be a powerful tool for detecting regulatory motifs when a low signal to noise ratio is present in the input data set. Comparing our results with two other motif detection algorithms points out the robustness of our algorithm. We developed an approach that can reliably identify multiple regulatory motifs lacking a high degree of overrepresentation in a set of coexpressed genes (motifs belonging to sparsely connected hubs in the regulatory network) by exploiting the advantages of using both coexpression and phylogenetic information.


Effectiveness of postoperative wound drains in one- and two-level cervical spine fusions.
Cervical drains have historically been used to avoid postoperative wound and respiratory complications such as excessive edema, hematoma, infection, re-intubation, delayed extubation, or respiratory distress. Recently, some surgeons have ceased using drains because they may prolong hospital stay, operative time, or patient discomfort. The objective of this retrospective case-control series is to investigate the effectiveness of postoperative drains following one- and two-level cervical fusions. A chart review was conducted at a single institution from 2010-2013. Outcome measures included operative time, hospital stay, estimated blood loss and incidence of wound complications (infection, hematoma, edema, and complications with wound healing or evacuation), respiratory complications (delayed extubation, re-intubation, and respiratory treatment), and overall complications (wound complications, respiratory complications, dysphagia, and other complications). Statistical analyses including independent samples t-test, chi-square, analysis of covariance, and linear regression were used to compare patients who received a postoperative drain to those who did not. The study population included 39 patients who received a postoperative drain and 42 patients who did not. There were no differences in demographics between the two groups. Patients with drains showed increased operative time (100.1 vs 69.3 min, p < 0.001), hospital stay (38.9 vs. 31.7 hrs, p = 0.021), and blood loss (62.7 vs 29.1 mL, p < 0.001) compared to patients without drains. The frequency of wound complications, respiratory complications, and overall complications did not vary significantly between groups. Cervical drains may not be necessary for patients undergoing one- and two-level cervical fusion. While there were no differences in incidence of complications between groups, patients treated with drains had significantly longer operative time and length of hospital stay. This could contribute to excessive costs for patients treated with drains, despite the lack of compelling evidence of the advantages of this treatment in the literature and in the current study.


Congenital disorders of glycosylation with emphasis on cerebellar involvement.
Congenital disorders of glycosylation (CDG) are genetic diseases due to defective glycosylation of proteins and lipids. The authors present an update on these disorders affecting the central nervous system with a focus on cerebellar involvement. The rate of identification of novel CDG shows an exponential increase. Some 76 CDG are actually known, not taking into account the defects in glycan-modifying proteins. Neurologic involvement is present in the large majority of CDG. Screening methods are limited to serum transferrin isoelectrofocusing (for N-glycosylation disorders with sialic acid deficiency), and serum apolipoprotein C-III isoelectrofocusing (for core 1 mucin-type O-glycosylation disorders). Whole exome/genome sequencing is increasingly used in the diagnostic workup of patients with CDG-X. Treatment is greatly lagging behind because only one CDG is efficiently treatable (MPI-CDG). Cerebellar involvement is an important feature of PMM2-CDG, the congenital muscular dystrophies due to dystroglycanopathy, and SRD5A3-CDG. It has also been reported in some patients with ALG1-CDG, ALG3-CDG, ALG9-CDG, ALG6-CDG, ALG8-CDG, PIGA-CDG, DPM1-CDG, DPM2-CDG, B4GALT1-CDG, SLC35A2-CDG, COG1-CDG, COG5-CDG, COG7-CDG, and COG8-CDG.


Defective graphene for electrocatalytic CO2 reduction.
The rational synthesis of earth-abundant materials with excellent electrocatalytic performances plays a critical role in electrochemical CO2 reduction (ECR) to obtain value-added chemical products or fuels. Here we demonstrate a defective graphene (DG) as such an electrocatalyst candidate via a nitrogen removal method. The graphene with a large amount of topological defects offered abundant catalytically active sites, high electronic conductivity and strong adsorption of CO2. Attributed to these features, the DG exhibited significantly higher electrocatalytic CO2 reduction performances with an excellent faradaic efficiency of ∼84% at -0.6 V vs. reversible hydrogen electrode and a larger current density, compared to pristine graphene, nitrogen-doped graphene and edge-rich graphene. This work suggests a promising method for further designing efficient metal-free electrocatalysts for CO2 reduction.


New biotechnological tools to accelerate scab-resistance trait transfer to apple.
Apple is a fruit crop cultivated worldwide. Apple orchards are exposed to a diverse set of environmental and biological factors that affect the productivity and sustainability of the culture. Many of the efforts and costs for apple production rely on reducing the incidence of fungal diseases, and one of the main diseases is apple scab caused by the fungus Venturia inaequalis. The economic impact of scab on apple productivity has guided many breeding programs to search for cultivars resistant to apple scab. Introgression from wild relatives has been successful to some extent, and genetic engineering for resistant cultivars has even been employed. This review presents the techniques used to the present time to obtain pathogen-resistant apple cultivars and introduces new biotechnological approaches based on plant plasmids that show promising results for delivering genetic traits with a short-term perspective.


Mainstream smoke of the waterpipe: does this environmental matrix reveal as significant source of toxic compounds?
In recent years the number of waterpipe smokers has increased substantially worldwide. Here we report on the concentrations of tobacco-specific nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) in waterpipe smoke and the analysis of selected biomarkers indicative for the body burden in waterpipe users. We further identify high amounts of unburned humectants (glycerol and propylene glycol) in the waterpipe smoke as main part of the so-called "tar" fraction. These results give cause for serious concern. For standardization we applied a machine smoking protocol. Smoke was collected on glass fiber filters and analyzed for nicotine, water, humectants, TSNAs, and PAHs. In addition, we determined carbon monoxide and found high amounts in the smoke being causative for high levels of carboxyhemoglobin (COHb) in the blood of smokers. In comparison to the reference cigarette 3R4F, the nicotine contents were 10-times higher, but TSNA levels were found lower in waterpipe smoke. This finding explained the low levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol detected in the urine of waterpipe smokers. Finally, the levels of benzo[a]pyrene were three times higher in waterpipe smoke compared to the reference cigarette. Altogether, the data presented in this study point to the health hazards associated with the consumption of waterpipes.


Therapeutic outcome of adjustable gastric banding in morbid obese patients.
We examined 77 obese patients treated with bariatric surgery in order to analyse treatment success, and compare those with a good or a poor outcome. The subjects, who were recruited one year after undergoing adjustable gastric banding, were asked questions concerning their sociodemographic status, postoperative course, past and present weight status, eating behaviours and difficulties in changing eating habits. Furthermore, we also used two body image questionnaires, and considered the patients' evaluations of positive and negative changes, as well as their wishes for the future. There were no preoperative differences between the 71% of patients in the good outcome group and the 29% in the poor outcome group. With regard to the postoperative course, the poor outcome group had more problems in adapting to new eating behaviours, experienced significantly more post-surgical complications, and had a persistently negative body evaluation. Both groups were satisfied with their achieved weight loss achieved, and their improved self-esteem and mobility. Adjustable gastric banding seems to be successful in inducing weight loss and allowing a better quality of life. However, factors such as postoperative complications, the ability and willingness to adopt new eating attitudes, and an improved body image seem to be crucial for therapeutic outcome.


Erythema multiforme after application of aural Gentisone HC drops.
Erythema multiforme is an uncommon acute self-limiting condition characterized by mucocutaneous lesions of varying severity with a variable pattern of recurrence. This is a case of a four-year-old girl who developed erythema multiforme secondary to topical aural application of Gentisone HC drops (hydrocortisone acetate one per cent, gentamicin 0.3 per cent (as sulphate)) prescribed as a treatment for otorrhoea following grommet insertion. The clinical features are described and the literature reviewed. To my knowledge, this is the first reported case in the literature, of erythema multiforme secondary to a topical aminoglycoside/steroid preparation.


Evaluation of Mechanical and Physical Properties of Light and Heat Polymerized UDMA for DLP 3D Printer.
The aims of this study were to investigate the feasibility of using a DLP 3D printer to fabricate a crown using scan data before tooth preparation, and to investigate the effect of additional heat curing on the mechanical properties of the urethane dimethacrylate (UDMA)-based 3D printed crown. A silicone fitting test was used to evaluate the internal adaptation of the crown. For ultimate tensile strength (UTS), the specimens were tested after 24 h storage in water at 37 °C or after 10,000 thermal cycles (TC) between 5-55 °C. For shear bond strength (SBS), a PMMA self-curing resin was filled into a Teflon ring mounted onto the polished UDMA specimens. The internal adaptation of the crowns fabricated with cement space was better than those with no cement space. There was no significant difference in UTS between light-curing and additional heat-curing groups after TC. As for the SBS, there was a significant difference after TC between the two groups. Crowns can be fabricated by a DLP 3D printer using pre-preparation scans with a cement space defined in the software. Additional heat curing of the UDMA-based crown reduced residual monomer and improved its mechanical properties.


Osteogenic effect of tricalcium phosphate substituted by magnesium associated with Genderm® membrane in rat calvarial defect model.
Beta-tricalcium phosphate (β-TCP) is one of the most widely employed bioresorbable materials for bone repair since it shows excellent biological compatibility, osteoconductivity and resorbability. The incorporation of divalent cations such as magnesium onto the β-TCP structure (β-TCMP) may improve the biological response to the material through the release of bioactive ions. The objective of this study was to evaluate, on a rat calvarial critical size grafting model, the bone regeneration process using β-TCP and β-TMCP granules by histomorphometric analysis. Results demonstrated that six months after bone grafting, the association of GBR (guided bone regeneration) using a membrane (GenDerm®) and granules of β-TCP and β-TCMP significantly improves bone repair in the treatment of critical-size defect in rat skulls, in comparison to untreated defects or GBR alone, leading to a bone level approximately four to five-fold greater than in the blood clot group. The β-TCMP+GenDerm® membrane group presented 40.5% of the defect area filled by newly-formed bone, even at the central part of the defect, rather than only at the border, as seen in the other experimental groups.


Cancer induction by the sulfate form of 4-(hydroxymethyl) benzenediazonium ion of Agaricus bisporus.
The sulfate form of 4-(hydroxymethyl) benzenediazonium ion (HMBD) of Agaricus bisporus was given by 26 weekly subcutaneous injections at 50 micrograms/g body weight to Swiss mice. As a result of treatment, tumors of subcutis and skin developed in 32% and 14% of the females and 40% and 4% of the males, respectively. The corresponding tumor incidences in the sodium sulfate-injected solvent control groups were 0% and 2% in females and 4% and 0% in males, respectively. Histopathologically, the tumors were fibrosarcomas, rhabdomyosarcomas and angiosarcomas of the subcutis, squamous cell papillomas and carcinomas of skin. The present finding discounts an earlier allegation that the tetrafluoroborate portion of the diazonium ion acted as a cocarcinogen. HMBD was found at a 0.6 ppm level in the mushroom of commerce Agaricus bisporus.


The Diminishing Returns of Mechanical Loading and Potential Mechanisms that Desensitize Osteocytes.
Adaptation to mechanical loading is critical to maintaining bone mass and offers therapeutic potential to preventing age-related bone loss and osteoporosis. However, increasing the duration of loading is met with "diminishing returns" as the anabolic response quickly becomes saturated. As a result, the anabolic response to daily activities and repetitive bouts of loading is limited by the underlying mechanisms that desensitize and render bone unresponsive at the cellular level. Osteocytes are the primary cells that respond to skeletal loading and facilitate the overall anabolic response. Although many of osteocytes' signaling mechanisms activated in response to loading are considered anabolic in nature, several of them can also render osteocytes insensitive to further stimuli and thereby creating a negative feedback loop that limits osteocytes' overall response. The purpose of this review is to examine the potential mechanisms that may contribute to the loss of mechanosensitivity. In particular, we examined the inactivation/desensitization of ion channels and signaling molecules along with the potential role of endocytosis and cytoskeletal reorganization. The significance in defining the negative feedback loop is the potential to identify unique targets for enabling osteocytes to maintain their sensitivity. In doing so, we can begin to cultivate new strategies that capitalize on the anabolic nature of daily activities that repeatedly load the skeleton.


Germanium-induced nephropathy: report of two cases and review of the literature.
We report two cases of renal failure following long-term ingestion of germanium dioxide (GeO2) and comment on eight other cases reported in Japan. Ge-induced nephropathy is characterized by insidious onset of renal failure without proteinuria or hematuria after oral intake of Ge-containing compounds for more than several months, and by degeneration of renal tubular cells with minor glomerular abnormality in histology. When patients ceased to ingest Ge compounds, renal function gradually recovered but never returned to the normal range. Serious extrarenal complication can contribute to an unfavorable prognosis.


Structures and Oxidation Properties of Phenylene-Bridged Diazacycloalkanes: Ring Size Effects on Structures and Properties.
Phenylenediamine derivatives have been investigated as functional molecules because of their characteristic oxidation properties. In this study, phenylene-bridged diazacycloalkanes, that is, C10, C12, and C14, in which numbers indicate the lengths of a side chain, were synthesized, and the effects of the macroring size on their structures and oxidation properties were investigated. X-ray crystallography revealed that the structures around the nitrogen atoms were remarkably dependent on the chain lengths. The benzene plane of C10 is arranged almost perpendicular to the macroring to avoid steric contact. However, the benzene plane of C14 and alkyl frame were co-planar. Stabilization resulting from conjugation was comparable to destabilization caused by macroring strain according to DFT calculations. Structural differences between C10 and C14 caused changes in the NMR chemical shifts of the inner methylene protons and first oxidation potentials in solution. Notably, the properties of C12 can be analyzed as those of distributed structures, which is of interest with respect to exploiting the metastable structure of the molecules. The observed relationships between the steric structures and properties can facilitate the design of functional molecules containing phenylenediamine moieties.


Li2ZrO3-Coated NCM622 for Application in Inorganic Solid-State Batteries: Role of Surface Carbonates in the Cycling Performance.
All-inorganic solid-state batteries (SSBs) currently attract much attention as next-generation high-density energy-storage technology. However, to make SSBs competitive with conventional Li-ion batteries, several obstacles and challenges must be overcome, many of which are related to interface stability issues. Protective coatings can be applied to the electrode materials to mitigate side reactions with the solid electrolyte, with lithium transition metal oxides, such as LiNbO3 or Li2ZrO3, being well established in research. In addition, it has been recognized lately that carbonates incorporated into the coating may also positively affect the interface stability. In this work, we studied the effect that surface carbonates in case of Li2ZrO3-coated Li1+x(Ni0.6Co0.2Mn0.2)1-xO2 (NCM622) cathode material have on the cyclability of pellet stack SSB cells with Li6PS5Cl and Li4Ti5O12 as a solid electrolyte and an anode, respectively. Both carbonate-rich and carbonate-poor hybrid coatings were produced by altering the synthesis conditions. The best cycling performance was achieved for carbonate-deficient Li2ZrO3-coated NCM622 due to decreased degradation of the argyrodite solid electrolyte at the interfaces, as determined by ex situ X-ray photoelectron spectroscopy and in situ differential electrochemical mass spectrometry. The results emphasize the importance of tailoring the composition and nature of protective coatings to improve the cyclability of bulk SSBs.


Factors associated with teenage pregnancy in the Scandinavian countries.
Teenage pregnancy may have negative consequences for the mother and the infant. The aim of the study was to examine whether selected individual factors occurring early in life were associated with teenage pregnancy. In a population-based, cross-sectional questionnaire study among 34,455 women from Denmark, Norway, and Sweden aged 20-45 years, who had first sexual intercourse (FSI) at age 13-19 years, we assessed the association between early smoking and drinking initiation (i.e., before the age of 13), contraceptive use at FSI, and teenage pregnancy. Log-linear binary regression models were fitted to estimate the relative risk (RR) with 95% confidence intervals (CIs) of teenage pregnancy according to the three exposure variables, overall and by age at FSI. Furthermore, the outcomes of the teenage pregnancies were examined according to age at FSI. Teenage pregnancy occurred in 11% of the population. Both early smoking initiation (RR: 1.6; 95% CI: 1.4-1.8), early drinking initiation (RR: 1.2; 95% CI: 1.0-1.4), and non-use of contraceptives at FSI (RR: 1.9; 95% CI: 1.8-2.0) were associated with teenage pregnancy. The associations for early smoking initiation and non-use of contraceptives remained when analyses were stratified by age at FSI. Almost 60% of all teenage pregnant women had an induced abortion and less than 30% gave birth. Individual factors, including early smoking and drinking initiation, and non-use of contraceptives at FSI, were associated with teenage pregnancy regardless of age at FSI. This emphasizes the necessity of focusing on early risk-taking behavior as a potential modifier to prevent teenage pregnancy.


Expression and oncogenic properties of membranous Notch1 in oral leukoplakia and oral squamous cell carcinoma.
Notch1 signaling is essential for tissue development and tumor progression. This signaling pathway has also been implicated in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC). However, the role of Notch1 expression in OL and its malignant transformation is unknown. This study aimed to examine the Notch1 expression patterns by immunohistochemistry (IHC) in a cohort of 78 Chinese patients with OL and to analyze the relationship between the patterns and progression of OL to OSCC. Strong Notch1 staining was observed in 10 (13%) of the 78 OL patients, but it was not associated with any of the clinicopathological parameters. However, we observed membranous Notch1 expression in 24 (31%) of the OL samples. Membranous Notch1 expression was significantly associated with the severity of dysplasia (P<0.001) and development of OSCC (P=0.003). By multivariate analysis, membranous Notch1 expression was found to be the only independent factor for OSCC development in the patient population (P=0.019). Among the 24 patients with membranous Notch1 expression, 11 (46%) developed OSCC compared to 8 (15%) of the 54 patients without such expression (P=0.001, determined by log‑rank test). Furthermore, we established a 4‑nitroquinoline‑1‑oxide (4NQO)‑induced murine OSCC model and studied the Notch1 expression patterns in different stages of carcinogenesis. We observed that the extent of expression of membranous Notch1 increased during carcinogenesis. These data indicated a relationship between membranous Notch1 expression and OSCC risk in patients with OL and suggested that membranous Notch1 served as a biomarker for assessing OSCC risk.


Analysis of clamping versus cutting of T3 sympathetic nerve for severe palmar hyperhidrosis.
Endoscopic thoracic sympathectomy can predictably eliminate the disabling symptoms of palmar hyperhidrosis. Debate has ensued over competing techniques, in particular, cutting versus clamping of the sympathetic chain. We subjectively assessed the sweat severity in different areas of the body and evaluated changes in the quality of life in patients undergoing either the cutting or clamping technique. Patients examined between June 2003 and March 2007 were asked to quantify the severity of their symptoms before and after endoscopic thoracic sympathectomy. The interviews were conducted approximately 1 year after the procedure. Only the patients undergoing sympathectomy at the T3 level for a chief complaint of palmar hyperhidrosis were included in the analysis (n = 152). In 45% of these patients, clamping of the sympathetic chain was performed, and the remaining 55% had the chain cut. After surgery, no patients had continued excessive sweating of the hands. Of all the patients, 95% were satisfied with the results after the cutting procedure and 97% were satisfied after clamping. No difference was seen in any outcome between the patients undergoing clamping versus cutting of the sympathetic chain, including sweating on the hands, face, armpits, feet, trunk, and thighs or in the quality of life. We found high rates of success and patient satisfaction when T3 sympathectomy was performed for palmar hyperhidrosis, with no differences found between the cutting and clamping techniques.


Increased levels of plasma D-dimer in the course of Henoch-Schönlein purpura.
Three cases of Henoch-Schönlein purpura (HSP) with elevated plasma D-dimer levels are described. In one case of acute course HSP we observed the beneficial influence of plasma and nadroparine treatment on the course of disease. In two cases plasma D-dimer increase did not correlate with severity of the disease. The possibility of coagulation disturbances in HSP with D-dimer rise (as well as decrease of plasma factor XIII and platelets described in relevant literature) should be taken into consideration. These results suggest presence of mild intravascular clotting process in course of the disease. However, we were not able to clarify the pathogenesis of the high D-dimer serum concentration in HSP. Thus, it is suggested that further research on the discussed condition should be conducted.


[Serological method of detecting antirabies antibodies].
The possibility of the determination of rabies antibodies by the serological method has been demonstrated, involving the use of culture rabies virus, strain Vnukovo-32, concentrated and purified by high speed centrifugation, for the sensitization of anserine erythrocytes. The neutralization test in mice and the passive hemagglutination test showed a correlation in rabies antibody titers in the sera of animlas immunized with rabies vaccines. The advantages of the passive hemagglutination test consist in the rapidity of obtaining the results, in a simple and economic method of carrying out the test.


Molecular survey and genetic identification of Anaplasma species in goats from central and southern China.
Anaplasma species are obligate intracellular rickettsial pathogens that impact the health of humans and animals. Few studies have been carried out on Anaplasma infections in central and southern China. This study was conducted to determine the coinfection rates of Anaplasma ovis, A. bovis, and A. phagocytophilum from 262 field blood samples of goats in these regions. The average prevalences of single infection of A. ovis, A. bovis, and A. phagocytophilum were 15.3, 16.0, and 6.1%, respectively. Coinfection of A. ovis and A. bovis was dominant, with an infection rate of 27.1%. Coinfection of A. ovis and A. phagocytophilum was 1.9% and that of A. bovis and A. phagocytophilum was 4.2%. Three-pathogen coinfection was found in three of four investigated provinces with a prevalence between 0 and 5.3%. The accuracy of the PCR results was corroborated by sequencing. Analysis of the 16S rRNA gene sequences of A. bovis and A. phagocytophilum confirmed the presence of these pathogens at the investigated sites and indicated the possible genetic diversity of A. phagocytophilum. Field blood inoculation of experimental animals led to successful identification and observation of the morphological shapes of A. bovis in the infected monocytes of sheep. Phylogenetic study with msp4 sequences of A. ovis indicated that the A. ovis genotypes from sheep in the north differed from the genotypes of goats in the investigated sites.


An Antipersister Strategy for Treatment of Chronic Pseudomonas aeruginosa Infections.
Bacterial persisters are a quasidormant subpopulation of cells that are tolerant to antibiotic treatment. The combination of the aminoglycoside tobramycin with fumarate as an antibacterial potentiator utilizes an antipersister strategy that is aimed at reducing recurrent Pseudomonas aeruginosa infections by enhancing the killing of P. aeruginosa persisters. Stationary-phase cultures of P. aeruginosa were used to generate persister cells. A range of tobramycin concentrations was tested with a range of metabolite concentrations to determine the potentiation effect of the metabolite under a variety of conditions, including a range of pH values and in the presence of azithromycin or cystic fibrosis (CF) patient sputum. In addition, 96-well dish biofilm and colony biofilm assays were performed, and the cytotoxicity of the tobramycin-fumarate combination was determined utilizing a lactate dehydrogenase (LDH) assay. Enhanced killing of up to 6 orders of magnitude of P. aeruginosa persisters over a range of CF isolates, including mucoid and nonmucoid strains, was observed for the tobramycin-fumarate combination compared to killing with tobramycin alone. Furthermore, significant fumarate-mediated potentiation was seen in the presence of azithromycin or CF patient sputum. Fumarate also reduced the cytotoxicity of tobramycin-treated P. aeruginosa to human epithelial airway cells. Finally, in mucoid and nonmucoid CF isolates, complete eradication of P. aeruginosa biofilm was observed in the colony biofilm assay due to fumarate potentiation. These data suggest that a combination of tobramycin with fumarate as an antibacterial potentiator may be an attractive therapeutic for eliminating recurrent P. aeruginosa infections in CF patients through the eradication of bacterial persisters.


The metabolomic signature of extreme longevity: naked mole rats versus mice.
The naked mole-rat (Heterocephalus glaber) is characterized by a more than tenfold higher life expectancy compared to another rodent species of the same size, namely, the laboratory mouse (Mus musculus). We used mass spectrometric metabolomics to analyze circulating plasma metabolites in both species at different ages. Interspecies differences were much more pronounced than age-associated alterations in the metabolome. Such interspecies divergences affected multiple metabolic pathways involving amino, bile and fatty acids as well as monosaccharides and nucleotides. The most intriguing metabolites were those that had previously been linked to pro-health and antiaging effects in mice and that were significantly increased in the long-lived rodent compared to its short-lived counterpart. This pattern applies to α-tocopherol (also known as vitamin E) and polyamines (in particular cadaverine, N8-acetylspermidine and N1,N8-diacetylspermidine), all of which were more abundant in naked mole-rats than in mice. Moreover, the age-associated decline in spermidine and N1-acetylspermidine levels observed in mice did not occur, or is even reversed (in the case of N1-acetylspermidine) in naked mole-rats. In short, the present metabolomics analysis provides a series of testable hypotheses to explain the exceptional longevity of naked mole-rats.


Low-dose memantine attenuated methadone dose in opioid-dependent patients: a 12-week double-blind randomized controlled trial.
Low-dose memantine might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. We investigated whether add-on memantine reduced cytokine levels and benefitted patients with opioid dependence undergoing methadone maintenance therapy (MMT) in a randomized, double-blind, controlled 12-week study. Patients were randomly assigned to a group: Memantine (5 mg/day) (n = 53) or Placebo (n = 75). The methadone dose required and retention in treatment were monitored. Plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-8, transforming growth factor (TGF)-β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. General linear mixed models were used to examine therapeutic effect. After 12 weeks, Memantine-group required a somewhat lower methadone dose than did Placebo-group (P = 0.039). They also had significantly lower plasma TNF-α and significantly higher TGF-β1 levels. We provide evidence of the benefit of add-on memantine in opioid dependent patients undergoing MMT.


IglG and IglI of the Francisella pathogenicity island are important virulence determinants of Francisella tularensis LVS.
The Gram-negative bacterium Francisella tularensis is the causative agent of tularemia, a disease intimately associated with the multiplication of the bacterium within host macrophages. This in turn requires the expression of Francisella pathogenicity island (FPI) genes, believed to encode a type VI secretion system. While the exact functions of many of the components have yet to be revealed, some have been found to contribute to the ability of Francisella to cause systemic infection in mice as well as to prevent phagolysosomal fusion and facilitate escape into the host cytosol. Upon reaching this compartment, the bacterium rapidly multiplies, inhibits activation of the inflammasome, and ultimately causes apoptosis of the host cell. In this study, we analyzed the contribution of the FPI-encoded proteins IglG, IglI, and PdpE to the aforementioned processes in F. tularensis LVS. The ΔpdpE mutant behaved similarly to the parental strain in all investigated assays. In contrast, ΔiglG and ΔiglI mutants, although they were efficiently replicating in J774A.1 cells, both exhibited delayed phagosomal escape, conferred a delayed activation of the inflammasome, and exhibited reduced cytopathogenicity as well as marked attenuation in the mouse model. Thus, IglG and IglI play key roles for modulation of the intracellular host response and also for the virulence of F. tularensis.


Fluorination and hydrolytic stability of water-soluble platinum complexes with a borane-bridged diphosphoramidite ligand.
The high fluorophilicity of borane-containing ligands offers promise for accessing new metallodrug candidates capable of bifunctional [18F]-positron emission tomography (PET) imaging, but this requires water soluble and hydrolytically stable ligands that can be fluorinated under mild conditions. Toward this goal, here we report the synthesis and characterization of water-soluble Pt(II) complexes containing a triaminoborane-bridged diphosphoramidite ligand called MeOTBDPhos that can be fluorinated using simple fluoride salts. NMR and XRD studies show that (MeOTBDPhos)PtCl2 (1) dissolves in water with cooperative H-OH addition across the bridgehead N-B bond to form 1-H2O. The B-OH bond in 1-H2O undergoes rapid displacement with fluoride (<10 min) when treated with CsF in MeCN to form 1-HF. 1-HF can also be prepared in <10 min by addition of KF to 1 in the presence Kryptofix® 222 and (HNEt3)Cl in MeCN. In addition to using fluoride salts, we show how mononuclear 1 can be fluorinated with HBF4·Et2O to form dinuclear [(MeOTBDPhos-HF)Pt(μ-Cl)]2(BF4)2 (4-HF). Comparative studies show that the B-F bond in 1-HF undergoes hydrolysis as soon as it is dissolved in water or saline, but the B-F bond persists for hours when the pH of the solution is lowered to pH ≤ 2. In contrast to 1-HF, the B-F bond in dinuclear 4-HF persists for days when dissolved in water, which may be attributed to slow, sacrificial release of fluoride from the BF4- anion. The results show how cooperative N-B reactivity on the ligand can be leveraged to rapidly fluorinate water-soluble MeOTBDPhos complexes under mild conditions and afford suggestions for how to enhance hydrolytic B-F stability, as required for use in biomedical applications.


DNA-wrapped multi-walled carbon nanotube modified electrochemical biosensor for the detection of Escherichia coli from real samples.
This paper introduces DNA-wrapped multi-walled carbon nanotube (MWCNT)-modified genosensor for the detection of Escherichia coli (E. coli) from polymerase chain reaction (PCR)-amplified real samples while Staphylococcus aureus (S. aureus) was used to investigate the selectivity of the biosensor. The capture probe specifically recognizing E. coli DNA and it was firstly interacted with MWCNTs for wrapping of single-stranded DNA (ssDNA) onto the nanomaterial. DNA-wrapped MWCNTs were then immobilised on the surface of disposable pencil graphite electrode (PGE) for the detection of DNA hybridization. Electrochemical behaviors of the modified PGEs were investigated using Raman spectroscopy and differential pulse voltammetry (DPV). The sequence selective DNA hybridization was determined and evaluated by changes in the intrinsic guanine oxidation signal at about 1.0V by DPV. Numerous factors affecting the hybridization were optimized such as target concentration, hybridization time, etc. The designed DNA sensor can well detect E. coli DNA in 20min detection time with 0.5pmole of detection limit in 30µL of sample volume.


Left-ventricular function and autonomic cardiac adaptations after short-term inpatient cardiac rehabilitation: a prospective clinical trial.
Cardiac rehabilitation is associated with cardiac autonomic and physiological benefits. However, it is unclear whether baseline left ventricular function (LVF) impacts on training-induced cardiac autonomic adaptations. The aim of this study was to assess the cardiac autonomic adaptations in patients with varying left ventricular function profiles undergoing coronary artery bypass grafting and cardiac rehabilitation. Assessor-blinded prospective trial. Forty-four patients undergoing coronary artery bypass grafting, divided into normal LVFN (≥ 55%, n = 23) or reduced LVFR (35-54%, n = 21) were evaluated. Cardiac autonomic function was evaluated by heart rate variability indexes obtained both pre- and post-cardiac rehabilitation. All patients participated in a short-term (approximately 5 days) supervised inpatient physiotherapy program. There were differences in heart rate variability indexes, correlation dimension and SD2 according to time and group (e.g. interaction time (effect of cardiac rehabilitation) vs group (LVFN vs LVFR), p = 0.04). Simple main effects analysis showed that the LVFR group benefited to a greater degree from cardiac rehabilitation compared with the LVFN group. Heart rate variability indexes increased significantly in the former group compared with the latter. Among post-coronary artery bypass grafting patients engaged in short-term inpatient rehabilitation, those with reduced left ventricular function are most likely to have better cardiac autonomic adaptations to exercise-based rehabilitation.


Faecal peritonitis secondary to perforated recto sigmoid colon by a large gallstone: a case report.
Large bowel obstruction is an important surgical emergency. The cause of obstruction may be benign or malignant, and include large bowel volvulus, polyps, intraperitoneal adhesions, strictures and neoplastic growths. Large bowel obstruction caused by gallstone(s) is a very rare phenomenon and not many cases are reported in the English literature. The present report describes a case of large bowel obstruction and faecal peritonitis caused by a gallstone perforating sigmoid colon. A database search (PubMed) did not locate any cases of large bowel perforation by a gallstone in the English literature, and hence this case report may be the first on this subject.


Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression.
Gram-negative bacterial infection or treatment of animals with bacterial lipopolysaccharide (LPS) induces a catabolic state with proteolysis, liver injury and an inhibition of the insulin-like growth factor-I (IGF-I) system. The purpose of this work was to elucidate the role of Kupffer cells in LPS-induced inhibition of the IGF-I/IGF-binding protein-3 (IGFBP-3) system. Adult male Wistar rats were either pretreated with the Kupffer cell inhibitor gadolinium chloride (10 mg/kg, i.v., 24 h prior to LPS exposure) or saline vehicle. Rats received two i.p. injections of 1 mg/kg LPS (at 17:30 and 08:30 h the following day) and were killed 4 h after the second injection. LPS administration induced a significant decrease in body weight and in serum concentrations of IGF-I and IGFBP-3 (P < 0.01), as well as in their gene expression in the liver. LPS-injected rats had increased serum concentrations of ACTH, corticosterone (P < 0.05), tumour necrosis factor-alpha (TNF-alpha) and nitrites (P < 0.01). Pretreatment of the animals with gadolinium chloride blocked the inhibitory effect of LPS on body weight, and on serum concentrations of IGF-I, IGFBP-3 and nitrites, as well as growth hormone receptor (GHR), IGF-I and IGFBP-3 gene expression in the liver. In contrast, gadolinium chloride administration did not modify the stimulatory effect of LPS on serum concentrations of ACTH, corticosterone and TNF-alpha. These results suggest that Kupffer cells are important mediators in the inhibitory effect of LPS on GHR, IGF-I and IGFBP-3 gene expression in the liver, leading to a decrease in serum concentrations of IGF-I and IGFBP-3.


Recommendations for a Combined Laparoscopic and Transanal Approach in Treating Deep Endometriosis of the Lower Rectum-The Rouen Technique.
The complete excision of low rectovaginal deep endometriosis is a demanding surgery associated with an increased risk of intra- and postoperative complications, which can impact the quality of life. Given the choices of optimal surgery procedures available, we would like to emphasize that a minimally invasive approach with plasma medicine and a transanal disc excision could significantly improve surgery for deep endometriosis, avoiding the lateral thermal damage of vascular and parasympathetic fibers of roots S2-S5 in the pelvic plexus. The management of low rectal deep endometriosis is distinct from other gastrointestinal-tract endometriosis nodules. Suggestions and explanations are presented for this minimal approach. These contribute to individualized medical care for deep endometriosis. In brief, a laparoscopic transanal disc excision (LTADE; Rouen technique) was performed through a laparoscopic deep rectal dissection, combined with plasma energy shaving, and followed by a transanal disc excision of the low and mid-rectal deep endometriotic nodules, with the use of a semi-circular stapler. LTADE is indicated as the first-line surgical treatment for low and mid-rectal deep endometriotic nodule excisions, because it can preserve rectal length and innervation. This technique requires a multidisciplinary team with surgical colorectal training.


Protein Electrostatic Properties Predefining the Level of Surface Hydrophobicity Change upon Phosphorylation.
We use explicit-solvent, molecular dynamics simulations to study the change in polar properties of a solvent-accessible surface for proteins undergoing phosphorylation. We analyze eight different pairs of proteins representing different structural classes in native and phosphorylated states and estimate the polarity of their surface using the molecular hydrophobicity potential approach. Whereas the phosphorylation-induced hydrophobicity change in the vicinity of phosphosites does not vary strongly among the studied proteins, the equivalent change for complete proteins covers a surprisingly wide range of effects including even an increase in the overall hydrophobicity in some cases. Importantly, the observed changes are strongly related to electrostatic properties of proteins, such as the net charge per residue, the distribution of charged side-chain contacts, and the isoelectric point. These features predefine the level of surface hydrophobicity change upon phosphorylation and may thus contribute to the phosphorylation-induced alteration of the interactions between a protein and its environment.


Emerging translational science discoveries, clonal approaches, and treatment trends in chronic myeloproliferative neoplasms.
The 60th American Society of Hematology (ASH) held in San Diego in December 2018 was followed by the 13th Post-ASH chronic myeloproliferative neoplasms (MPNs) workshop on December 4 and 5, 2018. This closed annual workshop, first introduced in 2006 by Goldman and Mughal, was organized in collaboration with Alpine Oncology Foundation and allowed experts in preclinical and clinical research in the chronic MPNs to discuss the current scenario, including relevant presentations at ASH, and address pivotal open questions that impact translational research and clinical management. This review is based on the presentations and deliberations at this workshop, and rather than provide a resume of the proceedings, we have selected some of the important translational science and treatment issues that require clarity. We discuss the experimental and observational evidence to support the intimate interaction between aging, inflammation, and clonal evolution of MPNs, the clinical impact of the unfolding mutational landscape on the emerging targets and treatment of MPNs, new methods to detect clonal heterogeneity, the challenges in managing childhood and adolescent MPN, and reflect on the treatment of systemic mastocytosis (SM) following the licensing of midostaurin.